bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration of clinical perspective into biomimetic bioreactor design for orthopedics
Authors: Drapal Victoria , Gamble Jordan M. , Robinson Jennifer L. , Tamerler Candan , Arnold Paul M. , Friis Elizabeth A. 
Published: September 2021

AbstractThe challenges to accommodate multiple tissue formation metrics in conventional bioreactors have resulted in an increased interest to explore novel bioreactor designs. Bioreactors allow researchers to isolate variables in controlled environments to quantify cell response. While current bioreactor designs can effectively provide either mechanical, electrical, or chemical stimuli to the controlled environment, these systems lack the ability to combine all these stimuli simultaneously to better recapitulate the physiological environment. Introducing a dynamic and systematic combination of biomimetic stimuli bioreactor systems could tremendously enhance its clinical relevance in research. Thus, cues from different tissue responses should be studied collectively and included in the design of a biomimetic bioreactor platform. This review begins by providing a summary on the progression of bioreactors from simple to complex designs, focusing on the major advances in bioreactor technology and the approaches employed to better simulate in vivo conditions. The current state of bioreactors in terms of their clinical relevance is also analyzed. Finally, this review provides a comprehensive overview of individual biophysical stimuli and their role in establishing a biomimetic microenvironment for tissue engineering. To date, the most advanced bioreactor designs only incorporate one or two stimuli. Thus, the cell response measured is likely unrelated to the actual clinical performance. Integrating clinically relevant stimuli in bioreactor designs to study cell response can further advance the understanding of physical phenomenon naturally occurring in the body. In the future, the clinically informed biomimetic bioreactor could yield more efficiently translatable results for improved patient care.
Clinical significance of kallikrein 5 as a novel prognostic biomarker in gastric adenocarcinoma
Authors: Abuduhadeer Xiaokaiti , Xu Xincai , Aihesan Kamali , Yilihamu Maimaiti , Zhao Yanjun , Zhang Wenbin 
Published: September 2021

AbstractBackgroundsGastric cancer is one of the most common cancers with unsatisfied prognosis. It is challenging to predict gastric cancer prognosis due to its highly heterogeneous nature. Kallikrein 5 (KLK5) belongs to the family of kallikreins, which plays a crucial role in serine proteolysis and exerts diverse physiological functions. The role of KLK5 in human gastric adenocarcinoma (GAC) has not been elucidated. In the present study, we aimed to examine the expression level of KLK5 and dissect whether the KLK5 expression was associated with GAC prognosis.Patients and methodsClinicopathological analyses were performed in a retrospective GAC patient cohort (n = 138). The expression of KLK5 was tested by quantitative RT‐PCR and immunohistochemistry staining. The prognostic role of KLK5 in GAC was assessed by univariate and multivariate analyses. The effects of KLK5 on cell proliferation, migration, and invasion were examined through cellular experiments.ResultsThe data showed that KLK5 expression was elevated in GAC tissues compared with normal stomach tissues. Protein expression of KLK5 was positively correlated with tumor invasion depth and lymph node metastasis. Patients with higher KLK5 expression had poorer overall survival. KLK5 was identified to be an independent risk factor according to multivariate analysis. Using human GAC cell lines, we found that KLK5 can promote tumor cell migration and invasion.ConclusionsOur study demonstrated that higher expression of KLK5 was significantly correlated with a poorer prognosis of GAC patients, implying the potential of KLK5 as a novel prognostic biomarker in GAC.
Genetic counseling for congenital heart disease – Practice resource of the National Society of Genetic Counselors
Authors: Ison Hannah E. , Griffin Emily L. , Parrott Ashley , Shikany Amy R. , Meyers Lindsay , Thomas Matthew J. , Syverson Erin , Demo Erin M. , Fitzgerald Kristi K. , Fitzgerald‐Butt Sara , Ziegler Katie L. , Schartman Allison F. , Stone Kristyne M. , Helm Benjamin M. 
Published: September 2021

AbstractCongenital heart disease (CHD) is an indication which spans multiple specialties across various genetic counseling practices. This practice resource aims to provide guidance on key considerations when approaching counseling for this particular indication while recognizing the rapidly changing landscape of knowledge within this domain. This resource was developed with consensus from a diverse group of certified genetic counselors utilizing literature relevant for CHD genetic counseling practice and is aimed at supporting genetic counselors who encounter this indication in their practice both pre‐ and postnatally.
A case of Wernicke encephalopathy in a dementia caregiver: The need for nutritional evaluation in family caregivers
Authors: Ishida Mayumi , Uchida Nozomu , Itami Kumi , Sato Izumi , Yoshioka Akira , Onishi Hideki 
Published: September 2021

AbstractA 63‐year‐old woman had started caring for her mother with dementia 6 months previously. A loss of appetite had appeared 2 months prior to her visit. Neurologically, she experienced mild unsteadiness, but she was fully conscious and had no ocular symptoms. MRI examination of her head did not reveal any notable findings. From these symptoms, the possibility of thiamine deficiency was considered, and her unsteadiness disappeared within a few days after an intravenous injection of thiamine. The burden of caring for a dementia patient may affect the nutritional status of the family caregiver.
Efficient synthesis of piperidine derivatives using dendrimer based catalytical pockets
Authors: Vettukattil Unnikrishnan , Govindan Avudaiappan , James Kiran , Anilkumar Ajay , Krishnapillai Sreekumar 
Published: September 2021

AbstractThe synthesis of highly functionalized piperidine derivatives using amine functionalized maltitol‐cored dendritic polymer (MAL‐G0) in acetonitrile as the reaction medium is reported. A variety of piperidine derivatives were synthesized and the reaction gave an excellent yield of 89%–95%. The highly functionalized nature of the catalyst provided large number of active sites which resulted in good yield within a short period of time. Maltitol is a carbohydrate polyol system which was chosen here as the core for the synthesis of the dendritic catalyst; it was an effective approach for the preparation of piperidine like medicinal compounds. Maltitol‐cored dendritic polymer was effectively synthesized and characterized using GPC, TG, UV–Visible, IR, and NMR techniques and also all the synthesized piperidine derivatives were characterized using LCMS, IR, and NMR techniques.
Whole‐Heart 4D Flow MRI for Evaluation of Normal and Regurgitant Valvular Flow: A Quantitative Comparison Between Pseudo‐Spiral Sampling and EPI Readout
Authors: Blanken Carmen P.S. , Gottwald Lukas M. , Westenberg Jos J.M. , Peper Eva S. , Coolen Bram F. , Strijkers Gustav J. , Nederveen Aart J. , Planken R. Nils , van Ooij Pim 
Published: September 2021

BackgroundPseudo‐spiral Cartesian sampling with compressed sensing reconstruction has facilitated highly accelerated 4D flow magnetic resonance imaging (MRI) in various cardiovascular structures. However, unlike echo planar imaging (EPI)‐accelerated 4D flow MRI, it has not been validated in whole‐heart applications.HypothesisPseudo‐spiral 4D flow MRI (PROUD [PROspective Undersampling in multiple Dimensions]) is comparable to EPI in robustness of valvular flow measurements and remains comparable as the undersampling factor is increased and scan time reduced.Study TypeProspective.PopulationTwelve healthy subjects and eight patients with valvular regurgitation.Field Strength/Sequence3.0 T; PROUD and EPI 4D flow sequences, 2D flow and balanced steady‐state free precession sequences.AssessmentValvular blood flow was quantified using valve tracking. PROUD‐ and EPI‐based measurements of aortic (AV) and pulmonary (PV) flow volumes and left and right ventricular stroke volumes were tested for agreement with 2D MRI‐based measurements. PROUD reconstructions with undersampling factors (R) of 9, 14, 28, and 56 were tested for intervalve consistency (per valve, compared to the other valves) and preservation of peak velocities and E/A ratios.Statistical TestsWe used repeated measures ANOVA, Bland‐Altman, Wilcoxon signed rank, and intraclass correlation coefficients. P < 0.05 was considered statistically significant.ResultsPROUD and EPI intervalve consistencies were not significantly different both in healthy subjects (valve‐averaged mean difference [limits of agreement width]: 3.2 ± 0.8 [8.7 ± 1.1] mL/beat for PROUD, 5.5 ± 2.9 [13.7 ± 2.3] mL/beat for EPI, P = 0.07) and in patients with valvular regurgitation (2.3 ± 1.2 [15.3 ± 5.9] mL/beat for PROUD, 0.6 ± 0.6 [19.3 ± 2.9] mL/beat for EPI, P = 0.47). Agreement between EPI and PROUD was higher than between 4D flow (EPI or PROUD) and 2D MRI for forward flow, stroke volumes, and regurgitant volumes. Up to R = 28 in healthy subjects and R = 14 in patients with valvular regurgitation, PROUD intervalve consistency remained comparable to that of EPI. Peak velocities and E/A ratios were preserved up to R = 9.ConclusionPROUD is comparable to EPI in terms of intervalve consistency and may be used with higher undersampling factors to shorten scan times further.Level of Evidence1Technical Efficacy Stage2
Rescheduling‐based congestion management by metaheuristic algorithm: Hybridizing lion and moth search models
Authors: Srivastava Jyoti , Yadav Naresh Kumar 
Published: September 2021

AbstractCongestion management (CM) is becoming a challenging task in the power system due to the increase in the system complexities in the deregulated environment. The congestion causes grave damage to the power system components if the outages tend to occur more frequently. Hence, in the present power system scenario, CM is a complex task of an independent system operator (ISO). This proposal intends to introduce a novel optimization‐based CM model with advanced soft computing techniques. A new hybrid algorithm is introduced in this paper, which optimizes the generating power of added generators with the bus system. Thereby manages the congestion with minimized rescheduling cost. The proposed optimization algorithm termed Lion Algorithm with Moth‐based Mutation (LA‐MM) hybridizes the concepts of both Lion Algorithm (LA) and Moth Search Algorithm (MS). Subsequently, the experimentation is conducted in two test bus systems like IEEE 14 and 30 bus systems. The performance of the proposed model is compared over other state‐of‐the‐art models concerning cost analysis and convergence analysis, respectively.
Anesthesia in mice activates discrete populations of neurons throughout the brain
Authors: Yatziv Shai‐lee , Yudco Or , Vaso Kristina , Mizrahi Adi , Devor Marshall 
Published: September 2021

AbstractThe brain undergoes rapid, dramatic, and reversible transitioning between states of wakefulness and unconsciousness during natural sleep and in pathological conditions such as hypoxia, hypotension, and concussion. Transitioning can also be induced pharmacologically using general anesthetic agents. The effect is selective. Mobility, sensory perception, memory formation, and awareness are lost while numerous housekeeping functions persist. How is selective transitioning accomplished? Classically a handful of brainstem and diencephalic “arousal nuclei” have been implicated in driving brain‐state transitions on the grounds that their net activity systematically varies with brain state. Here we used transgenic targeted recombination in active populations mice to label neurons active during wakefulness with one reporter and neurons active during pentobarbital‐induced general anesthesia with a second, contrasting reporter. We found ‘wake‐on’ and ‘anesthesia‐on’ neurons in widely distributed regions‐of‐interest, but rarely encountered neurons labeled with both reporters. Nearly all labeled neurons were either wake‐on or anesthesia‐on. Thus, anesthesia‐on neurons are not unique to the few nuclei discovered to date whose activity appears to increase during anesthesia. Rather neuronal populations selectively active during anesthesia are located throughout the brain where they likely play a causative role in transitioning between wakefulness and anesthesia. The widespread neuronal suppression reported in prior comparisons of the awake and anesthetized brain in animal models and noninvasive imaging in humans reflects only net differences. It misses the ubiquitous presence of neurons whose activity increases during anesthesia. The balance in recruitment of anesthesia‐on versus wake‐on neuronal populations throughout the brain may be a key driver of regional and global vigilance states.[Correction added on September 22, 2021, after first online publication: Due to a typesetting error, the abstract text was cut off. This has been corrected now.]
Overexpression of α‐synuclein inhibits mitochondrial Ca2+ trafficking between the endoplasmic reticulum and mitochondria through MAMs by altering the GRP75–IP3R interaction
Authors: Erustes Adolfo Garcia , D'Eletto Manuela , Guarache Gabriel Cicolin , Ureshino Rodrigo Portes , Bincoletto Claudia , da Silva Pereira Gustavo José , Piacentini Mauro , Smaili Soraya Soubhi 
Published: September 2021

AbstractMitochondria‐associated ER membranes (MAMs) are formed by close and specific components in the contact sites between the endoplasmic reticulum (ER) and mitochondria, which participate in several cell functions, including lipid metabolism, autophagy, and Ca2+ signaling. Particularly, the presence of α‐synuclein (α‐syn) in MAMs was previously demonstrated, indicating a physical interaction among some proteins in this region and a potential involvement in cell dysfunctions. MAMs alterations are associated with neurodegenerative diseases such as Parkinson's disease (PD) and contribute to the pathogenesis features. Here, we investigated the effects of α‐syn on MAMs and Ca2+ transfer from the ER to mitochondria in WT‐ and A30P α‐syn‐overexpressing SH‐SY5Y or HEK293 cells. We observed that α‐syn potentiates the mitochondrial membrane potential (Δψm) loss induced by rotenone, increases mitophagy and mitochondrial Ca2+ overload. Additionally, in α‐syn‐overexpressing cells, we found a reduction in ER–mitochondria contact sites through the impairment of the GRP75–IP3R interaction, however, with no alteration in VDAC1–GRP75 interaction. Consequently, after Ca2+ release from the ER, α‐syn‐overexpressing cells demonstrated a reduction in Ca2+ buffering by mitochondria, suggesting a deregulation in MAM activity. Taken together, our data highlight the importance of the α‐syn/MAMs/Ca2+ axis that potentially affects cell functions in PD.
Comparing axon regeneration in male and female mice after peripheral nerve injury
Authors: Jang Eun‐Hae , Bae Yun‐Hee , Yang Eun Mo , Gim Yunho , Suh Hyun‐Jun , Kim Subin , Park Seong‐min , Park Jong Bae , Hur Eun‐Mi 
Published: September 2021

AbstractAxons in the adult mammalian central nervous system fail to regenerate after injury. By contrast, spontaneous axon regeneration occurs in the peripheral nervous system (PNS) due to a supportive PNS environment and an increase in the intrinsic growth potential induced by injury via cooperative activation of multifaceted biological pathways. This study compared axon regeneration and injury responses in C57BL/6 male and female mice after sciatic nerve crush (SNC) injury. The extent of axon regeneration in vivo was indistinguishable in male and female mice when observed at 3 days after SNC injury, and primary dorsal root ganglion (DRG) neurons from injured, male and female mice extended axons to a similar length. Moreover, the induction of selected regeneration‐associated genes (RAGs), such as Atf3, Sprr1a, Gap43, Sox11, Jun, Gadd45a, and Smad1 were comparable in male and female DRGs when assessed by quantitative real‐time reverse transcription polymerase chain reaction. Furthermore, the RNA‐seq analysis of male and female DRGs revealed that differentially expressed genes (DEGs) in SNC groups compared to sham‐operated groups included many common genes associated with neurite outgrowth. However, we also found that a large number of genes in the DEGs were sex dependent, implicating the involvement of distinct gene regulatory network in the two sexes following peripheral nerve injury. In conclusion, we found that male and female mice mounted a comparable axon regeneration response and many RAGs were commonly induced in response to SNC. However, given that many DEGs were sex‐dependently expressed, future studies are needed to investigate whether they contribute to peripheral axon regeneration, and if so, to what extent.
Decline in executive function in patients with white matter hyperintensities from the static and dynamic perspectives of amplitude of low‐frequency fluctuations
Authors: Cao Shanshan , Zhang Jun , Chen Chen , Wang Xiaojing , Ji Yang , Nie Jiajia , Tian Yanghua , Qiu Bensheng , Wei Qiang , Wang Kai 
Published: September 2021

AbstractCognitive impairments are characteristics of patients with white matter hyperintensities (WMHs), and hypoperfusion is currently a relatively recognized mechanism of WMHs. Brain activity is closely coupled to the regulation of local blood flow. This study aimed to investigate the abnormal local brain activity of patients with WMHs from the viewpoint of the static amplitude of low‐frequency fluctuations (sALFF) and dynamic amplitude of low‐frequency fluctuations (dALFF). Seventy‐four patients with WMHs and 35 healthy controls (HCs) were included. Based on the Fazekas scale, patients with WMHs were further divided into a mild WMH group (n = 33, Fazekas score 1–2) and moderate‐severe WMH group (n = 41, Fazekas score 3–6). The sALFF and dALFF values were calculated separately and neuropsychological tests including the Montreal Cognitive Assessment (MoCA), Auditory Verbal Learning Test (AVLT), Trail Making Test (TMT), and Boston Naming Test (BNT) were completed by all participants. Patients with WMHs showed increased sALFF and dALFF values in the bilateral thalamus and decreased performance in the MoCA test, AVLT‐immediate, AVLT‐delay, AVLT‐recognition, TMT‐A, and BNT. The dALFF values in the bilateral thalamus was correlated with the MoCA in HCs. The sALFF values in the bilateral thalamus correlated with TMT‐B in patients with WMHs. Patients with WMHs showed abnormal brain activity and decreased functional stability of the bilateral thalamus, which may be a potential mechanism of decreased executive function.
Stochastic and sinusoidal electrical stimuli increase the irregularity and gain of Type A and B medial vestibular nucleus neurons, in vitro
Authors: Stefani Sebastian P. , Pastras Christopher J. , Serrador Jorge M. , Breen Paul P. , Camp Aaron J. 
Published: September 2021

AbstractGalvanic vestibular stimulation (GVS) has been shown to improve vestibular function potentially via stochastic resonance, however, it remains unknown how central vestibular nuclei process these signals. In vivo work applying electrical stimuli to the vestibular apparatus of animals has shown changes in neuronal discharge at the level of the primary vestibular afferents and hair cells. This study aimed to determine the cellular impacts of stochastic, sinusoidal, and stochastic + sinusoidal stimuli on individual medial vestibular nucleus (MVN) neurons of male and female C57BL/6 mice. All stimuli increased the irregularity of MVN neuronal discharge, while differentially affecting neuronal gain. This suggests that the heterogeneous MVN neuronal population (marked by differential expression of ion channels), may influence the impact of electrical stimuli on neuronal discharge. Neuronal subtypes showed increased variability of neuronal firing, where Type A and B neurons experienced the largest gain changes in response to stochastic and sinusoidal stimuli. Type C neurons were the least affected regarding neuronal firing variability and gain changes. The membrane potential (MP) of neurons was altered by sinusoidal and stochastic + sinusoidal stimuli, with Type B and C neuronal MP significantly affected. These results indicate that GVS‐like electrical stimuli impact MVN neuronal discharge differentially, likely as a result of heterogeneous ion channel expression.
Neuroimmunological complications arising from chemotherapy‐induced gut toxicity and opioid exposure in female dark agouti rats
Authors: Bajic Juliana Esma , Howarth Gordon Stanley , Mashtoub Suzanne , Whittaker Alexandra Louise , Bobrovskaya Larisa , Hutchinson Mark Rowland 
Published: September 2021

AbstractCancer patients may experience symptom clusters, including chemotherapy‐induced (CI) gut toxicity (CIGT) and cognitive impairment. Analgesic selection for pain associated with CIGT is difficult as opioids induce glial reactivity and unwanted side effects. This study quantified central glial reactivity and proinflammatory effects in rats with CIGT using three mechanistically different analgesics. Regional adaptations were indicative of immune‐to‐brain signaling routes. Utilizing a 5‐fluorouracil‐induced GT (5IGT) rat model and analgesic intervention (carprofen (CAR), buprenorphine (BUP), and tramadol (TRAM)), spinal and brain neuroimmune modulation was examined via microglial, astrocyte, and proinflammatory (cluster of differentiation molecule 11b; CD11b, glial fibrillary associated protein; GFAP, and interleukin‐1 beta; IL1β) reactivity marker expression changes by western blot analysis. 5IGT significantly increased thoracic GFAP (p < 0.05) and IL‐1β (p < 0.0001) expression, CAR and BUP ameliorated these effects. BUP and TRAM with 5‐FU synergistically increased hippocampal GFAP expression. CAR administered with 5IGT significantly elevated hippocampal and thoracic CD11b expression levels (p < 0.05). The neuroimmune responses observed in this study suggest activation of peripheral‐to‐central immune signaling pathways. We speculate that the opioid‐induced hippocampal changes inferred a humorally mediated mechanism, whereas thoracic neuroimmune modifications indicated activation of an indirect neural route. Although TRAM ameliorated 5IGT‐intestinal inflammation, this opioid presents complications relating to bodyweight and regional glial dysregulation (neuroinflammation) and may not be optimal in the management of pain associated with 5IGT. The chemotherapy‐induced gut‐derived neuroimmune consequences observed suggest a potential mechanistic contribution to central components of the cancer symptom cluster experience, while the opioid‐related glial changes have implications for optimal pain management in this setting warranting further investigation.