bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved therapeutic approach for spinal muscular atrophy via ubiquitination‐resistant survival motor neuron variant
Authors: Rhee Joonwoo , Kang Jong‐Seol , Jo Young‐Woo , Yoo Kyusang , Kim Ye Lynne , Hann Sang‐Hyeon , Kim Yea‐Eun , Kim Hyun , Kim Ji‐Hoon , Kong Young‐Yun 
Published: April 2024

AbstractBackgroundZolgensma is a gene‐replacement therapy that has led to a promising treatment for spinal muscular atrophy (SMA). However, clinical trials of Zolgensma have raised two major concerns: insufficient therapeutic effects and adverse events. In a recent clinical trial, 30% of patients failed to achieve motor milestones despite pre‐symptomatic treatment. In addition, more than 20% of patients showed hepatotoxicity due to excessive virus dosage, even after the administration of an immunosuppressant. Here, we aimed to test whether a ubiquitination‐resistant variant of survival motor neuron (SMN), SMNK186R, has improved therapeutic effects for SMA compared with wild‐type SMN (SMNWT).MethodsA severe SMA mouse model, SMA type 1.5 (Smn−/−; SMN2+/+; SMN∆7+/−) mice, was used to compare the differences in therapeutic efficacy between AAV9‐SMNWT and AAV9‐SMNK186R. All animals were injected within Postnatal Day (P) 1 through a facial vein or cerebral ventricle.ResultsAAV9‐SMNK186R‐treated mice showed increased lifespan, body weight, motor neuron number, muscle weight and functional improvement in motor functions as compared with AAV9‐SMNWT‐treated mice. Lifespan increased by more than 10‐fold in AAV9‐SMNK186R‐treated mice (144.8 ± 26.11 days) as compared with AAV9‐SMNWT‐treated mice (26.8 ± 1.41 days). AAV9‐SMNK186R‐treated mice showed an ascending weight pattern, unlike AAV9‐SMNWT‐treated mice, which only gained weight until P20 up to 5 g on average. Several motor function tests showed the improved therapeutic efficacy of SMNK186R. In the negative geotaxis test, AAV9‐SMNK186R‐treated mice turned their bodies in an upward direction successfully, unlike AAV9‐SMNWT‐treated mice, which failed to turn upwards from around P23. Hind limb clasping phenotype was rarely observed in AAV9‐SMNK186R‐treated mice, unlike AAV9‐SMNWT‐treated mice that showed clasping phenotype for more than 20 out of 30 s. At this point, the number of motor neurons (1.5‐fold) and the size of myofibers (2.1‐fold) were significantly increased in AAV9‐SMNK186R‐treated mice compared with AAV9‐SMNWT‐treated mice without prominent neurotoxicity. AAV9‐SMNK186R had fewer liver defects compared with AAV9‐SMNWT, as judged by increased proliferation of hepatocytes (P < 0.0001) and insulin‐like growth factor‐1 production (P < 0.0001). Especially, low‐dose AAV9‐SMNK186R (nine‐fold) also reduced clasping time compared with SMNWT.ConclusionsSMNK186R will provide improved therapeutic efficacy in patients with severe SMA with insufficient therapeutic efficacy. Low‐dose treatment of SMA patients with AAV9‐SMNK186R can reduce the adverse events of Zolgensma. Collectively, SMNK186R has value as a new treatment for SMA that improves treatment effectiveness and reduces adverse events simultaneously.
Membranes on the move: The functional role of the extracellular vesicle membrane for contact‐dependent cellular signalling
Authors: Jahnke Kevin , Staufer Oskar 
Published: April 2024

AbstractExtracellular vesicles (EVs), lipid‐enclosed structures released by virtually all life forms, have gained significant attention due to their role in intercellular and interorganismal communication. Despite their recognized importance in disease processes and therapeutic applications, fundamental questions about their primary function remain. Here, we propose a different perspective on the primary function of EVs, arguing that they serve as essential elements providing membrane area for long‐distance, contact‐dependent cellular communication based on protein‐protein interaction. While EVs have been recognized as carriers of genetic information, additional unique advantages that they could provide for cellular communication remain unclear. Here, we introduce the concept that the substantial membrane area provided by EVs allows for membrane contact‐dependent interactions that could be central to their function. This membrane area enables the lateral diffusion and sorting of membrane ligands like proteins, polysaccharides or lipids in two dimensions, promoting avidity‐driven effects and assembly of co‐stimulatory architectures at the EV‐cell interface. The concept of vesicle‐induced receptor sequestration (VIRS), for example, describes how EVs confine and focus receptors at the EV contact site, promoting a dense local concentration of receptors into signalosomes. This process can increase the signalling strength of EV‐presented ligands by 10‐1000‐fold compared to their soluble counterparts. The speculations in this perspective advance our understanding of EV‐biology and have critical implications for EV‐based applications and therapeutics. We suggest a shift in perspective from viewing EVs merely as transporters of relevant nucleic acids and proteins to considering their unique biophysical properties as presentation platforms for long‐distance, contact‐dependent signalling. We therefore highlight the functional role of the EV membrane rather than their content. We further discuss how this signalling mechanism might be exploited by virus‐transformed or cancer cells to enhance immune‐evasive mechanisms.
An all‐embracing science: The anthropological conception of Paolo Mantegazza
Authors: Scalese Fabio 
Published: April 2024

AbstractThis paper deals with the anthropological conception of the first modern Italian anthropologist, Paolo Mantegazza (1831–1910). We will begin by contextualizing the status of anthropology in Italy during the second half of the 19th century. Subsequently, we will delve into some of the inspirations that led the Italians to have such a multifaceted conception of the discipline. Next, we will outline the content of this approach and clarify the meaning of “omnicomprehensive science.” From there, we will come to understand the reason for the variety of interests of the anthropologist, who aimed to study the human being in all aspects of life. We will then mention the moral objective present in his professional journey: through an understanding of the complexity of human life, the anthropologist wanted to contribute to the progress and well‐being of society; in other words, to “living well.”
Risk factors for surgery in stricturing small bowel Crohn's disease: A retrospective cohort study from the GETAID pédiatrique
Authors: Lacotte Edouard , Boujonnier Louis , Martinez‐Vinson Christine , Viala Jérôme , Ley Delphine , Coopman Stéphanie , Lerisson Héloïse , Dabadie Alain , Dumant‐Forrest Clémentine , Pigneur Bénédicte , Ruemmele Frank , Enaud Raphael , Comte Aurélie , Rebeuh Julie , Bertrand Valérie , Caron Nicolas , Breton Anne , Duclaux‐Loras Rémi , Vasies Ioana , Dupont‐Lucas Claire 
Published: April 2024

AbstractObjectivesPrevious studies have shown rates of surgical resection of up to 41% in stricturing pediatric Crohn's disease (CD). In this retrospective multicenter study, our aims were to identify clinical risk factors and magnetic resonance enterography (MRE) features of small bowel strictures associated with surgery.MethodsPediatric patients with symptomatic stricturing small bowel CD (defined as obstructive symptoms or proximal dilatation on MRE) confirmed by MRE between 2010 and 2020 were recruited from 12 French tertiary hospitals. Patient characteristics were compared by surgical outcome multivariable Cox regression.ResultsFifty‐six patients (61% boys) aged 12.2 ± 2.7 years at diagnosis of CD were included. Median duration of CD before diagnosis of stricture was 11.7 months (interquartile range [IQR]: 25–75: 1.2–29.9). Nineteen (34%) patients had stricturing phenotype (B2) at baseline. Treatments received before stricture diagnosis included MODULEN‐IBD (n = 31), corticosteroids (n = 35), antibiotics (n = 10), anti‐TNF (n = 27), immunosuppressants (n = 28). Thirty‐six patients (64%) required surgery, within 4.8 months (IQR: 25–75: 1.8–17.3) after stricture diagnosis. Parameters associated with surgical resection were antibiotic exposure before stricture diagnosis (adjusted odds ratio [aOR]: 15.62 [3.35–72.73], p = 0.0005), Crohn's disease obstructive symptoms score (CDOS) > 4 (aOR: 3.04 [1.15–8.03], p = 0.02) and dilation proximal to stricture >28 mm (aOR: 3.62 [1.17–11.20], p = 0.03).ConclusionIn this study, antibiotic treatment before stricture diagnosis, intensity of obstructive symptoms, and diameter of dilation proximal to small bowel stricture on MRE were associated with risk for surgical resection.
Comparison of four in vitro test methods to assess nucleus pulposus replacement device expulsion risk
Authors: Rahman Tamanna , Kibble Matthew J. , Harbert Gianluca , Smith Nigel , Brewer Erik , Schaer Thomas P. , Newell Nicolas 
Published: April 2024

AbstractBackgroundNucleus replacement devices (NRDs) are not routinely used in clinic, predominantly due to the risk of device expulsion. Rigorous in vitro testing may enable failure mechanisms to be identified prior to clinical trials; however, current testing standards do not specify a particular expulsion test. Multiple methods have therefore been developed, complicating comparisons between NRD designs. Thus, this study assessed the effectiveness of four previously reported expulsion testing protocols; hula‐hoop (Protocol 1), adapted hula‐hoop (Protocol 2), eccentric cycling (Protocol 3), and ramp to failure (Protocol 4), applied to two NRDs, one preformed and one in situ curing.MethodsNucleus material was removed from 40 bovine tail intervertebral disks. A NRD was inserted posteriorly into each cavity and the disks were subjected to one of four expulsion protocols.ResultsNRD response was dependent on both the NRD design and the loading protocol. Protocol 1 resulted in higher migration and earlier failure rates compared to Protocol 2 in both NRDs. The preformed NRD was more likely to migrate when protocols incorporated rotation. The NRDs had equal migration (60%) and expulsion (60%) rates when using unilateral bending and ramp testing. Combining the results of multiple tests revealed complimentary information regarding the NRD response.ConclusionsAdapted hula‐hoop (Protocol 2) and ramp to failure (Protocol 4), combined with fluoroscopic analysis, revealed complimentary insights regarding migration and failure risk. Therefore, when adopting the surgical approach and animal model used in this study, it is recommended that NRD performance be assessed using both a cyclic and ramp loading protocol.
Functional anterior cruciate ligament braces may have a role in select patient groups although there is presently limited evidence supporting or refuting their routine use: A scoping review of clinical practice guidelines and an updated bracing classification
Authors: Geeslin Andrew G. , Moatshe Gilbert , Engebretsen Lars , Lind Martin , Hansson Frida , Stalman Anders , Barenius Bjorn , LaPrade Robert F. 
Published: April 2024

AbstractPurposeThe purpose of this study was to perform a scoping review of clinical practice guidelines (CPGs) concerning the use of functional anterior cruciate ligament (ACL) braces and to clarify the nomenclature for bracing relevant to ACL injury treatment in order to support prescribing clinicians.MethodsA PubMed search for CPGs for the use of braces following ACL injury or reconstruction was performed. CPGs on the treatment of ACL injuries with sufficient attention to postoperative braces were included in this scoping review. The references used for supporting the specific CPG recommendations were reviewed. Specific indications for brace use including brace type, period of use following surgery and activities requiring brace use were collected.ResultsSix CPGs were identified and included this this review. Three randomised trials provided the evidence for recommendations on functional brace use following ACL reconstruction in the six CPGs. Functional ACL braces were the primary focus of the three randomised trials, although extension braces (postoperative knee immobilisers) were also discussed. A novel dynamic ACL brace category has been described, although included CPGs did not provide guidance on this brace type.ConclusionsGuidance on the use of functional ACL braces following ACL reconstruction is provided in six CPGs supported by three randomised trials. However, the brace protocols and patient compliance in the randomised trials render these CPGs inadequate for providing guidance on the use of functional ACL braces in the general and high‐risk patient populations when returning to sport after ACL reconstruction. Functional ACL braces are commonly utilised during the course of ACL injury treatment although there is presently limited evidence supporting or refuting the routine use of these braces. Future studies are, therefore, necessary in order to provide guidance on the use of functional and dynamic ACL braces in high‐risk patient populations.Level of EvidenceLevel II.
Flexible and Rigid Bronchoscopy for Critically Ill Children on Extracorporeal Membrane Oxygenation
Authors: Young Ashley , Patel Krupa , Allen Kiona , Ghadersohi Saied , Rowland Matthew , Hazkani Inbal 
Published: April 2024

BackgroundWe aim to describe our experience with bronchoscopy to diagnose and relieve tracheobronchial obstruction in anticipation of decannulation in children on extracorporeal membrane oxygenation (ECMO) support.MethodsA retrospective cohort study of children on ECMO between 1/2018 and 12/2022.ResultsA total of 107 children required ECMO support during the study period for cardiac (n = 48, 45%), pulmonary (n = 38, 36%), or cardiopulmonary dysfunction (n = 21, 20%). Thirty‐seven (35%) patients underwent 99 bronchoscopies while on ECMO. Most (76%, n = 75) experienced no improvement or worsening of chest radiography 24 hours following bronchoscopy. Clinical improvement in tidal volumes 48 hours after the first bronchoscopy was noted in 13/25 patients with available data (p = 0.05). Adverse events were seen in 18 (49%) patients who underwent bronchoscopy, including pneumothorax (n = 8, 22%), pneumonia (n = 7, 19%), pulmonary hemorrhage (n = 6, 16%), and sepsis (n = 5, 14%). ECMO courses were longer (25.4 ± 37.2 vs 6.1 ± 8.8 days, p < 0.0001) and more likely to be complicated by pneumonia (p = 0.0004) and sepsis (p = 0.047) in patients who underwent bronchoscopy compared with those who did not. Adverse events following bronchoscopy were associated with the number of bronchoscopies (p = 0.0003) and the presence of obstructive materials but not with the type of bronchoscopy or indication for ECMO. Mortality rates were similar between patients who underwent bronchoscopy and those who did not.ConclusionChildren requiring bronchoscopy represent a subset of the sickest children on ECMO. Bronchoscopy may provide benefit in children with persistent cardiopulmonary failure who could not otherwise be decannulated. Adverse events are associated with the number of bronchoscopies and the presence of obstructive material.Level of Evidence4 Laryngoscope, 134:4134–4140, 2024
An impedance matching section based on composite right/left‐handed transmission line model in viewpoint of phase shift and noise figure
Authors: Günel Tayfun 
Published: April 2024

AbstractIn this paper, a genetic‐based synthesis approach for an impedance matching section based on a composite right‐/left‐handed (CRLH) transmission line model called CRLH transmission line impedance matching section (CRLHTLIMS) in viewpoint of transmission phase shift and noise figure is newly presented. To find the unknown values of right‐/left‐handed inductances and capacitances of a CRLHTLIMS, a type of global optimization algorithm called continuous parameter genetic algorithm is used. The length, transmission phase shift, and noise figure of the CRLHTLIMS are computed by using simple equations. Different examples for a uniform CRLHTLIMS are given. According to the results, this approach is an easy and effective way for the synthesis of transmission line impedance matching sections in viewpoint of transmission phase shift and noise figure.
Fully automated planning for anatomical fetal brain MRI on 0.55T
Authors: Neves Silva Sara , McElroy Sarah , Aviles Verdera Jordina , Colford Kathleen , St Clair Kamilah , Tomi‐Tricot Raphael , Uus Alena , Ozenne Valéry , Hall Megan , Story Lisa , Pushparajah Kuberan , Rutherford Mary A. , Hajnal Joseph V. , Hutter Jana 
Published: April 2024

AbstractPurposeWidening the availability of fetal MRI with fully automatic real‐time planning of radiological brain planes on 0.55T MRI.MethodsDeep learning‐based detection of key brain landmarks on a whole‐uterus echo planar imaging scan enables the subsequent fully automatic planning of the radiological single‐shot Turbo Spin Echo acquisitions. The landmark detection pipeline was trained on over 120 datasets from varying field strength, echo times, and resolutions and quantitatively evaluated. The entire automatic planning solution was tested prospectively in nine fetal subjects between 20 and 37 weeks. A comprehensive evaluation of all steps, the distance between manual and automatic landmarks, the planning quality, and the resulting image quality was conducted.ResultsProspective automatic planning was performed in real‐time without latency in all subjects. The landmark detection accuracy was 4.2 2.6 mm for the fetal eyes and 6.5 3.2 for the cerebellum, planning quality was 2.4/3 (compared to 2.6/3 for manual planning) and diagnostic image quality was 2.2 compared to 2.1 for manual planning.ConclusionsReal‐time automatic planning of all three key fetal brain planes was successfully achieved and will pave the way toward simplifying the acquisition of fetal MRI thereby widening the availability of this modality in nonspecialist centers.
Synthesis and characterization of barium titanate nanoplatelets/polyvinylidene fluoride nanocomposite for piezoelectric properties
Authors: Aldulaimi Hussein , Pircheraghi Gholamreza , Nemati Ali 
Published: April 2024

AbstractBarium titanate (BaTiO3) nanostructures with a tetragonal structure have unique mechanical and piezoelectric properties. BaTiO3 nanoplatelets (BTNPs) were synthesized via the precipitation of the hydroxide (Ba‐Ti‐OH) precursor, which was subsequently subjected to hydrothermal treatment. Polyvinylidene fluoride (PVDF) granules and BTNPs powder were compounded through melt‐mixing within a laboratory internal mixer to PVDF/BTNP nanocomposite. The dispersion of BTNPs were analyzed using FE‐SEM images. The examination of the polycrystalline structure of a PVDF/BTNP nanocomposite involved the utilization of FTIR, DSC, and XRD measurements. Further, the tensile test was carried out to study the mechanical properties of the nanocomposites. The piezoelectric tests showed that the PVDF nanocomposite with 10 wt.% of BTNP exhibited the highest output voltage and current due to its maximum crystallinity. The measured current increased from 0.03 μA for PVDF to 0.22 μA for PVDF/BTNP nanocomposite and further to 0.34 after polling. PVDF's piezoelectric properties experienced an 11‐fold enhancement due to alterations in its crystalline structure. Power density improved by 644% (7.5 times), and piezoelectric sensitivity rose by 173%. Consequently, the PVDF/BTNP nanocomposite demonstrates significant potential for applications in electronics and energy harvesting.Highlights
Unique Tetragonal nanoplatelets produced via controlled BTNP synthesis.
10% BTNP enhances nanocomposite crystallinity by 22.7%
PVDF‐10 displays increase in both voltage and current, enhancing piezoelectricity.
Nanocomposites show promise for energy and electronics.
Effect of layered transition metal dichalcogenide hybrid nanomaterials on the piezoelectric performance of non‐solvent induced phase separated polyvinylidene fluoride
Authors: Kacem Eya , Al‐Ejji Maryam , Yempally Swathi , Ponnamma Deepalekshmi 
Published: April 2024

AbstractLayered transition metal dichalcogenides (TMDs) with high aspect ratios enhance the alignment of polymer chains and induce a preferred orientation of the polymeric crystallites when incorporated into polyvinylidene fluoride (PVDF). In addition to offering an effective charge‐transfer mechanism, TMDs give PVDF more rigidity and piezoelectric qualities. This work reports the non‐solvent induced phase separation (NIPS) introduced while developing the PVDF/MoS2 composites. During the NIPS, the PVDF chains become phase‐separated, which induces high polarization in the PVDF matrix. Phase‐separated PVDF/MoS2 composites show high porosity and charge distribution attributed to the enhanced piezoelectric output voltage. While the neat PVDF demonstrated very feeble output voltage generation, the hybrid composite containing 2 wt.% of MoS2/ZnO facilitated almost 20 times higher performance (peak‐to‐peak voltage of 2.4 V). This work yielded a phase‐separated composite that finds uses in energy harvesting, sensors, and actuators, among other fields.Highlights
NIPS creates high‐porosity composites with improved charge distribution.
Layered TMDs improve charge‐transfer mechanism and PVDF's electrical properties.
2 wt.% MoS2/ZnO exhibits nearly 20 times higher voltage generation than neat PVDF.
Quasinormal Spectrum of (2+1)$(2+1)$‐Dimensional Asymptotically Flat, dS and AdS Black Holes
Authors: Skvortsova Milena 
Published: April 2024

AbstractWhile ‐dimensional black holes in the Einstein theory allow for only the anti‐de Sitter (AdS) asymptotic, when the higher curvature correction is tuned on, the asymptotically flat, de Sitter, and AdS cases are included. Here, a detailed study of the stability and quasinormal spectra of the scalar field perturbations around such black holes with all three asymptotics is proposed. Calculations of the frequencies are fulfilled with the help of the 6th order Wentzel–Kramers–Brillouin (WKB) method with Pade approximants, Bernstein polynomial method, and time‐domain integration. Results obtained by all three methods are in a very good agreement in their common range of applicability. When the multipole moment is equal to zero, the purely imaginary, i.e., non‐oscillatory, modes dominate in the spectrum for all types of the asymptotic behavior, while the spectrum at higher resembles that in four‐dimensional spacetime with the corresponding asymptotic.
Finite time disturbance observer based sliding mode control for PMSM with unknown disturbances
Authors: Zhufu Guanfeng , Wang Shubo , Wang Xue 
Published: April 2024

AbstractThis article proposes a finite time disturbance observer (FTDO) with modified non‐singular terminal sliding mode control (NTSMC) scheme for permanent magnet synchronous motor with unknown uncertainties such as system uncertainties and disturbances. A FTDO is used to estimate the unknown uncertainties and provides feed‐forward compensation in the control design. A novel fast sliding mode reaching law is developed, which can reduce the time to reach the sliding surface while the chattering phenomenon in the control signal. Then, by incorporating the FTDO into the modified sliding mode manifold, a finite time NTSMC scheme is presented. The developed control method can not only compensate the unknown uncertainties, but also achieve a finite time convergence. The finite time stability of the closed system under the presented control strategy is guaranteed via Lyapunov stability theory. The validity and feasibility of the presented control scheme are verified with simulations and experiments based on a motor driving system.