bluuebunny/crossref_metadata_2025 huggingface dataset:
Citrulline in the management of patients with urea cycle disorders
Authors: Imbard Apolline , Bouchereau Juliette , Arnoux Jean-Baptiste , Brassier Anaïs , Schiff Manuel , Bérat Claire-Marine , Pontoizeau Clément , Benoist Jean-François , Josse Constant , Montestruc François , de Lonlay Pascale
Published: July 2023

Background

Treatment recommendations for urea cycle disorders (UCDs) include supplementation with amino acids involved in the urea cycle (arginine and/or citrulline, depending on the enzyme deficiency), to maximize ammonia excretion through the urea cycle, but limited data are available regarding the use of citrulline. This study retrospectively reviewed clinical and biological data from patients with UCDs treated with citrulline and/or arginine at a reference center since 1990. The aim was to describe the prescription, impact, and safety of these therapies. Data collection included patient background, treatment details, changes in biochemical parameters (plasma ammonia and amino acids concentrations), decompensations, and patient outcomes.

Results

Overall, 79 patients (median age at diagnosis, 0.9 months) received citrulline and/or arginine in combination with a restricted protein diet, most with ornithine transcarbamylase (n = 57, 73%) or carbamoyl phosphate synthetase 1 (n = 15, 19%) deficiencies. Most patients also received ammonium scavengers. Median follow-up was 9.5 years and median exposure to first treatment with arginine + citrulline, citrulline monotherapy, or arginine monotherapy was 5.5, 2.5, or 0.3 years, respectively. During follow-up, arginine or citrulline was administered at least once (as monotherapy or in combination) in the same proportion of patients (86.1%); the overall median duration of exposure was 5.9 years for arginine + citrulline, 3.1 years for citrulline monotherapy, and 0.6 years for arginine monotherapy. The most common switch was from monotherapy to combination therapy (41 of 75 switches, 54.7%). During treatment, mean ammonia concentrations were 35.9 µmol/L with citrulline, 49.8 µmol/L with arginine, and 53.0 µmol/L with arginine + citrulline. Mean plasma arginine concentrations increased significantly from the beginning to the end of citrulline treatment periods (from 67.6 µmol/L to 84.9 µmol/L, P < 0.05). At last evaluation, mean height and weight for age were normal and most patients showed normal or adapted behavior (98.7%) and normal social life (79.0%). Two patients (2.5%) experienced three treatment-related gastrointestinal adverse reactions.

Conclusions

This study underlines the importance of citrulline supplementation, either alone or together with arginine, in the management of patients with UCDs. When a monotherapy is considered, citrulline would be the preferred option in terms of increasing plasma arginine concentrations.
Effects of miglustat therapy on neurological disorder and survival in early-infantile Niemann-Pick disease type C: a national French retrospective study
Authors: Freihuber Cécile , Dahmani-Rabehi Bahia , Brassier Anaïs , Broué Pierre , Cances Claude , Chabrol Brigitte , Eyer Didier , Labarthe François , Latour Philippe , Levade Thierry , Pichard Samia , Sevin Caroline , Vanier Marie T. , Héron Bénédicte
Published: July 2023

Background

Niemann-Pick disease type C (NP-C) is a rare neurovisceral lysosomal lipid storage disease characterized by progressive neurodegeneration and premature death. While miglustat can stabilize neurological manifestations in later onset forms of NP-C, its efficacy in the early-infantile neurological form has not been demonstrated. In this observational retrospective study, we compared long-term neurodevelopmental outcome and survival between an untreated and a treated group of early infantile NP-C patients.

Methods

Data available on all NP-C patients with early infantile neurological onset diagnosed in France between 1990 and 2013 were compiled. Patients with incomplete data or who had died from a systemic perinatal, rapidly fatal form were excluded.

Results

Ten patients were included in the treated group (year of birth: 2006–2012), and 16 patients in the untreated group [born 1987–2005 (n = 15), 2012 (n = 1)]. The median age at neurological onset was 9 months (5–18) in the treated group, and 12 months (3–18) in the untreated group (p = 0.22). Miglustat therapy was started at a median age of 24.5 months (9–29) and median duration was 30 months (11–56). Gastrointestinal adverse events were reported in 7/10 patients on miglustat. All patients developed loss of psychomotor acquisitions or additional neurological symptoms despite miglustat therapy. The ages of developmental milestones and neurological involvement did not significantly differ between the two groups. Four patients in the untreated group were lost to follow up. The 22 remaining patients had died by the end of the study and no patient survived beyond the age of 7.4 years. The median survival age was 4.42 years in the untreated group and 5.56 years in the treated group; the Kaplan–Meier survival curves were not significantly different (log-rank test: p = 0.11).

Conclusions

Miglustat allowed no significant long-term neurodevelopmental improvement nor significant increase of survival in patients with early infantile NP-C.
The Vasopressin Loading for Refractory septic shock (VALOR) study: a prospective observational study
Authors: Nakamura Kensuke , Nakano Hidehiko , Ikechi Daisuke , Mochizuki Masaki , Takahashi Yuji , Koyama Yasuaki , Hashimoto Hideki , Abe Toshikazu , Hayakawa Mineji , Yamakawa Kazuma
Published: July 2023

Background

Vasopressin is a second-line vasoactive agent for refractory septic shock. Vasopressin loading is not generally performed because of the lack of evidence for its effects and safety. However, based on our previous findings, we hypothesized it can predict the responsibility to vasopressin infusion with safety, and prospectively examined it in the present study.

Methods

Vasopressin loading was performed via the intravenous administration of a bolus of 1 U, followed by its continuous infusion at 1U/h in patients with septic shock treated with ≥ 0.2 μg/kg/min noradrenaline. An arterial pressure wave analysis was conducted, and endocrinological tests were performed immediately prior to vasopressin loading. We classified patients into responders/non-responders based on mean arterial pressure (MAP) changes after vasopressin loading. Based on our previous findings, the lower tertile of MAP changes was selected as the cut-off. The change in the catecholamine index (CAI) after 6 h was assigned as the primary outcome. Digital ischemia, mesenteric ischemia, and myocardial ischemia during the admission period were prospectively and systematically recorded as adverse events.

Results

Ninety-two patients were registered during the study period and examined. Sixty-two patients with a MAP change > 22 mmHg were assigned as responders and the others as non-responders. Blood adrenocorticotropic hormone levels were significantly higher in non-responders. Stroke volume variations were higher in responders before loading, while stroke volume and dP/dtmax were higher in responders after loading. Median CAI changes were − 10 in responders and 0 in non-responders, which was significantly lower in the former (p < 0.0001). AUROC of MAP change with vasopressin loading to predict CAI change < 0 after continuous infusion was 0.843 with sensitivity of 0.92 and specificity of 0.77. Ischemia events were observed in 5 cases (5.4%).

Conclusions

Vasopressin loading may be safely introduced for septic shock. Vasopressin loading may be used to predict responses to its continuous infusion and select appropriate strategies to increase blood pressure.
Human platelet lysate stimulates neurotrophic properties of human adipose-derived stem cells better than Schwann cell-like cells
Authors: Brambilla Stefania , Guiotto Martino , Torretta Enrica , Armenia Ilaria , Moretti Matteo , Gelfi Cecilia , Palombella Silvia , di Summa Pietro G.
Published: July 2023

Background

Trauma-associated peripheral nerve injury is a widespread clinical problem causing sensory and motor disabilities. Schwann cells (SCs) contribute to nerve regeneration, mainly by secreting nerve growth factor (NGF) and brain-derived neurotrophic factor. In the last years, adipose-derived stem cells (ASCs) differentiated into SCs (SC-ASCs) were considered as promising cell therapy. However, the cell trans-differentiation process has not been effectively showed and presents several drawbacks, thus an alternative approach for increasing ASCs neurotrophic properties is highly demanded. In the context of human cell-based therapies, Good Manufacturing Practice directions indicate that FBS should be substituted with a xenogeneic-free supplement, such as Human Platelet Lysate (HPL). Previously, we demonstrated that neurotrophic properties of HPL-cultured ASCs were superior compared to undifferentiated FBS-cultured ASCs. Therefore, as following step, here we compared the neurotrophic properties of differentiated SC-like ASCs and HPL-cultured ASCs.

Methods

Both cell groups were investigated for gene expression level of neurotrophic factors, their receptors and neuronal markers. Moreover, the expression of nestin was quantitatively evaluated by flow cytometry. The commitment toward the SC phenotype was assessed with immunofluorescence pictures. Proteomics analysis was performed on both cells and their conditioned media to compare the differential protein profile. Finally, neurotrophic abilities of both groups were evaluated with a functional co-culture assay, assessing dorsal root ganglia survival and neurite outgrowth.

Results

HPL-cultured ASCs demonstrated higher gene expression of NGF and lower expression of S100B. Moreover, nestin was present in almost all HPL-cultured ASCs and only in one quarter of SC-ASCs. Immunofluorescence confirmed that S100B was not present in HPL-cultured ASCs. Proteomics analysis validated the higher expression of nestin and the increase in cytoskeletal and ECM proteins involved in neural regeneration processes. The co-culture assay highlighted that neurite outgrowth was higher in the presence of HPL-ASCs or their conditioned medium compared to SC-ASCs.

Conclusions

All together, our results show that HPL-ASCs were more neurotrophic than SC-ASCs. We highlighted that the HPL triggers an immature neuro-induction state of ASCs, while keeping their stem properties, paving the way for innovative therapies for nerve regeneration.

Graphical Abstract
DiGeorge syndrome critical region gene 2 (DGCR2), a schizophrenia risk gene, regulates dendritic spine development through cell adhesion
Authors: Ren Dongyan , Luo Bin , Chen Peng , Yu Lulu , Xiong Mingtao , Fu Zhiqiang , Zhou Tian , Chen Wen-Bing , Fei Erkang
Published: July 2023

Background

Dendritic spines are the sites of excitatory synapses on pyramidal neurons, and their development is crucial for neural circuits and brain functions. The spine shape, size, or number alterations are associated with neurological disorders, including schizophrenia. DiGeorge syndrome critical region gene 2 (DGCR2) is one of the deleted genes within the 22q11.2 deletion syndrome (22q11DS), which is a high risk for developing schizophrenia. DGCR2 expression was reduced in schizophrenics. However, the pathophysiological mechanism of DGCR2 in schizophrenia or 22q11DS is still unclear.

Results

Here, we report that DGCR2 expression was increased during the neurodevelopmental period and enriched in the postsynaptic densities (PSDs). DGCR2-deficient hippocampal neurons formed fewer spines. In agreement, glutamatergic transmission and synaptic plasticity were decreased in the hippocampus of DGCR2-deficient mice. Further molecular studies showed that the extracellular domain (ECD) of DGCR2 is responsible for its transcellular interaction with cell adhesion molecule Neurexin1 (NRXN1) and spine development. Consequently, abnormal behaviors, like anxiety, were observed in DGCR2-deficient mice.

Conclusions

These observations indicate that DGCR2 is a novel cell adhesion molecule required for spine development and synaptic plasticity, and its deficiency induces abnormal behaviors in mice. This study provides a potential pathophysiological mechanism of DGCR2 in 22q11DS and related mental disorders.
Joint resource allocation and user association for multi-cell integrated sensing and communication systems
Authors: Zhang Jiahui , Fei Zesong , Wang Xinyi , Liu Peng , Huang Jingxuan , Zheng Zhong
Published: July 2023

The densification of the orthogonal frequency division multiplexing (OFDM) based fifth-generation communication systems, as well as the requirement of integrating sensing and communication functionalities, has promoted the development of integrated-sensing-and-communication (ISAC) dense cellular networks (DCNs). In the OFDM-based ISAC-DCN, multiple base stations simultaneously serve mobile users and sense targets based on the echo of downlink communication signals. In this paper, we establish the interference model in ISAC-DCN for sensing and communication. Focusing on the interference management of the ISAC-DCN, we investigate the multi-dimension resource allocation problem. In particular, we aim to maximize the network utility by jointly optimizing sub-band allocation, user association, and transmission power under the sensing signal-to-interference-plus-noise ratio constraint to be solved iteratively. The mixed-integer optimization problem is decoupled into three sub-problems. Specifically, a greedy genetic sub-band allocation scheme is proposed for sub-band allocation to reduce total interference. We employ the successive convex approximation technique to transform the transmission power control sub-problem and solve it via geometric programming. Simulation results illustrate the trade-off between sensing and communication performances, and show that the proposed algorithm significantly improves the network utility and achieves higher detection probability.
Variant rs17619600 in the gene encoding serotonin receptor 2B (HTR2B) increases the risk of gestational diabetes mellitus: a case–control study
Authors: Penno Juliana Regina Chamlian Zucare , Santos-Bezerra Daniele Pereira , Cavaleiro Ana Mercedes , da Silva Sousa Ana Maria , Zaccara Tatiana Assunção , da Costa Rafaela Alkmin , Francisco Rossana Pulcineli Vieira , Correa-Giannella Maria Lucia
Published: July 2023

Background

During pregnancy, the increase in maternal insulin resistance is compensated by hyperplasia and increased function of maternal pancreatic beta cells; the failure of this compensatory mechanism is associated with gestational diabetes mellitus (GDM). Serotonin participates in beta cell adaptation, acting downstream of the prolactin pathway; the blocking of serotonin receptor B (HTR2B) signaling in pregnant mice impaired beta cell expansion and caused glucose intolerance. Thus, given the importance of the serotoninergic system for the adaptation of beta cells to the increased insulin demand during pregnancy, we hypothesized that genetic variants (single nucleotide polymorphisms [SNPs]) in the gene encoding HTR2B could influence the risk of developing GDM.

Methods

This was a case–control study. Five SNPs (rs4973377, rs765458, rs10187149, rs10194776, and s17619600) in HTR2B were genotyped by real-time polymerase chain reaction in 453 women with GDM and in 443 pregnant women without GDM.

Results

Only the minor allele C of SNP rs17619600 conferred an increased risk for GDM in the codominant model (odds ratio [OR] 2.15; 95% confidence interval [CI] 1.53–3.09; P < 0.0001) and in the rare dominant model (OR 2.32; CI 1.61–3.37; P < 0.0001). No associations were found between the SNPs and insulin use, maternal weight gain, newborn weight, or the result of postpartum oral glucose tolerance test (OGTT). In the overall population, carriers of the XC genotype (rare dominant model) presented a higher area under the curve (AUC) of plasma glucose during the OGTT, performed for diagnostic purposes, compared with carriers of the TT genotype of rs17619600.

Conclusions

SNP rs17619600 in the HTR2B gene influences glucose homeostasis, probably affecting insulin release, and the presence of the minor allele C was associated with a higher risk of GDM.
Case Report: The application of sildenafil citrate treatment on cervical tuberculosis patient seeking IVF treatment
Authors: Ansari Alhera , More Akash , Dutta Shilpa , Chaudhari Namrata
Published: July 2023

This case report describes the application of sildenafil citrate treatment in a cervical tuberculosis (TB) patient seeking in vitro fertilization (IVF) treatment. The patient, a 34-year-old female with a history of cervical TB and primary infertility, underwent anti-TB treatment before fertility treatment. Cervical stenosis and a thin endometrium were identified during a transvaginal ultrasound, posing challenges to successful IVF outcomes. Sildenafil citrate, a phosphodiesterase-5 (PDE-5) inhibitor known to improve endometrial blood flow, was administered orally at a dosage of 50 mg, three times daily, starting on the fifth day of the menstrual cycle. The patient exhibited an increase in endometrial thickness, indicating improved receptivity. Clinical pregnancy was achieved. These findings suggest that sildenafil citrate may have the potential as an adjunct therapy to enhance IVF success in cervical TB patients, although further research is needed to validate these results in larger studies.
Courier Dispatch in On-Demand Delivery
Authors: Chen Mingliu , Hu Ming
Published: July 2023

We study a courier dispatching problem in an on-demand delivery system in which customers are sensitive to delay. Specifically, we evaluate the effect of temporal pooling by comparing systems using the dedicated strategy, with which only one order is delivered per trip, versus the pooling strategy, with which a batch of consecutive orders is delivered on each trip. We capture the courier delivery system’s spatial dimension by assuming that, following a Poisson process, demand arises at a uniformly generated point within a service region. With the same objective of revenue maximization, we find that the dispatching strategy depends critically on customers’ patience level, the size of the service region, and whether the firm can endogenize the demand. We obtain concise but informative results with a single courier and assuming that customers’ underlying arrival rate is large enough, meaning a crowded market, such as rush hour delivery. In particular, when the firm has a growth target and needs to achieve an exogenously given demand rate, using the pooling strategy is optimal if the service area is large enough to fully exploit the pooling efficiency in delivery. Otherwise, using the dedicated strategy is optimal. In contrast, if the firm can endogenize the demand rate by varying the delivery fee, using the dedicated strategy is optimal for a large service area. The reason is that it is optimal for the firm to sustain a relatively low demand rate by charging a high fee for a large service radius: within this large area, the pooling strategy leads to a long wait because it takes a long time for multiple orders to accumulate. Moreover, with an exogenous demand rate to meet, customers’ patience level has no impact on the dispatch strategy. However, when the demand rate can be endogenized, the dedicated strategy is preferable if customers are impatient. Furthermore, we extend our model to account for social welfare maximization, a hybrid contingent delivery policy, a general arrival rate that does not have to be large, a nonuniform distribution of orders in the service region, and multiple couriers. We also conduct numerical analysis and simulations to complement our main results and find that most insights in our base model still hold in these extensions and numerical studies.

This paper was accepted by Jeannette Song, operations management.

Funding: This work was supported by the Natural Sciences and Engineering Research Council of Canada [Grants RGPIN-2015-06757 and RGPIN-2021-04295].

Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2023.4858 .
Highly-sensitive temperature sensor based on photopolymerized-waveguide embedded Mach-Zehnder interferometer
Authors: Wang Jiabin , Yang Xingyu , Kou Yanru , Tong Di , Wang Anzhi , Niu Chong , Meng Haoran , Li Song , Geng Tao , Sun Weimin
Published: July 2023

Biology, medicine, and chemistry all rely heavily on highly sensitive optical fiber temperature sensors. To the best of our knowledge, this research introduces a unique design framework for high-performance fiber temperature sensors that helps eliminate the all-fiber interferometers’ sensitivity bottleneck. A section of photopolymerized waveguide is embedded in a typical Mach-Zehnder interferomenter framework with multimode fiber-single mode fiber-multimode fiber (MSM) structure. The thermal-optical coefficient (TOC) of the photopolymerized waveguide core, which is created via the fiber-end lithography technique, differs dramatically from that of the resin cladding. Due to the considerable TOC difference, the phase difference between the interfering beams significantly increases as the temperature changes. The fundamental variables affecting temperature sensitivity are conceptually explored and experimentally verified. The suggested device achieves a typical temperature sensitivity of 1.15 nm/∘C in the range of 30–100∘C, which is about 10 times as high as that of the all-fiber MSM sensors. The suggested designing framework offers a fresh thought for creating high-performing fiber optic temperature sensors.
Integral imaging three-dimensional display system with anisotropic backlight for the elimination of voxel aliasing and separation
Authors: Zhao Chong-Ji , Guo Zhao-Da , Deng Huan , Yang Cui-Ni , Bai Yu-Cheng
Published: July 2023

Compared with conventional scattered backlight systems, integral imaging (InIm) display system with collimated backlight can reduce the voxel size, but apparent voxel separation and severe graininess still exist in reconstructed 3D images. In this paper, an InIm 3D display system with anisotropic backlight control of sub-pixels was proposed to resolve both voxel aliasing and voxel separation simultaneously. It consists of an anisotropic backlight unit (ABU), a transmissive liquid crystal panel (LCP), and a lens array. The ABU with specific horizontal and vertical divergence angles was proposed and designed. Within the depth of field, the light rays emitted from sub-pixels are controlled precisely by the ABU to minimize the voxel size as well as stitch adjacent voxels seamlessly, thus improving the 3D image quality effectively. In the experiment, the prototype of our proposed ABU-type InIm system was developed, and the spatial frequency was nearly two times of conventional scattered backlight InIm system. Additionally, the proposed system eliminated the voxel separation which usually occurs in collimated backlight InIm system. As a result, voxels reconstructed by our proposed system were stitched in space without aliasing and separation, thereby greatly enhancing the 3D resolution and image quality.
Fisheye lens-based UWOC system with an FOV of ±90°
Authors: Hua Yan , Xiong Jianmin , Gao Yunhai , Zhang Hao , Yang Xingqi , Zhang Yufan , Cai Chengye , Wang Liang , Li YanLong , Xu Jing
Published: July 2023

The link alignment is a challenge in underwater wireless optical communication (UWOC). This paper proposes a UWOC system adopting a fisheye lens with a field of view (FOV) of ±90° at the receiver to alleviate alignment requirement, and a mobile scanning device (MSD) is exploited to track the variation of the imaging position generated by the fisheye lens due to different incidence angles. In a 7-m tap water channel, a transmission with a data rate of 400 Mbps and an FOV of ±90° is realized with 16-quadrature amplitude modulating-orthogonal frequency division multiplexing (16-QAM-OFDM) modulation and orthogonal matching pursuit (OMP) channel estimation algorithm.
Baf155 regulates skeletal muscle metabolism via HIF-1a signaling
Authors: Kang Jong-Seol , Kim Dongha , Rhee Joonwoo , Seo Ji-Yun , Park Inkuk , Kim Ji-Hoon , Lee Daewon , Lee WonUk , Kim Ye Lynne , Yoo Kyusang , Bae Sunghwan , Chung Jongkyeong , Seong Rho Hyun , Kong Young-Yun
Published: July 2023

During exercise, skeletal muscle is exposed to a low oxygen condition, hypoxia. Under hypoxia, the transcription factor hypoxia-inducible factor-1α (HIF-1α) is stabilized and induces expressions of its target genes regulating glycolytic metabolism. Here, using a skeletal muscle-specific gene ablation mouse model, we show that Brg1/Brm-associated factor 155 (Baf155), a core subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, is essential for HIF-1α signaling in skeletal muscle. Muscle-specific ablation of Baf155 increases oxidative metabolism by reducing HIF-1α function, which accompanies the decreased lactate production during exercise. Furthermore, the augmented oxidation leads to high intramuscular adenosine triphosphate (ATP) level and results in the enhancement of endurance exercise capacity. Mechanistically, our chromatin immunoprecipitation (ChIP) analysis reveals that Baf155 modulates DNA-binding activity of HIF-1α to the promoters of its target genes. In addition, for this regulatory function, Baf155 requires a phospho-signal transducer and activator of transcription 3 (pSTAT3), which forms a coactivator complex with HIF-1α, to activate HIF-1α signaling. Our findings reveal the crucial role of Baf155 in energy metabolism of skeletal muscle and the interaction between Baf155 and hypoxia signaling.
Neural activity induces strongly coupled electro-chemo-mechanical interactions and fluid flow in astrocyte networks and extracellular space—A computational study
Authors: Sætra Marte J. , Ellingsrud Ada J. , Rognes Marie E.
Published: July 2023

The complex interplay between chemical, electrical, and mechanical factors is fundamental to the function and homeostasis of the brain, but the effect of electrochemical gradients on brain interstitial fluid flow, solute transport, and clearance remains poorly quantified. Here, via in-silico experiments based on biophysical modeling, we estimate water movement across astrocyte cell membranes, within astrocyte networks, and within the extracellular space (ECS) induced by neuronal activity, and quantify the relative role of different forces (osmotic, hydrostatic, and electrical) on transport and fluid flow under such conditions. We find that neuronal activity alone may induce intracellular fluid velocities in astrocyte networks of up to 14μm/min, and fluid velocities in the ECS of similar magnitude. These velocities are dominated by an osmotic contribution in the intracellular compartment; without it, the estimated fluid velocities drop by a factor of ×34–45. Further, the compartmental fluid flow has a pronounced effect on transport: advection accelerates ionic transport within astrocytic networks by a factor of ×1–5 compared to diffusion alone.
Theoretical efficiency limits and speed-efficiency trade-off in myosin motors
Authors: Vilfan Andrej , Šarlah Andreja
Published: July 2023

Muscle myosin is a non-processive molecular motor that generates mechanical work when cooperating in large ensembles. During its cyle, each individual motor keeps attaching and detaching from the actin filament. The random nature of attachment and detachment inevitably leads to losses and imposes theoretical limits on the energetic efficiency. Here, we numerically determine the theoretical efficiency limit of a classical myosin model with a given number of mechano-chemical states. All parameters that are not bounded by physical limits (like rate limiting steps) are determined by numerical efficiency optimization. We show that the efficiency is limited by the number of states, the stiffness and the rate-limiting kinetic steps. There is a trade-off between speed and efficiency. Slow motors are optimal when most of the available free energy is allocated to the working stroke and the stiffness of their elastic element is high. Fast motors, on the other hand, work better with a lower and asymmetric stiffness and allocate a larger fraction of free energy to the release of ADP. Overall, many features found in myosins coincide with the findings from the model optimization: there are at least 3 bound states, the largest part of the working stroke takes place during the first transition, the ADP affinity is adapted differently in slow and fast myosins and there is an asymmetry in elastic elements.
Prediction of lymphoma response to CAR T cells by deep learning-based image analysis
Authors: Tong Yubing , Udupa Jayaram K. , Chong Emeline , Winchell Nicole , Sun Changjian , Zou Yongning , Schuster Stephen J. , Torigian Drew A.
Published: July 2023

Clinical prognostic scoring systems have limited utility for predicting treatment outcomes in lymphomas. We therefore tested the feasibility of a deep-learning (DL)-based image analysis methodology on pre-treatment diagnostic computed tomography (dCT), low-dose CT (lCT), and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) images and rule-based reasoning to predict treatment response to chimeric antigen receptor (CAR) T-cell therapy in B-cell lymphomas. Pre-treatment images of 770 lymph node lesions from 39 adult patients with B-cell lymphomas treated with CD19-directed CAR T-cells were analyzed. Transfer learning using a pre-trained neural network model, then retrained for a specific task, was used to predict lesion-level treatment responses from separate dCT, lCT, and FDG-PET images. Patient-level response analysis was performed by applying rule-based reasoning to lesion-level prediction results. Patient-level response prediction was also compared to prediction based on the international prognostic index (IPI) for diffuse large B-cell lymphoma. The average accuracy of lesion-level response prediction based on single whole dCT slice-based input was 0.82+0.05 with sensitivity 0.87+0.07, specificity 0.77+0.12, and AUC 0.91+0.03. Patient-level response prediction from dCT, using the “Majority 60%” rule, had accuracy 0.81, sensitivity 0.75, and specificity 0.88 using 12-month post-treatment patient response as the reference standard and outperformed response prediction based on IPI risk factors (accuracy 0.54, sensitivity 0.38, and specificity 0.61 (p = 0.046)). Prediction of treatment outcome in B-cell lymphomas from pre-treatment medical images using DL-based image analysis and rule-based reasoning is feasible. This approach can potentially provide clinically useful prognostic information for decision-making in advance of initiating CAR T-cell therapy.
Improved Simultaneous Multi-slice imaging with Composition of k-space Interpolations (SMS-COOKIE) for myocardial T1 mapping
Authors: Demirel Ömer Burak , Weingärtner Sebastian , Moeller Steen , Akçakaya Mehmet
Published: July 2023

The aim of this study is to develop and evaluate a regularized Simultaneous Multi-Slice (SMS) reconstruction method for improved Cardiac Magnetic Resonance Imaging (CMR). The proposed reconstruction method, SMS with COmpOsition of k-space IntErpolations (SMS-COOKIE) combines the advantages of Iterative Self-consistent Parallel Imaging Reconstruction (SPIRiT) and split slice-Generalized Autocalibrating Partially Parallel Acquisitions (GRAPPA), while allowing regularization for further noise reduction. The proposed SMS-COOKIE was implemented with and without regularization, and validated using a Saturation Pulse-Prepared Heart rate Independent inversion REcovery (SAPPHIRE) myocardial T1 mapping sequence. The performance of the proposed reconstruction method was compared to ReadOut (RO)–SENSE-GRAPPA and split slice-GRAPPA, on both retrospectively and prospectively three-fold SMS-accelerated data with an additional two-fold in-plane acceleration. All SMS reconstruction methods yielded similar T1 values compared to single band imaging. SMS-COOKIE showed lower spatial variability in myocardial T1 with significant improvement over RO-SENSE-GRAPPA and split slice-GRAPPA (P < 10−4). The proposed method with additional locally low rank (LLR) regularization reduced the spatial variability, again with significant improvement over RO-SENSE-GRAPPA and split slice-GRAPPA (P < 10−4). In conclusion, improved reconstruction quality was achieved with the proposed SMS-COOKIE, which also provided lower spatial variability with significant improvement over split slice-GRAPPA.
Attenuation Aβ1-42-induced neurotoxicity in neuronal cell by 660nm and 810nm LED light irradiation
Authors: Thammasart Siriluk , Namchaiw Poommaree , Pasuwat Kwanchanok , Tonsomboon Khaow , Khantachawana Anak
Published: July 2023

Oligomeric amyloid-β 1–42 (Aβ1–42) has a close correlation with neurodegenerative disorder especially Alzheimer’s disease (AD). It induces oxidative stress and mitochondrial damage in neurons. Therefore, it is used to generate AD-likein vitromodel for studying neurotoxicity and neuroprotection against amyloid-β. A low-level light therapy (LLLT) is a non-invasive method that has been used to treat several neurodegenerative disorders. In this study, the red wavelength (660nm) and near infrared wavelength (810nm) at energy densities of 1, 3, and 5 J/cm2were used to modulate biochemical processes in the neural cells. The exposure of Aβ1–42resulted in cell death, increased intracellular reactive oxygen species (ROS), and retracted neurite outgrowth. We showed that both of LLLT wavelengths could protect neurons form Aβ1-42-induced neurotoxicity in a biphasic manner. The treatment of LLLT at 3 J/cm2potentially alleviated cell death and recovered neurite outgrowth. In addition, the treatment of LLLT following Aβ1–42exposure could attenuate the intracellular ROS generation and Ca2+influx. Interestingly, both wavelengths could induce minimal level of ROS generation. However, they did not affect cell viability. In addition, LLLT also stimulated Ca2+influx, but not altered mitochondrial membrane potential. This finding indicated LLLT may protect neurons through the stimulation of secondary signaling messengers such as ROS and Ca2+. The increase of these secondary messengers was in a functional level and did not harmful to the cells. These results suggested the use of LLLT as a tool to modulate the neuronal toxicity following Aβ1–42accumulation in AD’s brain.
Accelerated high-throughput imaging and phenotyping system for small organisms
Authors: Kose Talha , Lins Tiago F. , Wang Jessie , O’Brien Anna M. , Sinton David , Frederickson Megan E.
Published: July 2023

Studying the complex web of interactions in biological communities requires large multifactorial experiments with sufficient statistical power. Automation tools reduce the time and labor associated with setup, data collection, and analysis in experiments that untangle these webs. We developed tools for high-throughput experimentation (HTE) in duckweeds, small aquatic plants that are amenable to autonomous experimental preparation and image-based phenotyping. We showcase the abilities of our HTE system in a study with 6,000 experimental units grown across 2,000 treatments. These automated tools facilitated the collection and analysis of time-resolved growth data, which revealed finer dynamics of plant-microbe interactions across environmental gradients. Altogether, our HTE system can run experiments with up to 11,520 experimental units and can be adapted for other small organisms.
“It feels like medically promoted disordered eating”: The psychosocial impact of gestational diabetes mellitus in the perinatal period
Authors: Benton Madeleine , Silverio Sergio A. , Ismail Khalida
Published: July 2023

Background

The global prevalence of gestational diabetes mellitus (GDM) is increasing, and it can significantly impact women’s psychosocial outcomes in the perinatal period. The aim of this study was to explore the psychosocial impacts including experiences of support for women with GDM in the antenatal and postnatal period.

Methods

Semi-structured individual interviews were conducted with women (n = 33) living in the UK, who were either pregnant and recently diagnosed with GDM or had a previous GDM diagnosis within the past three years. Interviews were recorded, transcribed, and analysed using reflexive thematic analysis.

Findings

Analysis revealed six themes: 1. Diagnostic related frustration; 2. Impact on mental health; 3. The medicalisation of eating; 4. Losing agency to gain control; 5. Sourcing networks of support; 6. Current pregnancy; and future reproductive health. Each theme provides a unique insight into the experiences and psychological strain associated with GDM. From confusion and frustration at diagnosis, to the profound knock-on impact a diagnosis, associated lifestyle changes and medical appointments had on women’s mental health, and the perceived medicalisation of their eating behaviours and patterns.

Conclusion

Given the increasing prevalence of GDM and its wide-ranging psychosocial impacts, this study emphasises the need for healthcare professionals to consider the potential implications of GDM on women’s psychosocial outcome, and to consider alternative support options outside of the medical system, such as peer support.
Evaluation of the diagnostic accuracy of two point-of-care tests for COVID-19 when used in symptomatic patients in community settings in the UK primary care COVID diagnostic accuracy platform trial (RAPTOR-C19)
Authors: Nicholson Brian D. , Turner Philip J. , Fanshawe Thomas R. , Williams Alice J. , Amirthalingam Gayatri , Tonner Sharon , Zambon Maria , Body Richard , Davies Kerrie , Perera Rafael , de Lusignan Simon , Hayward Gail N. , Hobbs F.D. Richard ,   on behalf of the RAPTOR-C19 Study Group and the CONDOR Steering Committee
Published: July 2023

Background and objective

Point-of-care lateral flow device antigen testing has been used extensively to identify individuals with active SARS-CoV-2 infection in the community. This study aimed to evaluate the diagnostic accuracy of two point-of-care tests (POCTs) for SARS-CoV-2 in routine community care.

Methods

Adults and children with symptoms consistent with suspected current COVID-19 infection were prospectively recruited from 19 UK general practices and two COVID-19 testing centres between October 2020 and October 2021. Participants were tested by trained healthcare workers using at least one of two index POCTs (Roche-branded SD Biosensor Standard™ Q SARS-CoV-2 Rapid Antigen Test and/or BD Veritor™ System for Rapid Detection of SARS-CoV-2). The reference standard was laboratory triplex reverse transcription quantitative PCR (RT-PCR) using a combined nasal/oropharyngeal swab. Diagnostic accuracy parameters were estimated, with 95% confidence intervals (CIs), overall, in relation to RT-PCR cycle threshold and in pre-specified subgroups.

Results

Of 663 participants included in the primary analysis, 39.2% (260/663, 95% CI 35.5% to 43.0%) had a positive RT-PCR result. The SD Biosensor POCT had sensitivity 84.0% (178/212, 78.3% to 88.6%) and specificity 98.5% (328/333, 96.5% to 99.5%), and the BD Veritor POCT had sensitivity 76.5% (127/166, 69.3% to 82.7%) and specificity 98.8% (249/252, 96.6% to 99.8%) compared with RT-PCR. Sensitivity of both devices dropped substantially at cycle thresholds ≥30 and in participants more than 7 days after onset of symptoms.

Conclusions

Both POCTs assessed exceed the Medicines and Healthcare products Regulatory Agency target product profile’s minimum acceptable specificity of 95%. Confidence intervals for both tests include the minimum acceptable sensitivity of 80%. In symptomatic patients, negative results on these two POCTs do not preclude the possibility of infection. Tests should not be expected to reliably detect disease more than a week after symptom onset, when viral load may be reduced.

Registration

ISRCTN142269.
Curve forming prediction of coal mine roadway based on RBF interpolation
Authors: LIU Zhixiang , ZOU Kang , SUN Zhan
Published: July 2023

Underground roadway excavation is a complex process, especially roadway curved excavation. In addition, the rationality of the design of coal mine roadway excavation scheme directly affects the speed of roadway excavation. The more reasonable the scheme design, the more conducive to rapid excavation. In order to avoid the influence of invalid construction on the efficiency of roadway excavation, this paper studies the forming of roadway bend. Based on the analysis of the tunneling process of the roadway curve, the mathematical model of the roadway curve is established. Taking the turning radius of the roadway curve as the evaluation index, the influence of various factors on the roadway curve excavation is analyzed. The research shows that the radius of the roadway curve increases with the increase of the feed rate, the working space position of the roadheader and the required width of the roadway, and decreases with the increase of the working space angle. Then, combined with the advantages of KNN algorithm, an interpolation model for calculating the radius of the curve is established based on RBF algorithm, and the radius of the tunnel curve is reconstructed and predicted. It provides a basis for the rational design of the construction process of the roadway bend and a reliable numerical algorithm for the design of the radius of the roadway bend. It also provides a theoretical basis for improving the efficiency of high roadway excavation in coal mines.
Settlement on asphalt concrete pavement in permafrost regions under the dynamic load of aircraft
Authors: Liu Xiaolan , Chen Yixiang , Fu Chuanwei
Published: July 2023

The settlement in permafrost regions has a significant effect on the safety of the aircraft. Therefore, a numerical model of asphalt concrete pavement and subgrade in permafrost regions is proposed and verified by comparing with previous studies. Numerical models under the dynamic load of aircraft are used to analyze the settlement nephogram, time-dependent curve, and settlement curve. Results show that the influences of different parameters on settlements decrease slowly at the depth of 0–1.45m, then decrease quickly at the depth of 1.45-2m, finally tend to be stable. The peaks of settlements increase with the growth of international roughness index, taxiing speed, and aircraft’s weight. The settlement increases little when the international roughness index is more than 3. The settlement varies significantly when the taxiing speed is from 30m/s to 70m/s. The study provides a theoretical basis for the construction and maintenance of asphalt concrete pavement and subgrade in permafrost.
Change management in higher education: A sequential mixed methods study exploring employees’ perception
Authors: Ezzeddine Rima , Otaki Farah , Darwish Sohaib , AlGurg Reem
Published: July 2023

Background

Higher education institutions need to put change management as a pivotal part of their strategy. The challenge is to effectively contextualize existing change management models to the respective work environment. Failing to properly adapt existing models to match the intricacies of the environment could lead to plenty of setbacks. For such a contextualization to take place, gauging employees’ engagement and satisfaction becomes of paramount importance. As such, the overall purpose of the current study is to explore the perception of employees of a medical and health sciences university in Middle East and North Africa (MENA) region, in relation to change management and agility, and to showcase how the captured perspectives can be systemically interpreted to inform decision-making in the context of the study.

Method

This research study relied on a sequential mixed methods design, which started with an exploration of the perception of Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU) leaders. Qualitative data was collected through a focus group session and was inductively analysed (based on constructivist epistemology). The output of the qualitative analysis contributed to the development of the quantitative data collection tool. The quantitative data was analysed by SPSS-version-27.

Findings

The qualitative analysis generated three key themes: Trigger, Execution, and Results, along with a thorough outline of lessons learned and opportunities for improvement. The Cronbach’s Alpha reliability score was 92.8%. The percentage of the total average of agreement was 72.3%, and it appeared that 83.2% of the variance can be explained by the instrument (p<0.001).

Conclusion

The current study generated a novel conceptual framework that can be leveraged by educational leadership and administration to reinforce their decisions and optimize their agility in terms of managing change. The study also introduces a data collection tool which captures the perception of higher education stakeholders regarding the way their respective institutions handle change. This tool proved to be reliable and valid in the context of the study.
An evolutionary game analysis of digital transformation of multiagents in digital innovation ecosystems
Authors: Liu Baotong , Zou Hua , Qin Hao , Ji Huimin , Guo Yongquan
Published: July 2023

In an innovation ecosystem, the digital transformation decisions and game mechanisms of entities are paramount issues to be studied. Consequently, this study constructs a digital transformation SD evolutionary game model based on expectancy theory and Lyapunov’s first law to address the above issues. The results demonstrate the following: (1) Digital technology empowerment benefits, spillover effects, and supervision benefits are positively correlated with the willingness of the three players to engage in digital transformation; (2) Regardless of how the initial will of the players changes, the decision of the evolutionary game system is ultimately stable in (empower, transform, supervise). Compared with governments, platform centers, and nodal enterprises have a stronger will for digital transformation. However, the governments’ will is the key to the convergence speed of the game system to the equilibrium point. (3) If the static/dynamic spillover effect can cover the transformation loss, even if the transformation profits of nodal enterprises are negative, nodal enterprises will still choose the game strategy of "transformation". When the government subsidies are less than the initial value of 2, the game system has two possible strategy choices: (empower, nontransform, nonsupervise) and (empower, transform, supervise). As such, this study can fill the research gaps and address the barriers to digital transformation among stakeholders.
Transformative live-action roleplay and Dagorhir costumes: Regulation, consumption and power dynamics, 1977 to the present
Authors: Hixson Sarah West , Reddy-Best Kelly L.
Published: July 2023

Dagorhir is one of the largest and oldest documented live-action roleplay groups. Dagorhir organizers have published multiple game regulations via handbooks with much emphasis on costumes since the 1970s. Dagorhir facilitates community building, identity negotiation and creative storytelling that expands beyond the game through transformative play. In our research, we examine how these costume regulations have influenced fantasy character and real-world identities, how the regulations have influenced perceived costume authenticity over time and how the handbook regulations have engaged with power dynamics related to intersectional identities. We analysed costume-related content in the three handbooks while drawing upon content analysis and historical methods. We found that as the regulations evolved since the 1970s, the rules increasingly centred costumes, indicating the prominence of costume in this escapist community. However, while these spaces centred on the costumed body, Dagorhir regulations reinforced oppressive intersectional norms. Our work has implications for society and business, that is, our findings can help individuals understand why people participate in live-action roleplay, which may reduce stigma surrounding this activity. Additionally, costume producers and retailers can make informed business decisions based upon our findings. Last, live-action roleplay communities can utilize our findings to reject oppressive written and unwritten regulations.