bluuebunny/crossref_metadata_2025 huggingface dataset:
p140Cap Controls Female Fertility in Mice Acting via Glutamatergic Afference on Hypothalamic Gonadotropin-Releasing Hormone Neurons
Authors: Camera Mattia , Russo Isabella , Zamboni Valentina , Ammoni Alessandra , Rando Simona , Morellato Alessandro , Cimino Irene , Angelini Costanza , Giacobini Paolo , Oleari Roberto , Amoruso Federica , Cariboni Anna , Franceschini Isabelle , Turco Emilia , Defilippi Paola , Merlo Giorgio R.
Published: February 2022

p140Cap, encoded by the gene SRCIN1 (SRC kinase signaling inhibitor 1), is an adaptor/scaffold protein highly expressed in the mouse brain, participating in several pre- and post-synaptic mechanisms. p140Cap knock-out (KO) female mice show severe hypofertility, delayed puberty onset, altered estrus cycle, reduced ovulation, and defective production of luteinizing hormone and estradiol during proestrus. We investigated the role of p140Cap in the development and maturation of the hypothalamic gonadotropic system. During embryonic development, migration of Gonadotropin-Releasing Hormone (GnRH) neurons from the nasal placode to the forebrain in p140Cap KO mice appeared normal, and young p140Cap KO animals showed a normal number of GnRH-immunoreactive (-ir) neurons. In contrast, adult p140Cap KO mice showed a significant loss of GnRH-ir neurons and a decreased density of GnRH-ir projections in the median eminence, accompanied by reduced levels of GnRH and LH mRNAs in the hypothalamus and pituitary gland, respectively. We examined the number of kisspeptin (KP) neurons in the rostral periventricular region of the third ventricle, the number of KP-ir fibers in the arcuate nucleus, and the number of KP-ir punctae on GnRH neurons but we found no significant changes. Consistently, the responsiveness to exogenous KP in vivo was unchanged, excluding a cell-autonomous defect on the GnRH neurons at the level of KP receptor or its signal transduction. Since glutamatergic signaling in the hypothalamus is critical for both puberty onset and modulation of GnRH secretion, we examined the density of glutamatergic synapses in p140Cap KO mice and observed a significant reduction in the density of VGLUT-ir punctae both in the preoptic area and on GnRH neurons. Our data suggest that the glutamatergic circuitry in the hypothalamus is altered in the absence of p140Cap and is required for female fertility.
Neuromorphic Engineering Needs Closed-Loop Benchmarks
Authors: Milde Moritz B. , Afshar Saeed , Xu Ying , Marcireau Alexandre , Joubert Damien , Ramesh Bharath , Bethi Yeshwanth , Ralph Nicholas O. , El Arja Sami , Dennler Nik , van Schaik André , Cohen Gregory
Published: February 2022

Neuromorphic engineering aims to build (autonomous) systems by mimicking biological systems. It is motivated by the observation that biological organisms—from algae to primates—excel in sensing their environment, reacting promptly to their perils and opportunities. Furthermore, they do so more resiliently than our most advanced machines, at a fraction of the power consumption. It follows that the performance of neuromorphic systems should be evaluated in terms of real-time operation, power consumption, and resiliency to real-world perturbations and noise using task-relevant evaluation metrics. Yet, following in the footsteps of conventional machine learning, most neuromorphic benchmarks rely on recorded datasets that foster sensing accuracy as the primary measure for performance. Sensing accuracy is but an arbitrary proxy for the actual system's goal—taking a good decision in a timely manner. Moreover, static datasets hinder our ability to study and compare closed-loop sensing and control strategies that are central to survival for biological organisms. This article makes the case for a renewed focus on closed-loop benchmarks involving real-world tasks. Such benchmarks will be crucial in developing and progressing neuromorphic Intelligence. The shift towards dynamic real-world benchmarking tasks should usher in richer, more resilient, and robust artificially intelligent systems in the future.
The Impact of Glutamatergic Synapse Dysfunction in the Corticothalamocortical Network on Absence Seizure Generation
Authors: Leitch Beulah
Published: February 2022

Childhood absence epilepsy (CAE) is the most common pediatric epilepsy affecting 10–18% of all children with epilepsy. It is genetic in origin and the result of dysfunction within the corticothalamocortical (CTC) circuitry. Network dysfunction may arise from multifactorial mechanisms in patients from different genetic backgrounds and thus account for the variability in patient response to currently available anti-epileptic drugs; 30% of children with absence seizures are pharmaco-resistant. This review considers the impact of deficits in AMPA receptor-mediated excitation of feed-forward inhibition (FFI) in the CTC, on absence seizure generation. AMPA receptors are glutamate activated ion channels and are responsible for most of the fast excitatory synaptic transmission throughout the CNS. In the stargazer mouse model of absence epilepsy, the genetic mutation is in stargazin, a transmembrane AMPA receptor trafficking protein (TARP). This leads to a defect in AMPA receptor insertion into synapses in parvalbumin-containing (PV+) inhibitory interneurons in the somatosensory cortex and thalamus. Mutation in the Gria4 gene, which encodes for the AMPA receptor subunit GluA4, the predominant AMPA receptor subunit in cortical and thalamic PV + interneurons, also leads to absence seizures. This review explores the impact of glutamatergic synapse dysfunction in the CTC network on absence seizure generation. It also discusses the cellular and molecular mechanisms involved in the pathogenesis of childhood absence epilepsy.
Clinical Practice Guidelines Using GRADE and AGREE II for the Impact of Genetic Variants on Plasma Lipid/Lipoprotein/Apolipoprotein Responsiveness to Omega-3 Fatty Acids
Authors: Keathley Justine , Garneau Véronique , Marcil Valérie , Mutch David M. , Robitaille Julie , Rudkowska Iwona , Sofian Gabriela , Desroches Sophie , Vohl Marie-Claude
Published: February 2022

Background

A recent systematic review, which used the GRADE methodology, concluded that there is strong evidence for two gene-diet associations related to omega-3 and plasma triglyceride (TG) responses. Systematic reviews can be used to inform the development of clinical practice guidelines (CPGs).

Objective

To provide guidance for clinical practice related to genetic testing for evaluating responsiveness to dietary/supplemental omega-3s and their impact on plasma lipids/lipoproteins/apolipoproteins.

Design

Using the results of the abovementioned systematic review, the first CPGs in nutrigenetics were developed using the established GRADE methodology and AGREE II approach.

Results

Three clinical practice recommendations were developed. Most gene-diet associations identified in the literature lack adequate scientific and clinical validity to warrant consideration for implementing in a practice setting. However, two gene-diet associations with strong evidence (GRADE quality: moderate and high) can be considered for implementation into clinical practice in certain cases: male APOE-E4 carriers (rs429358, rs7412) and TG changes in response to the omega-3 fatty acids eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) as well as a 31-SNP nutrigenetic risk score and TG changes in response to EPA+DHA among adults with overweight/obesity. Ethical and regulatory implications must be considered when providing APOE nutrigenetic tests given the well-established link between APOE genetic variation and Alzheimer's Disease.

Conclusion

Most of the evidence in this area is not ready for implementation into clinical practice primarily due to low scientific validity (low quality of evidence). However, the first CPGs in nutrigenetics have been developed for two nutrigenetic associations with strong scientific validity, related to dietary/supplemental omega-3 and TG responses.
Neoadjuvant Treatment for Resectable and Borderline Resectable Pancreatic Cancer: Chemotherapy or Chemoradiotherapy?
Authors: Versteijne Eva , de Hingh Ignace H. J. T. , Homs Marjolein Y. V. , Intven Martijn P. W. , Klaase Joost M. , van Santvoort Hjalmar C. , de Vos-Geelen Judith , Wilmink Johanna W. , van Tienhoven Geertjan
Published: February 2022

Worldwide, there is a shifting paradigm from immediate surgery with adjuvant treatment to a neoadjuvant approach for patients with resectable or borderline resectable pancreatic cancer (RPC or BRPC). Comparison of neoadjuvant and adjuvant studies is extremely difficult because of a great difference in patient selection. The evidence from randomized studies shows that overall survival by intention-to-treat improves after neoadjuvant gemcitabine-based chemoradiotherapy or chemotherapy (various regimens), as compared to immediate surgery followed by adjuvant chemotherapy. Radiotherapy appears to play an important role in mediating locoregional effects. Yet, since more effective chemotherapy regimens are currently available, in particular FOLFIRINOX and Gemcitabine/Nab-paclitaxel, these chemotherapy regimens should be investigated in future randomized trials combined with (stereotactic) radiotherapy to further improve outcomes of RPC and BRPC.
Effect of Early-Stage Human Breast Carcinoma on Monocyte Programming
Authors: Patysheva Marina , Larionova Irina , Stakheyeva Marina , Grigoryeva Evgeniya , Iamshchikov Pavel , Tarabanovskaya Natalia , Weiss Christel , Kardashova Julia , Frolova Anastasia , Rakina Militsa , Prostakishina Elizaveta , Zhuikova Lilia , Cherdyntseva Nadezhda , Kzhyshkowska Julia
Published: February 2022

Circulating monocytes are a major source of tumor-associated macrophages (TAMs). TAMs in human breast cancer (BC) support primary tumor growth and metastasis. Neoadjuvant chemotherapy (NAC) is a commonly used treatment for BC patients. The absence of the response to NAC has major negative consequences for the patient: increase of tumor mass, delayed surgery, and unnecessary toxicity. We aimed to identify the effect of BC on the subpopulation content and transcriptome of circulating monocytes. We examined how monocyte phenotypes correlate with the response to NAC. The percentage of CD14-, CD16-, CD163-, and HLA-DR-expressing monocytes was quantified by flow cytometry for patients with T1-4N0-3M0 before NAC. The clinical efficacy of NAC was assessed by RECIST criteria of RECIST 1.1 and by the pathological complete response (pCR). The percentage of CD14+ and СD16+ monocytes did not differ between healthy women and BC patients and did not differ between NAC responders and non-responders. The percentage of CD163-expressing CD14lowCD16+ and CD14+CD16+ monocytes was increased in BC patients compared to healthy women (99.08% vs. 60.00%, p = 0.039, and 98.08% vs. 86.96%, p = 0.046, respectively). Quantitative immunohistology and confocal microscopy demonstrated that increased levels of CD163+ monocytes are recruited in the tumor after NAC. The percentage of CD14lowCD16+ in the total monocyte population positively correlated with the response to NAC assessed by pCR: 8.3% patients with pCR versus 2.5% without pCR (p = 0.018). Search for the specific monocyte surface markers correlating with NAC response evaluated by RECIST 1.1 revealed that patients with no response to NAC had a significantly lower amount of CD14lowCD16+HLA-DR+ cells compared to the patients with clinical response to NAC (55.12% vs. 84.62%, p = 0.005). NGS identified significant changes in the whole transcriptome of monocytes of BC patients. Regulators of inflammation and monocyte migration were upregulated, and genes responsible for the chromatin remodeling were suppressed in monocyte BC patients. In summary, our study demonstrated that presence of BC before distant metastasis is detectable, significantly effects on both monocyte phenotype and transcriptome. The most striking surface markers were CD163 for the presence of BC, and HLA-DR (CD14lowCD16+HLA-DR+) for the response to NAC.
Durable Clinical Response to ALK Tyrosine Kinase Inhibitors in Epithelioid Inflammatory Myofibroblastic Sarcoma Harboring PRRC2B-ALK Rearrangement: A Case Report
Authors: Wang Zhan , Geng Yan , Yuan Ling-Yan , Wang Miao-Miao , Ye Chen-Yang , Sun Li , Dai Wei-Ping , Zang Yuan-Sheng
Published: February 2022

Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm and patients with IMT tend to have a favorable outcome after complete surgical resection. However, some tumors of IMT cases have recurred and grown rapidly after successful surgery. Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a highly aggressive intra-abdominal IMT variant with epithelioid-to-round cell morphology. Currently, no standard therapy exists for recurrent or invasive IMTs and EIMS, but anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are recommended for those harboring ALK gene rearrangements. We herein report the first case of PRRC2B-ALK fusion associated IMTs with clinical and pathological manifestation matched the diagnosis criteria of EIMS and the durable clinical response of the sequential use of ALK TKIs (crizotinib, alectinib, ceritinib, and lorlatinib). A female patient with EIMS of the greater omentum was suffering from a rapid recurrence after cytoreductive surgery was done. Crizotinib was administered when PRRC2B-ALK fusion was detected, and partial response was achieved. The progression-free survival (PFS) of crizotinib was 5 months. Alectinib was administered based on the results of second next-generation sequencing (NGS) analysis, which identified the secondary mutation ALK R1192P. The best overall response of alectinib treatment was a partial response (PR) and the PFS was 5.5 months. Ceritinib was prescribed as third-line therapy after alectinib resistance with ALK L1196M mutation. PR was achieved and the PFS of ceritinib was 6 months. The patient was taking lorlatinib after ceritinib resistance and achieved a stable disease at 2 months with the PFS more than 5 months. The overall survival was more than two years as of the time of manuscript preparation. We describe an EIMS of greater omentum caused by PRRC2B-ALK fusion gene and showed durable clinical response to the sequential use of ALK TKIs.
Treatment Patterns and Outcomes of Elderly Patients With Potentially Curable Esophageal Cancer
Authors: Yang Yang , Chen Mengyuan , Xie Jiping , Ji Yongling , Sheng Liming , Qiu Guoqin , Du Xianghui , Wei Qichun
Published: February 2022

Objectives

The proportion of elderly patients with esophageal cancer (EC) is increasing due to prolonged life expectancy and aging process. The aim of the study is to explore the optimal treatment strategy for elderly patients (aged ≥70 years) with locally advanced EC.

Methods

Eligible patients with cT2-4aNxM0 EC were identified in the Surveillance, Epidemiology, and End Results database from 2010 to 2016. Treatment patterns were divided into six groups: surgical resection (S), chemoradiotherapy (CRT), trimodality therapy (CRT+S), radiotherapy (RT), chemotherapy (CT), or observation with no treatment (Obs). Survival between groups was compared using the log-rank test, and the Cox proportional hazards model was used to identify factors associated with overall survival (OS).

Results

A total of 2917 patients with potentially curable EC were identified. Of all the patients included, 6.7%, 51.8%, 18.0%, 9.4% and 3.6%received S, CRT, CRT+S, RT, and CT, respectively, whereas 10.6% underwent Obs. The 3-year OS estimates were 30.2% (95% confidence interval [CI]: 23.5–38.9%), 25.4% (95% CI: 22.8–28.3%),44.3% (95% CI: 39.3–49.9%), 11.4% (95% CI: 7.7–17.0%), 16.1% (95% CI: 9.1–28.3%), and 5.6% (95% CI: 3.2–9.8%) for S, CRT, CRT+S RT, CT, and Obs (p<0.001), respectively. Overall, patents underwent CRT+S had the longest OS, compared to other treatment patterns, and the survival difference was not significant between patients receiving CRT and S (p=0.12) in the elderly population. However, the survival benefits of trimodality therapy over CRT gradually weakened with the increase in age, and became statistically non-significant for EC patients aged ≥80 years (p=0.35). Multivariate analysis showed that treatment patterns, age, sex, tumor grade, T stage, N stage, and marital status were significantly associated with OS.

Conclusion

Generally, the use of trimodality therapy was associated with the longest OS, the survival benefits were comparable between CRT and S alone, and CRT was superior to RT or CT alone in elderly patients with curable EC. For patients intolerable to surgery or aged ≥80 years, definitive CRT should be considered as a preferable option.
Molecular Subtypes and Prognostic Signature of Pyroptosis-Related lncRNAs in Glioma Patients
Authors: Tanzhu Guilong , Li Na , Li Zhanzhan , Zhou Rongrong , Shen Liangfang
Published: February 2022

The relationship between pyroptosis-related long non-coding RNAs (pyroptosis-related lncRNAs) and glioma prognosis have not been studied clearly. Basing on The Cancer Genome Atlas and The Chinese Glioma Genome Atlas datasets, we firstly identified 23 pyroptosis-related lncRNAs with Pearson coefficient |r| > 0.5 and p < 0.001. The survival probability was lower in cluster 1. 13 lncRNAs was included into signature and divided all the glioma patients into two groups, among which survival probability of the high-risk group was lower than that in low-risk group (P<0.001). The risk score was higher in the age>60, dead grade 3, cluster 1 and immune score high groups. Furthermore, subgroup analysis showed patients with different grades, IDH and 1p19ql state distinguished by the median of risk score had different survival probability. Risk score was one of independent factors for glioma prognosis, and 1-, 3-, 5-years survival were calculated in nomogram. Meanwhile, the same as the median risk score in TCGA cohort, the glioma patients from CGGA were categorized into two groups and validated the outcome mentioned above(P<0.01). GO and KEGG analysis revealed the immunity process of the targeted genes. Thus, the immune filtration we compared showed naive B cell, resting dendritic cells, activated NK cells, activated Mast cells, monocytes are higher in low-risk group. Moreover, level of the activated NK cells, M0-and M1 Macrophages was in positive relationship with the risk score. Besides, competing endogenous RNA (ceRNA) network display interaction among microRNA, lncRNAs and their targeted genes. Pyroptosis-related lncRNAs could be a dependent prognosis factor and maybe linked to the immune response in glioma. This prognosis signature had potential value in estimate the survival of the patients with glioma.
HER2 Aberrations as a Novel Marker in Advanced Biliary Tract Cancer
Authors: Kim Hongsik , Kim Ryul , Kim Hye Ryeon , Jo Hyunji , Kim Hana , Ha Sang Yun , Park Joon Oh , Park Young Suk , Kim Seung Tae
Published: February 2022

HER2 aberrations have been reported as a novel biomarker in HER2-directed therapy or as a prognostic marker in various tumor types. However, in advanced biliary tract cancer (BTC), there have been few studies regarding HER2 aberrations as a biomarker. We analyzed 121 advanced BTC patients who had been treated with Gemcitabine/Cisplatin (GP) as a 1st line therapy between November 2019 and April 2021. Next-generation sequencing (NGS), namely, HER2 aberrations was performed in all patients. The TruSight™ Oncology 500 assay from Illumina was used for the NGS panel. Among 121 patients with advanced BTC, HER2 aberrations were observed in 18 patients (14.9%). For subtypes of HER2 aberrations, point mutation was observed in 5 patients (27.8%), gene amplification in 11 patients (61.1%), and both point mutation and gene amplification in 2 patients (11.1%). The frequency of HER2 aberrations was significantly different according to the primary tumor (p = 0.009). In gallbladder cancer, HER2 aberrations were observed at a relatively high frequency (36.4%). The tumor response to GP did not differ between patients with and without HER2 aberrations (33.3%, vs. 26.2%, respectively, p = 0.571). The median progression-free survival (PFS) to GP was 4.7 months (95% CI, 4.0 to 5.5 months) in patients with HER2 aberrations and 7.0 months (95% CI, 5.2 to 8.8 months) without HER2 aberrations (p = 0.776). The median overall survival (OS) was not reached and not reached in patients with and without HER2 aberrations (p = 0.739), respectively. The univariate analysis for PFS to GP and OS showed that HER2 aberrations were not an independent factor for survival. This study showed that the HER2 aberrations were observed in 14.9% of advanced BTC and were not an independent biomarker for survival.
SPHK Inhibitors and Zoledronic Acid Suppress Osteoclastogenesis and Wear Particle-Induced Osteolysis
Authors: Gu Minghui , Pan Baiqi , Chen Weishen , Xu Hai , Wu Xiaoyu , Hu Xuantao , Zheng Linli , Ye Yongyu , Meng Qing , Xian Guoyan , Zhang Ziji , Sheng Puyi
Published: February 2022

Background: Inflammatory osteolysis induced by wear particles is the major cause of prosthetic loosening after artificial joint replacement, and its prevention and treatment are difficult worldwide. Our previous study confirmed that sphingosine kinases (SPHKs) are important mediators regulating the wear particle-induced macrophage inflammatory response. However, it is unclear whether SPHKs can modulate chronic inflammation and alleviate osteolysis. Zoledronic acid (ZA), an imidazole-containing bisphosphonate, directly affects osteoclasts and prevents bone mineral-related diseases. However, the effects of SPHK inhibitors and ZA used to treat periprosthetic osteolysis are unknown.

Methods: We applied tartrate-resistant acid phosphatase (TRAP) staining to evaluate bone destruction in the interface membranes of patients with aseptic loosening and a control group. A murine calvarial osteolysis model was used to examine the preventative effect of SPHK inhibitors and ZA on osteolysis. Micro-CT scanning, immunohistochemistry (IHC), and histomorphometric analysis were conducted to determine the variations in inflammatory osteolysis. The effects of different drug concentrations on cell viability were evaluated using the Cell Counting Kit-8 (CCK-8) assay. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis was performed to confirm the reduced expression of osteoclast-specific genes after drug and titanium treatment. The osteoclast formation and functions of the drugs were analyzed using TRAP staining in vivo and in vitro. The effect of SPHKs/S1P-TRAF2-BECN1 signaling pathways was verified via RT-qPCR and tissue IHC.

Results: In this study, we found that SPHK inhibitors (ABC294640 and FTY720) combined with ZA decreased the degree of inflammatory osteolysis in vivo. However, ABC294640 and ZA suppressed osteoclast differentiation and osteoclast-specific genes in vitro. SPHKs regulate the inflammatory osteolysis induced by wear particles by increasing the expression of SPHKs/S1P-TRAF2-BECN1.

Conclusion: Our study revealed that wear particles could induce inflammatory osteolysis by upregulating SPHKs/S1P-TRAF2-BECN1 and SPHK inhibitors/ZA inhibit osteoclastogenesis in vitro and prevent inflammatory osteolysis in vivo, suggesting that SPHK inhibitors and ZA can be a new perspective and scientific basis for the prevention and treatment of prosthesis loosening.
Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Extracellular Vesicles Promotes Hepatic Stellate Cell Activation, Liver Fibrosis and β-Catenin Signaling Pathway
Authors: Wang Tianqi , Zhang Chong , Meng Xiaoming , Zhu Benshuai , Wang Siyu , Yuan Wenkang , Zhang Sumei , Xu Jiegou , Zhang Chao
Published: February 2022

Evidence shows that the long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (Lnc-MALAT1) is associated with activation of hepatic stellate cells (HSCs) and liver fibrosis in animal and in vitro studies. However, its roles in human liver fibrosis and the underlying mechanism in HSC activation are not yet defined. In our current study, the expression of Lnc-MALAT1 in the fibrotic liver tissues and in the plasma extracelllar vesicles (EVs) of liver fibrosis patients was detected by FISH and qRT-PCR. The results revealed that enhanced expression of Lnc-MALAT1 was co-localized with increased expression of the fibrotic markers (collagen I and α-SMA) and the Wnt/β-catenin signaling proteins (β-catenin, cyclinD1 and c-myc) in the fibrotic liver tissues. The level of Lnc-MALAT1 in the plasma EVs isolated from 60 liver fibrosis patients was significantly increased compared with that of the 46 control patients, and area under receiver operating curve (AUROC) analysis showed that plasma EVs-Lnc-MALAT1 was a potential diagnostic marker for liver fibrosis, especially for high liver fibrosis. Plasma EVs with highly expressed Lnc-MALAT1 derived from high liver fibrosis patients up-regulated the expression of the fibrotic markers and enhanced the Wnt/β-catenin signaling in human hepatic stellate cells LX-2, and the fibrogenic effects in LX-2 were inhibited by Lnc-MALAT1 knock-down. Interestingly, TGF-β1, a potent pro-fibrotic cytokine, promoted the expression of Lnc-MALAT1 in LX-2 and its pro-fibrotic effects were also abolished by siRNA for Lnc-MALAT1, suggesting that Lnc-MALAT1 probably functions as a common mediator in the activation and fibrogenesis of HSCs. Our results indicate that enhanced expression of Lnc-MALAT1 in the fibrotic liver stimulate the activation of HSCs and thus promote their fibrogenic activity. These results also provide evidences that Lnc-MALAT1 is a potential therapeutic target and plasma EVs-Lnc-MALAT1 is a potential diagnostic biomarker for liver fibrosis.
Extracellular Vesicles Derived From Murine Cementoblasts Possess the Potential to Increase Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclastogenesis
Authors: Sato Rei , Maruyama Kentaro , Nemoto Eiji , Sakisaka Yukihiko , Suzuki Shigeki , Li Jiajun , Numazaki Kento , Tada Hiroyuki , Yamada Satoru
Published: February 2022

Cementum resorption, unlike bone resorption, is clinically known to occur only with limited pathological stimuli, such as trauma, orthodontic forces, and large apical periodontitis; however, the molecular mechanisms that control osteoclast formation on the cementum surface remain unclear. In this study, we focused on extracellular vesicles (EVs) secreted by cementoblasts and analyzed their effects on osteoclast differentiation. EVs were extracted from the conditioned medium (CM) of the mouse cementoblast cell line OCCM-30. Transmission electron microscopy (TEM) analysis confirmed the presence of EVs with a diameter of approximately 50–200 nm. The effect of the EVs on osteoclast differentiation was examined using the mouse osteoclast progenitor cell line RAW 264.7 with recombinant receptor activator of nuclear factor (NF)-κB ligand (rRANKL) stimulation. EVs enhanced the formation of tartrate-resistant acid phosphatase (TRAP) activity-positive cells upon rRANKL stimulation. EVs also enhanced the induction of osteoclast-associated gene and protein expression in this condition, as determined by real-time PCR and Western blotting, respectively. On the other hand, no enhancing effect of EVs was observed without rRANKL stimulation. A Western blot analysis revealed no expression of receptor activator of NF-κB ligand (RANKL) in EVs themselves. The effect on rRANKL-induced osteoclast differentiation was examined using the CM of cementoblasts in terms of TRAP activity-positive cell formation and osteoclast-associated gene expression. The conditioned medium partly inhibited rRANKL-induced osteoclast differentiation and almost completely suppressed its enhancing effect by EVs. These results indicate that cementoblasts secreted EVs, which enhanced RANKL-induced osteoclast differentiation, and simultaneously produced soluble factors that neutralized this enhancing effect of EVs, implicating this balance in the regulation of cementum absorption. A more detailed understanding of this crosstalk between cementoblasts and osteoclasts will contribute to the development of new therapies for pathological root resorption.
Social Entrepreneurship Orientation and Enterprise Fortune: An Intermediary Role of Social Performance
Authors: Zafar Zuhaib , Wenyuan Li , Bait Ali Sulaiman Mohammed Ali , Siddiqui Kamran Akhtar , Qalati Sikandar Ali
Published: February 2022

Social entrepreneurship orientation (SEO) is a behavioral construct of social entrepreneurship (SE); therefore, we examined the influence of SEO of the organization on social and financial performance. A random sample of 810 employees was drawn from social enterprises of Pakistan during the COVID-19 pandemic. Although increasing research focuses on SE, the discipline continues to disintegrate, and this has led to appeals for a careful investigation of the associations of firms’ SE. In the recent decade, “social entrepreneurship” has earned its importance as a segment of entrepreneurship. Instead of mixed activity, firms are more likely to engage in either for-profit or non-profit activities. The causes for and consequences of this conduct has been mainly studied using objective measures of SEO, social performance, and financial performance, with little attention paid to the subjective experiences of social enterprises. We rely on the theory of stakeholder and mixed structuring to postulate that social performance intermediates the SEO-financial performance relation. By assessing a sample of 810 employees from active enterprises, we discover that social performance mediates positively and partially between SEO and financial performance, and both direct and indirect paths are in the same direction and significant. Our findings exhibit that social performance variance explained 74% of the mediating role, and the remaining 26% of the effect is because of SEO. We consider the functions by which an SEO influences enterprise performance and delivers more prominent understanding into multiple spectrums of performance. We discuss the prospective suggestions of our research and foster an encouraging pathway for more enquiry on the SEO paradigm. The study adds contribution to the literature, which has not been testified before on hybrid firms. SEO is a newly defined construct and requires more prospective research. This research gives the researchers/scholars new directions to address related disciplines and further explore this domain.
Stigma and Quality of Life in Women With Breast Cancer: Mediation and Moderation Model of Social Support, Sense of Coherence, and Coping Strategies
Authors: Zamanian Hadi , Amini-Tehrani Mohammadali , Jalali Zahra , Daryaafzoon Mona , Ramezani Fatemeh , Malek Negin , Adabimohazab Maede , Hozouri Roghayeh , Rafiei Taghanaky Fereshteh
Published: February 2022

Objectives

The breast cancer stigma affects Health-related quality of life (HRQoL), while general resilience resources (GRRs), namely, sense of coherence (SOC), social support, and coping skills, are thought to alleviate this effect. The study aimed to explore the mediating/moderation role of GRRs in the relationship between stigma and HRQoL and its dimensions in Iranian patients with breast cancer.

Methods

In this cross-sectional study, Stigma Scale for Chronic Illness 8-item version (SSCI-8), SOC-13, Medical Outcome Survey- Social Support Scale (MOS-SSS), Brief COPE, and Functional Assessment of Cancer Therapy-Breast (FACT-B) were investigated in a convenience sample of Iranian women with confirmed non-metastatic breast cancer. Following the establishment of correlations using Pearson’s correlation, single and parallel mediation analysis and moderation analysis were conducted to determine the extent to which each GRR might be impacted by stigma or decrease the adverse impact of stigma on HRQoL.

Results

An analysis of 221 women (response rate of 87.5%) with the mean age of 47.14 (9.13) showed that stigma was negatively correlated to all HRQoL’s dimensions (r = −0.27∼0.51, p < 0.05), SOC (r = −0.26∼0.35, p < 0.01), social support (r = −0.23∼0.30, p < 0.01), and the bulk of coping skills. In the single mediation analysis, stigma affected all facets of SOC, all subscales of social support, and positive reframing, which partially reduced breast cancer HRQoL. Stigma affects general HRQoL through damaging meaningfulness, social support (except for tangible), and positive reframing. Meaningfulness was marked as the most impacted GRR in terms of all domains of HRQoL. In parallel mediation, reduced meaningfulness, total social support, and positive reframing were highlighted as the pathways of diminished breast cancer HRQoL. Moderation analysis indicated the higher levels of humor, behavioral disengagement, and use of instrumental support behaviors to be functional in protecting different dimensions of HRQoL, while the results were mixed for venting, especially in patients with mastectomy surgery.

Conclusion

While GRRs may be impacted by stigma, they exert a relatively small protective effect against the impact of stigma on HRQoL. This study provides some novel findings, but longitudinal studies are needed to further verify these before any causal conclusion or recommendations for health policy can be drawn.
Occupational Stigma Perception, Emotional Exhaustion State, and Professional Commitment Response: Understanding the Mechanisms Underlying Hotel Interns’ Perceptions of Career Prospects
Authors: Wen Lei Lei , Xiang Keheng , Gao Fan , Zhou Jieling
Published: February 2022

This study uses an integrated model of resource conservation theory and social learning theory to explore the antecedents of hotel interns’ perceptions of occupational stigma and to explore the mechanisms inherent to retention willingness. This study first manipulated relevant subjects’ experimental materials through a contextual experiment and used a one-way ANOVA to test the effects of competence stereotypes and occupational stereotypes on hotel interns’ stigma perceptions, respectively, and then used partial least squares structural equation modeling (PLS-SEM) as a statistical tool and the SmartPLS 3.0 program to validate the model of hotel interns’ occupational stigma perceptions-intention. The effects of both competence stereotypes and occupational stereotypes on hotel interns’ perceptions of occupational stigma were significant. The results of the partial least squares structural equation model showed that hotel interns’ perceptions of occupational stigma significantly contributed to emotional exhaustion and that emotional exhaustion significantly influenced hotel interns’ retention willingness, hotel interns’ perceptions of occupational stigma had a significant effect on their retention willingness, while the role of emotional exhaustion as a mediating variable and occupational commitment as a moderator. The inner psychological and behavioral linkage mechanisms of hotel interns’ occupational stigma perceptions and their retention willingness under COVID-19 were explored, and the resource dynamics operating mechanism and professional commitment were also confirmed.
Structural Variability Shows Power-Law Based Organization of Vowel Systems
Authors: Zhang Menghan , Gong Tao
Published: February 2022

Speech sounds are an essential vehicle of information exchange and meaning expression in approximately 7,000 spoken languages in the world. What functional constraints and evolutionary mechanisms lie behind linguistic diversity of sound systems is under ongoing debate; in particular, it remains conflicting whether there exists any universal relationship between these constraints despite of diverse sounds systems cross-linguistically. Here, we conducted cross-linguistic typological and phylogenetic analyses to address the characteristics of constraints on linguistic diversity of vowel systems. First, the typological analysis revealed a power-law based dependence between the global structural dispersion and the local focalization of vowel systems and validated that such dependence was independent of geographic region, language family, and linguistic affiliation. Second, the phylogenetic analysis further illustrated that the observed dependence resulted from correlated evolutions of these two structural properties, which proceeded in an adaptive process. These results provide empirical evidence that self-organization mechanisms helped shape vowel systems and common functional constraints took effect on the evolution of vowel systems in the world’s languages.
Working Memory and Transcranial-Alternating Current Stimulation—State of the Art: Findings, Missing, and Challenges
Authors: Al Qasem Wiam , Abubaker Mohammed , Kvašňák Eugen
Published: February 2022

Working memory (WM) is a cognitive process that involves maintaining and manipulating information for a short period of time. WM is central to many cognitive processes and declines rapidly with age. Deficits in WM are seen in older adults and in patients with dementia, schizophrenia, major depression, mild cognitive impairment, Alzheimer’s disease, etc. The frontal, parietal, and occipital cortices are significantly involved in WM processing and all brain oscillations are implicated in tackling WM tasks, particularly theta and gamma bands. The theta/gamma neural code hypothesis assumes that retained memory items are recorded via theta-nested gamma cycles. Neuronal oscillations can be manipulated by sensory, invasive- and non-invasive brain stimulations. Transcranial alternating-current stimulation (tACS) and repetitive transcranial magnetic stimulation (rTMS) are frequency-tuned non-invasive brain stimulation (NIBS) techniques that have been used to entrain endogenous oscillations in a frequency-specific manner. Compared to rTMS, tACS demonstrates superior cost, tolerability, portability, and safety profile, making it an attractive potential tool for improving cognitive performance. Although cognitive research with tACS is still in its infancy compared to rTMS, a number of studies have shown a promising WM enhancement effect, especially in the elderly and patients with cognitive deficits. This review focuses on the various methods and outcomes of tACS on WM in healthy and unhealthy human adults and highlights the established findings, unknowns, challenges, and perspectives important for translating laboratory tACS into realistic clinical settings. This will allow researchers to identify gaps in the literature and develop frequency-tuned tACS protocols with promising safety and efficacy outcomes. Therefore, research efforts in this direction should help to consider frequency-tuned tACS as a non-pharmacological tool of cognitive rehabilitation in physiological aging and patients with cognitive deficits.
Genome-Wide Association Study on Three Behaviors Tested in an Open Field in Heterogeneous Stock Rats Identifies Multiple Loci Implicated in Psychiatric Disorders
Authors: Gunturkun Mustafa Hakan , Wang Tengfei , Chitre Apurva S. , Garcia Martinez Angel , Holl Katie , St. Pierre Celine , Bimschleger Hannah , Gao Jianjun , Cheng Riyan , Polesskaya Oksana , Solberg Woods Leah C. , Palmer Abraham A. , Chen Hao
Published: February 2022

Many personality traits are influenced by genetic factors. Rodents models provide an efficient system for analyzing genetic contribution to these traits. Using 1,246 adolescent heterogeneous stock (HS) male and female rats, we conducted a genome-wide association study (GWAS) of behaviors measured in an open field, including locomotion, novel object interaction, and social interaction. We identified 30 genome-wide significant quantitative trait loci (QTL). Using multiple criteria, including the presence of high impact genomic variants and co-localization of cis-eQTL, we identified 17 candidate genes (Adarb2, Ankrd26, Cacna1c, Cacng4, Clock, Ctu2, Cyp26b1, Dnah9, Gda, Grxcr1, Eva1a, Fam114a1, Kcnj9, Mlf2, Rab27b, Sec11a, and Ube2h) for these traits. Many of these genes have been implicated by human GWAS of various psychiatric or drug abuse related traits. In addition, there are other candidate genes that likely represent novel findings that can be the catalyst for future molecular and genetic insights into human psychiatric diseases. Together, these findings provide strong support for the use of the HS population to study psychiatric disorders.
Maybe It's Not the Meth: Considering Biopsychosocial Contributors to Cognitive Impairment in Methamphetamine Polydrug Use
Authors: Gooden James R. , Petersen Vanessa , Bolt Georgia L. , Curtis Ashlee , Manning Victoria , Cox Catherine A. , Lubman Dan I. , Arunogiri Shalini
Published: February 2022

Objective

In considering the cognitive harms of methamphetamine (MA) use, there is currently a limited appreciation of the profile of pre-existing, comorbid, or modifiable risk factors for cognitive impairment in individuals with MA-polydrug use who present to clinical services. This is in contrast to the well-recognized evidence in alcohol use groups. The aim of this study was to investigate the biopsychosocial and neuropsychological profiles of MA-polysubstance using individuals reporting cognitive impairment in comparison to an alcohol-using group.

Methods

A retrospective file audit was undertaken of individuals who presented for assessment to a specialist addiction neuropsychology service and reported either more than 1 year of heavy MA use as part of a polydrug use history (n = 40) or having only used alcohol (n = 27). Clinical histories including demographic, medical, mental health, substance use, and neuropsychological assessment results were extracted from medical records. Between group comparisons were conducted to explore differences in the MA-polydrug vs. the alcohol group.

Results

Individuals in the MA-polydrug group were significantly younger, commenced substance use at an earlier age, were more likely to have an offending history, and experienced an overdose than those in the alcohol group. No differences in comorbid neurodevelopmental, psychiatric or acquired brain injury diagnoses were observed between groups. For neuropsychological functioning, significant group differences were observed in overall IQ, semantic verbal fluency, and psychomotor tracking, where individuals in the alcohol group performed significantly worse.

Conclusions

Neuropsychological profiles were largely equivalent between groups across cognitive domains, with minor differences in favor of the MA-polydrug group. Relative to the general population, cognitive functioning was reduced for both groups across a range of domains. High rates of comorbid mental health concerns were common across both groups, however, individuals in the MA-polydrug group presented with a higher risk of overall harm from substance use at a significantly younger age which is a unique concern for this group. These findings highlight the importance of considering the biopsychosocial factors, such as age of first use, emotional distress, indirect substance related harms including overdose and blood born virus infection that may be relevant to experiences of cognitive difficulty in MA-polydrug users.
Dashboard Layout Effects on Drivers' Searching Performance and Heart Rate: Experimental Investigation and Prediction
Authors: Yang Hao , Wang Yueran , Jia Ruoyu
Published: February 2022

Carsharing scale has been increasing rapidly with sharing economy. However, many users are reluctant to rent cars any longer due to the low-quality of interactive experience and usability, especially in terms of the dashboard design. This challenge should be urgently addressed in order to maintain the sustainable development of car-sharing industry and its environmental benefits. This study aims to investigate the relationship between users' driving activities (e.g., searching time, reading time, eye movement, heart rate) and dashboard layout. This study was conducted based on the experimental investigation among 58 respondents who were required to complete driving tasks in four types of cars with different dashboard layouts. Afterwards, a prediction model was developed to predict users heart rate (HR) based on the long short-term memory model, and logistic models were used to examine the relationship between the occurrence probability of minimum HR and dashboard reading. The results showed that the system usability of a dashboard was related to the drivers' eye movement characteristics including fixation duration, fixation times and pupil diameter. Most indicators had significant effects (p < 0.05) on the system usability score of corresponding dashboard. The long short-term memory model network (RMSE = 1.105, MAE = 0.009) was capable of predicting heart rate (HR) that happened in the process of instrument reading, which presented a periodic pattern rather than a continuous increase or decrease. It reflected that the network could better fit the non-linear and time-sequential laws of HR data. Furthermore, the probability of the lowest heart rate occurrence during the interaction with four dashboards was influenced by the average searching time, reading time and reading accuracy that were related to a specific layout. Overall, this study provided a theoretical reference for uncovering users' adaptive behaviors with the central control screen and for the optimal choice of a suitable dashboard layout in interface design.
Exploratory State Representation Learning
Authors: Merckling Astrid , Perrin-Gilbert Nicolas , Coninx Alex , Doncieux Stéphane
Published: February 2022

Not having access to compact and meaningful representations is known to significantly increase the complexity of reinforcement learning (RL). For this reason, it can be useful to perform state representation learning (SRL) before tackling RL tasks. However, obtaining a good state representation can only be done if a large diversity of transitions is observed, which can require a difficult exploration, especially if the environment is initially reward-free. To solve the problems of exploration and SRL in parallel, we propose a new approach called XSRL (eXploratory State Representation Learning). On one hand, it jointly learns compact state representations and a state transition estimator which is used to remove unexploitable information from the representations. On the other hand, it continuously trains an inverse model, and adds to the prediction error of this model ak-step learning progress bonus to form the maximization objective of a discovery policy. This results in a policy that seeks complex transitions from which the trained models can effectively learn. Our experimental results show that the approach leads to efficient exploration in challenging environments with image observations, and to state representations that significantly accelerate learning in RL tasks.