bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient numerical method for Stokes flows in unbounded domains with informative boundary condition using axial Green function method
Authors: Jo Junhong , Lee Wanho , Kim Do Wan
Published: June 2023

Flow calculations in an unbounded domain have limitations and challenges due to its infiniteness. A common approach is to impose a far‐field asymptotic condition to determine a unique flow. The leading behavior of the flow is identified at the far field, and then an unknown coefficient is assumed for the second behavior. This allows us to propose an efficient numerical method to solve two‐dimensional steady Stokes and potential flows in a truncated domain along with the coefficients. The second term provides crucial hydrodynamic information for the flow and is referred to as the informative boundary condition. The truncation creates artificial boundaries requiring boundary conditions for the approximate solution. The axial Green function method (AGM), combined with a specific one‐dimensional Green function over a semi‐infinite axis‐parallel line extended to infinity, allows us to implement the informative boundary condition in the truncated domain. AGMs, designed for complicated domains, are now applied to infinite domain cases because AGMs' versatility enables implementing the informative boundary condition by changing only the axial Green function. This approach's efficiency, accuracy, and consistency are investigated through several appealing Stokes flow problems including potential ones in infinite domains.
Analyzing and forecasting electricity price using regime‐switching models: The case of New Zealand market
Authors: Kapoor Gaurav , Wichitaksorn Nuttanan , Zhang Wenjun
Published: June 2023

This paper aims to study the forecasting capabilities of several models under the Markov regime‐switching (MRS) and the extreme value theory (EVT) frameworks applied to daily electricity prices in the New Zealand electricity market. The MRS models in this study include up to five regimes, with time‐varying transition probabilities and incorporation of external market variables. We apply Hamilton's filter with maximum likelihood estimation for parameter estimation. The EVT peaks‐over‐threshold (EVT‐PoT) framework is also considered, and its relationship to the MRS class of models is discussed. We generate out‐of‐sample forecasts under various market scenarios. The MRS models are able to replicate real price densities under stable market conditions. The EVT‐PoT model performs well despite its lack of complexity compared to the MRS framework. We attribute this to the usage of the generalized Pareto distribution to model price extremities.
Temperature‐controlled microextrusion printing for mesoscale interfacial designing in solid oxide fuel cells
Authors: Ding Cheng , Seo Haewon , Kishimoto Masashi , Iwai Hiroshi
Published: June 2023

A temperature‐controlled microextrusion printing technique is proposed to realize the increased aspect ratio of mesoscale convex structures at the anode–electrolyte interface in solid oxide fuel cells (SOFCs). The rheological properties of the anode ink for microextrusion printing are experimentally measured at various temperatures, and it is found that the viscosity of the ink and the wettability of the ink to the anode substrate decrease at lower temperatures, which is desirable for the ink to retain its shape on the substrate. The anode‐supported SOFC button cells are fabricated by microextrusion printing with and without temperature control and compared in terms of their interfacial structures and electrochemical performance. The aspect ratio of the interfacial structure is increased from 0.16 to 0.28 by lowering the ink temperature, resulting in a higher interface enlargement of 25%. Owing to the enlarged interfacial area, enhanced cell performance is also achieved.
Clinicopathological study and survival outcomes of sialoblastoma: A systematic review
Authors: Cruz Vitória Maria Sousa , Pérez‐de‐Oliveira Maria Eduarda , dos Santos Leite Éder Gerardo , Louredo Brendo Vinicius Rodrigues , Bezerra Hélen Kaline Farias , Lopes Márcio Ajudarte , Vargas Pablo Agustin , Santos‐Silva Alan Roger , Kowalski Luiz Paulo , da Cruz Perez Danyel Elias
Published: June 2023

Sialoblastoma is a rare malignant salivary gland tumor. The aim of this study was to review the available published data on sialoblastoma in a comprehensive analysis of its clinicopathologic characteristics, treatment, and outcomes. An unrestricted electronic search was performed in the following databases: MEDLINE/PubMed, EMBASE, Scopus, Web of science, and gray literature databases. Eligibility criteria included publications with sufficient clinical, imaging, and histopathological information to confirm the diagnosis of sialoblastoma. Data were evaluated descriptively and analytically. A total of 52 studies met the eligibility criteria. In total, 62 patients were evaluated. There was no gender predilection, with the parotid being the most affected primary site (n = 28; 45.2%). In the log‐rank test, there was a significant increase in disease‐associated survival in patients younger than 1 year of age (82.8% vs. 44.4%; p = 0.003), individuals with lesions in major salivary glands (79.4% vs. 38.5%; p = 0.005), patients without metastases (77.8% vs. 14.3%; p = 0.011), encapsulated lesions (85.7% vs. 0%; p < 0.0001), congenital lesions (83.3% vs. 25.0%; p < 0.0001), and lesions that do not show perineural invasion (89.5% vs. 40%; p = 0.035). Kaplan–Meier curves estimated overall survival and disease‐free survival at 5 years of 95.5% and 68.1%, respectively. In the multivariate Cox regression model, only the presence of metastasis was identified as an independent prognostic factor (hazard ratio [HR] = 9.81; p = 0.010). Although sialoblastoma presents good prognosis, the tumor has a high recurrence rate.
Heat stable carbetocin or oxytocin for prevention of postpartum hemorrhage among women at risk: A secondary analysis of the CHAMPION trial
Authors: Ghosh Rakesh , Owa Olorunfemi , Santos Nicole , Butrick Elizabeth , Piaggio Gilda , Widmer Mariana , Althabe Fernando , Qureshi Zahaida , Lumbiganon Pisake , Katageri Geetanjali , Walker Dilys
Published: June 2023

Objective

To examine whether the observed non‐inferiority of heat‐stable carbetocin (HSC), compared with oxytocin, was influenced by biologic (macrosomia, parity 3 or more, or history of postpartum hemorrhage [PPH]) and/or pharmacologic (induction or augmentation) risk factors for PPH.

Methods

The present study is a secondary analysis of the CHAMPION non‐inferiority randomized trial—a two‐arm, double‐blind, active‐controlled study conducted at 23 hospitals in 10 countries, between July 2015 and January 2018. Women with singleton pregnancies, expected to deliver vaginally with cervical dilatation up to 6 cm were eligible. Randomization was stratified by country, with 1:1 assignment. Women in the intervention and control groups received a single intramuscular injection of 100 μg of HSC or 10 IU of oxytocin, respectively. The drugs were administered immediately after birth, and the third stage of labor was managed according to the WHO guidelines. Blood was collected using a plastic drape. For this analysis, we defined a woman as being at risk if she had any one or more of the biologic or pharmacologic risk factor(s).

Results

The HSC and oxytocin arms contained 14 770 and 14 768 women, respectively. The risk ratios (RR) for PPH were 1.29 (95% confidence interval [CI] 1.08–1.53) or 1.73 (95% CI 1.51–1.98) for those with only biologic (macrosomia, parity 3 or more, and PPH in the previous pregnancy) or only pharmacologic (induced or augmented) risk factors, respectively, compared with those with neither risk factors.

Conclusions

Findings reinforce previous evidence that macrosomia, high parity, history of PPH, and induction/augmentation are risk factors for PPH. We did not find a difference in effects between HSC and oxytocin for PPH among women who were neither induced nor augmented or among those who were induced or augmented.
Toward α‐1,3/4 fucosyltransferases targeted drug discovery: In silico uncovering of promising natural inhibitors of fucosyltransferase 6
Authors: Magdaleno Jorge Samuel Leon , Grewal Ravneet K. , Medina‐Franco José L. , Oliva Romina , Shaikh Abdul Rajjak , Cavallo Luigi , Chawla Mohit
Published: June 2023

Sialyl Lewis X (sLex) antigen is a fucosylated cell‐surface glycan that is normally involved in cell‐cell interactions. The enhanced expression of sLex on cell surface glycans, which is attributed to the upregulation of fucosyltransferase 6 (FUT6), has been implicated in facilitating metastasis in human colorectal, lung, prostate, and oral cancers. The role that the upregulated FUT6 plays in the progression of tumor to malignancy, with reduced survival rates, makes it a potential target for anticancer drugs. Unfortunately, the lack of experimental structures for FUT6 has hampered the design and development of its inhibitors. In this study, we used in silico techniques to identify potential FUT6 inhibitors. We first modeled the three‐dimensional structure of human FUT6 using AlphaFold. Then, we screened the natural compound libraries from the COCONUT database to sort out potential natural products (NPs) with best affinity toward the FUT6 model. As a result of these simulations, we identified three NPs for which we predicted binding affinities and interaction patterns quite similar to those we calculated for two experimentally tested FUT6 inhibitors, that is, fucose mimetic‐1 and a GDP‐triazole derived compound. We also performed molecular dynamics (MD) simulations for the FUT6 complexes with identified NPs, to investigate their stability. Analysis of the MD simulations showed that the identified NPs establish stable contacts with FUT6 under dynamics conditions. On these grounds, the three screened compounds appear as promising natural alternatives to experimentally tested FUT6 synthetic inhibitors, with expected comparable binding affinity. This envisages good prospects for future experimental validation toward FUT6 inhibition.
An information‐theoretic approach to basis‐set fitting of electron densities and other non‐negative functions
Authors: Tehrani Alireza , Anderson James S. M. , Chakraborty Debajit , Rodriguez‐Hernandez Juan I. , Thompson David C. , Verstraelen Toon , Ayers Paul W. , Heidar‐Zadeh Farnaz
Published: June 2023

The numerical ill‐conditioning associated with approximating an electron density with a convex sum of Gaussian or Slater‐type functions is overcome by using the (extended) Kullback–Leibler divergence to measure the deviation between the target and approximate density. The optimized densities are non‐negative and normalized, and they are accurate enough to be used in applications related to molecular similarity, the topology of the electron density, and numerical molecular integration. This robust, efficient, and general approach can be used to fit any non‐negative normalized functions (e.g., the kinetic energy density and molecular electron density) to a convex sum of non‐negative basis functions. We present a fixed‐point iteration method for optimizing the Kullback–Leibler divergence and compare it to conventional gradient‐based optimization methods. These algorithms are released through the free and open‐source BFit package, which also includes a L2‐norm squared optimization routine applicable to any square‐integrable scalar function.
METTL16 promotes osteosarcoma progression by downregulating VPS33B in an m6A‐dependent manner
Authors: Cheng Jun , Xu Zhihao , Tan Wei , He Jinpeng , Pan Boyu , Zhang Yan , Deng Youwen
Published: June 2023

N6‐methyladenosine (m6A) is one of the main epitranscriptomic modifications that accelerates the progression of malignant tumors by modifying RNA. Methyltransferase‐like 16 (METTL16) is a newly identified methyltransferase that has been found to play an important oncogenic role in a few malignancies; however, its function in osteosarcoma (OS) remains unclear. In this study, METTL16 was found to be upregulated in OS tissues, and associated with poor prognosis in OS patients. Functionally, METTL16 substantially promoted OS cell proliferation, migration, and invasion in vitro and OS growth in vivo. Mechanistically, vacuolar protein sorting protein 33b (VPS33B) was identified as the downstream target of METTL16, which induced m6A modification of VPS33B and impaired the stability of the VPS33B transcript, thereby degrading VPS33B. In addition, VPS33B was found to be downregulated in OS tissues, VPS33B knockdown markedly attenuated shMETTL16‐mediated inhibition on OS progression. Finally, METTL16/VPS33B might facilitate OS progression through PI3K/AKT pathway. In summary, this study revealed an important role for the METTL16‐mediated m6A modification in OS progression, implying it as a promising target for OS treatment.
Novel approach for downstream processing of phytosterol bioconversion
Authors: Khomutov Sergey M , Shutov Andrey A , Averin Aleksey D , Dovbnya Dmitry V , Donova Marina V
Published: June 2023

BACKGROUND

Downstream processing is an important part of industrial steroid biotechnology. The traditional recovery methods require significant amounts of the organic solvents which are associated with environmental risks. There is a need for environmentally friendly downstream processing which also may open the prospects for regeneration and repeated use of the costly materials.

RESULTS

Microbial conversion of phytosterol to C17‐ketosteroids in methylated cyclodextrin (mCD) solutions was studied as a model bioprocess. Quantitative aspects of competitive complexation of mCD and natural β‐CD (β‐CD) with steroids were studied under different temperature modes and CD concentrations. The method of steroid recovery based on precipitation of insoluble β‐CD complexes ensured the complete isolation of androst‐4‐ene‐3,17‐dione, androsta‐1,4‐diene‐3,17‐dione, 9α‐hydroxyandrost‐4‐ene‐3,17‐dione, 20‐hydroxymethyl‐pregna‐1,4‐dien‐3‐one and 3β‐hydroxyandrost‐5‐en‐17‐one from aqueous media. Analysis of the 1H nuclear magnetic resonance (NMR) spectra showed a constant molar ratio of β‐CD to steroid equal to 2 in the obtained steroid β‐CD complexes. The extraction of the steroid from the β‐CD complex by small volumes of organic solvent provided a quantitative yield. The method developed ensures regeneration and repeated use of the mCDs without decrease of the basic bioconversion outputs, as was demonstrated in a series of phytosterol to androsta‐1,4‐diene‐3,17‐dione bioconversions by Mycolicibacterium neoaurum VKM Ac‐1816D.

CONCLUSIONS

Downstream processing based on manipulation of steroid solubility in aqueous cyclodextrin solutions is a promising alternative to traditional steroid extraction with organic solvents. This environmentally friendly approach ensures re‐use of materials without decrease in bioconversion outputs. © 2023 Society of Chemical Industry (SCI).
A novel cubic‐exp evaluation algorithm considering non‐symmetrical axial response signals of confocal microscopes
Authors: Hagemeier Sebastian , Pahl Tobias , Breidenbach Johannes , Lehmann Peter
Published: June 2023

The depth discrimination in confocal microscopy is based on the digital analysis of depth response signals obtained by each camera pixel during measurement. Various signal‐processing algorithms are used for this purpose. The accuracy of these algorithms is inter alia restricted by the axial symmetry of the signals. However, in practice response signals are rather asymmetrical especially in case of measurement objects with critical surface structures such as edges or steep flanks. We present a novel signal‐processing algorithm based on an exponential function with a cubic argument to handle asymmetrical and also symmetrical depth response signals. Results obtained by this algorithm are compared to those of commonly used signal processing algorithms. It turns out that the novel algorithm is more robust, more accurate and exhibits a repeatability of a similar order compared to other algorithms.

Research Highlights

A novel, more robust algorithm with improved accuracy in peak extraction especially for asymmetrical response signals in confocal microscopy is introduced and validated.

Improved accuracy is demonstrated for height and layer thickness measurements.
Embryonic pattern of cartilaginous head development in the European toad, Bufo bufo
Authors: Lukas Paul
Published: June 2023

The craniofacial skeleton of vertebrates is a major innovation of the whole clade. Its development and composition requires a precisely orchestrated sequence of chondrification events which lead to a fully functional skeleton. Sequential information on the precise timing and sequence of embryonic cartilaginous head development are available for a growing number of vertebrates. This enables a more and more comprehensive comparison of the evolutionary trends within and among different vertebrate clades. This comparison of sequential patterns of cartilage formation enables insights into the evolution of development of the cartilaginous head skeleton. The cartilaginous sequence of head formation of three basal anurans (Xenopus laevis, Bombina orientalis, Discoglossus scovazzi) was investigated so far. This study investigates the sequence and timing of larval cartilaginous development of the head skeleton from the appearance of mesenchymal Anlagen until the premetamorphic larvae in the neobatrachian species Bufo bufo. Clearing and staining, histology, and 3D reconstruction enabled the tracking of 75 cartilaginous structures and the illustration of the sequential changes of the skull as well as the identification of evolutionary trends of sequential cartilage formation in the anuran head. The anuran viscerocranium does not chondrify in the ancestral anterior to posterior direction and the neurocranial elements do not chondrify in posterior to anterior direction. Instead, the viscerocranial and neurocranial development is mosaic‐like and differs greatly from the gnathostome sequence. Strict ancestral anterior to posterior developmental sequences can be observed within the branchial basket. Thus, this data is the basis for further comparative developmental studies of anuran skeletal development.
Direct infiltration of clonal plasma cells causes renal insufficiency in patients with monoclonal gammopathy of undetermined significance
Authors: Naka Ryosuke , Shimomura Yoshimitsu , Kanda‐Kato Madoka , Hiramoto Nobuhiro , Hara Shigeo , Ishikawa Takayuki
Published: June 2023

Monoclonal gammopathy of undetermined significance (MGUS) is a benign but precancerous condition that can progress to multiple myeloma. Patients with MGUS are typically monitored closely for signs of disease progression, but in some cases, they may also develop renal insufficiency, a condition known as monoclonal gammopathy of renal significance (MGRS). In MGRS, M‐protein secreted by a nonmalignant or premalignant cell clone triggers renal damage by definition. Herein, we report a case of a 66‐year‐old Asian male with MGUS complicated by renal insufficiency. A kidney biopsy showed no evidence of renal injury mediated by M‐protein; instead, the direct infiltration of clonal cells into renal tissues was observed. Although five similar cases have been previously reported, our case is unique in that the involvement of clonal cells was directly confirmed by fluorescence in situ hybridization. Our findings suggest the need to consider a novel disease concept, as this phenomenon appears to be reproduced.
Predictors of Stroke Outcomes in Conservatively Treated Patients With Moyamoya Disease: A Follow‐up MRI Study
Authors: Zhang Hongtao , Lu Mingming , Liu Shitong , Liu Dongqing , Liu Xu , Shen Xuxuan , Han Cong , Sheng Fugeng , Cai Jianming
Published: June 2023

Background

Little is known about the association between stroke and imaging and clinical features in conservatively treated patients with moyamoya disease (MMD).

Purpose

To investigate independent risk factors for stroke in conservatively treated patients with MMD during a long‐term follow‐up.

Study Type

Prospective study.

Subjects

One hundred sixty conservatively managed patients with MMD (median age 46 years, 89 male).

Field Strength/Sequence

Time of flight, turbo inversion recovery magnitude T1WI, turbo spin echo (TSE) T2WI, echo‐planar imaging DWI, T2‐fluid attenuated inversion recovery, dynamic susceptibility contrast‐magnetic resonance imaging, and pre‐ and post‐contrast 3D TSE T1WI sequences at 3.0 Tesla.

Assessment

Patients were assessed at baseline and followed yearly. Ischemic and hemorrhagic stroke incidence rates were determined. Multiple demographic, clinical (modified Rankin score [mRS]), and cerebral imaging (cerebral blood volume [CBV] and concentric enhancement of arterial wall) factors at baseline were considered as potential predictors of stroke during the follow‐up period.

Statistical Tests

Univariable and multivariable Cox proportional hazards models to calculate the hazard ratios (HRs) and corresponding 95% confidence interval (CI) for stroke. Cumulative risk of stroke was estimated by the Kaplan–Meier product‐limit method. A P value <0.05 was considered statistically significant.

Results

The median follow‐up duration was 47 months. During the follow‐up period, 18 (11.25%) patients experienced stroke events (13 [8.13%] ischemic, 5 [3.12%] hemorrhagic). Univariable analysis showed that 11 factors were significantly associated with stroke. After adjustment for clinical characteristics, multivariable analysis showed that mRS score ≥3 (HR, 1.99; 95% CI, 1.26–3.14), decreased CBV (HR, 5.31; 95% CI, 2.32–12.13), and concentric enhancement of the arterial wall (HR, 4.16; 95% CI, 1.55–11.15) were significantly associated with stroke.

Data Conclusion

Decreased CBV, mRS score ≥ 3, and concentric enhancement of the arterial wall were significantly associated with increased incidence of stroke in conservatively treated MMD.

Evidence Level

2

Technical Efficacy

Stage 4
Beta‐hydroxy‐beta‐methylbutyrate supplementation and functional outcomes in multitrauma patients: A pilot randomized controlled trial
Authors: Wittholz Kym , Fetterplace Kate , Karahalios Amalia , Ali Abdelhamid Yasmine , Beach Lisa , Read David , Koopman René , Presneill Jeffrey J. , Deane Adam M.
Published: June 2023

Background

Beta‐hydroxy‐beta‐methylbutyrate (HMB) is a nutrition supplement that may attenuate muscle wasting from critical illness. This trial aimed to determine feasibility of administering a blinded nutrition supplement in the intensive care unit (ICU) and continuing it after ICU discharge.

Methods

Single‐center, parallel‐group, blinded, placebo‐controlled, randomized feasibility trial. After traumatic injury necessitating admission to ICU, participants were randomized to receive an enteral study supplement of 3 g of HMB (intervention) or placebo daily for 28 days or until hospital discharge. Primary outcome was feasibility of administering the study supplement, quantified as protocol adherence. Secondary outcomes included change in quadriceps muscle thickness, measured weekly until day 28 or hospital discharge by using ultrasound and analyzed by using a linear mixed model.

Results

Fifty randomized participants (intervention, n = 26; placebo, n = 24) showed comparable baseline characteristics. Participants received 862 (84.3%) of the 1022 prescribed supplements during hospitalization with 543 (62.8%) delivered via an enteral feeding tube. The median (IQR) number of study supplements successfully administered per participant was 19.5 (13.0–24.0) in the intervention group and 16.5 (8.5–23.5) in the placebo group. Marked loss of quadriceps muscle thickness occurred in both groups, with the point estimate favoring attenuated muscle loss with the intervention, albeit with wide CIs (mean intervention difference after 28 days, 0.26 cm [95% CI, −0.13 to 0.64]).

Conclusion

A blinded, placebo‐controlled, randomized clinical trial of daily enteral HMB supplementation for up to 28 days in hospital is feasible. Any effect of HMB supplementation to attenuate muscle wasting after traumatic injury remains uncertain.
Effect of heat treatment on protein quality of rapeseed protein isolate compared with non‐heated rapeseed isolate, soy and whey protein isolates, and rice and pea protein concentrates
Authors: Bailey Hannah M. , Fanelli Natalia S. , Stein Hans H.
Published: June 2023

BACKGROUND

Rapeseed protein isolate is used in the food industry, and heating is often used during rapeseed processing. However, the digestible indispensable amino acid score (DIAAS) for heat‐treated rapeseed protein isolate is unknown. The present study aimed to test the hypothesis that heating rapeseed protein isolate improves protein quality resulting in DIAAS that is greater than for pea and rice protein concentrates, and comparable to that of soy and whey protein isolates.

RESULTS

Standardized ileal digestibility (SID) of amino acids (AA), except leucine and methionine, was not different between heat‐treated rapeseed protein isolate and soy protein isolate, but SID of most AA was greater (P < 0.001) for heat‐treated rapeseed protein isolate than for brown rice protein concentrate, pea protein concentrate, rapeseed protein isolate and soy protein isolate, but not whey protein isolate. Non‐heated rapeseed protein isolate had a reduced (P < 0.001) DIAAS for 6‐month‐old to 3‐year‐old children compared with soy protein isolate, but this was greater (P < 0.001) than for pea and brown rice protein concentrates. The DIAAS for heat‐treated rapeseed protein isolate was greater (P < 0.001) than for non‐heated rapeseed protein isolate for all age groups. Heat‐treated rapeseed protein isolate and whey protein isolate had a DIAAS > 100 for individuals older than 3 years.

CONCLUSION

Rapeseed protein isolate had a DIAAS comparable to soy protein isolate, but heat‐treated rapeseed protein isolate and whey protein isolate had DIAAS ≥ 100, qualifying these proteins as ‘excellent’. Rice and pea protein concentrates had DIAAS < 75. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Imaging of the Diaphragm Following Cardiac Surgery: Focus on Ultrasonographic Assessment
Authors: Rizza Vincenzo , Maranta Francesco , Cianfanelli Lorenzo , Cartella Iside , Alfieri Ottavio , Cianflone Domenico
Published: June 2023

Diaphragm dysfunction is a common complication following cardiac surgery. Its clinical impact is variable, ranging from the absence of symptoms to the acute respiratory failure. Post‐operative diaphragm dysfunction may negatively affect patients' prognosis delaying the weaning from the mechanical ventilation (MV), extending the time of hospitalization and increasing mortality. Ultrasonography is a valid tool to evaluate diaphragmatic impairment in different settings, like the Intensive Care Unit, to predict successful weaning from the MV, and the Cardiovascular Rehabilitation Unit, to stratify patients in terms of risk of functional recovery failure. The aim of this review is to describe the pathophysiology of post‐cardiac surgery diaphragm dysfunction, the techniques used for its diagnosis and the potential applications of diaphragm ultrasound.
Efficacy and safety of abrocitinib in patients with moderate‐to‐severe atopic dermatitis with prior exposure to oral systemic immunosuppressants or biologic therapies: A post hoc analysis of the JADE clinical trials
Authors: Gooderham Melinda J. , Ardern‐Jones Michael R. , Guttman‐Yassky Emma , Ameen Mahreen , Simpson Eric L. , Chan Gary , Biswas Pinaki , Chiu Wing S. , Watkins Melissa
Published: June 2023

Background

Patients with moderate‐to‐severe atopic dermatitis (AD) refractory to topical therapy might require treatment with systemic therapies, including biologics.

Objectives

To assess the efficacy and safety of abrocitinib monotherapy in patients who previously received systemic therapies.

Methods

This post hoc analysis included patients receiving abrocitinib (200 mg/100 mg) or placebo in the phase 2b and phase 3 JADE MONO‐1 and MONO‐2, REGIMEN (abrocitinib 200 mg; open‐label period) and EXTEND (patients enrolled from MONO‐1 and MONO‐2) trials. Patients who were systemic therapy‐naive or had received prior oral systemic or biologic therapies were assessed for Investigator's Global Assessment (IGA) response of 0 (clear) or 1 (almost clear) and ≥2‐point improvement from baseline, ≥75% or ≥90% improvement in Eczema Area and Severity Index (EASI‐75 or EASI‐90), ≥4‐point improvement in Peak Pruritus Numerical Rating Scale (PP‐NRS4), PP‐NRS score of 0 or 1 and change from baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) and Patient‐Oriented Eczema Measure (POEM) scores. Safety was assessed.

Results

This analysis included 1579 patients (systemic therapy‐naive, n = 997; prior exposure to oral systemic, n = 429; biologic therapies, n = 153). At Week 12, IGA 0/1 response rates (95% confidence intervals) among patients who were systemic therapy‐naive, had received prior oral systemic therapy or had received biologic therapy were 44.4% (37.5–51.4), 34.5% (22.3–46.7) and 43.5% (23.2–63.7) with abrocitinib 200 mg, 30.9% (24.2–37.5), 16.4% (7.1–25.7) and 24.1% (8.6–39.7) with abrocitinib 100 mg and 9.6% (4.2–14.9), 5.9% (0.0–13.8) and 0.0% (0.0–23.2) with placebo in the pooled monotherapy trials; and 67.0% (62.8–71.2), 62.2% (56.4–68.0) and 53.5% (42.9–64.0) in REGIMEN. Across subgroups, abrocitinib showed greater improvement in EASI‐75, PP‐NRS4, EASI‐90, PP‐NRS 0/1, PSAAD and POEM scores versus placebo. Similar results were seen at Week 48. No new safety signals were observed.

Conclusions

Prior use of oral systemic or biologic therapies did not seem to impact the efficacy and safety of abrocitinib in patients with moderate‐to‐severe AD.
Thoroughly Hydrophilized Electrospun Poly(L‐Lactide)/ Poly(ε‐Caprolactone) Sponges for Tissue Engineering Application
Authors: Xu Chengzhang , Cheong Jun Young , Mo Xiumei , Jérôme Valérie , Freitag Ruth , Agarwal Seema , Gharibi Reza , Greiner Andreas
Published: June 2023

Biodegradable electrospun sponges are of interest for various applications including tissue engineering, drug release, dental therapy, plant protection, and plant fertilization. Biodegradable electrospun poly(l‐lactide)/poly(ε‐caprolactone) (PLLA/PCL) blend fiber‐based sponge with hierarchical pore structure is inherently hydrophobic, which is disadvantageous for application in tissue engineering, fertilization, and drug delivery. Contact angles and model studies for staining with a hydrophilic dye for untreated, plasma‐treated, and surfactant‐treated PLLA/PCL sponges are reported. Thorough hydrophilization of PLLA/PCL sponges is found only with surfactant‐treated sponges. The MTT assay on the leachates from the sponges does not indicate any cell incompatibility. Furthermore, the cell proliferation and penetration of the hydrophilized sponges are verified by in vitro cell culture studies using MG63 and human fibroblast cells.
Fast Visible‐Light 3D Printing of Conductive PEDOT:PSS Hydrogels
Authors: Lopez‐Larrea Naroa , Gallastegui Antonela , Lezama Luis , Criado‐Gonzalez Miryam , Casado Nerea , Mecerreyes David
Published: June 2023

Functional inks for light‐based 3D printing are actively being searched for being able to exploit all the potentialities of additive manufacturing. Herein, a fast visible‐light photopolymerization process is showed of conductive PEDOT:PSS hydrogels. For this purpose, a new Type II photoinitiator system (PIS) based on riboflavin (Rf), triethanolamine (TEA), and poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is investigated for the visible light photopolymerization of acrylic monomers. PEDOT:PSS has a dual role by accelerating the photoinitiation process and providing conductivity to the obtained hydrogels. Using this PIS, full monomer conversion is achieved in less than 2 min using visible light. First, the PIS mechanism is studied, proposing that electron transfer between the triplet excited state of the dye (3Rf*) and the amine (TEA) is catalyzed by PEDOT:PSS. Second, a series of poly(2‐hydroxyethyl acrylate)/PEDOT:PSS hydrogels with different compositions are obtained by photopolymerization. The presence of PEDOT:PSS negatively influences the swelling properties of hydrogels, but significantly increases its mechanical modulus and electrical properties. The new PIS is also tested for 3D printing in a commercially available Digital Light Processing (DLP) 3D printer (405 nm wavelength), obtaining high resolution and 500 µm hole size conductive scaffolds.
Long‐Term Follow‐Up of Pediatric Patients with Dyskinetic Cerebral Palsy and Deep Brain Stimulation
Authors: Koy Anne , Kühn Andrea A. , Schiller Petra , Huebl Julius , Schneider Gerd‐Helge , Eckenweiler Matthias , Rensing‐Zimmermann Cornelia , Coenen Volker Arnd , Krauss Joachim K. , Saryyeva Assel , Hartmann Hans , Lorenz Delia , Volkmann Jens , Matthies Cordula , Schnitzler Alfons , Vesper Jan , Gharabaghi Alireza , Weiss Daniel , Bevot Andrea , Marks Warren , Howser Angela , Monbaliu Elegast , Mueller Joerg , Prinz‐Langenohl Reinhild , Visser‐Vandewalle Veerle , Timmermann Lars ,   the STIM‐CP investigators
Published: June 2023

Background

Deep brain stimulation (DBS) has been increasingly used in the management of dyskinetic cerebral palsy (DCP). Data on long‐term effects and the safety profile are rare.

Objectives

We assessed the efficacy and safety of pallidal DBS in pediatric patients with DCP.

Methods

The STIM‐CP trial was a prospective, single‐arm, multicenter study in which patients from the parental trial agreed to be followed‐up for up to 36 months. Assessments included motor and non‐motor domains.

Results

Of the 16 patients included initially, 14 (mean inclusion age 14 years) were assessed. There was a significant change in the (blinded) ratings of the total Dyskinesia Impairment Scale at 36 months. Twelve serious adverse events (possibly) related to treatment were documented.

Conclusion

DBS significantly improved dyskinesia, but other outcome parameters did not change significantly. Investigations of larger homogeneous cohorts are needed to further ascertain the impact of DBS and guide treatment decisions in DCP. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Milk Exosomes from Gestational Diabetes Mellitus (GDM) and Healthy Parturient Exhibit Differential miRNAs Profiles and Distinct Regulatory Bioactivity on Hepatocyte Proliferation
Authors: Zheng Zhongdaixi , Mo Jiaqi , Lin Fengjuan , Wang Jiexian , Chen Junbin , Luo Huiyu , Liu Yuguo , Su Chuhong , Gu Xiangfu , Xiong Fei , Zha Longying
Published: June 2023

Scope

Exosomes, a novel type of bioactive component in human milk (HM), affect infant development, growth, and health. Recent studies indicate that HM exosomes and miRNAs relate to gestational diabetes mellitus (GDM). However, the miRNAs profiles and functionalities of HM exosomes from GDM parturient remain unclear. This study aims to compare the differential miRNAs in HM exosomes from GDM and healthy parturient, and investigate the HM exosomes bioactivities in regulating hepatocyte proliferation and insulin sensitivity.

Methods and Results

This study extracted HM exosomes from GDM (GDM‐EXO) and healthy (NOR‐EXO) parturient by ultracentrifugation, high‐throughput sequenced and compared the exosomal miRNAs profiles, and explored the regulatory bioactivities on hepatocyte proliferation in HepG2 cells and Balb/c mice. As compared to NOR‐EXO, GDM‐EXO has similar morphology, size, concentration, and exosome‐specific markers (CD9 and TSG101) expression. GDM‐EXO and NOR‐EXO specifically harbor 1299 and 8 miRNAs, respectively. Moreover, GDM‐EXO had 176 upregulated and 47 downregulated miRNAs compared with NOR‐EXO. Both GDM‐EXO and NOR‐EXO were absorbed in cultured HepG2 hepatocytes and mice liver. GDM‐EXO inhibited hepatocytes proliferation by downregulating mammalian target of rapamycin (mTOR) possibly via exosomal miR‐101‐3p delivery.

Conclusion

HM exosomes from GDM and healthy parturient exhibit differential miRNAs profiles and distinct regulatory bioactivity on hepatocyte proliferation.
Validation of an automatic method for reconstruction, delineation, and measurement of levator hiatus in clinical practice
Authors: Chen Ying , Lin Xin , Zhang Man , Qu Enze , Huang Dongmei , Mao Yongjiang , Huang Zeping , Zhang Xinling
Published: June 2023

Objectives

To evaluate the concordance between an automatic software program and manual evaluation in reconstructing, delineating, and measuring the levator hiatus (LH) on maximal Valsalva maneuver.

Methods

This was a retrospective study analyzing archived raw ultrasound imaging data of 100 patients underwent transperineal ultrasound (TPUS) examination. Each data were assessed by the automatic Smart Pelvic System software program and manual evaluation. The Dice similarity index (DSI), mean absolute distance (MAD), and Hausdorff distance (HDD) were calculated to quantify delineation accuracy of LH. Agreement between automatic and manual measurement of levator hiatus area was assessed by intraclass correlation coefficient (ICC) and Bland–Altman method.

Results

The satisfaction rate of automatic reconstruction was 94%. Six images were recognized as unsatisfactory reconstructed images for some gas in the rectum and anal canal. Compared with satisfactory reconstructed images, DSI of unsatisfactory reconstructed images was lower, MAD and HDD were larger (p = 0.001, p = 0.001, p = 0.006, respectively). The ICC was up to 0.987 in 94 satisfactory reconstructed images.

Conclusions

The Smart Pelvic System software program had good performance in reconstruction, delineation, and measurement of LH on maximal Valsalva maneuver in clinical practice, despite misidentification of the border of posterior aspect of LH due to the influence of gas in the rectum.
Psychological and mental impact of long‐standing incontinence on children and adolescents with complex urologic disorders
Authors: Wadie Bassem S. , Ashour Rawdy , Ali Ibtihal M.
Published: June 2023

Purpose

Incontinence has a negative impact on the quality of life and is associated with psychiatric disturbances in humans. This study evaluates the impact of long‐standing incontinence on psychological and mental development.

Methods

This is a cohort study carried out in a tertiary care urologic facility. After obtaining an IRB approval, we enrolled 49 children with severe incontinence (incontinence for at least 1 year duration and one surgical intervention) and interviewed between October 2019 and March 2020. Child Behavior Checklist (CBCL) and intelligence quotient (IQ) testing was performed for each using Stanford‐Binet—4th edition. An age‐matched control group was recruited for comparison. A total of 51 children in the control group were later recruited from March 2020 to October 2020 from the Psychiatry Department.

Results

A total of 49 children fulfilled the inclusion criteria. Mean age was 9.93 years, 31 males and 18 females. The etiology of incontinence was neuropathic bladder in 30, exstrophy in 8, incontinent epispadius in 4, valve bladder in 4; common urogenital sinus in 2, and refractory OAB in 1. Median number of procedures was 2 (Range 0–9). Median pads were 5 per day and median hospital stay was 32 days. Median total score of CBCL was 26.5 compared to 7 for the control group (p = 0.00023). Mean IQ of the study group was 88.3 as compared to that of the control (94.65), the difference is significant (p = 0.00023).

Conclusion

Children with severe degree of incontinence suffered from significant psychiatric disorders and negative affection of their intelligence. A multidisciplinary approach is advised for management of those children
Controlling for false discoveries subsequently to large scale one‐way ANOVA testing in proteomics: Practical considerations
Authors: Burger Thomas
Published: June 2023

In discovery proteomics, as well as many other “omic” approaches, the possibility to test for the differential abundance of hundreds (or of thousands) of features simultaneously is appealing, despite requiring specific statistical safeguards, among which controlling for the false discovery rate (FDR) has become standard. Moreover, when more than two biological conditions or group treatments are considered, it has become customary to rely on the one‐way analysis of variance (ANOVA) framework, where a first global differential abundance landscape provided by an omnibus test can be subsequently refined using various post‐hoc tests (PHTs). However, the interactions between the FDR control procedures and the PHTs are complex, because both correspond to different types of multiple test corrections (MTCs). This article surveys various ways to orchestrate them in a data processing workflow and discusses their pros and cons.
Determination of the Gurney velocity for the unconventional aluminum‐water explosive**
Authors: Frost Thanasi , Novac Bucur M. , Danilov Don , Senior Peter
Published: June 2023

The present work is dedicated to the determination of the Gurney velocity of the unconventional aluminum‐water explosive. The paper presents the experimental arrangement, the diagnostic equipment used, and the main results that have been obtained. The experiments report the accurate velocity measurement of projectiles accelerated by aluminum and copper underwater exploding wires. Based on the results obtained, a Gurney velocity of 1.88 km/s has been obtained for the unconventional aluminum‐water explosive. The result is discussed and compared with typical values for standard explosives.
Low/intermediate speed impact‐induced ignition and damage of a novel high‐energy solid propellant
Authors: Wu Yi , Fan Yingnan , Chen Xiaoxu , Wen Junjie , Wang Qianlong , Huang Junyu
Published: June 2023

The damage and ignition response of a novel propellant is investigated using a modified split Hopkinson pressure bar (SHPB). The mechanical response of the propellant exhibits strong strain rate dependency following a power law. The whole process from mechanical damage to onset of ignition, deflagration and potential deflagration to detonation transition (DDT) under different strain rates (1000–5000 s−1) is captured via high‐speed photography and digital image correlation (DIC). To clarify the onset and extent of the resulting reaction in terms of the mechanical damage caused by impact, meso‐scale analysis is used to evaluate the propellant before and after dynamic impact loading. The ignition response under impact loading is mainly caused by shear flow, and ignition after multiple impacts due to the reflection of stress waves. Dense debris clouds produced by the first impact are observed in the case of a strain rate of 5000 s−1 leading to DDT when the second impact initiated ignition.
Combining pairwise structural similarity and deep learning interface contact prediction to estimate protein complex model accuracy in CASP15
Authors: Roy Raj S. , Liu Jian , Giri Nabin , Guo Zhiye , Cheng Jianlin
Published: June 2023

Estimating the accuracy of quaternary structural models of protein complexes and assemblies (EMA) is important for predicting quaternary structures and applying them to studying protein function and interaction. The pairwise similarity between structural models is proven useful for estimating the quality of protein tertiary structural models, but it has been rarely applied to predicting the quality of quaternary structural models. Moreover, the pairwise similarity approach often fails when many structural models are of low quality and similar to each other. To address the gap, we developed a hybrid method (MULTICOM_qa) combining a pairwise similarity score (PSS) and an interface contact probability score (ICPS) based on the deep learning inter‐chain contact prediction for estimating protein complex model accuracy. It blindly participated in the 15th Critical Assessment of Techniques for Protein Structure Prediction (CASP15) in 2022 and performed very well in estimating the global structure accuracy of assembly models. The average per‐target correlation coefficient between the model quality scores predicted by MULTICOM_qa and the true quality scores of the models of CASP15 assembly targets is 0.66. The average per‐target ranking loss in using the predicted quality scores to rank the models is 0.14. It was able to select good models for most targets. Moreover, several key factors (i.e., target difficulty, model sampling difficulty, skewness of model quality, and similarity between good/bad models) for EMA are identified and analyzed. The results demonstrate that combining the multi‐model method (PSS) with the complementary single‐model method (ICPS) is a promising approach to EMA.
Principle, development and application of time–temperature indicators for packaging
Authors: Liu Yang , Li Lin , Yu Zhumin , Ye Changqing , Pan Liao , Song Yanlin
Published: June 2023

Time–temperature indicators (TTIs) can visually reflect the remaining shelf life of various products, especially in cold chain transportation, by taking consideration of both time and temperature influences. Though various TTIs have been developed, few have been commercialized. This review aims at providing a timely reference to scientific community and valuable guidance for the future design of TTIs to boost the commercialization. This review firstly introduces the general principle and models for TTIs including key parameters of reaction rate constants, activation energies and activation energy matching. Then, four classical types of TTIs covering diffusion‐based, polymer‐based, enzyme‐based, and microbial TTIs are introduced regarding their working mechanisms, advantages and disadvantages as well as commercialized TTI products as examples. The development trend of TTI design and fabrication is highlighted from three categories including nanoparticles, electrospun nanofibers and printable inks. Furthermore, the review summarizes recent application of TTIs for monitoring the quality and safety of various products (meat, seafood, dairy, vaccines and fruits and vegetables). We also point our concerns from the perspective of safety, accuracy, multifunctionality and commercialization for the future development of TTIs.
Room‐Temperature Polarized Light‐Emitting Diode‐Based on a 2D Monolayer Semiconductor
Authors: Shi Xiuqi , Li Wenfei , Lan Xinhui , Guo Qianqian , Zhu Guangpeng , Du Wei , Wang Tao
Published: June 2023

Transition metal dichalcogenide (TMD)‐based 2D monolayer semiconductors, with the direct bandgap and the large exciton binding energy, are widely studied to develop miniaturized optoelectronic devices, e.g., nanoscale light‐emitting diodes (LEDs). However, in terms of polarization control, it is still quite challenging to realize polarized electroluminescence (EL) from TMD monolayers, especially at room temperature. Here, by using Ag nanowire top electrode, polarized LEDs are demonstrated based on 2D monolayer semiconductors (WSe2, MoSe2, and WS2) at room temperature with a degree of polarization (DoP) ranging from 50% to 63%. The highly anisotropic EL emission comes from the 2D/Ag interface via the electron/hole injection and recombination process, where the EL emission is also enhanced by the polarization‐dependent plasmonic resonance of the Ag nanowire. These findings introduce new insights into the design of polarized 2D LED devices at room temperature and may promote the development of miniaturized 2D optoelectronic devices.