bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knockdown of SPON2 inhibits the growth of triple-negative breast cancer
Authors: Hu Xueyi , Su Caiwu , Wei Jian 
Published: March 2023

ObjectiveSpondin-2 (SPON2) is highly expressed in a variety of tumors and has been associated with poor prognosis, but the relationship to triple-negative breast cancer (TNBC) is unclear. The aim of this study is to investigate the expression of SPON2 in TNBC and its function.MethodsImmunohistochemistry was used to detect the expression of the SPON2 protein in TNBC and in normal tissue adjacent to cancer and breast fibroadenoma. The GEO database GSE76275 dataset was used to study the expression of SPON2 mRNA in TNBC and non-TNBC. ​The expression of SPON2 mRNA was detected by qPCR in TNBC cells MDA-MB-231, non-TNBC breast cancer cells MCF-7, and normal breast cells MCF-10A. ​Kaplan Meier-Plotter database was used to analyze the relationship between SPON2 expression and TNBC prognosis. ​ShRNA lentivirus was used to knock down high expression of SPON2 in TNBC cells. The effects of knockdown of SPON2 expression on the proliferation, migration, invasion, apoptosis, and subcutaneous tumorigenic ability of TNBC cells in nude mice were analyzed using CCK8, clone formation assay, scratch assay, transwell migration assay, transwell invasion assay, Hoechst apoptosis assay, and tumorigenic ability in nude mice. Transcriptome sequencing of TNBC cells with knockdown SPON2 expression. ​In combination with the GEO database, GO and KEGG analyses were performed, and psychophysiological interaction Protein-Protein Interaction Networks (PPI) analysis was performed for transcriptome sequencing of the differentially expressed genes. ​The changes in the expression of PI3K-ATK pathway proteins after SPON2 knockdown were detected by Western blot.ResultsOur study shows that upregulation of SPON2 in TNBC is associated with poorer patient outcomes. Knockdown of SPON2 inhibited TNBC cell proliferation, clone formation, migration, invasion, and tumorigenic ability and promoted apoptosis. Knockdown of SPON2 up-regulated TNBC cell adhesion and down-regulated PI3K-ATK pathway, and PPI results showed that CCL2 was the key protein.ConclusionsSPON2 may be a valuable biomarker for the diagnosis and prognosis of TNBC and is a potential therapeutic target for TNBC.
Using optogenetics to dissect rod inputs to OFF ganglion cells in the mouse retina
Authors: Sladek Asia L. , Thoreson Wallace B. 
Published: March 2023

IntroductionLight responses of rod photoreceptor cells traverse the retina through three pathways. The primary pathway involves synapses from rods to ON-type rod bipolar cells with OFF signals reaching retinal ganglion cells (RGCs) via sign-inverting glycinergic synapses. Secondly, rod signals can enter cones through gap junctions. Finally, rods can synapse directly onto cone OFF bipolar cells.MethodsTo analyze these pathways, we obtained whole cell recordings from OFF-type α RGCs in mouse retinas while expressing channelrhodopsin-2 in rods and/or cones.ResultsOptogenetic stimulation of rods or cones evoked large fast currents in OFF RGCs. Blocking the primary rod pathway with L-AP4 and/or strychnine reduced rod-driven optogenetic currents in OFF RGCs by ~1/3. Blocking kainate receptors of OFF cone bipolar cells suppressed both rod- and cone-driven optogenetic currents in OFF RGCs. Inhibiting gap junctions between rods and cones with mecloflenamic acid or quinpirole reduced rod-driven responses in OFF RGCs. Eliminating the exocytotic Ca2+ sensor, synaptotagmin 1 (Syt1), from cones abolished cone-driven optogenetic responses in RGCs. Rod-driven currents were not significantly reduced after isolating the secondary pathway by eliminating Syt1 and synaptotagmin 7 (Syt7) to block synaptic release from rods. Eliminating Syt1 from both rods and cones abolished responses to optogenetic stimulation. In Cx36 KO retinas lacking rod-cone gap junctions, optogenetic activation of rods evoked small and slow responses in most OFF RGCs suggesting rod signals reached them through an indirect pathway. Two OFF cells showed faster responses consistent with more direct input from cone OFF bipolar cells.DiscussionThese data show that the secondary rod pathway supports robust inputs into OFF α RGCs and suggests the tertiary pathway recruits both direct and indirect inputs.
A Canadian, retrospective, multicenter experience with selexipag for a heterogeneous group of pediatric pulmonary hypertension patients
Authors: Youssef David , Richards Susan , Lague Sabine , Sheppard Catherine , Smith Jenna , Vorhies Erika , Hosking Martin , Pietrosanu Matthew , Bates Angela 
Published: March 2023

IntroductionSelexipag, an oral nonprostanoid prostaglandin receptor agonist, has led to reduced morbidity and mortality in adults with pulmonary arterial hypertension (PAH). While the adult literature has been extrapolated to suggest selexipag as an oral treatment for severe pediatric pulmonary hypertension (PH), longitudinal, multicenter data on the benefits of selexipag in this population are lacking. The purpose of this study is to present a longitudinal, multicentre experience with selexipag in a relatively large cohort of pediatric PH patients and add to the existing selexipag literature.Materials and methodsWe performed a retrospective, multicenter review describing the clinical outcomes of pediatric PH patients receiving selexipag in addition to standard oral pulmonary vasodilator therapy across three Canadian centers between January 2005 and June 2021.ResultsTwenty-four pediatric patients (fifteen female) with a mean age of 9.7 (range 2.0–15.5) years were included. Of this cohort, eighteen (75.0%) were in group 1, one (4.2%) was in group 2, four (16.7%) were in group 3, and one (4.2%) was in group 4. Twenty-two (91.7%) patients were on dual PH therapy after six months. Dosing was targeted to achieve 20–30 mcg/kg/dose orally every twelve hours. Median dose after twelve months was 30 mcg/kg/dose. Twelve months following selexipag initiation, median decreases of 0.2 cm in tricuspid annular plane systolic excursion, 3.5 mmHg in right-ventricular systolic pressure, and 6.1 mmHg in mean pulmonary arterial pressure were observed; none of these changes were statistically significant. Three patients died, one clinically deteriorated and required admission to a pediatric intensive care unit, ten had gastrointestinal symptoms, and three had flushing.ConclusionSelexipag appears to be a safe and effective adjunctive therapy for pediatric PH patients and has a tolerable adverse effect profile aside from gastrointestinal disturbances. Additional prospective studies of changes in hemodynamics and functional classification over a longer period and with a larger sample are needed. Future research should aim to identify subgroups that stand to benefit from the addition of selexipag as well as optimal timing and dosing for the pediatric population.
A horse or a zebra? Unusual manifestations of common cutaneous infections in primary immunodeficiency pediatric patients
Authors: Ollech Ayelet , Simon Amos J , Lev Atar , Stauber Tali , Sherman Gilad , Solomon Michal , Barzilai Aviv , Somech Raz , Greenberger Shoshana 
Published: March 2023

BackgroundPatients with primary immunodeficiency disorders (PIDs) often suffer from recurrent infections because of their inappropriate immune response to both common and less common pathogens. These patients may present with unique and severe cutaneous infectious manifestations that are not common in healthy individuals and may be more challenging to diagnose and treat.ObjectiveTo describe a cohort of patients with PIDs with atypical presentations of skin infections, who posed a diagnostic and/or therapeutic challenge.MethodsThis is a retrospective study of pediatric patients with PID with atypical presentations of infections, who were treated at the immunodeficiency specialty clinic and the pediatric dermatology clinic at the Sheba Medical Center between September 2012 and August 2022. Epidemiologic data, PID diagnosis, infectious etiology, presentation, course, and treatment were recorded.ResultsEight children with a diagnosis of PID were included, five of whom were boys. The average age at PID diagnosis was 1.7 (±SD 3.2) years. The average age of cutaneous infection was 6.9 (±SD 5.9) years. Three patients were born to consanguineous parents. The PIDs included the following: common variable immunodeficiency, severe combined immunodeficiency, DOCK8 deficiency, ataxia telangiectasia, CARD11 deficiency, MALT1 deficiency, chronic granulomatous disease, and a combined cellular and humoral immunodeficiency syndrome of unknown etiology. The infections included the following: ulcerative-hemorrhagic varicella-zoster virus (two cases) atypical fungal and bacterial infections, resistant Norwegian scabies, giant perianal verrucae (two cases), and diffuse molluscum contagiosum.ConclusionsIn this case series, we present unusual manifestations of infectious skin diseases in pediatric patients with PID. In some of the cases, recognition of the infectious process prompted life-saving treatment. Increasing familiarity with these dermatological manifestations, as well as keeping a high index of suspicion, is important to enabling early diagnosis of cutaneous infections in PIDs and initiation of prompt suitable treatment.
Banzhilian formula alleviates psoriasis-like lesions via the LCN2/MMP-9 axis based on transcriptome analysis
Authors: Xing Meng , Yan Xiaoning , Guo Jiangtao , Li Wenbin , Li ZhangJun , Dong Chun , Guo Jiao , Qu Keshen , Luo Ying 
Published: March 2023

Introduction: Oral Banzhilian formula (BZLF) is effective in the clinical treatment of psoriasis. However, the effectiveness and mechanism of different drug delivery routes deserve further study.Methods: First, we established the mouse model of psoriasis using imiquimod (IMQ), and high-performance liquid chromatography (HPLC) was used for the quality control of BZLF. Secondly, Total RNA Sequencing and bioinformatics analysis were used to explore the regulatory mechanism of BZLF in improving psoriatic lesions. Finally, further verification was based on animal experiments.Results: we externally applied BZLF for skin lesions in an imiquimod-induced psoriasis mouse model and found that BZLF alleviated psoriasis-like skin lesions while inhibiting the expression of Ki67 and inflammatory factors (Il17a, Tnf-α, S100a7 and Cxcl1) in skin lesions. Transcriptome sequencing results suggested that BZLF inhibited signalling pathways closely related to psoriatic inflammation, such as the IL-17 signalling pathway, chemokine signalling pathway, TNF signalling pathway, and NF-kappa B signalling pathway, and the protein-protein interaction (PPI) network identified LCN2 as one of the core target genes and screened out its regulated downstream gene MMP9.Discussion: Our findings suggest that the anti-psoriatic mechanism of BZLF involved in downregulating the LCN2/MMP-9 axis.
Pharmacogenetic association of the NR1H3 promoter variant with antihypertensive response among patients with hypertension: A longitudinal study
Authors: Chen Yu , Han Yuqing , Wu Yiyi , Hui Rutai , Yang Yunyun , Zhong Yixuan , Zhang Shuyuan , Zhang Weili 
Published: March 2023

Background: The genetic factors in assessing therapeutic efficacy and predicting antihypertensive drug response are unclear. Therefore, this study aims to identify the associations between variants and antihypertensive drug response.Methods: A longitudinal study including 1837 hypertensive patients was conducted in Northern China and followed up for a median 2.24 years. The associations of 11 candidate variants with blood pressure changes in response to antihypertensive drugs and with the risk of cardiovascular events during the follow-up were examined. The dual-luciferase assay was carried out to assess the effect of genetic variants on gene transcriptional activity.Results: The variant rs11039149A&gt;G in the promoter of nuclear receptor subfamily 1 group H member 3 (NR1H3) was associated with the change in systolic blood pressure (ΔSBP) in response to calcium channel blockers (CCBs) monotherapy. Patients carrying rs11039149AG genotype showed a significant increase of systolic blood pressure (SBP) at follow-up compared with AA carriers, and the difference of ΔSBP between AG and AA carriers was 5.94 mm Hg (95%CI: 2.09–9.78, p = 0.002). In 1,184 patients with CCBs therapy, SBP levels decreased in AA carriers, but increased in AG carriers, the difference of ΔSBP between AG and AA carriers was 8.04 mm Hg (95%CI: 3.28–12.81, p = 0.001). Further analysis in 359 patients with CCBs monotherapy, the difference of ΔSBP between AG and AA carriers was 15.25 mm Hg (95%CI: 6.48–24.02, p = 0.001). However, there was no significant difference in ΔSBP between AG and AA carriers with CCBs multitherapy. The rs11039149A&gt;G was not associated with the cardiovascular events incidence during the follow-up. Additionally, transcriptional factor forkhead box C1 (FOXC1) bound to the NR1H3 promoter containing rs11039149A and significantly increased the transcriptional activity, while rs11039149 A to G change led to a loss-of-function and disabled FOXC1 binding. For the other 10 variants, associations with blood pressure changes or risk of cardiovascular events were not observed.Conclusion: Hypertensive patients with rs11039149AG genotype in the NR1H3 gene have a significant worse SBP control in response to CCBs monotherapy compared with AA carriers. Our findings suggest that the NR1H3 gene might act as a promising genetic factor to affect individual sensitivity to antihypertensive drugs.
Measuring affect and complex working memory in natural and urban environments
Authors: Scott Emily E. , Crabtree Kaedyn W. , McDonnell Amy S. , LoTemplio Sara B. , McNay Glen D. , Strayer David L. 
Published: March 2023

IntroductionResearch suggests that spending time in natural environments is associated with cognitive and affective benefits, while increased use of technology and time spent in urban environments are associated with depletion of cognitive resources and an increasing prevalence of mental illness. Attention Restoration Theory suggests that exposure to natural environments can restore depleted attentional resources and thereby improve cognitive functioning and mood. Specifically, recent meta-analyses have revealed that the most improved cognitive abilities after nature exposure include selective attention, working memory, and cognitive flexibility.MethodsWhile existing studies examined these cognitive abilities, few have examined the Operation Span (OSPAN), a complex measure of working memory capacity. Therefore, the current study (N = 100) compared performance on the OSPAN and self-reported mood using the Positive and Negative Affect Schedule before and after a 30-min walk in a natural or urban environment.ResultsResults from the study showed that both groups exhibited an increase in positive affect and a decrease in negative affect, suggesting that going outside for a walk can boost mood regardless of environment type. Inconsistent with past work, there were no significant changes in OSPAN scores before and after the walk for either environment type.DiscussionFuture studies should analyze how the length of time spent in the environment, certain characteristics of the environment, and individual differences in connectedness to nature may impact attention restoration to gain insight on nature’s ability to improve our affect and cognition.
“Our City Will Be the First to Hold Both Summer and Winter Olympics”: A comparative analysis of how media coverage and public opinion were framed on social media in the lead up to the Beijing 2022 winter Olympic games
Authors: Yang Zesheng , Ruan Yang , Zhang Jianing 
Published: March 2023

IntroductionBeijing is the first city to host both the Summer and Winter Olympic Games. Mega sporting events such as the Olympic Games, which attract mass audiences, benefit greatly from social media. This article examines how the news coverage and public opinion about the Beijing 2022 were articulated on social media in the lead up to the Beijing 2022.MethodWe employed computational content analysis to examine 9,439 individual posts and 450 official media posts that appeared before the Beijing 2022 Olympics. We also used ROSTCM6 to investigate the sentiment of official media and public opinion toward Beijing 2022.ResultsThe results of this study reveal that members of public are more inclined to highlight certain aspects of Beijing 2022 based on their individual perspectives. Official media, whose work generally aligns with the government’s interests. Through a sentiment analysis of these posts, we found strongly positive attitudes concerning Beijing 2022 among the Chinese public and the media.DiscussionOur results provide ample evidence of an overall relative convergence of positions between public opinion and news coverage about the Beijing 2022, despite their divergences. This study indicates that social media presents itself as a space for broader public statements, and empowers ordinary people to discuss China’s social issues of concern. Meanwhile, official media represents the government’s position, strategically framing Beijing 2022 as a landmark event in the new era of China.
Cognition and social functioning in first episode psychosis: A systematic review of longitudinal studies
Authors: Montaner-Ferrer Maria José , Gadea Marien , Sanjuán Julio 
Published: March 2023

IntroductionThis systematic review aimed to answer whether we can predict subsequent social functioning in first episode psychosis (FEP) by means of an initial cognitive examination. In order to do this, we gathered longitudinal studies which evaluated neurocognition and/or social cognition regarding their impact on long-term social functioning of FEP patients.MethodsThe MOOSE method was employed and 28 studies covering data from a total of 2572 patients with longitudinal trajectories from 2 months to 5 years were reviewed.ResultsIn general, cognitive deficits impacted on the social functioning of the FEP patients across the time. The neurocognitive domains which most closely predicted social functioning were processing speed, sustained attention and working memory. An overall cognitive dysfunction, low IQ and the academic trajectory were also found predictive. Regarding social cognition, the findings were not unanimous.DiscussionIn addition of the impact of each variable, several of the articles found a complex relationship between social cognition, neurocognition, social functioning and negative symptoms, pointing social cognition as a modulator of neurocognition but being modulated as well by negative symptoms. The principal clinical implication of this review is that the initial assessment of FEP patients and their rehabilitation must take cognition into account.
The impact of perceived social support on sleep quality in a sample of patients undergoing hemodialysis in Somalia
Authors: Mohamed Nur Adam , Mohamed Yusuf Abdirisak , Eraslan Asir , Kose Samet 
Published: March 2023

ObjectiveThe main objective of the present study is to examine the relationship between perceived social support and the quality of sleep and to determine the predictors of sleep quality in a sample of patients undergoing hemodialysis (HD) in Somalia.MethodsA sample of 200 patients with end-stage renal disease (ESRD) who were undergoing hemodialysis treatment approximately two to three times a week were included. All participants were administered a sociodemographic data form, the Multidimensional Scale of Perceived Social Support (MSPSS), the Insomnia Severity Index (ISI), and the Pittsburgh Sleep Quality Index (PSQI). Patients undergoing HD for less than 3 months prior to the study date were excluded.ResultsOf the patients undergoing hemodialysis, 200 patients aged between 18 and 68 years (mean = 52.29; SD = 14.13) gave consent and participated in the study. Sixty-three subjects (31.5%) reported poor sleep quality, defined as having a total PSQI score &gt; 5. Forty-one subjects (20.5%) reported clinically significant (moderate-to-severe) insomnia. The majority of our patients undergoing HD reported remarkably high family support, but low friends and significant other support. Poor sleep quality significantly correlated with perceived friends’ support and perceived total social support. While perceived family support significantly correlated with both family income and the duration of chronic kidney disease (CKD), perceived friends’ support significantly correlated with age and family income. Hierarchical regression analyses showed that perceived family support and friends’ support were significant predictors of poor sleep quality. Perceived friends’ support was a significant predictor of insomnia severity. Perceived family support was a significant predictor of subjective sleep quality and sleep duration. Perceived friends’ support was a significant predictor of subjective sleep quality, sleep duration, sleep latency, sleep disturbance, and daytime dysfunction. Family income was a significant predictor of sleep duration. Age and gender were significant predictors of sleep efficiency. The duration of CKD and duration of HD were significant predictors of sleep disturbance.ConclusionThis present study has highlighted the value of family as a principal support system in Somalian culture. Understanding the impact of perceived social support on the quality of sleep in patients undergoing HD will help healthcare providers and social services to focus on and improve the social support systems of the patients as an integral part of their treatment.
Drinking alcohol to cope with hyperactive ADHD? Self-reports vs. continuous performance test in patients with ADHD and/or alcohol use disorder
Authors: Luderer Mathias , Seidt Johanna , Gerhardt Sarah , Hoffmann Sabine , Vollstädt-Klein Sabine , Reif Andreas , Sobanski Esther 
Published: March 2023

RationaleAttention deficit/hyperactivity disorder (ADHD) is common in alcohol use disorder (AUD). Continuous performance tests (CPTs) allow to measure ADHD related deficits in a laboratory setting. Most studies on this topic focused on CPTs measuring inattention or impulsivity, disregarding hyperactivity as one of the core symptoms of ADHD.MethodsWe examined N = 47 in three groups (ADHD N = 19; AUD N = 16; ADHD + AUD N = 12) with questionnaires on ADHD core symptoms, executive functioning (EF), mind wandering, and quality of life (QoL). N = 46 (ADHD N = 16; AUD N = 16; ADHD + AUD N = 14) were examined with a CPT (QbTest®) that also measures motor activity objectively.ResultsInattention and impulsivity were significantly increased in AUD vs. ADHD and in AUD vs. ADHD + AUD. Hyperactivity was significantly higher in ADHD + AUD vs. ADHD and ADHD + AUD vs. AUD, but not in ADHD vs. AUD. EF was lower in both ADHD groups vs. AUD. Mind wandering was increased in both ADHD groups vs. AUD. QoL was significantly lower in ADHD + AUD compared to AUD. In contrast, results of the QbTest were not significantly different between groups.ConclusionQuestionnaires are more useful in assessing ADHD core symptoms than the QbTest®. Hyperactivity appears to be a relevant symptom in ADHD + AUD, suggesting a possible pathway from ADHD to AUD. The lower QoL in ADHD + AUD emphasizes the need for routine screening, diagnostic procedures and treatment strategies for this patient group.