bluuebunny/crossref_metadata_2025 huggingface dataset:
Facilitators and Barriers to Uptake of Community-Based Diabetes Prevention Program Among Multi-Ethnic Asian Patients With Prediabetes
Authors: Yoon Sungwon , Wee Sharon , Loh Dionne H. F. , Bee Yong Mong , Thumboo Julian
Published: February 2022

Objective

This study aimed to identify facilitators and barriers to the uptake of a community-based diabetes prevention program (DPP) from the perspectives of decliners with prediabetes in a multi-ethnic Asian community.

Methods

Semi-structured interviews were conducted with 29 individuals with prediabetes who declined participation in a large community-based diabetes prevention program in Singapore. Thematic analysis was undertaken to identify themes, which were subsequently mapped onto the Capacity-Opportunity-Motivation and Behavior model (COM-B).

Results

We identified 16 key themes under three COM-B domains. Health status at the time of invitation, perceived ability of self-management, understanding of prediabetes condition and/or the program intention (Capability) were important determinants. Family commitment had the strong potential to enable or hinder physical and social Opportunity related to participation. Many participants desired involvement of physician as part of program invitation and component. Fear of exacerbation coupled with an automatic aversion for suffering influenced Motivation for participation.

Conclusion

Identifying facilitators and barriers embedded in the COM-B will assist systematic program modifications to increase participation of individuals with prediabetes. How information about modifiable risk factors is communicated by physicians at the point of diagnosis and program introduction is key to participation. Co-locating programs with family activity, development of mHealth, readiness assessment, and tailored explanation of program purpose may increase participation. These findings will be used to guide future national interventions in the community to ensure successful implementation.
Molecular Signatures Correlated With Poor IVF Outcomes: Insights From the mRNA and lncRNA Expression of Endometriotic Granulosa Cells
Authors: Shi Libing , Wei Xianjiang , Wu Bingbing , Yuan Chunhui , Li Chao , Dai Yongdong , Chen Jianmin , Zhou Feng , Lin Xiang , Zhang Songying
Published: February 2022

The outcomes of in vitro fertilization (IVF) for endometriotic women are significantly worse than for patients without ovarian endometriosis (OEM), as shown by fewer retrieved oocytes. However, the exact pathophysiological mechanism is still unknown. Thus, we conducted a prospective study that analyzed mRNA and lncRNA transcriptome between granulosa cells (GCs) from patients with fewer retrieved oocytes due to OEM and GCs from controls with male factor (MF) infertility using an RNA sequencing approach. We found a group of significantly differentially expressed genes (DEGs), including NR5A2, MAP3K5, PGRMC2, PRKAR2A, DEPTOR, ITGAV, KPNB1, GPC6, EIF3A, and SMC5, which were validated to be upregulated and negatively correlated with retrieved oocyte numbers in GCs of patients with OEM, while DUSP1 demonstrated the opposite. The molecular functions of these DEGs were mainly enriched in pathways involving mitogen-activated protein kinase (MAPK) signaling, Wnt signaling, steroid hormone response, apoptosis, and cell junction. Furthermore, we performed lncRNA analysis and identified a group of differentially expressed known/novel lncRNAs that were co-expressed with the validated DEGs and correlated with retrieved oocyte numbers. Co-expression networks were constructed between the DEGs and known/novel lncRNAs. These distinctive molecular signatures uncovered in this study are involved in the pathological regulation of ovarian reserve dysfunction in OEM patients.
Estrogen Receptor Function: Impact on the Human Endometrium
Authors: Yu Kun , Huang Zheng-Yuan , Xu Xue-Ling , Li Jun , Fu Xiang-Wei , Deng Shou-Long
Published: February 2022

The physiological role of estrogen in the female endometrium is well established. On the basis of responses to steroid hormones (progesterone, androgen, and estrogen), the endometrium is considered to have proliferative and secretory phases. Estrogen can act in the endometrium by interacting with estrogen receptors (ERs) to induce mucosal proliferation during the proliferative phase and progesterone receptor (PR) synthesis, which prepare the endometrium for the secretory phase. Mouse knockout studies have shown that ER expression, including ERα, ERβ, and G-protein-coupled estrogen receptor (GPER) in the endometrium is critical for normal menstrual cycles and subsequent pregnancy. Incorrect expression of ERs can produce many diseases that can cause endometriosis, endometrial hyperplasia (EH), and endometrial cancer (EC), which affect numerous women of reproductive age. ERα promotes uterine cell proliferation and is strongly associated with an increased risk of EC, while ERβ has the opposite effects on ERα function. GPER is highly expressed in abnormal EH, but its expression in EC patients is paradoxical. Effective treatments for endometrium-related diseases depend on understanding the physiological function of ERs; however, much less is known about the signaling pathways through which ERs functions in the normal endometrium or in endometrial diseases. Given the important roles of ERs in the endometrium, we reviewed the published literature to elaborate the regulatory role of estrogen and its nuclear and membrane-associated receptors in maintaining the function of endometrium and to provide references for protecting female reproduction. Additionally, the role of drugs such as tamoxifen, raloxifene, fulvestrant and G-15 in the endometrium are also described. Future studies should focus on evaluating new therapeutic strategies that precisely target specific ERs and their related growth factor signaling pathways.
Estimating Peak Shaving Capacity Demand of Gas-Fired Power in China From a Regional Coordination Perspective
Authors: Zhang Shuquan , Wang Ye , Zhao Xu , Duan Xuqiang , Luo Dongkun
Published: February 2022

To meet the carbon neutralization goal and renewable energy development, it is of great significance to promote the construction of gas-fired power generation for power peak shaving. From the perspective of regional coordination (corresponding to three scenarios), this paper systematically calculates the power peak shaving demand and the demand for gas-fired power generation capacity in regions of China, by using Mathematical Programming and Shapley value. Compared with the existing research, this paper may make theoretical contributions to the following aspects: studying more spatial scopes and time scales of peak shaving, analyzing the complete system of “coal power—renewable energy—gas power”, and applying cooperative game model to peak shaving issue. We find that, firstly, compared with the scenario of independent peak shaving in a single province (Scenario 1), the peak shaving demands of load and renewable energy are greatly reduced in the scenarios of areal coordination (Scenario 2) and national coordination (Scenario 3), especially renewable energy; secondly, abandonment of 110,766 MWh of renewable energy power occurring in Scenario 2 is avoided in Scenario 3. Compared with Scenario 2, the final peak shaving demands of seven areas in China are simultaneously reduced in Scenario 3. The largest reduction rate is 14% from East China. Thirdly, with deep peak shaving restricted by certain constraints, gas power generation for start-stop peak shaving is inevitable. Compared with Scenario 2, national coordination (Scenario 3) can eliminate 120,714 MW of start-stop peak shaving demand (SS-PSD); finally, flexibility retrofit of existing facilities can further significantly curtail SS-PSD. Based on the above research results, some recommendations are put forward, including developing areal coordination and national coordination mechanisms for peak shaving, clarifying allocation plan of SS-PSD based on the fairness principle (i.e., Shapley value) as soon as possible, encouraging East China, Central China, and North China to take the lead in establishing trading markets of SS-PSD, giving priority to meeting the most urgent and economic peak shaving demand, and establishing a coordination mechanism between new and old units for flexibility retrofit.
Application of Soft Computing in Predicting Groundwater Quality Parameters
Authors: Hanoon Marwah Sattar , Ammar Amr Moftah , Ahmed Ali Najah , Razzaq Arif , Birima Ahmed H. , Kumar Pavitra , Sherif Mohsen , Sefelnasr Ahmed , El-Shafie Ahmed
Published: February 2022

Evaluating the quality of groundwater in a specific aquifer could be a costly and time-consuming procedure. An attempt was made in this research to predict various parameters of water quality called Fe, Cl, SO4, pH and total hardness (as CaCO3) by measuring properties of total dissolved solids (TDSs) and electrical conductivity (EC). This was reached by establishing relations between groundwater quality parameters, TDS and EC, using various machine learning (ML) models, such as linear regression (LR), tree regression (TR), Gaussian process regression (GPR), support vector machine (SVM), and ensembles of regression trees (ER). Data for these variables were gathered from five unrelated groundwater quality studies. The findings showed that the TR, GPR, and ER models have satisfactory performance compared to that of LR and SVM with respect to different assessment criteria. The ER model attained higher accuracy in terms of R2 in TDS 0.92, Fe 0.89, Cl 0.86, CaCO3 0.87, SO4 0.87, and pH 0.86, while the GPR model attained an EC 0.98 compared to all developed models. Moreover, comparisons among the different developed models were performed using accuracy improvement (AI), improvement in RMSE (PRMSE), and improvement in PMAE to determine a higher accuracy model for predicting target properties. Generally, the comparison of several data-driven regression methods indicated that the boosted ensemble of the regression tree model offered better accuracy in predicting water quality parameters. Sensitivity analysis of each parameter illustrates that CaCO3 is most influential in determining TDS and EC. These results could have a significant impact on the future of groundwater quality assessments.
The Outer Membrane Lipoprotein Tp0136 Stimulates Human Platelet Activation and Aggregation Through PAR1 to Enhance Gq/Gi Signaling
Authors: Xu Qiu-Yan , Wang Yong-Jing , Lin Li-Rong , Liu Li-Li , Yang Tian-Ci
Published: February 2022

Background

Chancre self-healing, a typical clinical phenomenon of primary syphilis, is essentially wound healing. The first response to a wound is constriction of the injured blood vessels and activation of platelets to form a fibrin clot. However, the role of Treponema pallidum in platelet activation and clot formation remains unclear.

Objectives

We aimed to elucidate the role of the outer membrane Treponema pallidum lipoprotein Tp0136 in human platelet activation and aggregation and explore the related mechanism.

Methods

A series of experiments were performed to assess the effects of Tp0136 on human platelet activation and aggregation in vitro. The effect of Tp0136 on platelet receptors was studied by detecting PAR1 protein levels and studying related receptor sites. The involvement of the Gq/Gi signaling pathway downstream of PAR1 was explored.

Results

Tp0136 significantly accelerated the formation of human platelet clots as well as platelet adhesion to and diffusion on fibrinogen to promote platelet aggregation. Tp0136 also potentiated P-selectin expression and PF4 release to promote platelet activation and downregulated PAR1 expression. The activation and aggregation induced by Tp0136 were reverted by the specific PAR1 antagonist RWJ56110 and the human PAR1 antibody. In addition, Tp0136 significantly enhanced Gq and Gi signaling activation, thereby triggering p38 phosphorylation and Akt-PI3K activation, increasing the release of intraplatelet Ca2+ and attenuating the release of cytosolic cAMP. Furthermore, the specific PAR1 antagonist RWJ56110 significantly suppressed Gq and Gi signaling activation.

Conclusions

Our results showed that the Treponema pallidum Tp0136 protein stimulated human platelet activation and aggregation by downregulating PAR1 and triggered PAR1-dependent Gq and Gi pathway activation. These findings may contribute to our understanding of the self-healing of chancroid in early syphilis.
Peptidomes and Structures Illustrate How SLA-I Micropolymorphism Influences the Preference of Binding Peptide Length
Authors: Wei Xiaohui , Li Shen , Wang Suqiu , Feng Guojiao , Xie Xiaoli , Li Zhuolin , Zhang Nianzhi
Published: February 2022

Polymorphisms can affect MHC-I binding peptide length preferences, but the mechanism remains unclear. Using a random peptide library combined with LC-MS/MS and de novo sequencing (RPLD-MS) technique, we found that two swine MHC-I molecules with high sequence homology, SLA-1*04:01 and SLA-1*13:01, had significant differences in length preference of the binding peptides. Compared with SLA-1*04:01, SLA-1*13:01 binds fewer short peptides with 8-10 amino acids, but more long peptides. A dodecapeptide peptide (RW12) can bind to both SLA-1*04:01 and SLA-1*13:01, but their crystal structures indicate that the binding modes are significantly different: the entirety of RW12 is embedded in the peptide binding groove of SLA-1*04:01, but it obviously protrudes from the peptide binding groove of SLA-1*13:01. The structural comparative analysis showed that only five differential amino acids of SLA-1*13:01 and SLA-1*04:01 were involved in the binding of RW12, and they determine the different ways of long peptides binding, which makes SLA-1*04:01 more restrictive on long peptides than SLA-1*13:01, and thus binds fewer long peptides. In addition, we found that the N terminus of RW12 extends from the groove of SLA-1*13:01, which is similar to the case previously found in SLA-1*04:01. However, this unusual peptide binding does not affect their preferences of binding peptide length. Our study will be helpful to understand the effect of polymorphisms on the length distribution of MHC-I binding peptides, and to screen SLA-I-restricted epitopes of different lengths and to design effective epitope vaccines.
Mechanisms of MHC-I Downregulation and Role in Immunotherapy Response
Authors: Taylor Brandie C. , Balko Justin M.
Published: February 2022

Immunotherapy has become a key therapeutic strategy in the treatment of many cancers. As a result, research efforts have been aimed at understanding mechanisms of resistance to immunotherapy and how anti-tumor immune response can be therapeutically enhanced. It has been shown that tumor cell recognition by the immune system plays a key role in effective response to T cell targeting therapies in patients. One mechanism by which tumor cells can avoid immunosurveillance is through the downregulation of Major Histocompatibility Complex I (MHC-I). Downregulation of MHC-I has been described as a mechanism of intrinsic and acquired resistance to immunotherapy in patients with cancer. Depending on the mechanism, the downregulation of MHC-I can sometimes be therapeutically restored to aid in anti-tumor immunity. In this article, we will review current research in MHC-I downregulation and its impact on immunotherapy response in patients, as well as possible strategies for therapeutic upregulation of MHC-I.
Empiric Addition of Quinolones to First-Line Tuberculosis Treatment Is Associated With Increased Odds of XDR-TB
Authors: Udwadia Zarir F. , Patel Palak P. , Sharma Samridhi , Gupta Amita , Tornheim Jeffrey A.
Published: February 2022

Background

Multidrug-resistant tuberculosis (MDR-TB) represents a significant clinical and public health challenge worldwide. Out of concern for possible resistance, some providers prescribe first- and second-line tuberculosis treatment together before completing drug susceptibility testing (DST), which may increase emergent resistance.

Methods

MDR-TB patients at an Indian referral center were enrolled in an observational cohort. Participants with drug susceptibility test (DST) results were categorized as prescribed fluoroquinolones, streptomycin, both, or neither with first-line treatment before DST. Odds of additional resistance to fluoroquinolones and aminoglycosides (XDR-TB) were calculated in association with empiric combined first- and second-line treatment before DST.

Results

Of 494 participants, 130 (26.3%) received a fluoroquinolone or streptomycin with first-line drugs before DST. Odds of XDR-TB were associated with fluoroquinolone prescription before DST [odds ratio (OR): 2.19, 95% confidence interval (CI): 1.26–3.76). The association with XDR-TB persisted in multivariable analysis (adjusted OR: 2.43, 95% CI: 1.19-4.91). Combined empiric first- and second-line treatment before DST was not associated with eventual outcomes.

Conclusion

Many participants received empiric combined first- and second-line drugs before DST, which was associated with XDR-TB. To minimize emerging resistance, treatment-associated side effects, and provide the best possible care, this approach should be discouraged in favor of early DST and DST-guided TB treatment.
Stable Isotope Analysis Revealed Ontogenetic Changes in Trophic Ecology and Migration Patterns of Sepia esculenta in the Northern Coastal Waters of China
Authors: Wang Linlong , Liu Yang , Zhang Xiumei
Published: February 2022

Golden cuttlefish (Sepia esculenta), the most economically important cephalopod in the northern coastal seas of China, had experienced greatly reduced population biomass due to continuous fishing pressure in recent decades. Understanding the trophic ecology and clarifying the spatial distribution of wintering ground can help develop management plans for this species. In this study, the ontogenetic changes in the trophic ecology of S. esculenta in the Qingdao coastal water were determined, and the migration patterns were studied using stable isotope analysis. Cluster analysis based on isotopic values divided S. esculenta with different lengths into groups: 11–20, 21–100, and 121–200 mm. A significant difference in the δ13C values between the groups 11–20 mm (−17.10‰) and 21–100 mm (−15.89‰) illustrates an ontogenetic change in the feeding habits. Due to the migratory habits of S. esculenta, the δ13C value of the group 121–200 mm (−16.39‰) was lower than that of the group 21–100 mm. The δ15N values of S. esculenta were found to increase in length, and there was a clear linear relationship between different S. esculenta groups, suggesting that the wintering ground may locate in the same latitude as the spawning ground (i.e., the middle Yellow Sea). Furthermore, the trophic relationship between S. esculenta and coexisting species was assessed, revealing that the group 11–20 mm of S. esculenta has some overlap of carbon isotope space with other species, suggesting that these species may feed on it as prey. Thus, slightly increasing the length to more than 20 mm may reduce the pressure of being the prey of post-release juveniles of S. esculenta and improve the effect of release.
Deep Convection Along the Continental Slope in the East/Japan Sea: A Large-Eddy Simulation Study
Authors: Kim Bong-Gwan , Cho Yang-Ki , Noh Yign
Published: February 2022

Sparse observations in the East/Japan Sea (EJS) suggested that open-ocean deep convection occurs south of Vladivostok; however, more recent observations suggest that deep convection occurs along the continental slope, resulting in bottom water formation in the EJS. We investigated the process of deep convection along the EJS continental slope using large-eddy simulation (LES), which demonstrated that dense water, formed by strong wintertime cooling in the shelf, flows down along the slope as a bottom Ekman current. The characteristics of the initial dense water were relatively well conserved on the continental slope during convection, but they changed rapidly by mixing with the surrounding waters in the open ocean. Accordingly, slope convection penetrated deeper compared to open-ocean convection under the same surface heat flux. Our numerical experiments showed that, under typical surface cooling during winter (i.e., 200 W m–2), slope convection reaches depths greater than 2,700 m, generating a potential ventilation process for deep- and bottom-water formations, whereas open-ocean convection reaches approximately 700 m depth, contributing to the intermediate- and central-water formations in the EJS. Various topography experiments revealed that downward speed was proportional to the continental-slope inclination; the initial characteristics remained relatively well conserved at a small continental-slope inclination. Increased salinity due to brine rejection in the shelf could accelerate the slope convection.
Inpatient Administration of Alpha-1-Adrenergic Receptor Blocking Agents Reduces Mortality in Male COVID-19 Patients
Authors: Li Shilong , Jun Tomi , Tyler Jonathan , Schadt Emilio , Kao Yu-Han , Wang Zichen , Konig Maximilian F. , Bettegowda Chetan , Vogelstein Joshua T. , Papadopoulos Nickolas , Parsons Ramon E. , Chen Rong , Schadt Eric E. , Li Li , Oh William K.
Published: February 2022

Apha-1-adrenergic receptor antagonists (α1-blockers) can suppress pro-inflammatory cytokines, thereby potentially improving outcomes among patients with COVID-19. Accordingly, we evaluated the association between α1-blocker exposure (before or during hospitalization) and COVID-19 in-hospital mortality. We identified 2,627 men aged 45 or older who were admitted to Mount Sinai hospitals with COVID-19 between February 24 and May 31, 2020, in New York. Men exposed to α1-blockers (N = 436) were older (median age 73 vs. 64 years, P < 0.001) and more likely to have comorbidities than unexposed men (N = 2,191). Overall, 777 (29.6%) patients died in hospital, and 1,850 (70.4%) were discharged. Notably, we found that α1-blocker exposure was independently associated with improved in-hospital mortality in a multivariable logistic analysis (OR 0.699; 95% CI, 0.498-0.982; P = 0.039) after adjusting for patient demographics, comorbidities, and baseline vitals and labs. The protective effect of α1-blockers was stronger among patients with documented inpatient exposure to α1-blockers (OR 0.624; 95% CI 0.431-0.903; P = 0.012). Finally, age-stratified analyses suggested variable benefit from inpatient α1-blocker across age groups: Age 45-65 OR 0.483, 95% CI 0.216-1.081 (P = 0.077); Age 55-75 OR 0.535, 95% CI 0.323-0.885 (P = 0.015); Age 65-89 OR 0.727, 95% CI 0.484-1.092 (P = 0.124). Taken together, clinical trials to assess the therapeutic value of α1-blockers for COVID-19 complications are warranted.
Heat Stress Affects Faecal Microbial and Metabolic Alterations of Rabbits
Authors: Bai Xue , Shi Yu , Tang Lipeng , Chen Li , Fan Huimei , Wang Haoding , Wang Jie , Jia Xianbo , Chen Shiyi , Lai Songjia
Published: February 2022

Heat stress can impair the rabbit immune system, induce oxidative stress, and cause many complications. These diseases are characterized by metabolic disorders, but the underlying mechanism is unknown. As a result, the current research determines the effects of HS on intestinal microorganisms in rabbits and the metabolic pathway disorders caused by HS. Twelve rabbits were randomly assigned to one of two groups: CON (22–24°C) and HS (30°C–32°C). Both the groups were treated for 15 days. Blood and fecal samples were collected on day 15. Serum immune oxidation indices were determined using a commercial ELISA kit, and the microbiome of rabbit feces was studied using 16S rRNA gene sequencing. Non-targeted metabolomics was analyzed using ultra-high-performance liquid chromatography-mass spectrometry (UHPC MS/MS). The findings revealed that HS significantly increased IgG and T-AOC levels in serum, whereas it decreased TNF-α and IL-10. NMDS analysis revealed a substantial difference in bacterial community composition between HS and CON groups. At the phylum level, the abundance of Firmicutes, Protobacteria, and Verrucomicrobiota was significantly higher in the HS group, whereas the abundance of Bacteriodota was reduced in the CON group. V9D2013 group, Haloplasma, Comamonas, Clostridium sensu stricto 1, Ruminiclostridium, Syntrophus Lutispora, at the genus level Syntrophorhabdus, Paeniclostridium, Clostridium sensu stricto 6, Candidatus Caldatribacterium, Spirochaeta Synergistaceae, Syner-01, [Eubacterium] xylanophilum group, Cellulosilyticum, ADurb.Bin120, and Devosia were significantly upregulated in the HS group. The metabolism of the HS group was considerably upregulated compared with the metabolism of the CON group, according to principal component analysis (PCA) and least-squares discriminant analysis (PLS-DA). HS increased the concentrations of 4-pyridoxic acid, kynurenine, 20-OH-leukotriene B4, and dopamine and decreased the concentration of pyridoxal. In the rabbit gut, these compounds primarily impact the metabolic pathways of vitamin B6, tryptophan, neutrophil activation, and prolactin. 4-Pyridoxic acid, pyridoxal, kynurenine, 20-OH-leukotriene B4, and dopamine are essential inflammatory response markers and oxidative stress.
Antibody-Drug Conjugates Targeting the Human Epidermal Growth Factor Receptor Family in Cancers
Authors: Yu Jinfeng , Fang Tong , Yun Chengyu , Liu Xue , Cai Xiaoqing
Published: February 2022

Members of the human epidermal growth factor receptor (HER) family, which includes HER1 (also known as EGFR), HER2, HER3 and HER4, have played a central role in regulating cell proliferation, survival, differentiation and migration. The overexpression of the HER family has been recognized as one of the most common cellular dysregulation associated with a wide variety of tumor types. Antibody-drug conjugates (ADCs) represent a new and promising class of anticancer therapeutics that combine the cancer specificity of antibodies with cytotoxicity of chemotherapeutic drugs. Two HER2-directed ADCs, trastuzumane-emtansine (T-DM1) and trastuzumab-deruxtecan (DS-8201a), have been approved for HER2-positive metastatic breast cancer by the U.S. Food and Drug Administration (FDA) in 2013 and 2019, respectively. A third HER2-directed ADC, disitamab vedotin (RC48), has been approved for locally advanced or metastatic gastric or gastroesophageal junction cancer by the NMPA (National Medical Products Administration) of China in 2021. A total of 11 ADCs that target HER family receptors (EGFR, HER2 or HER3) are currently under clinical trials. In this review article, we summarize the three approved ADCs (T-DM1, DS-8201a and RC48), together with the investigational EGFR-directed ADCs (ABT-414, MRG003 and M1231), HER2-directed ADCs (SYD985, ARX-788, A166, MRG002, ALT-P7, GQ1001 and SBT6050) and HER3-directed ADC (U3-1402). Lastly, we discuss the major challenges associated with the development of ADCs, and highlight the possible future directions to tackle these challenges.
Genetic and Molecular Evaluation of SQSTM1/p62 on the Neuropathologies of Alzheimer’s Disease
Authors: Dong Wei , Cui Meng-Chao , Hu Wen-Zheng , Zeng Qi , Wang Yi-Long , Zhang Wei , Huang Yue
Published: February 2022

Sequestosome 1 (SQSTM1)/p62 is a multifunctional scaffolding protein and plays a major role in the cellular processes of autophagy, upregulation of which has been shown in several neurodegenerative disorders, including Alzheimer’s disease (AD). To investigate its genetic effects and relationship with AD pathologies, we analyzed the genetic associations of SQSTM1 rs4935 with the risk of AD and the levels of AD biomarkers using the AD Neuroimaging Initiative (ADNI) Database. We further analyzed the distribution pattern of p62 immunoreactivity in relation to AD pathologies in the postmortem human brain tissues from AD and non-AD controls. We found that SQSTM1 rs4935 was not associated with the risk of AD, but its T allele was significantly associated with decreased β-amyloid (1–42) (Aβ42) levels in the cerebral spinal fluid (CSF) of patients with AD (β = −9.336, p = 0.022). In addition, p62 immunoreactivity in AD is increased, but it shows an inverse relationship to Aβ deposition. A small proportion of senile plaques show p62 positive neurites. Our results suggest that SQSTM1/p62 may play an important role in the progression of AD via associations with Aβ42 levels in CSF and Aβ deposition in the brain of patients with AD.
Response Selectivity of the Lateral Posterior Nucleus Axons Projecting to the Mouse Primary Visual Cortex
Authors: Kondo Satoru , Kiyohara Yuko , Ohki Kenichi
Published: February 2022

Neurons in the mouse primary visual cortex (V1) exhibit characteristic response selectivity to visual stimuli, such as orientation, direction and spatial frequency selectivity. Since V1 receives thalamic visual inputs from the lateral geniculate nucleus (LGN) and lateral posterior nucleus (LPN), the response selectivity of the V1 neurons could be influenced mostly by these inputs. However, it remains unclear how these two thalamic inputs contribute to the response selectivity of the V1 neurons. In this study, we examined the orientation, direction and spatial frequency selectivity of the LPN axons projecting to V1 and compared their response selectivity with our previous results of the LGN axons in mice. For this purpose, the genetically encoded calcium indicator, GCaMP6s, was locally expressed in the LPN using the adeno-associated virus (AAV) infection method. Visual stimulations were presented, and axonal imaging was conducted in V1 by two-photon calcium imaging in vivo. We found that LPN axons primarily terminate in layers 1 and 5 and, to a lesser extent, in layers 2/3 and 4 of V1, while LGN axons mainly terminate in layer 4 and, to a lesser extent, in layers 1 and 2/3 of V1. LPN axons send highly orientation- and direction-selective inputs to all the examined layers in V1, whereas LGN axons send highly orientation- and direction-selective inputs to layers 1 and 2/3 but low orientation and direction selective inputs to layer 4 in V1. The distribution of preferred orientation and direction was strongly biased toward specific orientations and directions in LPN axons, while weakly biased to cardinal orientations and directions in LGN axons. In spatial frequency tuning, both the LPN and LGN axons send selective inputs to V1. The distribution of preferred spatial frequency was more diverse in the LPN axons than in the LGN axons. In conclusion, LPN inputs to V1 are functionally different from LGN inputs and may have different roles in the orientation, direction and spatial frequency tuning of the V1 neurons.
A Novel Perspective on the Proactive and Reactive Controls of Executive Function in Chronic Stroke Patients
Authors: Yu Qiuhua , Huang Xiaomin , Zhang Baofeng , Li Zhicheng , Zhang Tao , Hu Ziwei , Ding Minghui , Liang Zhenwen , Lo Wai Leung Ambrose
Published: February 2022

Objectives

To investigate the proactive and reactive control process when executing a complex task in patients with stroke. Proactive control is the preparatory process before the target stimulus, whereas reactive control is an imperative resolution of interference after the target stimulus.

Methods

In total, 17 patients with chronic stroke and 17 healthy individuals were recruited. The proactive and reactive control of executive function was assessed by the task-switching paradigm and the AX version of the Continuous Performance Task (AX-CPT). The general executive function was assessed by Color Trial Test (CTT) and Stroop Test. The behavioral data of the task-switching paradigm were analyzed by a three-way repeated-measures ANOVA, and the AX-CPT data were analyzed by two-way repeated-measures ANOVA.

Results

For efficiency scores in the task-switching paradigm, trial (repeat vs. switch) × group (stroke or control group) interaction effect was significant. Post-hoc analysis on trial × group effect showed a significant between-trial difference in accuracy rates in the repeat trial in the control group regardless of 100 or 50% validity. For the AX-CPT, the main effects of condition and group on response time were statistically significant. The interaction effect of condition (AY or BX) × group (stroke or control group) was also significant. Post-hoc analysis for condition × group indicated that the stroke group had a significantly longer response time in the BX condition than the control group and longer completion time in CTT2 and larger word interference for completion time in the Stroop test than the control cohort.

Conclusions

Post-stroke survivors showed deficits in the performance of proactive control but not in the performance of reactive control. Deficits in proactive control may be related to the impairment of working memory. Interventions that focus on proactive control may result in improved clinical outcomes.
Comparison of the Efficacy of D2 Gastrectomy Plus Liver Radiofrequency Combined With Chemotherapy Versus Chemotherapy Alone in the Treatment of Advanced Gastric Cancer With Unresectable Synchronous Liver Metastases: A Multicenter Randomized Controlled Trial Protocol
Authors: Wang Weidong , Gao Ruiqi , Yu Pengfei , Mo Zhenchang , Dong Danhong , Yang Xisheng , Li Xiaohua , Ji Gang
Published: February 2022

Background

Whether patients with advanced gastric cancer with unresectable synchronous liver metastases require surgical treatment remains a controversial topic among surgeons. Recently, an open-label multicenter, international RCT study show that compared with chemotherapy alone, gastric resection combined with chemotherapy had no survival advantage for advanced gastric cancer with unresectable synchronous liver metastases. A limitation of this study was that gastrectomy for gastric cancers was restricted to D1 lymphadenectomy and no metastatic lesions were removed. Whether D2 gastrectomy plus liver radiofrequency plus postoperative chemotherapy could provide benefits to these patients is worthy of further confirmation by high-level evidence-based medicine.

Methods/Design

This study will investigate the efficacy of D2 gastrectomy plus liver radiofrequency plus postoperative chemotherapy compared to chemotherapy alone in a prospective, multicenter, randomized controlled trial that will enroll 200 patients who have advanced gastric cancer with unresectable synchronous liver metastases. The patients will be randomly divided into two groups: the test group (D2 gastrectomy plus liver radiofrequency plus postoperative chemotherapy, n=100) and the control group (chemotherapy alone, n=100). The patients’ general information, past medical history, laboratory tests, imaging results, surgery details, and chemotherapy details will be recorded and analysed. The overall survival (OS) will be recorded as primary endpoints. Progression-free survival (PFS) and the total incidence of complications will be recorded as secondary endpoints.

Discussion

This study is to establish a multicentre randomized controlled trial to compare the efficacy of D2 gastrectomy plus liver radiofrequency combined with postoperative chemotherapy versus chemotherapy alone.

Trial Registration

Chinese Clinical Trial Registry, Approved No. of ethics committee:ChiECRCT20200331. Registered on 15 November 2020. Registration number:ChiCTR2000039964. The study has received full ethical and institutional approval.

Advantages and Limitations of this Study

This is the first clinical trial that will provide evidence on the efficacy of D2 gastrectomy plus liver radiofrequency combined with chemotherapy versus chemotherapy alone for the treatment of advanced gastric cancer with unresectable synchronous liver metastases. A prospective RCT with 200 patients who have advanced gastric cancer with unresectable synchronous liver metastases.

Clinical Trial Registration

[https://www.chictr.org.cn/], identifier ChiCTR2000039964.
Genomic And Tumor Microenvironment Differences Between Cell Cycle Progression Pathway Altered/Non-Altered Patients With Lung Adenocarcinoma
Authors: Shan Guangyao , Bi Guoshu , Bian Yunyi , Valeria Besskaya , Zeng Dejun , Zhang Huan , Yao Guangyu , Zhang Yi , Fan Hong , Zhan Cheng
Published: February 2022

Background

Identified as a hallmark of cancer, the dysregulated cell cycle progression plays an important role in the promotion and progression of lung adenocarcinoma (LUAD). However, the genomic and microenvironment differences between cell cycle progression pathway altered/non-altered LUAD patients remain to be elucidated.

Materials and Methods

Data of this study were obtained from The Cancer Genome Atlas (TCGA), including simple nucleotide variation, copy number variation (CNV), RNA-seq gene expression, miRNA expression, survival, and clinical information. Besides, 34 LUAD samples from our institution were used as a validation cohort. Differentially expressed genes (DEGs), enrichment analysis, and immune cell infiltration were detected. At last, we built a LASSO-binary Logistic regression model to predict the cell-cycle-related gene mutation (CDKN2A, CCND1, CDK4, CCNE1, and RB1) in LUAD patients and further verified it in the samples from our institution.

Results

Based on the cell cycle progression pathway status, the LUAD patients were divided into the mutation (n=322) and wild (n=46) groups. Compared to the wild group, the mutation group had a higher mutational load and CNV. Among the 16684 protein-coding genes analyzed, 302 were upregulated, and 354 were downregulated in the mutation group. Enrichment analysis indicated that these DEGs were closely related to metabolism items. After performing immune cell infiltration analysis of 22 immune cells, we found the proportion of 5 immune cells such as monocytes (P<0.01) and dendritic cells (P<0.01) were higher in the wild group. Finally, a cell-cycle-related 15-signature model was built by LASSO-Logistic regression analysis, which could predict the cell cycle progression pathway-related gene mutation (CDKN2A, CCND1, CDK4, CCNE1, and RB1) in LUAD patients. The validation cohorts showed the sensitivity and specificity of this model were 0.667 and 0.929, respectively.

Conclusion

The genomic and microenvironment characteristics differed between the cell cycle progression pathway altered/non-altered patients with LUAD. Our findings may provide new insight into personalized treatment for LUAD patients.
Exploring the Experiences of Co-morbid Pain and Depression in Older African American Women and Their Preferred Management Strategies
Authors: Drazich Brittany F. , Jenkins Emerald , Nkimbeng Manka , Abshire Saylor Martha , Szanton Sarah L. , Wright Rebecca , Beach Mary Catherine , Taylor Janiece L.
Published: February 2022

The intersection of race, gender, and age places older African American women at an increased risk for untreated physical pain and depression that can significantly diminish their quality of life. The objectives of this study were to (1) explore older African American women's perceptions of pain and depressive symptoms and how these symptoms influence each other, and (2) explore effective pain and depression alleviation strategies used by the women. We conducted five focus groups with older African American women (N = 18). We used deductive coding to analyze focus group transcripts and qualitative description to summarize themes. We identified five major themes: (1) Spiritual Suffering from Linked Pain and Depression, (2) Lack of Understanding from Healthcare Providers, (3) Push Through and Live Through, (4) Medications Not Worth the Risk and, (5) Strategies for Pain and Depression. This study offers insight into the experiences of pain and depression in older African American women, and alleviation strategies they perceive as effective. These qualitative findings may be used to inform interventions for older African American women who experience pain and depressive symptoms.
BGIG10116_34868: A Newly Discovered Gene Regulating Ejaculation Function
Authors: Gao Jingjing , Gao Rui , Li Hu , Liu Xi , Gao Pan , Du Junhua , Jiang Hui , Zhang Xiansheng
Published: February 2022

Ejaculation is a complex biphasic process involving a series of neurophysiological activities, such as the contraction of a large number of muscle groups and the ejaculation of semen from the urethra anterior. Due to the complexity of the process, many related factors have not been fully clarified, resulting in ejaculation dysfunction. As a common ejaculation dysfunction, lifelong premature ejaculation (LPE) is a problem for many people. Notably, gene polymorphism might play an important role in the etiology of LPE. However, the quest for identifying the actual genetic loci that contribute to LPE etiology has not been successful. Due to discrepancies in the design and methods of research, the correlation of most reports was not obtained in subjective replication experiments, and the conclusions may be inconsistent. In our study, three groups of ejaculation rats, namely, “rapid, normal, and delayed,” were selected based on the animal model of premature ejaculation (PE) in rats and the theory of ejaculation. Among them, the rats in the “rapid” ejaculation group can be used to stimulate humans with PE. Subsequently, we used the rat brain tissue for whole-transcriptome sequencing to screen the differential genes among the three groups. We tried to identify the actual genetic loci that contribute to PE etiology and provide a theoretical basis for the targeted therapy of PE.
The Factor Structure and External Validity of the COPE 60 Inventory in Slovak Translation
Authors: Halamová Júlia , Kanovský Martin , Krizova Katarina , Greškovičová Katarína , Strnádelová Bronislava , Baránková Martina
Published: February 2022

The COPE Inventory (Carver et al., 1989) is the most frequently used measure of coping; yet previous studies examining its factor structure yielded mixed results. The purpose of the current study, therefore, was to validate the factor structure of the COPE Inventory in a representative sample of over 2,000 adults in Slovakia. Our second goal was to evaluate the external validity of the COPE inventory, which has not been done before. Firstly, we performed the exploratory factor analysis (EFA) with half of the sample. Subsequently, we performed the confirmatory factor analysis with the second half of the sample. Both factor analyses with 15 factor solutions showed excellent fit with the data. Additionally, we performed a hierarchical factor analysis with fifteen first-order factors (acceptance, active coping, behavioral disengagement, denial, seeking emotional support, humor, seeking instrumental support, mental disengagement, planning, positive reinterpretation, religion, restraint, substance use, suppression of competing activities, and venting) and three second-order factors (active coping, social emotional coping, and avoidance coping) which showed good fit with the data. Moreover, the COPE Inventory’s external validity was evaluated using consensual qualitative research (CQR) analysis on data collected by in-depth interviews. Categories of coping created using CQR corresponded with all COPE first-order factors. Moreover, we identified two additional first-order factors that were not present in the COPE Inventory: self-care and care for others. Our study shows that the Slovak translation of the COPE Inventory is a reliable, externally valid, and well-structured instrument for measuring coping in the Slovak population.
Student Subjectivity in the Marketised University
Authors: Bunn Geoff , Langer Susanne , Fellows Nina K.
Published: February 2022

We present data from an exploratory qualitative interview-based pedagogical research project on the development of student agency in higher education. Our aim was to respond to Nick Zepke’s claim that what is often missing from the current neoliberal discourse of higher education ‘is students having a voice in what and how they learn and how they can action their voice in the wider community as agentic citizens.’ Informed by Lacanian discourse analysis, our project investigated the opportunities and threats facing some of our undergraduate students as they struggled to exercise agency and develop autonomy in the marketised university. Repeat interviews (n = 15) with final year students focussed on the psychosocial categories of power, affect, intersubjectivity and desire. The analysis was guided by Lacan’s theory of the four discourses, an account of the vicissitudes of agency. We found that students can move between discourses depending on the extent to which their agency (operationalised here as Lacan’s ‘object cause of desire,’ the objet petit a) was enabled or thwarted. Our critique of the metaphor of the ‘student journey’ addresses the implications for learning and teaching and the university’s mission to develop its students in light of perceived commercial pressures.
Coronavirus Disease 2019 Safety Measures for Sustainable Tourism: The Mediating Effect of Tourist Trust
Authors: Sarfraz Muddassar , Raza Mohsin , Khalid Rimsha , Ivascu Larisa , Albasher Gadah , Ozturk Ilknur
Published: February 2022

Coronavirus disease 2019 (COVID-19) pandemic is continuing to have severe effects on tourism-related industries, as safety precautions have become essential to follow. Based on this, this study aims to explore the role of perceptions of the tourist of safety in tourism destination choice with the mediating effect of tourist trust (TT) in the context of the Chinese tourism sector. In addition, this study considers improvements to safety measures for sustainable tourism and the benefits of the technology transformation in the travel industry because of COVID-19. For this study, a quantitative approach was used, and data were collected through convenient sampling. The questionnaire was measured on a 5-point Likert scale, and a cross-sectional approach was adopted for data analysis. The findings of this study show that the effect of the perceived safety of the social environment, perceived safety of facility and equipment elements, perceived safety of human elements, perceived safety of management elements, and perceived safety of natural environments is significant and positive on the tourist destination choice (TDC). In addition, TT is a significant mediator between these elements and TDC. Furthermore, this study concluded that COVID-19 had increased travel anxiety, with particularly negative effects on the Chinese tourism sector, but that the adoption of perceived safety measures could be beneficial in regaining TT for traveling, eventually giving tourists confidence in choosing their traveling destination.
Use of Virtual Reality in Psychiatric Diagnostic Assessments: A Systematic Review
Authors: Geraets Chris N. W. , Wallinius Märta , Sygel Kristina
Published: February 2022

Background

Technological developments such as Virtual reality (VR) provide new opportunities to extend and innovate mental healthcare. VR as a tool for clinical assessment has been described as promising, as it can enable real-time assessment within real-like environments or contexts as opposed to self-report and behavioral tasks in laboratory settings.

Objective

With this systematic review we aimed to provide an overview of recent studies using VR in the assessment of psychiatric disorders.

Methods

A systematic search was performed using Pubmed, Embase, PsycInfo, and Web of Science between 2016 and 2020. Studies were included if they used immersive VR, concerned assessment of psychiatric symptoms/disorders, and included adult patients with psychiatric disorders.

Results

The search resulted in 3,163 potentially eligible articles, from which a total of 27 studies fulfilled inclusion criteria. Most studies considered anxiety (n = 7), addictive, (n = 7), or psychotic disorders (n = 5). Regarding ADHD (n = 3), PTSD (n = 3), and pedophilic disorder (n = 1), a few studies had been performed since 2016. The majority of the included studies compared patient groups to healthy control groups.

Discussion

Recent studies on VR-assisted psychiatric assessments have been conducted to validate VR environments, to assess symptoms for diagnostics or therapy goals, search for biomarkers, and to gain knowledge on psychiatric disorders. VR tasks were able to detect some difference between patient and healthy control groups, mainly with regard to self-report measures. Despite previous, promising prospects, the use of VR as a tool in clinical assessments must still be considered as a field in need of continued developments and evaluations.

Systematic Review Registration

www.crd.york.ac.uk/prospero, identifier: CRD42021233772.