bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of PLXNA1, NRP1, and NRP2 variants in a cohort of patients with isolated hypogonadotropic hypogonadism
Authors: Men Meichao , Chen Dan‐Na , Li Jia‐Da , Wang Xinying , Zeng Wang , Jiang Fang , Zheng Ruizhi , Dai Wenting 
Published: October 2021

AbstractBackgroundIsolated hypogonadotropic hypogonadism (IHH) is a clinical syndrome described by failure of gonadal function secondary to defects on the synthesis, secretion, or action of the gonadotropin‐releasing hormone (GnRH). The secreted glycoprotein SEMA3A binds its receptors NRP1 or NRP2 and PLXNA to participate in axonal projection, dendritic branching, synaptic formation, and neuronal migration. Deficiency in SEMA3A, NRP1, NRP2, and PLXNA1 have been related to abnormal GnRH neuron development in mice and IHH in humans.MethodsThe aim of this study was to examine the genotypic and phenotypic spectra of the NRP1, NRP2, and PLXNA1 genes in a large cohort of IHH probands from China. We screened NRP1, NRP2, and PLXNA1 variants in Chinese IHH patients by whole exome sequencing and pedigree analysis.ResultsWe identified 10 heterozygous missense variants in PLXNA1, five heterozygous missense variants in NRP1, and two heterozygous missense variants in NRP2. NRP1 variants were found only in IHH patients with defective olfaction (i.e., Kallmann syndrome, KS). In addition, 85% (17/20) of patients harbored variants in other IHH‐associated genes.ConclusionOur study greatly enriched the genotypic and phenotypic spectra of PLXNA1, NRP1, and NRP2 in IHH. It may be conducive to the genetic counseling, diagnosis, and treatment of IHH with mutations in the PLXNA1, NRP1, and NRP2 genes. Furthermore, our results indicated that NRP1 were strongly linked to hearing loss.
Fetal akinesia deformation sequence and massive perivillous fibrin deposition resulting in fetal death in six fetuses from one consanguineous couple, including literature review
Authors: Tjon Jill K. , Lakeman Phillis , van Leeuwen Elisabeth , Waisfisz Quinten , Weiss Marjan M. , Tan‐Sindhunata Gita M. B. , Nikkels Peter G. J. , van der Voorn Patrick J. P. , Salomons Gajja S. , Burchell George L. , Linskens Ingeborg H. , van der Knoop Bloeme J. , de Vries Johanna I. P. 
Published: October 2021

AbstractBackgroundMassive perivillous fibrin deposition (MPFD) is associated with adverse pregnancy outcomes and is mainly caused by maternal factors with limited involvement of fetal or genetic causes. We present one consanguineous couple with six fetuses developing Fetal Akinesia Deformation Sequence (FADS) and MPFD, with a possible underlying genetic cause. This prompted a literature review on prevalence of FADS and MPFD.MethodsFetal ultrasound examination, motor assessment, genetic testing, postmortem examination, and placenta histology are presented (2009–2019). Literature was reviewed for the association between congenital anomalies and MPFD.ResultsAll six fetuses developed normally during the first trimester. Thereafter, growth restriction, persistent flexed position, abnormal motility, and contractures in 4/6, consistent with FADS occurred. All placentas showed histologically confirmed MPFD. Genetic analyses in the five available cases showed homozygosity for two variants of unknown significance in two genes, VARS1 (OMIM*192150) and ABCF1 (OMIM*603429). Both parents are heterozygous for these variants. From 63/1999 manuscripts, 403 fetal outcomes were mobilized. In 14/403 fetuses, congenital abnormalities in association with MPFD were seen of which two fetuses with contractures/FADS facial anomalies.ConclusionThe low prevalence of fetal contractures/FADS facial anomalies in association with MPFD in the literature review supports the possible fetal or genetic contribution causing FADS and MPFD in our family. This study with literature review supports the finding that fetal, fetoplacental, and/or genetic components may play a role in causing a part of MPFDs.
Overcoming severe calcified lower extremity artery in lower limb salvage operation by using the Fogarty catheter and vein graft
Authors: Kim Dong Yeon , Kim Yesol , Moon Suk‐Ho 
Published: October 2021

AbstractBackgroundWith severe vascular calcifications, vascular clamp application and utilizing the vessel for free flap recipient vessel becomes impossible. These obstacles can be overcome with the Fogarty catheter and vein graft.Patients and methodsWhen unclampable artery was encountered intraoperatively, a vein graft was used to make a clampable recipient site for six diabetic foot patients (ages from 42 to 80). The end of the Fogarty catheter was inserted into the proximal end of the vein graft and the transected calcified vessel in sequence, and the balloon of the catheter was used as an intraluminal tourniquet. The remaining end of the vein graft was connected to the distal vessel with a vascular clamp.ResultsFive short vein graft revascularization for segmental arterial occlusion, one long vein graft for recipient artery elongation was done (lengths from 2 to 13.8 cm). Three delayed, and two immediate anterolateral thigh flaps (sizes from 15 to 150 cm2) were performed, and one patient received vein graft revascularization surgery only. Postoperative vascular sonography of all six patients showed well‐maintained patency. Minor flap marginal disruption occurred at two patients but healed with conservative care. Postoperative follow‐up was done for 1–18 months (average 7.17). Limb salvage was achieved for five patients and all five free flaps survived. However, for one patient, arterial restenosis at popliteal artery a month later lead to major amputation.ConclusionUsing a Fogarty catheter and a vein graft may obtain perfect hemostasis during micro‐anastomosis and achieve successful microvascular reconstruction in patients with severely calcified vessels.
Assessment of fully automatic segmentation of pulmonary artery and aorta on noncontrast CT with optimal surface graph cuts
Authors: Sedghi Gamechi Zahra , Arias‐Lorza Andres M. , Saghir Zaigham , Bos Daniel , de Bruijne Marleen 
Published: October 2021

AbstractPurposeAccurate segmentation of the pulmonary arteries and aorta is important due to the association of the diameter and the shape of these vessels with several cardiovascular diseases and with the risk of exacerbations and death in patients with chronic obstructive pulmonary disease. We propose a fully automatic method based on an optimal surface graph‐cut algorithm to quantify the full 3D shape and the diameters of the pulmonary arteries and aorta in noncontrast computed tomography (CT) scans.MethodsThe proposed algorithm first extracts seed points in the right and left pulmonary arteries, the pulmonary trunk, and the ascending and descending aorta by using multi‐atlas registration. Subsequently, the centerlines of the pulmonary arteries and aorta are extracted by a minimum cost path tracking between the extracted seed points, with a cost based on a combination of lumen intensity similarity and multiscale medialness in three planes. The centerlines are refined by applying the path tracking algorithm to curved multiplanar reformatted scans and are then smoothed and dilated nonuniformly according to the extracted local vessel radius from the medialness filter. The resulting coarse estimates of the vessels are used as initialization for a graph‐cut segmentation. Once the vessels are segmented, the diameters of the pulmonary artery (PA) and the ascending aorta (AA) and the ratio are automatically calculated both in a single axial slice and in a 10 mm volume around the automatically extracted PA bifurcation level. The method is evaluated on noncontrast CT scans from the Danish Lung Cancer Screening Trial (DLCST). Segmentation accuracy is determined by comparing with manual annotations on 25 CT scans. Intraclass correlation (ICC) between manual and automatic diameters, both measured in axial slices at the PA bifurcation level, is computed on an additional 200 CT scans. Repeatability of the automated 3D volumetric diameter and ratio calculations (perpendicular to the vessel axis) are evaluated on 118 scan–rescan pairs with an average in‐between time of 3 months.ResultsWe obtained a Dice segmentation overlap of 0.94 ± 0.02 for pulmonary arteries and 0.96 ± 0.01 for the aorta, with a mean surface distance of 0.62 ± 0.33 mm and 0.43 ± 0.07 mm, respectively. ICC between manual and automatic in‐slice diameter measures was 0.92 for PA, 0.97 for AA, and 0.90 for the ratio, and for automatic diameters in 3D volumes around the PA bifurcation level between scan and rescan was 0.89, 0.95, and 0.86, respectively.ConclusionThe proposed automatic segmentation method can reliably extract diameters of the large arteries in non‐ECG‐gated noncontrast CT scans such as are acquired in lung cancer screening.
Reduction of motion effects in myocardial arterial spin labeling
Authors: Aramendía‐Vidaurreta Verónica , Gordaliza Pedro M. , Vidorreta Marta , Echeverría‐Chasco Rebeca , Bastarrika Gorka , Muñoz‐Barrutia Arrate , Fernández‐Seara María A. 
Published: October 2021

PurposeTo evaluate the accuracy and reproducibility of myocardial blood flow measurements obtained under different breathing strategies and motion correction techniques with arterial spin labeling.MethodsA prospective cardiac arterial spin labeling study was performed in 12 volunteers at 3 Tesla. Perfusion images were acquired twice under breath‐hold, synchronized‐breathing, and free‐breathing. Motion detection based on the temporal intensity variation of a myocardial voxel, as well as image registration based on pairwise and groupwise approaches, were applied and evaluated in synthetic and in vivo data. A region of interest was drawn over the mean perfusion‐weighted image for quantification. Original breath‐hold datasets, analyzed with individual regions of interest for each perfusion‐weighted image, were considered as reference values.ResultsPerfusion measurements in the reference breath‐hold datasets were in line with those reported in literature. In original datasets, prior to motion correction, myocardial blood flow quantification was significantly overestimated due to contamination of the myocardial perfusion with the high intensity signal of blood pool. These effects were minimized with motion detection or registration. Synthetic data showed that accuracy of the perfusion measurements was higher with the use of registration, in particular after the pairwise approach, which probed to be more robust to motion.ConclusionSatisfactory results were obtained for the free‐breathing strategy after pairwise registration, with higher accuracy and robustness (in synthetic datasets) and higher intrasession reproducibility together with lower myocardial blood flow variability across subjects (in in vivo datasets). Breath‐hold and synchronized‐breathing after motion correction provided similar results, but these breathing strategies can be difficult to perform by patients.
Longitudinal relaxation in fat‐water mixtures and its dependence on fat content at 3 T
Authors: Fortier Véronique , Levesque Ives R. 
Published: October 2021

Longitudinal (T1) relaxation of triglyceride molecules and water is of interest for fat‐water separation and fat quantification. A better understanding of T1 relaxation could benefit modeling for applications in fat quantification and relaxation mapping. This work investigated T1 relaxation of spectral resonances of triglyceride molecules and water in liquid fat‐water mixtures and its dependence on the fat fraction. Dairy cream and a safflower oil emulsion were used. These were diluted with distilled water to produce a variety of fat mass fractions (4.4% to 35% in dairy cream and 6.3% to 52.3% in safflower oil emulsion). T1 was measured at room temperature at 3 T using an inversion recovery STimulated Echo Acquisition Mode (STEAM) MR spectroscopy method with a series of inversion times. T1 variations as a function of fat fraction were investigated for various resonances. A two‐component model was developed to describe the relaxation in a fat‐water mixture as a function of the fat fraction. The T1 of water and of all fat resonances studied in this work decreased as the fat fraction increased. The relative variation in T1 was different for each fat resonance. The T1 of the methylene resonance showed the least variation as a function of the fat fraction. The proposed two‐component model closely fits the observed T1 variations. In conclusion, this work clarifies how the T1 of major and minor fat resonances and of the water resonance varies as a function of the fat fraction in fat‐water mixtures. Knowledge of these variations could serve modeling, analysis of MRI measurements in fat‐water mixtures, and phantom preparation.
The effects of written catharsis on anger relief
Authors: Zhan Jun , Yu Shuhan , Cai Ruyi , Xu Hongfei , Yang Yue , Ren Jun , Luo Jing 
Published: October 2021

AbstractPrevious studies have found that “general catharsis”, such as hitting sandbags, does not reduce but increases an individual's anger feeling and aggressive behavior. Although the “goal catharsis” that is directed at attacking targets can temporarily relieve anger, there is a risk of increasing the tendency of aggressive personality if it is used for a long time. These findings raise serious doubts and challenges to the traditional view that “anger must be released” held by the classic catharsis theory that many people still trust. The present study compared the effects of “general catharsis” and “goal catharsis” on anger‐related responses among Chinese people, and the Chinese written form of catharsis was used in this study. The results showed that after participants were provoked, the aggressive behavior of participants who wrote down their dissatisfaction (general catharsis condition) was significantly higher than that of participants who wrote to attack someone who irritated them (goal catharsis condition) as well as that of participants who completed a simple recall task (control condition), and there was no significant difference in the aggressive behavior level between the latter two cases. These results suggest that the catharsis effect is no better than a simple recall task similar to attention distraction, that is, aggressive catharsis is not an effective way for anger relief.
Biochemical investigation of an N‐acetyltransferase from Helicobacter pullorum
Authors: Griffiths William A. , Spencer Keelan D. , Thoden James B. , Holden Hazel M. 
Published: October 2021

AbstractN‐acetylated sugars are often found, for example, on the lipopolysaccharides of Gram‐negative bacteria, on the S‐layers of Gram‐positive bacteria, and on the capsular polysaccharides. Key enzymes involved in their biosynthesis are the sugar N‐acetyltransferases. Here, we describe a structural and functional analysis of one such enzyme from Helicobacter pullorum, an emerging pathogen that may be associated with gastroenteritis and gallbladder and liver diseases. For this analysis, the gene BA919‐RS02330 putatively encoding an N‐acetyltransferase was cloned, and the corresponding protein was expressed and purified. A kinetic analysis demonstrated that the enzyme utilizes dTDP‐3‐amino‐3,6‐dideoxy‐d‐glucose as a substrate as well as dTDP‐3‐amino‐3,6‐dideoxy‐d‐galactose, albeit at a reduced rate. In addition to this kinetic analysis, a similar enzyme from Helicobacter bilis was cloned and expressed, and its kinetic parameters were determined. Seven X‐ray crystallographic structures of various complexes of the H. pullorum wild‐type enzyme (or the C80T variant) were determined to resolutions of 1.7 Å or higher. The overall molecular architecture of the H. pullorum N‐acetyltransferase places it into the Class II left‐handed‐β‐helix superfamily (LβH). Taken together, the data presented herein suggest that 3‐acetamido‐3,6‐dideoxy‐d‐glucose (or the galactose derivative) is found on either the H. pullorum O‐antigen or in another of its complex glycoconjugates. A BLAST search suggests that more than 50 non‐pylori Helicobacter spp. have genes encoding N‐acetyltransferases. Given that there is little information concerning the complex glycans in non‐pylori Helicobacter spp. and considering their zoonotic potential, our results provide new biochemical insight into these pathogens
Modularity‐based parallel protein design algorithm with an implementation using shared memory programming
Authors: Pal Abantika , Mulumudy Rohith , Mitra Pralay 
Published: October 2021

AbstractGiven a target protein structure, the prime objective of protein design is to find amino acid sequences that will fold/acquire to the given three‐dimensional structure. The protein design problem belongs to the non‐deterministic polynomial‐time‐hard class as sequence search space increases exponentially with protein length. To ensure better search space exploration and faster convergence, we propose a protein modularity–based parallel protein design algorithm. The modular architecture of the protein structure is exploited by considering an intermediate structural organization between secondary structure and domain defined as protein unit (PU). Here, we have incorporated a divide‐and‐conquer approach where a protein is split into PUs and each PU region is explored in a parallel fashion. It has been further analyzed that our shared memory implementation of modularity‐based parallel sequence search leads to better search space exploration compared to the case of traditional full protein design. Sequence‐based analysis on design sequences depicts an average of 39.7% sequence similarity on the benchmark data set. Structure‐based comparison of the modeled structures of the design protein with the target structure exhibited an average root‐mean‐square deviation of 1.17 Å and an average template modeling score of 0.89. The selected modeled structures of the design protein sequences are validated using 100 ns molecular dynamics simulations where 80% of the proteins have shown better or similar stability to the respective target proteins. Our study informs that our modularity‐based protein design algorithm can be extended to protein interaction design as well.
Exposure–response analysis of adverse events associated with molibresib and its active metabolites in patients with solid tumors
Authors: Krishnatry Anu Shilpa , Hanze Eva , Bergsma Tim , Dhar Arindam , Prohn Marita , Ferron‐Brady Geraldine 
Published: October 2021

AbstractMolibresib (GSK525762) is an investigational orally bioavailable small‐molecule bromodomain and extraterminal (BET) protein inhibitor for the treatment of advanced solid tumors. In the first‐time‐in‐human BET115521 study of molibresib in patients with solid tumors, thrombocytopenia was the most frequent treatment‐related adverse event (AE), QT prolongation was an AE of special interest based on preclinical signals, and gastrointestinal (GI) AEs (nausea, vomiting, diarrhea, and dysgeusia) were often observed. The aims of this analysis were the following: (i) develop a population pharmacokinetic (PK)/pharmacodynamic (PD) model capable of predicting platelet time courses in individual patients after administration of molibresib and identify covariates of clinical interest; (ii) evaluate the effects of molibresib (and/or its two active metabolites [GSK3529246]) exposure on cardiac repolarization by applying a systematic modeling approach using high‐quality, intensive, PK time‐matched 12‐lead electrocardiogram measurements; (iii) evaluate the exposure–response (ER) relationship between molibresib and/or GSK3529246 exposures and the occurrence of Grade 2 or higher GI AEs. Overall, the PK/PD model (including a maximal drug effect model and molibresib concentration) adequately described platelet counts following molibresib treatment and was used to simulate the impact of molibresib dosing on thrombocytopenia at different doses and regimens. ER analyses showed no clinically meaningful QT interval prolongation with molibresib at up to 100 mg q.d., and no strong correlation between molibresib exposure and the occurrence of Grade 2 or higher GI AEs. The models described here can aid dosing/schedule and drug combination strategies and may support a thorough QT study waiver request for molibresib.
Preclinical implementation of a steerable, Da Vinci Xi® compatible CO2‐laser fibre carrier for transoral robotic surgery (TORS): A cadaveric feasibility study
Authors: Meulemans Jeroen , Vandebroek Tom , Ourak Mouloud , Vander Poorten Emmanuel , Vander Poorten Vincent 
Published: October 2021

AbstractIntroductionMonopolar electrocautery is the most common dissection and coagulation tool during transoral robotic surgery (TORS) but causes significant collateral tissue damage as opposed to CO2 laser. We aimed at combining both modalities in one robotic instrument arm.MethodsWe developed a steerable CO2‐laser fibre carrier serving as an add‐on to the existing Endowrist® monopolar spatula of the Da Vinci Xi. Feasibility and safety were assessed in a preclinical setting.ResultsOne radical tonsillectomy with monopolar cautery and three with the instrument prototype were performed in two cadavers by two surgeons. No serious prototype‐related intra‐operative difficulties were observed. Safe and efficient switching between energy sources proved possible in all simulated intra‐operative bleeding events. Prototype use allowed for the identification of the majority of key anatomical structures and was scored favourably on NASA‐TLX questionnaires.DiscussionThe reported prototype successfully combines the advantages of CO2‐laser with the advantages of TORS
Successive Chebyshev pseudospectral convex optimization method for nonlinear optimal control problems
Authors: Li Yang , Chen Wanchun , Yang Liang 
Published: October 2021

AbstractThis article aims at proposing a successive Chebyshev pseudospectral convex optimization method for solving general nonlinear optimal control problems (OCPs). First, Chebyshev pseudospectral discrete scheme is used to discretize a general nonlinear OCP. At the same time, a convex subproblem is formulated by using the first‐order Taylor expansion to convexify the discretized nonlinear dynamic constraints. Second, a trust‐region penalty term is added to the performance index of the subproblem, and a successive convex optimization algorithm is proposed to solve the subproblem iteratively. Noted that the trust‐region penalty parameters can be adjusted according to the linearization error in iterative process, which improves convergence rate. Third, the Karush–Kuhn–Tucker conditions of the subproblem are derived, and furthermore, a proof is given to show that the algorithm will iteratively converge to the subproblem. Additionally, the global convergence of the algorithm is analyzed and proved, which is based on three key lemmas. Finally, the orbit transfer problem of spacecraft is used to test the performance of the proposed method. The simulation results demonstrate the optimal control is bang‐bang form, which is consistent with the result of theoretical proof. Also, the algorithm is of efficiency, fast convergence rate, and high accuracy. Therefore, the proposed method provides a new approach for solving nonlinear OCPs online and has great potential in engineering practice.
Finite‐time output regulation by bounded linear time‐varying controls with applications to the satellite formation flying
Authors: Zhang Kai , Zhou Bin , Jiang Huaiyuan , Duan Guangren 
Published: October 2021

AbstractThis article studies the finite‐time output regulation problem for linear time‐invariant continuous‐time systems. By using the solution to a parametric Lyapunov equation (PLE) and regulator equations, three bounded linear time‐varying (LTV) state controllers composed of the LTV feedback gain and the LTV feedforward gain are designed, such that (prescribed) finite‐time output regulation is solved. As a further result, a linear LTV observer‐based controller is also designed. The most significant advantages of this article are that the system under consideration is more general and the output regulation problem is achieved within a user‐chosen regulation time. Finally, the developed LTV state controllers are utilized to the design of the satellite formation flying control system and simulation results verify the effectiveness of the proposed approaches.