bluuebunny/crossref_metadata_2025 huggingface dataset:
From Climate Change to Pandemics: Decision Science Can Help Scientists Have Impact
Authors: Baker Christopher M. , Campbell Patricia T. , Chades Iadine , Dean Angela J. , Hester Susan M. , Holden Matthew H. , McCaw James M. , McVernon Jodie , Moss Robert , Shearer Freya M. , Possingham Hugh P.
Published: February 2022

Scientific knowledge and advances are a cornerstone of modern society. They improve our understanding of the world we live in and help us navigate global challenges including emerging infectious diseases, climate change and the biodiversity crisis. However, there is a perpetual challenge in translating scientific insight into policy. Many articles explain how to better bridge the gap through improved communication and engagement, but we believe that communication and engagement are only one part of the puzzle. There is a fundamental tension between science and policy because scientific endeavors are rightfully grounded in discovery, but policymakers formulate problems in terms of objectives, actions and outcomes. Decision science provides a solution by framing scientific questions in a way that is beneficial to policy development, facilitating scientists’ contribution to public discussion and policy. At its core, decision science is a field that aims to pinpoint evidence-based management strategies by focussing on those objectives, actions, and outcomes defined through the policy process. The importance of scientific discovery here is in linking actions to outcomes, helping decision-makers determine which actions best meet their objectives. In this paper we explain how problems can be formulated through the structured decision-making process. We give our vision for what decision science may grow to be, describing current gaps in methodology and application. By better understanding and engaging with the decision-making processes, scientists can have greater impact and make stronger contributions to important societal problems.
Prognostication of Pancreatic Cancer Using The Cancer Genome Atlas Based Ferroptosis-Related Long Non-Coding RNAs
Authors: Li Jiayu , Zhang Jinghui , Tao Shuiliang , Hong Jiaze , Zhang Yuyan , Chen Weiyan
Published: February 2022

Background: Long non-coding RNAs (lncRNAs) are key regulators of pancreatic cancer development and are involved in ferroptosis regulation. LncRNA transcript levels serve as a prognostic factor for pancreatic cancer. Therefore, identifying ferroptosis-related lncRNAs (FRLs) with prognostic value in pancreatic cancer is critical.

Methods: In this study, FRLs were identified by combining The Cancer Genome Atlas (TCGA) and FerrDb databases. For training cohort, univariate Cox, Lasso, and multivariate Cox regression analyses were applied to identify prognosis FRLs and then construct a prognostic FRLs signature. Testing cohort and entire cohort were applied to validate the prognostic signature. Moreover, the nomogram was performed to predict prognosis at different clinicopathological stages and risk scores. A co-expression network with 76 lncRNA-mRNA targets was constructed.

Results: Univariate Cox analysis was performed to analyze the prognostic value of 193 lncRNAs. Furthermore, the least absolute shrinkage and selection operator and the multivariate Cox analysis were used to assess the prognostic value of these ferroptosis-related lncRNAs. A prognostic risk model, of six lncRNAs, including LINC01705, AC068620.2, TRAF3IP2-AS1, AC092171.2, AC099850.3, and MIR193BHG was constructed. The Kaplan Meier (KM) and time-related receiver operating characteristic (ROC) curve analysis were performed to calculate overall survival and compare high- and low-risk groups. There was also a significant difference in survival time between the high-risk and low-risk groups for the testing cohort and the entire cohort, with AUCs of .723, .753, respectively. Combined with clinicopathological characteristics, the risk model was validated as a new independent prognostic factor for pancreatic adenocarcinoma through univariate and multivariate Cox regression. Moreover, a nomogram showed good prediction.

Conclusion: The signature of six FRLs had significant prognostic value for pancreatic adenocarcinoma. They may be a promising therapeutic target in clinical practice.
Shotgun Proteomics Identifies Active Metabolic Pathways in Bleached Coral Tissue and Intraskeletal Compartments
Authors: Axworthy Jeremy B. , Timmins-Schiffman Emma , Brown Tanya , Rodrigues Lisa J. , Nunn Brook L. , Padilla-Gamiño Jacqueline L.
Published: February 2022

Coral bleaching events are increasing with such frequency and intensity that many of the world’s reef-building corals are in peril. Some corals appear to be more resilient after bleaching but the mechanisms underlying their ability to recover from bleaching and persist are not fully understood. We used shotgun proteomics to compare the proteomes of the outer layer (OL) tissue and inner core (IC) tissue and skeleton compartments of experimentally bleached and control (i.e., non-bleached) colonies of Montipora capitata, a perforate Hawaiian species noted for its resilience after bleaching. We identified 2,361 proteins in the OL and IC compartments for both bleached and non-bleached individuals. In the OL of bleached corals, 63 proteins were significantly more abundant and 28 were significantly less abundant compared to the OL of non-bleached corals. In the IC of bleached corals, 22 proteins were significantly more abundant and 17 were significantly less abundant compared to the IC of non-bleached corals. Gene ontology (GO) and pathway analyses revealed metabolic processes that were occurring in bleached corals but not in non-bleached corals. The OL of bleached corals used the glyoxylate cycle to derive carbon from internal storage compounds such as lipids, had a high protein turnover rate, and shifted reliance on nitrogen from ammonia to nitrogen produced from the breakdown of urea and betaine. The IC of bleached corals compartmentalized the shunting of glucose to the pentose phosphate pathway. Bleached corals increased abundances of several antioxidant proteins in both the OL and IC compartments compared to non-bleached corals. These results highlight contrasting strategies for responding to bleaching stress in different compartments of bleached M. capitata and shed light on some potential mechanisms behind bleaching resilience.
Pregnancy in Women With Preexisting Glomerular Diseases: A Single-Center Experience
Authors: Marinaki Smaragdi , Tsiakas Stathis , Skalioti Chrysanthi , Kapsia Eleni , Lionaki Sophia , Vallianou Kalliopi , Boletis John
Published: February 2022

Aim

Women with glomerular diseases are often of childbearing age. Besides lupus nephritis, data regarding pregnancy in patients with glomerular diseases are limited, posing a challenging task to attending nephrologists. This study aimed to investigate the pregnancy outcomes and the impact on the underlying glomerular disease among women followed in our institution.

Methods

A single-center retrospective cohort study of women with biopsy-proven glomerular diseases who experienced pregnancy between 2010 and 2020. We analyzed data before, during, and after gestation.

Results

A total of 22 women, 13 women with primary and 9 women with secondary glomerular diseases, were included in this study. Most patients (82%) had received immunosuppressive treatment at various times before pregnancy. All the women were in remission, either complete (62%) or partial (38%), with well-preserved renal function (82%) before conception. A total of 30 live births and 1 stillbirth were recorded; the rate of preterm delivery was 23%. Renal function and proteinuria remained stable during pregnancy. Preeclampsia was observed in 6.7% of patients and disease relapse in 6.9% of the pregnancies.

Conclusion

Pregnancy was associated with a low frequency of adverse events in women with underlying glomerular diseases, provided they have quiescent disease and preserved renal function.
Genetic Variations of ALDH (rs671) Are Associated With the Persistence of HBV Infection Among the Chinese Han Population
Authors: Shang Dabao , Wang Peng , Tang Weiliang , Mo Ruidong , Lai Rongtao , Lu Jie , Li Ziqiang , Wang Xiaolin , Cai Wei , Wang Hui , Zhao Gangde , Xie Qing , Xiang Xiaogang
Published: February 2022

Alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2), members of the alcohol dehydrogenase family, have important roles in liver diseases. The roles of the polymorphisms of ADH1B rs1229984 and ALDH2 rs671 in hepatitis B virus (HBV) susceptibility and persistent infection were investigated in the present study. Total 1,034 patients with hepatitis B [99 acute hepatitis B (AHB), 521 chronic hepatitis B (CHB), 158 acute-on-chronic liver failure (ACLF), 159 liver cirrhosis (LC), and 97 hepatocellular carcinoma (HCC)] and 1,262 healthy controls (HCs) of the Chinese Han population were recruited, and single nucleotide polymorphisms (SNPs) of rs671 and rs1229984 were genotyped. Independent and joint roles of rs671 and rs1229984 in HBV infection were analyzed. The results showed that rs671 genotypes had a significantly different distribution among different subgroups. Compared with HCs, the frequency of rs671-AA genotype was higher in hepatitis B individuals, especially in the CHB group [adjusted OR (95%CI) = 1.899 (1.232–2.928), p = 0.003, in the co-dominant model], which showed a significant positive association. It was further confirmed that CHB individuals who carried ALDH2 rs671-AA genotype had a higher risk of persistent HBV infection and higher HBV-DNA quantitation compared with those with GG/GA genotype. In addition, the rs671-AA genotype might predict HCC incidence in patients with CHB. There were no different distributions of alleles or genotypes in rs671 mutant among AHB, ACLF, LC, or HCC groups compared with HCs. These data suggested the possible hazardous role of rs671-AA variant in HBV infection and persistence.
Human T-Cell Lymphotropic Virus Type 1 and Strongyloides stercoralis Co-infection: A Systematic Review and Meta-Analysis
Authors: Ye Lingqing , Taylor Graham P. , Rosadas Carolina
Published: February 2022

Background

The distribution of human T cell lymphotropic virus type 1 (HTLV-1) overlaps with that of Strongyloides stercoralis. Strongyloides stercoralis infection has been reported to be impacted by co-infection with HTLV-1. Disseminated strongyloidiasis and hyperinfection syndrome, which are commonly fatal, are observed in HTLV-1 co-infected patients. Reduced efficacy of anti-strongyloidiasis treatment in HTLV-1 carriers has been reported. The aim of this meta-analysis and systematic review is to better understand the association between HTLV-1 and S. stercoralis infection.

Methods

PubMed, Embase, MEDLINE, Global Health, Healthcare Management Information Consortium databases were searched. Studies regarding the prevalence of S. stercoralis, those evaluating the frequency of mild or severe strongyloidiasis, and treatment response in people living with and without HTLV-1 infection were included. Data were extracted and odds ratios were calculated. Random-effect meta-analysis was used to assess the pooled OR and 95% confidence intervals.

Results

Fourteen studies were included after full-text reviewing of which seven described the prevalence of S. stercoralis and HTLV-1. The odds of S. stercoralis infection were higher in HTLV-1 carriers when compared with HTLV-1 seronegative subjects (OR 3.2 95%CI 1.7–6.2). A strong association was found between severe strongyloidiasis and HTLV-1 infection (OR 59.9, 95%CI 18.1–198). Co-infection with HTLV-1 was associated with a higher rate of strongyloidiasis treatment failure (OR 5.05, 95%CI 2.5–10.1).

Conclusion

Strongyloides stercoralis infection is more prevalent in people living with HTLV-1. Co-infected patients are more likely to develop severe presentation and to fail treatment. Screening for HTLV-1 and Strongyloides sp. should be routine when either is diagnosed.
Questionnaire Analysis on Incidence and Risk Factors of Dry Eye in Children From a Myopia Outpatient Clinic
Authors: Wang Ning , Zhuang XiaoYun , Zhong XiaoWei , Zhang Ju , Li GuangWei , Li Suxia
Published: February 2022

Objective

To analyze the incidence and risk factors of dry eye in children from a myopia outpatient clinic via a questionnaire and Keratograph 5M.

Methods

A cross–sectional study was performed. sThere were 214 children (428 eyes) selected from the myopia outpatient clinic of the affiliated Eye Hospital of Shandong First Medical University from July 2021 to September 2021, including 105 boys (210 eyes) and 109 girls (218 eyes), with an average age of 10.1 ± 2.5 years. The incidence rate and influence factors for dry eye were calculated.

Results

Thirty–four of 214 children were diagnosed with dry eye, accounting for 15.9% of the patients. The correlation between fussy eating and the tear meniscus height was statistically significant (Z = −2.158, p = 0.039), along with the correlation between short–distance use of eyes and the tear meniscus height (Z = −2.135, p = 0.033). The degree of meibomian gland deficiency was graded. The meibomian gland was graded as grade 1 in 242 eyes (68.9%), grade 2 in 104 eyes (29.6%), and grade 3 in 5 eyes (1.4%). There was a significant difference in the correlation between eye rubbing and the incidence of dry eye in children (Z = −2.747, p = 0.008). There was also a significant difference in the correlation between picky eating and the incidence of dry eye in children (Z = −2.347; p = 0.024). There was a statistically significant correlation between the time of looking at electronic products and the morphology of the meibomian gland (Z = −2.201, p = 0.028). The results showed that the effect of mild and moderate ametropia on the non–invasive tear breakup time in children was statistically significant (Z = −2.027; p = 0.043).

Conclusion

There is a high incidence of dry eye in children in the myopia outpatient clinic. There is a significant correlation between picky eating, eye rubbing, and the incidence of dry eye. Looking at electronic products for a long time will also affect the morphology of the meibomian gland in children.
The Transcription Factor Lrp of Pantoea stewartii subsp. stewartii Controls Capsule Production, Motility, and Virulence Important for in planta Growth
Authors: Bartholomew Holly P. , Reynoso Guadalupe , Thomas Brandi J. , Mullins Chase M. , Smith Chastyn , Gentzel Irene N. , Giese Laura A. , Mackey David , Stevens Ann M.
Published: February 2022

The bacterial phytopathogen Pantoea stewartii subsp. stewartii causes leaf blight and Stewart’s wilt disease in susceptible corn varieties. A previous RNA-Seq study examined P. stewartii gene expression patterns during late-stage infection in the xylem, and a Tn-Seq study using a P. stewartii mutant library revealed genes essential for colonization of the xylem. Based on these findings, strains with in-frame chromosomal deletions in the genes encoding seven transcription factors (NsrR, IscR, Nac, Lrp, DSJ_00125, DSJ_03645, and DSJ_18135) and one hypothetical protein (DSJ_21690) were constructed to further evaluate the role of the encoded gene products during in vitro and in planta growth. Assays for capsule production and motility indicate that Lrp plays a role in regulating these two key physiological outputs in vitro. Single infections of each deletion strain into the xylem of corn seedlings determined that Lrp plays a significant role in P. stewartii virulence. In planta xylem competition assays between co-inoculated deletion and the corresponding complementation or wild-type strains as well as in vitro growth curves determined that Lrp controls functions important for P. stewartii colonization and growth in corn plants, whereas IscR may have a more generalized impact on growth. Defining the role of essential transcription factors, such as Lrp, during in planta growth will enable modeling of key components of the P. stewartii regulatory network utilized during growth in corn plants.
Amyloid Formation by Globular Proteins: The Need to Narrow the Gap Between in Vitro and in Vivo Mechanisms
Authors: Faravelli Giulia , Mondani Valentina , Mangione P. Patrizia , Raimondi Sara , Marchese Loredana , Lavatelli Francesca , Stoppini Monica , Corazza Alessandra , Canetti Diana , Verona Guglielmo , Obici Laura , Taylor Graham W. , Gillmore Julian D. , Giorgetti Sofia , Bellotti Vittorio
Published: February 2022

The globular to fibrillar transition of proteins represents a key pathogenic event in the development of amyloid diseases. Although systemic amyloidoses share the common characteristic of amyloid deposition in the extracellular matrix, they are clinically heterogeneous as the affected organs may vary. The observation that precursors of amyloid fibrils derived from circulating globular plasma proteins led to huge efforts in trying to elucidate the structural events determining the protein metamorphosis from their globular to fibrillar state. Whereas the process of metamorphosis has inspired poets and writers from Ovid to Kafka, protein metamorphism is a more recent concept. It is an ideal metaphor in biochemistry for studying the protein folding paradigm and investigating determinants of folding dynamics. Although we have learned how to transform both normal and pathogenic globular proteins into fibrillar polymers in vitro, the events occurring in vivo, are far more complex and yet to be explained. A major gap still exists between in vivo and in vitro models of fibrillogenesis as the biological complexity of the disease in living organisms cannot be reproduced at the same extent in the test tube. Reviewing the major scientific attempts to monitor the amyloidogenic metamorphosis of globular proteins in systems of increasing complexity, from cell culture to human tissues, may help to bridge the gap between the experimental models and the actual pathological events in patients.
Modulation of miRISC-Mediated Gene Silencing in Eukaryotes
Authors: Jungers Courtney F. , Djuranovic Sergej
Published: February 2022

Gene expression is regulated at multiple levels in eukaryotic cells. Regulation at the post-transcriptional level is modulated by varioustrans-acting factors that bind to specific sequences in the messenger RNA (mRNA). The binding of differenttransfactors influences various aspects of the mRNA such as degradation rate, translation efficiency, splicing, localization, etc. MicroRNAs (miRNAs) are short endogenous ncRNAs that combine with the Argonaute to form the microRNA-induced silencing complex (miRISC), which uses base-pair complementation to silence the target transcript. RNA-binding proteins (RBPs) contribute to post-transcriptional control by influencing the mRNA stability and translation upon binding tocis-elements within the mRNA transcript. RBPs have been shown to impact gene expression through influencing the miRISC biogenesis, composition, or miRISC-mRNA target interaction. While there is clear evidence that those interactions between RBPs, miRNAs, miRISC and target mRNAs influence the efficiency of miRISC-mediated gene silencing, the exact mechanism for most of them remains unclear. This review summarizes our current knowledge on gene expression regulation through interactions of miRNAs and RBPs.
Photoclick Reaction Constructs Glutathione-Responsive Theranostic System for Anti-Tuberculosis
Authors: Zheng Judun , Long Xun , Chen Hao , Ji Zhisheng , Shu Bowen , Yue Rui , Liao Yechun , Ma Shengchao , Qiao Kun , Liu Ying , Liao Yuhui
Published: February 2022

Tuberculosis (TB) is a virulent form of an infectious disease that causes a global burden due to its high infectivity and fatality rate, especially the irrepressible threats of latent infection. Constructing an efficient strategy for the prevention and control of TB is of great significance. Fortunately, we found that granulomas are endowed with higher reducibility levels possibly caused by internal inflammation and a relatively enclosed microenvironment. Therefore, we developed the first targeted glutathione- (GSH-) responsive theranostic system (RIF@Cy5.5-HA-NG) for tuberculosis with a rifampicin- (RIF-) loaded near-infrared emission carrier, which was constructed by photoclick reaction-actuated hydrophobic-hydrophobic interaction, enabling the early diagnosis of tuberculosis through granulomas-tracking. Furthermore, the loaded rifampicin was released through the dissociation of disulfide bond by the localized GSH in granulomas, realizing the targeted tuberculosis therapy and providing an especially accurate treatment mapping for tuberculosis. Thus, this targeted theranostic strategy for tuberculosis exhibits the potential to realize both granulomas-tracking and anti-infection of tuberculosis.
Disease-Specific Contribution of Pulvinar Dysfunction to Impaired Emotion Recognition in Schizophrenia
Authors: Martínez Antígona , Tobe Russell H. , Gaspar Pablo A. , Malinsky Daniel , Dias Elisa C. , Sehatpour Pejman , Lakatos Peter , Patel Gaurav H. , Bermudez Dalton H. , Silipo Gail , Javitt Daniel C.
Published: February 2022

One important aspect for managing social interactions is the ability to perceive and respond to facial expressions rapidly and accurately. This ability is highly dependent upon intact processing within both cortical and subcortical components of the early visual pathways. Social cognitive deficits, including face emotion recognition (FER) deficits, are characteristic of several neuropsychiatric disorders including schizophrenia (Sz) and autism spectrum disorders (ASD). Here, we investigated potential visual sensory contributions to FER deficits in Sz (n = 28, 8/20 female/male; age 21–54 years) and adult ASD (n = 20, 4/16 female/male; age 19–43 years) participants compared to neurotypical (n = 30, 8/22 female/male; age 19–54 years) controls using task-based fMRI during an implicit static/dynamic FER task. Compared to neurotypical controls, both Sz (d = 1.97) and ASD (d = 1.13) participants had significantly lower FER scores which interrelated with diminished activation of the superior temporal sulcus (STS). In Sz, STS deficits were predicted by reduced activation of early visual regions (d = 0.85, p = 0.002) and of the pulvinar nucleus of the thalamus (d = 0.44, p = 0.042), along with impaired cortico-pulvinar interaction. By contrast, ASD participants showed patterns of increased early visual cortical (d = 1.03, p = 0.001) and pulvinar (d = 0.71, p = 0.015) activation. Large effect-size structural and histological abnormalities of pulvinar have previously been documented in Sz. Moreover, we have recently demonstrated impaired pulvinar activation to simple visual stimuli in Sz. Here, we provide the first demonstration of a disease-specific contribution of impaired pulvinar activation to social cognitive impairment in Sz.
Risk Pathways Contributing to the Alcohol Harm Paradox: Socioeconomic Deprivation Confers Susceptibility to Alcohol Dependence via Greater Exposure to Aversive Experience, Internalizing Symptoms and Drinking to Cope
Authors: Shuai Ruichong , Anker Justin J. , Bravo Adrian J. , Kushner Matt G. , Hogarth Lee
Published: February 2022

Socioeconomic deprivation is associated with greater alcohol problems despite lower alcohol consumption, but the mechanisms underpinning this alcohol harm paradox remain obscure. Fragmented published evidence collectively supports a multistage causal risk pathway wherein socioeconomic deprivation increases the probability of exposure to aversive experience, which promotes internalizing symptoms (depression and anxiety), which promotes drinking alcohol to cope with negative affect, which in turn accelerates the transition from alcohol use to dependence. To evaluate this proposed risk pathway, 219 hazardous drinkers from an undergraduate population completed questionnaires assessing these constructs in a single, cross sectional, online survey. Partial correlation coefficients revealed that each variable showed the strongest unique association with the next variable in the proposed multistage model, when adjusting for the other variables. Bootstrapped serial mediation analysis revealed that the indirect pathway linking all the variables in the proposed serial order was significant, while all other permutations were non-significant. Network centrality analysis corroborated the serial order of this indirect path. Finally, risk ratios estimated by categorizing the variables suggested that socioeconomic deprivation increased the risk of aversive experience by 32%, which increased the risk of internalizing symptoms by 180%, which increased the risk of drinking to cope by 64%, which increased susceptibility to alcohol dependence by 59%. These preliminary findings need to be corroborated by future research, nevertheless, they call for prevention strategies founded on social justice and the minimization of aversive experience in socially deprived individuals to mitigate mental health problems, maladaptive coping and addiction.
Baicalein Induces Mitochondrial Autophagy to Prevent Parkinson's Disease in Rats via miR-30b and the SIRT1/AMPK/mTOR Pathway
Authors: Chen Min , Peng Li , Gong Ping , Zheng Xiaoli , Sun Tao , Zhang Xiaoqiao , Huo Jiangtao
Published: February 2022

Parkinson's disease (PD) is a prevailing neurodegenerative disorder. Baicalein has neuroprotective effects on PD animals, but its mechanism is not clarified. We explored baicalein effects on PD rats. PD rat models were established by injecting 6-hydroxydopamine into the striatum of substantia nigra on the left side of the rat brain and treated with baicalein. Dopamine (DA) content, neuronal apoptosis, neuronal injury, neuronal mitochondria, and autophagy were assessed. Baicalein-treated PD rats were treated with autophagy inhibitor 3-methyladenine to identify the role of autophagy in PD. PD rats were injected with AgomiR-30b-5p or sh-SIRT1 plasmids and treated with baicalein. PD rats elicited decreased neurological score and DA secretion of the striatum, increased neuronal apoptosis, and injury, and reduced number of mitochondria and autophagy, whereas baicalein alleviated neuronal injury and partly recovered mitochondrial dysfunction, 3-methyladenine inhibited the protection of baicalein. miR-30b-5p was elevated and SIRT1 was diminished in PD rats and inhibited by baicalein. miR-30b-5p targeted SIRT1. miR-30b-5p overexpression or SIRT1 silencing annulled the protection of baicalein. The phosphorylation level of AMPK in the substantia nigra of PD rats was decreased and mTOR was increased, whereas baicalein annulled these trends. Briefly, baicalein activated mitochondrial autophagy via miR-30b-5p and the SIRT1/AMPK/mTOR pathway, thus protecting PD rats.
Brain Structure as a Correlate of Odor Identification and Cognition in Type 2 Diabetes
Authors: Chen Mimi , Wang Jie , Zhou Shanlei , Zhang Cun , Deng Datong , Liu Fujun , Luo Wei , Zhu Jiajia , Yu Yongqiang
Published: February 2022

Background: It has been reported that type 2 diabetes (T2DM) is associated with olfactory identification (OI) impairments and cognitive decline. However, the relationship between OI impairments and cognitive decline is largely unknown in T2DM patients.

Methods: Sixty-eight T2DM patients and 68 healthy controls underwent 3D-T1 MRI scans, olfactory and cognitive assessments. The cortical thickness of olfaction-related brain regions, olfactory and cognitive scores were compared between groups. Correlation analyses were carried out among cognition, olfaction, and cortical thickness of olfaction-related brain regions.

Results: First, the cognitive and olfactory test scores of T2DM patients were lower than healthy subjects. Second, higher olfactory scores were associated with increased cortical thickness in the left parahippocampal gyrus and bilateral insula in T2DM. Third, higher olfactory scores were associated with higher cognitive performance in T2DM. Fourth, some cognitive performances were related to cortical thickness in the left parahippocampal gyrus and left insula in T2DM.

Conclusion: These findings indicated that olfactory dysfunction may be useful for future applications that attempt to predict cognitive decline or develop tailored therapies in T2DM patients.
Impulsivity and Emotional Dysregulation Predict Choice Behavior During a Mixed-Strategy Game in Adolescents With Borderline Personality Disorder
Authors: Parr Ashley C. , Calancie Olivia G. , Coe Brian C. , Khalid-Khan Sarosh , Munoz Douglas P.
Published: February 2022

Impulsivity and emotional dysregulation are two core features of borderline personality disorder (BPD), and the neural mechanisms recruited during mixed-strategy interactions overlap with frontolimbic networks that have been implicated in BPD. We investigated strategic choice patterns during the classic two-player game, Matching Pennies, where the most efficient strategy is to choose each option randomly from trial-to-trial to avoid exploitation by one’s opponent. Twenty-seven female adolescents with BPD (mean age: 16 years) and twenty-seven age-matched female controls (mean age: 16 years) participated in an experiment that explored the relationship between strategic choice behavior and impulsivity in both groups and emotional dysregulation in BPD. Relative to controls, BPD participants showed marginally fewer reinforcement learning biases, particularly decreased lose-shift biases, increased variability in reaction times (coefficient of variation; CV), and a greater percentage of anticipatory decisions. A subset of BPD participants with high levels of impulsivity showed higher overall reward rates, and greater modulation of reaction times by outcome, particularly following loss trials, relative to control and BPD participants with lower levels of impulsivity. Additionally, BPD participants with higher levels of emotional dysregulation showed marginally increased reward rate and increased entropy in choice patterns. Together, our preliminary results suggest that impulsivity and emotional dysregulation may contribute to variability in mixed-strategy decision-making in female adolescents with BPD.
Partial Restoration of Spinal Cord Neural Continuity via Sural Nerve Transplantation Using a Technique of Spinal Cord Fusion
Authors: Ren Xiaoping , Zhang Weihua , Mo Jian , Qin Jie , Chen Yi , Han Jie , Feng Xinjian , Han Linxuan , Feng Sitan , Liang Haibo , Cen Liangjue , Wu Xiaofei , Huang Chunxing , Deng Haixuan , Cao Zhenbin , Yao Huihui , Lan Rongyu , Wang Xiaogang , Ren Shuai
Published: February 2022

Background

Spinal cord injury (SCI) can cause paralysis and serious chronic morbidity, and there is no effective treatment. Based on our previous experimental results of spinal cord fusion (SCF) in mice, rats, beagles, and monkeys, we developed a surgical protocol of SCF for paraplegic human patients. We designed a novel surgical procedure of SCF, called sural nerve transplantation (SNT), for human patients with lower thoracic SCI and distal cord dysfunction.

Methods

We conducted a clinical trial (ChiCTR2000030788) and performed SNT in 12 fully paraplegic patients due to SCI between T1 and T12. We assessed pre- and postoperative central nerve pain, motor function, sensory function, and autonomic nerve function. Conduction of action potentials across the sural nerve transplant was evaluated. Neural continuity was also examined by diffusion tensor imaging (DTI).

Results

Among the 12 paraplegic patients enrolled in this clinical trial, seven patients demonstrated improved autonomic nerve functions. Seven patients had clinically significant relief of their symptoms of cord central pain. One patient, however, developed postoperative cord central pain (VAS: 4). Five patients had varying degrees of recovered sensory and/or motor functions below the single neurologic level 1 month after surgery. One patient showed recovery of electrophysiologic, motor-evoked potentials 6 months after the operation. At 6 months after surgery, DTI indicated fusion and nerve connections of white cord and sural nerves in seven patients.

Conclusion

SNT was able to fuse the axonal stumps of white cord and sural nerve and at least partially improve the cord central pain in most patients. Although SNT did not restore the spinal cord continuity in white matter in some patients, SNT could restore spinal cord continuity in the cortico-trunco-reticulo-propriospinal pathway, thereby restoring in part some motor and sensory functions. SNT may therefore be a safe, feasible, and effective method to treat paraplegic patients with SCI. Future clinical trials should be performed to optimize the type/technique of nerve transplantation, reduce surgical damage, and minimize postoperative scar formation and adhesion, to avoid postoperative cord central pain.

Clinical Trial Registration

[http://www.chictr.org.cn/showproj.aspx?proj=50526], identifier [ChiCTR2000030788].
Blood Glutamate Scavenging With Pyruvate as a Novel Preventative and Therapeutic Approach for Depressive-Like Behavior Following Traumatic Brain Injury in a Rat Model
Authors: Frank Dmitry , Gruenbaum Benjamin F. , Shelef Ilan , Zvenigorodsky Vladislav , Severynovska Olena , Gal Ron , Dubilet Michael , Zlotnik Alexander , Kofman Ora , Boyko Matthew
Published: February 2022

Depression is a common and serious complication following traumatic brain injury (TBI). Both depression and TBI have independently been associated with pathologically elevated extracellular brain glutamate levels. In the setting of TBI, blood glutamate scavenging with pyruvate has been widely shown as an effective method to provide neuroprotection by reducing blood glutamate and subsequent brain glutamate levels. Here we evaluate pyruvate as a novel approach in the treatment and prevention of post-TBI depression-like behavior in a rat model. Rats were divided into five groups: (1) sham-operated control with pyruvate, (2) sham-operated control with placebo, (3) post-TBI with placebo, (4) post-TBI given preventative pyruvate, and (5) post-TBI treated with pyruvate. These groups had an equal number of females and males. Rats were assessed for depressive-like behavior, neurological status, and glutamate levels in the blood and brain. Post-TBI neurological deficits with concurrent elevations in glutamate levels were demonstrated, with peak glutamate levels 24 h after TBI. Following TBI, the administration of either prophylactic or therapeutic pyruvate led to reduced glutamate levels, improved neurologic recovery, and improved depressive-like behavior. Glutamate scavenging with pyruvate may be an effective prophylactic and therapeutic option for post-TBI depression by reducing associated elevations in brain glutamate levels.
Dietary Factors and Risk of Glioma in Adults: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies
Authors: Zhang Weichunbai , Jiang Jing , Li Xinyi , He Yongqi , Chen Feng , Li Wenbin
Published: February 2022

Background

Gliomas are the most common primary intracranial tumors in adults. Inappropriate dietary habits are thought to be a risk factor for most human cancer, and glioma is no exception. However, the effect of dietary factors on glioma is not clear.

Objective

This review aims to quantitatively evaluate the association between various dietary intakes and glioma using a meta-analysis.

Methods

We searched articles on PubMed, the Cochrane Library, the Web of Science, and EMBASE from their inception until October 11, 2021. According to heterogeneity, the fixed-effects or random-effects model was selected to obtain the relative risk (RR) of merger. Based on the methods described by Greenland and Longnecker, we explored the dose-response relationship between dietary intakes and the risk of glioma. Subgroup analysis, sensitivity analysis, and publication bias were also used.

Results

This study reviewed 33 articles, including 3,606,015 controls and 8,831 patients with glioma. This study included 12 food groups. Compared with the lowest intakes, the highest intakes of tea (RR = 0.82, 95%CI:0.71–0.93), total vegetables (RR = 0.84, 95%CI: 0.70–1.00), green vegetables (RR = 0.80, 95%CI: 0.66–0.98), and orange vegetables (RR = 0.79, 95%CI: 0.66–0.96) significantly reduced the risk of glioma, while the highest intakes of grains (RR = 1.39, 95%CI: 1.16–1.66), processed meats (RR = 1.19, 95%CI: 1.00–1.42), and processed fish (RR = 1.37, 95%CI: 1.03–1.84) significantly increased the risk of glioma. The results of subgroup and sensitivity analyses remained unchanged. In the dose-response relationship, only tea was statistically significant. Taking an extra cup of tea every day reduced the risk of glioma by 4%.

Conclusions

Our analysis suggests that the intakes of tea, total vegetables, green vegetables, and orange vegetables may reduce the risk of glioma, while the intakes of grains, processed meats, and processed fish may increase the risk of glioma. Therefore, the effect of dietary factors on glioma should not be ignored.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, CRD42022296658.
Inward Outward Signaling in Ovarian Cancer: Morpho-Phospho-Proteomic Profiling Upon Application of Hypoxia and Shear Stress Characterizes the Adaptive Plasticity of OVCAR-3 and SKOV-3 Cells
Authors: Bileck Andrea , Bortel Patricia , Kriz Michelle , Janker Lukas , Kiss Endre , Gerner Christopher , Del Favero Giorgia
Published: February 2022

With the onset of resistance, ovarian cancer cells display almost unpredictable adaptive potential. This may derive from the tumor genetic ancestry and can be additionally tailored by post translational protein modifications (PTMs). In this study, we took advantage of high-end (phospho)-proteome analysis combined with multiparametric morphometric profiling in high-grade serous (OVCAR-3) and non-serous (SKOV-3) ovarian carcinoma cells. For functional experiments, we applied two different protocols, representing typical conditions of the abdominal cavity and of the growing tumor tissue: on the one side hypoxia (oxygen 1%) which develops within the tumor mass or is experienced during migration/extravasation in non-vascularized areas. On the other hand, fluid shear stress (250 rpm, 2.8 dyn/cm2) which affects tumor surface in the peritoneum or metastases in the bloodstream. After 3 hours incubation, treatment groups were clearly distinguishable by PCA analysis. Whereas basal proteome profiles of OVCAR-3 and SKOV-3 cells appeared almost unchanged, phosphoproteome analysis revealed multiple regulatory events. These affected primarily cellular structure and proliferative potential and consolidated in the proteome signature after 24h treatment. Upon oxygen reduction, metabolism switched toward glycolysis (e.g. upregulation hexokinase-2; HK2) and cell size increased, in concerted regulation of pathways related to Rho-GTPases and/or cytoskeletal elements, resembling a vasculogenic mimicry response. Shear stress regulated proteins governing cell cycle and structure, as well as the lipid metabolism machinery including the delta(14)-sterol reductase, kinesin-like proteins (KIF-22/20A) and the actin-related protein 2/3 complex. Independent microscopy-based validation experiments confirmed cell-type specific morphometric responses. In conclusion, we established a robust workflow enabling the description of the adaptive potential of ovarian cancer cells to physical and chemical stressors typical for the abdominal cavity and supporting the identification of novel molecular mechanisms sustaining tumor plasticity and pharmacologic resistance.
The Hyperphagia Questionnaire: Insights From a Multicentric Validation Study in Individuals With Prader Willi Syndrome
Authors: Licenziati Maria Rosaria , Bacchini Dario , Crinò Antonino , Grugni Graziano , Fintini Danilo , Osimani Sara , Ragusa Letizia , Sacco Michele , Iughetti Lorenzo , De Sanctis Luisa , Franzese Adriana , Wasniewska Malgorzata Gabriela , Faienza Maria Felicia , Delvecchio Maurizio , Esposito Concetta , Valerio Giuliana
Published: February 2022

Background/Objectives

The present study aimed to validate the Italian version of the Hyperphagia Questionnaire (HQ), a 11-items questionnaire developed to assess hyperphagia in individuals with Prader-Willi syndrome (PWS). This is a complex neurodevelopmental disorder characterized by endocrine dysfunction, hypotonia, intellectual disability, psychiatric disorders and obesity.

Methods

Parents of 219 individuals with PWS (age range 3–54 years; Mage = 17.90; 108 Males), recruited in 12 hospitals in Italy responded to HQ during routine visits. In function of the level of analyses the sample was divided into two subgroups (<18> years) or into four age-subgroups (2.5–4.5; 4.5–8; 8–18; >18 years) corresponding to different clinical stages.

Results

Confirmatory factor analysis (CFA) confirmed the three hyperphagic subdimensions of the original structure (behavior, drive, and severity), but one item was dropped out, reducing the final version to 10 items. Using multi-group CFA, HQ showed satisfactory indexes of measurement invariance by age. Good indexes of internal consistency (Cronbach's alpha and McDonald's Omega coefficients) were found for each subdimension. The three hyperphagia subdimensions positively converged with other food-related measures: emotional overeating, food enjoyment, food responsiveness, and satiety responsiveness. A significant increase of all hyperphagic subdimensions was found across age groups. Higher hyperphagic levels were found in participants with higher body mass index. Hyperphagic drive differently increased in function of the interaction between age and underlying genetic mechanisms.

Conclusion

The Italian version of the HQ is a psychometrically valid and reliable instrument for assessing hyperphagia in individuals with PWS. This tool may prove useful to evaluate the efficacy of pharmacologic and rehabilitative treatments.
Neurologic Toxicity of Immune Checkpoint Inhibitors: A Review of Literature
Authors: Albarrán Víctor , Chamorro Jesús , Rosero Diana Isabel , Saavedra Cristina , Soria Ainara , Carrato Alfredo , Gajate Pablo
Published: February 2022

Immune checkpoint inhibitors have entailed a change of paradigm in the management of multiple malignant diseases and are acquiring a key role in an increasing number of clinical sceneries. However, since their mechanism of action is not limited to the tumor microenvironment, their systemic activity may lead to a wide spectrum of immune-related side effects. Although neurological adverse events are much less frequent than gastrointestinal, hepatic, or lung toxicity, with an incidence of <5%, their potential severity and consequent interruptions to cancer treatment make them of particular importance. Despite them mainly implying peripheral neuropathies, immunotherapy has also been associated with an increased risk of encephalitis and paraneoplastic disorders affecting the central nervous system, often appearing in a clinical context where the appropriate diagnosis and early management of neuropsychiatric symptoms can be challenging. Although the pathogenesis of these complications is not fully understood yet, the blockade of tumoral inhibitory signals, and therefore the elicitation of cytotoxic T-cell-mediated response, seems to play a decisive role. The aim of this review was to summarize the current knowledge about the pathogenic mechanisms, clinical manifestations, and therapeutic recommendations regarding the main forms of neurotoxicity related to checkpoint inhibitors.
An Integrated Pharmacology-Based Strategy to Investigate the Potential Mechanism of Xiebai San in Treating Pediatric Pneumonia
Authors: Luo Zhuohui , Huang Jiawen , Li Ennian , He Xinqian , Meng Qiqi , Huang Xinan , Shen Xiaoling , Yan Changkai
Published: February 2022

Xiebai San (XBS) is a traditional Chinese medicine (TCM) prescription that has been widely used to treat pediatric pneumonia since the Song dynasty. To reveal its underlying working mechanism, a network pharmacology approach was used to predict the active ingredients and potential targets of XBS in treating pediatric pneumonia. As a result, 120 active ingredients of XBS and 128 potential targets were screened out. Among them, quercetin, kaempferol, naringenin, licochalcone A and isorhamnetin showed to be the most potential ingredients, while AKT1, MAPK3, VEGFA, TP53, JUN, PTGS2, CASP3, MAPK8 and NF-κB p65 showed to be the most potential targets. IL-17 signaling pathway, TNF signaling pathway and PI3K-Akt signaling pathway, which are involved in anti-inflammation processes, immune responses and apoptosis, showed to be the most probable pathways regulated by XBS. UPLC-Q/Orbitrap HRMS analysis was then performed to explore the main components of XBS, and liquiritin, quercetin, kaempferol, licochalcone A and glycyrrhetinic acid were identified. Molecular docking analysis of the compounds to inflammation-associated targets revealed good binding abilities of quercetin, kaempferol, licochalcone A and liquiritin to NF-κB p65 and of quercetin and kaempferol to Akt1 or Caspase-3. Moreover, molecular dynamics (MD) simulation for binding of quercetin or kaempferol to NF-κB p65 revealed dynamic properties of high stability, high flexibility and lowbinding free energy. In the experiment with macrophages, XBS markedly suppressed the (Lipopolysaccharides) LPS-induced expression of NF-κB p65 and the production of pro-inflammatory cytokines IL-6 and IL-1β, supporting XBS to achieve an anti-inflammatory effect through regulating NF-κB p65. XBS also down-regulated the expression of p-Akt (Ser473)/Akt, Bax and Caspase-3 and up-regulated the expression of Bcl-2, indicating that regulating Akt1 and Caspase-3 to achieve anti-apoptotic effect is also the mechanism of XBS for treating pediatric pneumonia. Our study helped to reveal the pharmacodynamics material basis as well as the mechanism of XBS in treating pediatric pneumonia.
Yunpi Qufeng Chushi Formula for Pre-Rheumatoid Arthritis: Study Protocol for a Multiple-Center, Double-Blind, Placebo-Controlled Randomized Controlled Trial
Authors: Tang Yujun , Li Haichang , Huang Lin , Wang Qiao , Han Yongmei , Wu Huaxiang , Su Xiao , Hou Xiujuan , Huang Chuanbing , Lin Changsong , Tao Qingwen , Tang Jinyang , Cao Wei , Xie Zhijun , Wen Chengping
Published: February 2022

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive bone erosion on diarthrodial joints. RA patients usually experienced three stages before final diagnosis: the health period, the pre-clinical period (immune response exists without clinical symptoms), and the pre-RA period (immune response exists with mild inflammatory manifestation). Presently, there is seldom guidance referring to early intervention which is a benefit for stable disease conditions and low morbidity. Prophylactic treatment is a major feature of traditional Chinese medicine (TCM). In this present study, a multi-center, double-blind, placebo-controlled clinical trial is carried out to evaluate both efficacy and safety in preventing RA progression on Yunpi Qufeng Chushi formula (YQCF).

Method: The multi-center, double-blind, placebo-controlled clinical trial is conducted in 13 hospitals nationwide. A total of 390 patients ages between 18 and 70 will be recruited in the trial. They will be randomly assigned to the intervention group (YQCF) and placebo group. The follow-up visit will be taken every 3 months from baseline to 1 year. Diagnosis, disease activity scores, clinical disease activity index (CDAI), simplified disease activity index (SDAI), TCM syndrome scores, and safety assessments will be recorded at every visit. Joint color doppler ultrasound, health assessment questionnaire-disability index (HAQ-DI), and functional assessment of chronic illness therapy-fatigue (FACIT-F) will be recorded at baseline and the last visit.

Discussion: This work will provide evidence of YQCF in preventing RA progression. However, whether early intervention would benefit the controlling RA disease still needs a long-term follow-up.

Ethics and dissemination: Protocol version 2 (201910-1). This research was approved by the medical ethics committee of Zhejiang Chinese Medical University (2019-045). Results will be published in a peer-reviewed academic journal.

Trial registration numbers:http://www.chictr.org.cn/index.aspx, ChiCTR1900024166.