bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and efficacy of the tumor-selective adenovirus enadenotucirev, in combination with nivolumab, in patients with advanced/metastatic epithelial cancer: a phase I clinical trial (SPICE)
Authors: Fakih Marwan , Harb Wael , Mahadevan Daruka , Babiker Hani , Berlin Jordan , Lillie Tom , Krige David , Carter Jo , Cox Chris , Patel Minesh , Parfitt Lola , Powell Mark , Rosen Lee
Published: April 2023

Background

Novel combination therapies to overcome anti-PD-1 resistance are required. Enadenotucirev, a tumor-selective blood stable adenoviral vector, has demonstrated a manageable safety profile and ability to increase tumor immune-cell infiltration in phase I studies in solid tumors.

Methods

We conducted a phase I multicenter study of intravenous enadenotucirev plus nivolumab in patients with advanced/metastatic epithelial cancer not responding to standard therapy. Co-primary objectives were safety/tolerability and maximum tolerated dose and/or maximum feasible dose (MTD/MFD) of enadenotucirev plus nivolumab. Additional endpoints included response rate, cytokine responses, and anti-tumor immune responses.

Results

Overall, 51 heavily pre-treated patients were treated, 45/51 (88%) of whom had colorectal cancer (35/35 patients with information available were microsatellite instability-low/microsatellite stable) and 6/51 (12%) had squamous cell carcinoma of the head and neck. The MTD/MFD of enadenotucirev plus nivolumab was not reached, with the highest dose level tested (1×1012 vp day 1; 6×1012 vp days 3 and 5) shown to be tolerable. Overall, 31/51 (61%) patients experienced a grade 3–4 treatment-emergent adverse event (TEAE), most frequently anemia (12%), infusion-related reaction (8%), hyponatremia (6%), and large intestinal obstruction (6%). Seven (14%) patients experienced serious TEAEs related to enadenotucirev; the only serious TEAE related to enadenotucirev occurring in >1 patient was infusion-related reaction (n=2). Among the 47 patients included in efficacy analyses, median progression-free survival was 1.6 months, objective response rate was 2% (one partial response for 10 months), and 45% of patients achieved stable disease. Median overall survival was 16.0 months; 69% of patients were alive at 12 months. Persistent increases in Th1 and related cytokines (IFNγ, IL-12p70, IL-17A) were seen from ~day 15 in two patients, one of whom had a partial response. Among the 14 patients with matching pre-tumor and post-tumor biopsies, 12 had an increase in intra-tumoral CD8+T-cell infiltration and 7 had increased markers of CD8 T-cell cytolytic activity.

Conclusions

Intravenously dosed enadenotucirev plus nivolumab demonstrated manageable tolerability, an encouraging overall survival and induced immune cell infiltration and activation in patients with advanced/metastatic epithelial cancer. Studies of next-generation variants of enadenotucirev (T-SIGn vectors) designed to further re-program the tumor microenvironment by expressing immune-enhancer transgenes are ongoing.

Trial registration number

NCT02636036.
Global, regional and national burdens of gout in the young population from 1990 to 2019: a population-based study
Authors: Zhang Jing , Jin Chenye , Ma Bing , Sun Hao , Chen Yanmei , Zhong Ying , Han Cheng , Liu Tingting , Li Yongze
Published: April 2023

Objective

To use data from the Global Burden of Disease (GBD) Study 2019 to report the global, regional and national rates and trends of annual incidence, point prevalence and years lived with disability (YLD) for gout in adolescents and young adults aged 15–39 years.

Methods

We conducted a serial cross-sectional study of gout burden in the young population aged 15–39 years using data from GBD Study 2019. We extracted rates per 100 000 population of incidence, prevalence and YLD of gout, then calculated their average annual percentage changes (AAPCs) at the global, regional and national level between 1990 and 2019 by sociodemographic index (SDI).

Results

The global gout prevalent cases in individuals aged 15–39 years was 5.21 million in 2019, with the annual incidence substantially increasing from 38.71 to 45.94 per 100 000 population during 1990–2019 (AAPC 0.61, 95% CI 0.57 to 0.65). This substantial increase was observed in all SDI quintiles (low, low-middle, middle, high-middle and high) and every age subgroup (15–19, 20–24, 25–29, 30–34 and 35–39 years). Males accounted for 80% of the gout burden. High-income North America and East Asia were facing a substantial increase in gout incidence and YLD simultaneously. Elimination of high body mass index can reduce 31.74% of the gout YLD globally in 2019, which varied from 6.97% to 59.31% regionally and nationally.

Conclusion

Gout incidence and YLD in the young population grew simultaneously and substantially in both developed and developing countries. Improving representative national-level data on gout, interventions for obesity and awareness in young populations are strongly suggested.
Cerebral haemodynamics in symptomatic intracranial atherosclerotic disease: a narrative review of the assessment methods and clinical implications
Authors: Liu Yuying , Li Shuang , Tian Xuan , Leung Thomas W , Liu Liping , Liebeskind David S , Leng Xinyi
Published: April 2023

Intracranial atherosclerotic disease (ICAD) is a common cause of ischaemic stroke and transient ischaemic attack (TIA) with a high recurrence rate. It is often referred to as intracranial atherosclerotic stenosis (ICAS), when the plaque has caused significant narrowing of the vessel lumen. The lesion is usually considered ‘symptomatic ICAD/ICAS’ (sICAD/sICAS) when it has caused an ischaemic stroke or TIA. The severity of luminal stenosis has long been established as a prognostic factor for stroke relapse in sICAS. Yet, accumulating studies have also reported the important roles of plaque vulnerability, cerebral haemodynamics, collateral circulation, cerebral autoregulation and other factors in altering the stroke risks across patients with sICAS. In this review article, we focus on cerebral haemodynamics in sICAS. We reviewed imaging modalities/methods in assessing cerebral haemodynamics, the haemodynamic metrics provided by these methods and application of these methods in research and clinical practice. More importantly, we reviewed the significance of these haemodynamic features in governing the risk of stroke recurrence in sICAS. We also discussed other clinical implications of these haemodynamic features in sICAS, such as the associations with collateral recruitment and evolution of the lesion under medical treatment, and indications for more individualised blood pressure management for secondary stroke prevention. We then put forward some knowledge gaps and future directions on these topics.
Development of the Canadian Food Intake Screener to assess alignment of adults’ dietary intake with the 2019 Canada's Food Guide healthy food choices recommendations
Authors: Hutchinson Joy M. , Williams Tabitha E. , Westaway Ailish M. , Bédard Alexandra , Pitre Camille , Lemieux Simone , Dodd Kevin W. , Lamarche Benoît , Guenther Patricia M. , Haines Jess , Wallace Angela , Martin Alicia , Louzada Maria Laura da Costa , Jessri Mahsa , Olstad Dana Lee , Prowse Rachel , Simpson Janis Randall , Vena Jennifer E. , Kirkpatrick Sharon I.
Published: April 2023

The objective of this project was to develop a brief self-administered dietary screener, in English and French, to rapidly assess alignment of adults’ dietary intake with the 2019 Canada's Food Guide healthy food choices recommendations. In consultation with Health Canada and external advisors ( n = 15), guiding principles were defined. Existing screeners were scanned, and the healthy food choices recommendations were mapped to inform questions and response options. Cognitive interviews were conducted in English ( n = 17) and French ( n = 16) with adults aged 18–65 years from April to June 2021 to assess understanding of questions and face validity; recruitment emphasized variation in sociodemographic characteristics. Face and content validity were assessed with experts in nutrition, surveillance, and public health ( n = 13 English, 3 French) from April to May 2021. The testing indicated that the screener was well understood overall but informed refinements to improve comprehension of the questions and their alignment with the healthy food choices recommendations. The resulting Canadian Food Intake Screener/Questionnaire court canadien sur les apports alimentaires includes 16 questions to rapidly assess alignment of intake with the 2019 Canada's Food Guide healthy food choices recommendations, including healthy foods and foods to limit, in situations in which comprehensive dietary assessment is not feasible.

Novelty

The Canadian Food Intake Screener was developed to rapidly assess alignment of adults’ dietary intake over the past month with the Food Guide's healthy food choices recommendations. The screener was developed and evaluated through an iterative process that included three rounds of cognitive interviews in each of English and French, along with ongoing feedback from external advisors and face and content validity testing with a separate panel of content experts. The 16-question screener is intended for use with adults, aged 18–65 years, with marginal and higher health literacy in research and surveillance contexts in which comprehensive dietary assessment is not possible.
Machine learning-aided reliability analysis of rainfall-induced landslide of root-reinforced slopes
Authors: Świtała Barbara Maria , Guardiani Carlotta , Soranzo Enrico , Wu Wei
Published: April 2023

Estimating the failure probability of rainfall-induced landslides is often challenging as the triggering mechanism is influenced by a number of parameters whose uncertainty is difficult to quantify and, in practice, is neglected. The reinforcing effect of vegetation on natural slopes adds to the complexity of the stability analysis. In this study, we present the application of a coupled hydro-mechanical model for the effect of plant roots on soil shear strength. First, a deterministic approach is adopted. Then, a reliability analysis of a root-reinforced slope subjected to rainfall is performed by considering the inherent variability of the soil and root properties. The probability of failure is estimated with machine learning surrogate models, which approximate the nonlinear relationship between constitutive parameters and slope displacements at different time steps. The machine learning algorithms are trained on a small dataset. The extreme gradient boosting is the best-performing algorithm with R2 ≥ 0.975 and is then employed to estimate the probability of failure on a larger dataset of one million datapoints with higher accuracy.
Comparison between MERRA-2 and CWEEDS for use in pavement mechanistic-empirical design in Canada
Authors: Shafiee Mohammad , Maadani Omran , Cobo Juan Hiedra
Published: April 2023

To improve the climate resiliency of existing and new pavements, it is important to carry out pavement designs using continuous climate records at high temporal frequencies. Over the years, significant research efforts have been dedicated to obtain high-quality climatic data for pavement design including the latest adoption of the Modern-Era Retrospective analysis for Research and Applications, version 2 (MERRA-2). The purpose of this study is to assess how MERRA-2 performs when compared to the Canadian Weather Energy and Engineering Datasets (CWEEDS), which provides hourly meteorological data for many parts of the country from various periods. In the first part, climate parameters at nine locations were directly compared to determine the correlation between two data sets. In the second part, long-term performances were simulated for typical flexible pavement to assess the relative impact of each climate scenario. As detailed in this paper, observed differences between MERRA-2 and CWEEDS indicate the need for further improvement of climate data quality and availability for designing resilient pavements in Canada.
Complexity-free solution generated by gravitational decoupling for anisotropic self-gravitating star in symmetric teleparallel f(Q)-gravity theory
Authors: Maurya S. K. , Errehymy Abdelghani , Jasim M. K. , Daoud Mohammed , Al-Harbi Nuha , Abdel-Aty Abdel-Haleem
Published: April 2023

In this work, we attempt to find an anisotropic solution for a compact star generated by gravitational decoupling in f(Q)-gravity theory having a null complexity factor. To do this, we initially derive the complexity factor condition in f(Q) gravity theory using the definition given by Herrera (Phys Rev D 97:044010, 2018) and then derived a bridge equation between gravitational potentials by assuming complexity factor to be zero (Contreras and Stuchlik in Eur Phys J C 82:706, 2022). Next, we obtain two systems of equations using the complete geometric deformation (CGD) approach. The first system of equations is assumed to be an isotropic system in f(Q)-gravity whose isotropic condition is similar to GR while the second system is dependent on deformation functions. The solution of the first system is obtained by Buchdahl’s spacetime geometry while the governing equations for the second system are solved through the mimic constraint approach along with vanishing complexity condition. The novelty of our work is to generalize the perfect fluid solution into an anisotropic domain in f(Q)-gravity theory with zero complexity for the first time. We present the solution’s analysis to test its physical viability. We exhibit that the existence of pressure anisotropy due to gravitational within the self-gravitating bounded object plays a vital role to stabilize the f(Q) gravity system. In addition, we show that the constant involved in the solution controls the direction of energy flow between the perfect fluid and generic fluid matter distributions.
The One-Way Communication Complexity of Submodular Maximization with Applications to Streaming and Robustness
Authors: Feldman Moran , Norouzi-Fard Ashkan , Svensson Ola , Zenklusen Rico
Published: April 2023

We consider the classical problem of maximizing a monotone submodular function subject to a cardinality constraint, which, due to its numerous applications, has recently been studied in various computational models. We consider a clean multiplayer model that lies between the offline and streaming model, and study it under the aspect of one-way communication complexity. Our model captures the streaming setting (by considering a large number of players), and, in addition, two-player approximation results for it translate into the robust setting. We present tight one-way communication complexity results for our model, which, due to the connections mentioned previously, have multiple implications in the data stream and robust setting.

Even for just two players, a prior information-theoretic hardness result implies that no approximation factor above 1/2 can be achieved in our model, if only queries to feasible sets (i.e., sets respecting the cardinality constraint) are allowed. We show that the possibility of querying infeasible sets can actually be exploited to beat this bound, by presenting a tight 2/3-approximation taking exponential time, and an efficient 0.514-approximation. To the best of our knowledge, this is the first example where querying a submodular function on infeasible sets leads to provably better results. Through the link to the (non-streaming) robust setting mentioned previously, both of these algorithms improve on the current state of the art for robust submodular maximization, showing that approximation factors beyond 1/2 are possible. Moreover, exploiting the link of our model to streaming, we settle the approximability for streaming algorithms by presenting a tight 1/2+ɛ hardness result, based on the construction of a new family of coverage functions. This improves on a prior 0.586 hardness and matches, up to an arbitrarily small margin, the best-known approximation algorithm.
Structural, Thermoelectric, Electronic, and Magnetic Properties of Pristine Intermetallic Rare-Earth-Based XMn2Si2 (X=Dy, Er) Compounds
Authors: Zada Zeshan , Khan Junaid , Khan Abdul Ahad , Reshak Ali H. , Ali Dania , Rehman Fazal Ur , Urrahman Inayat , Saqib Muhammad , Irfan Muhammad , Ramli Muhammad M.
Published: April 2023

Detailed Structural, thermoelectric, electronic and magnetic properties of the ternary rare-Earth based XMn2Si2 (X=Dy, Er) Compounds, are investigated using the full-potential linearized augmented-plane wave (FP-LAPW) method with generalized gradient approximation (GGA+U) in ferromagnetic phase. The basic calculations of optimization are found with the support of (PBE-GGA) to realize theoretical consistency with existing experimental consequences, although for the enhancement of magneto-electronic part the (GGA+U) technique is employed. We have identified theoretically that the ferromagnetic is the most suitable phase among three studied phases for these compounds agree well with previous experimental works. The electronic band structure indicates that these compounds are metallic through both spin channels in the FM phase. A secure hybridization occurs between the elements Dy/Er-f and Mn-d states in the valence band and the Si-p state in the conduction band. The total magnetic moments verify that the rare-Earth based DyMn2Si2 ternary inter-metallic compound showcases stronger ferromagnetic behavior patterns than the ErMn2Si2 compound. We estimated the Seebeck coefficient S, electrical and thermal conductivities, and the ZT in this study over the temperature range of 0 to 800 K. The ErMn2Si2 is a viable contender for high-temperature applications in waste heat management because of its high ZT values in the high-temperature region in thermoelectric devices.
Osteoporosis Screening Disparities among Ethnic and Racial Minorities: A Systematic Review
Authors: Calikyan Anoush , Silverberg Jillian , McLeod Katherine M.
Published: April 2023

Background. Osteoporosis is a preventable disease that is simple and cost-effective to screen based on clinical practice guidelines, yet many patients go undiagnosed and untreated leading to increased burden of the disease. Specifically, racial and ethnic minorities have lower rates of dual energy absorptiometry (DXA) screening. Inadequate screening may lead to an increased risk of fracture, higher health care costs, and increased morbidity and mortality disproportionately experienced by racial-ethnic minority populations. Purpose. This systematic review assessed and summarized the racial and ethnic disparities that exist for osteoporosis screening by DXA. Methods. Using terms related to osteoporosis, racial and ethnic minorities, and DXA, an electronic search of databases was performed in SCOPUS, CINAHL, and PubMed. Articles were screened using predefined inclusion and exclusion criteria which dictated the final articles used in the review. Full text articles that were selected for inclusion underwent quality appraisal and data extraction. Once extracted, data from the articles were combined at an aggregate level. Results. The search identified 412 articles. After screening, a total of 16 studies were included in the final review. The overall quality of the studies included was high. Of the 16 articles reviewed, 14 identified significant disparities between racial minority and majority groups and determined that the eligible patients in racial minority groups were less likely to be referred to DXA screening. Conclusion. There is a significant disparity in osteoporosis screening among racial and ethnic minorities. Future efforts should focus on addressing these inconsistencies in screening and removing bias from the healthcare system. Additional research is required to determine the consequence of this discrepancy in screening and methods of equitizing osteoporosis care.
Evaluation of County Economic Resilience in Henan Province Based on the Entropy Weight-Normal Cloud Model
Authors: Peng Qingxiu , Xuan Lifang
Published: April 2023

As new urbanization constantly develops, the county economy plays a vital role between country and city, and high economic resilience is necessary to support and safeguard for smooth functioning of the county development. The paper constructs the index system of county economic resilience in Henan Province from three dimensions: risk resistance ability, self-stability, and sustainable development ability, and to empirically analyze the economic resilience of 104 counties and cities in the province from 2013 to 2020 using the entropy weight-normal cloud model. The results show that Henan counties’ economic resilience increases slowly over time and decreases spatially from the center to the surrounding region, with Zhengzhou as the main center and Luoyang and Sanmenxia as the subcenter; risk resistance ability and self-stabilization are more influential than the sustainable development ability; the key indicators affecting economic resilience are GDP per capita, retail sales of social consumer goods per capita, financial self-sufficiency rate, education expenditure per capita, and population mobility. Therefore, the counties in Henan should find the right positioning to improve economic resilience; central cities such as Zhengzhou and Luoyang should play their strong functions, while strengthening support for peripheral counties.
[Retracted] Heterogeneous Network‐Based Inductive Matrix Methods for Predicting Biomedical Gene Disease
Authors: Das Pranjit , Kumar Loveleen , Degadwala Sheshang , Alam Md. Nasre , Jakhmola Vikash , Bhat C. Rohith
Published: April 2023

Prediction of gene‐disease associations has grown in popularity in recent biomedical research. However, positive and unlabeled (PU) issues and limited gene‐disease association data are common concerns with present association prediction algorithms. A gene‐disease association prediction approach based on Katz‐enhanced inductive matrix completion is suggested in light of the abovementioned flaws. Preestimate based on the Katz technique and refined estimation based on the inductive matrix completion approach makes the model. The Katz technique is utilized to preestimate the gene‐disease association on the basis of gene‐disease heterogeneous network to mitigate the effects of association data‐sparse and PU issues. The Katz technique, however, necessarily introduces some noise when predicting gene‐disease connections due to the similarity network’s quality limitations. Therefore, the elastic net regularization approach is utilized to increase the resilience of the conventional inductive matrix completion model. As a result, the prediction effect of gene‐disease connections is increased using robustness and a better inductive matrix completion model. The experimental findings demonstrate that the proposed model has dramatically increased recall and precision compared to widely used gene‐disease association prediction approaches. It can also resolve the typical cold‐start issue in association prediction. The proposed KIMC method may consider integrating more diverse biological data sources in the future and also aid in the effective extraction of the feature data of genes and diseases with higher correlation from this biological data to improve the prediction effect.
A Brief Review on Medicinal Plants-At-Arms against COVID-19
Authors: Srivastava Shivani , He Fangzhou , Huang Yuanding , Niu Meng , Adholeya Alok , Peng Weng Kung
Published: April 2023

COVID-19 pandemic caused by the novel SARS-CoV-2 has impacted human livelihood globally. Strenuous efforts have been employed for its control and prevention; however, with recent reports on mutated strains with much higher infectivity, transmissibility, and ability to evade immunity developed from previous SARS-CoV-2 infections, prevention alternatives must be prepared beforehand in case. We have perused over 128 recent works (found on Google Scholar, PubMed, and ScienceDirect as of February 2023) on medicinal plants and their compounds for anti-SARS-CoV-2 activity and eventually reviewed 102 of them. The clinical application and the curative effect were reported high in China and in India. Accordingly, this review highlights the unprecedented opportunities offered by medicinal plants and their compounds, candidates as the therapeutic agent, against COVID-19 by acting as viral protein inhibitors and immunomodulator in (32 clinical trials and hundreds of in silico experiments) conjecture with modern science. Moreover, the associated foreseeable challenges for their viral outbreak management were discussed in comparison to synthetic drugs.
The Role of Benralizumab in Eosinophilic Immune Dysfunctions: A Case Report-Based Literature Review
Authors: Gomes Margarida , Mendes Ana , Ferreira Filipa , Branco Joana , Tonin Fernanda S. , Pedro M. Elisa
Published: April 2023

In the past years, the knowledge of eosinophils playing a primary pathophysiologic role in several associated conditions has led to the development of biologics targeting therapies aiming at normalizing the immune response, reducing chronic inflammation, and preventing tissue damage. To better illustrate the potential relationship between different eosinophilic immune dysfunctions and the effects of biological therapies in this scenario, here, we present a case of a 63-year-old male first referred to our department in 2018 with a diagnosis of asthma, polyposis, and rhinosinusitis and presenting a suspicion of nonsteroidal anti-inflammatory drugs’ allergy. He also had a past medical history of eosinophilic gastroenteritis/duodenitis (eosinophilia counts >50 cells/high-power field HPF). The use of multiple courses of corticosteroid therapy failed to completely control these conditions. In October 2019, after starting benralizumab (an antibody directed against the alpha chain of the IL-5 cytokine receptor) as add-on treatment for severe eosinophilic asthma, important clinical improvements were reported both on the respiratory (no asthma exacerbations) and gastrointestinal systems (eosinophilia count 0 cells/HPF). Patients’ quality of life also increased. Since June 2020, systemic corticosteroid therapy was reduced without worsening of gastrointestinal symptoms or eosinophilic inflammation. This case warns of the importance of early recognition and appropriate individualized treatment of eosinophilic immune dysfunctions and suggests the conduction of further larger studies on the use of benralizumab in gastrointestinal syndromes aiming at better understanding its relying mechanisms of action in the intestinal mucosa.
Pathology and Epidemiology of Fungal Infections in Layer Chicken Flocks
Authors: El-Sharkawy Hanem , Abd El-Salam Ahmed M. , Tahoun Amin
Published: April 2023

Fungal infections have a key effect on the commercial poultry production and welfare. Infections caused by fungi and their food contaminants are zoonotic and influence food safety. Eggs and cooked meats remain major public health concerns. Therefore, this research is aimed at examining the pathology and understanding the epidemiology of fungal infection in layer chicken flocks. The study was carried out on twenty-layer flocks from Kafrelsheikh Governorate, Egypt, from January 2019 to December 2020. In total, 600 samples were collected from 100 healthy and diseased layer chickens from different organs (skin, liver, lung, kidney, spleen, and ovary). In this work, we present the clinical and pathological characteristics of some fungal pathogens (Aspergillus spp. and Fusarium spp.) in layer chicken flocks, as they are responsible for reducing the egg production. In total, 19 fungal strains were isolated from individual chickens, and these were analysed to determine the fungal species. The total proportion of fungal infections at the farm level was (3/20) 15%. The main clinical signs were emaciation and mortalities that reached

4.34
%
±
0.84

. We report the first isolation of Aspergillus piperis and Fusarium species from the ovary of poultry, which is the main reason for egg retention and multiple numerous nodules of occasional caseating centers in layer ovaries. The histopathological findings of Aspergillus infection are indicated by the presence of branched hyphae that tend to be numerous and progressive. Furthermore, we found spherules with multiple endospores of Fusarium spp. in the ovaries. Morphological and molecular identification and analysis were performed to confirm the etiological agents.
Examining Cognitive Biases Uniquely Associated with Schizotypy
Authors: Zahid Aqsa , Best Michael W.
Published: April 2023

Introduction: Individuals with schizotypy can experience a number of cognitive biases that may increase their risk in developing schizophrenia-spectrum psychopathology. However, cognitive biases are also present in mood and anxiety disorders, and it is currently unclear which biases are specific to schizotypy and which may be a result of comorbid depression and/or anxiety. Methods: 462 participants completed measures of depression, anxiety, cognitive biases, cognitive schemas, and schizotypy. Correlation analyses were conducted to examine the relationship between these constructs. Three hierarchical regression analyses were conducted to examine if schizotypy, depression, and anxiety explained a statistically significant amount of variance in cognitive biases after controlling for depression and anxiety, schizotypy and anxiety, and schizotypy and depression, respectively. Moderated regression analyses were also conducted to investigate the moderating role of biological sex and ethnicity in the association between cognitive biases and schizotypy. Results: Self-referential processing, belief inflexibility, and attention for threat were associated with schizotypy. The belief inflexibility bias and social cognition problems were specifically associated with schizotypy after controlling for depression and anxiety and were not directly associated with either depression or anxiety. These associations were not moderated by biological sex or ethnicity. Conclusion: The belief inflexibility bias may be an important cognitive bias underlying schizotypal personality, and further research will be important to determine whether this bias is also associated with an increased likelihood of transitioning to psychosis.
Liver-Expressed Antimicrobial Peptide 2 Is a Hepatokine That Predicts Weight Loss and Complete Remission of Type 2 Diabetes Mellitus after Vertical Sleeve Gastrectomy in Japanese Individuals
Authors: Nabekura Hiroki , Islam Md Nurul , Sakoda Hideyuki , Yamaguchi Takashi , Saiki Atsuhito , Nabekura Taiki , Oshiro Takashi , Tanaka Yuri , Murayama Shinya , Zhang Weidong , Tatsuno Ichiro , Nakazato Masamitsu
Published: April 2023

Introduction: Vertical sleeve gastrectomy (VSG) is considered one of the most effective treatments for sustained weight loss and complete remission of type 2 diabetes mellitus (CR-T2DM). Liver-expressed antimicrobial peptide 2 (LEAP2), a ghrelin receptor antagonist peptide, is a metabolic hormone regulated by VSG. However, it is unknown whether LEAP2 can be used to predict the outcomes of VSG. This study aimed to evaluate LEAP2 as a predictive factor for weight loss and CR-T2DM after VSG. Methods: This retrospective study included 39 Japanese participants with obesity who underwent VSG. Serum LEAP2, des-acyl ghrelin (DAG), and other metabolic and anthropometric parameters were studied before and at 12 months after VSG. Receiver operating characteristics (ROC) curve was generated to evaluate predictive score for weight loss with cut-off value of >50 percent excess weight loss. ROC curve was also generated to assess CR-T2DM. Results: Serum LEAP2 levels were significantly higher in participants with body mass index (BMI) 32–50 kg/m2 than in those with normal weight. Participants with BMI >50 kg/m2 had lower serum LEAP2 concentrations than those with BMI 32–50 kg/m2. VSG caused a significant reduction in serum DAG concentrations, but it did not affect serum LEAP2 concentrations in either male or female participants. Preoperative serum LEAP2 concentration of 2.88 pmol/mL was the optimal cutoff value for predicting weight loss after VSG, with sensitivity of 80.0% and specificity of 75.9%. Preoperative serum LEAP2 level higher than 4.67 pmol/mL predicted CR-T2DM after VSG with sensitivity of 100% and specificity of 58.8%. Conclusion: Preoperative serum LEAP2 could predict weight loss and CR-T2DM as outcomes of VSG.
Association of Alopecia Areata with Sensorineural Hearing Loss: A Systematic Review and Meta-analysis
Authors: Lien Kuang-Hsu , Ger Tzong-Yun , Chi Ching-Chi
Published: April 2023

Background: Immune-mediated melanocyte-related pathogenesis in alopecia areata (AA) may cause sensorineural hearing loss (SNHL). However, the relation between AA and SNHL has been unclear. Therefore, we aimed to investigate this association between AA and SNHL. Methods: We performed a systematic review and searched MEDLINE and Embase on July 25, 2022, for cross-sectional, case-control, or cohort studies that examined the association of AA with SNHL. The Newcastle-Ottawa Scale was used to evaluate their risk of bias. A random-effects model meta-analysis was performed to obtain the mean differences in frequency-specific hearing thresholds between AA patients and age-matched healthy controls and the pooled odds ratio for SNHL in relation to AA. Results: We included 5 case-control studies and 1 cohort study, with none of them rated with high risk of biases. The meta-analysis showed AA patients had significantly higher mean differences in pure-tone hearing thresholds at 4,000 Hz and 12,000–12,500 Hz. The meta-analysis also found increased odds for SNHL among patients with AA (OR: 3.18; 95% CI: 2.06–4.89; I2 = 0%). Conclusions: AA is associated with an increase of SNHL, especially at high frequencies. Otologic consultation may be indicated if AA patients present with hearing loss or tinnitus.
A Novel Intronic Deletion in PDE6B Causes Autosomal Recessive Retinitis Pigmentosa by Interfering with RNA Splicing
Authors: Ullah Mukhtar , Rehman Atta Ur , Folcher Marc , Ullah Adnan , Usman Faisal , Rashid Abdur , Khan Bilal , Quinodoz Mathieu , Ansar Muhammad , Rivolta Carlo
Published: April 2023

Introduction: Retinitis pigmentosa (RP) is a rare degenerative retinal disease caused by mutations in approximately seventy genes. Currently, despite the availability of large-scale DNA sequencing technologies, ∼30–40% of patients still cannot be diagnosed at the molecular level. In this study, we investigated a novel intronic deletion of PDE6B, encoding the beta subunit of phosphodiesterase 6 in association with recessive RP. Methods: Three unrelated consanguineous families were recruited from the northwestern part of Pakistan. Whole exome sequencing was performed for the proband of each family, and the data were analyzed according to an in-house computer pipeline. Relevant DNA variants in all available members of these families were assessed through Sanger sequencing. A minigene-based splicing assay was also performed. Results: The clinical phenotype for all patients was compatible with rod cone degeneration, with the onset during childhood. Whole exome sequencing revealed a homozygous 18 bp intronic deletion (NM_000283.3:c.1921-20_1921-3del) in PDE6B, which co-segregated with disease in 10 affected individuals. In vitro splicing tests showed that this deletion causes aberrant RNA splicing of the gene, leading to the in-frame deletion of 6 codons and, likely, to disease. Conclusion: Our findings further expand the mutational spectrum of the PDE6B gene.
Changes in Visual Long-Term Potentiation Show Preserved Cyclicity in Human Females Taking Combined Oral Contraceptives
Authors: Stone Elizabeth , Alshakhouri Malak , Shaw Alexander , Muthukumaraswamy Suresh , Sumner Rachael L.
Published: April 2023

Introduction: The combined oral contraceptive (COC) pill is often employed to address physical and neurological symptoms in menstrual cycle-related disorders by suppressing shifts in endogenous gonadal hormone fluctuations. Symptom persistence, especially in the lead up to the hormone-free interval (HFI), suggests an underlying neurobiological mechanism of preserved cycling. Our study utilised a non-invasive method of visually inducing long-term potentiation (LTP) to index changes in neural plasticity in the absence of hormonal fluctuations. Methods: Visually induced LTP was recorded using electroencephalography in 24 healthy female COC users across three sessions: days 3 and 21 during active hormone pills, and day 24 during the HFI. The Daily Record of the Severity of Problems (DRSP) questionnaire tracked premenstrual symptoms. Dynamic causal modelling (DCM) was used to elucidate the neural connectivity and receptor activity changes associated with LTP across different days of COC. Results: Visually induced LTP was greater on day 21 than day 3 (p = 0.011) and was localised to the P2 visually evoked potential. There was no effect of the HFI (day 24) on LTP. DCM of differences between days 3 and 21 showed changes to inhibitory interneuronal gating of LTP in cortical layer VI. The DRSP only showed a significant increase in symptoms in the HFI, meaning the LTP result appeared more sensitive to cyclicity. Conclusions: This study provides objective evidence of preserved cyclicity in COC users through enhanced LTP on day 21 compared to day 3 of a 28-day COC regimen, indicating that relatively higher excitation in the brain despite peripheral gonadal suppression may underlie and exacerbate menstrual cycle-related disorders.
De Diderot a Freud: o tear como metáfora e modelo
Authors: Delon Michel , Souza Maria das Graças de
Published: April 2023

Diderot escreve, na Enciclopédia, um longo verbete, “Tear de meias”, no qual compara o tear a um raciocínio cuja conclusão seria o têxtil. Ele retoma esta comparação na Refutação de Helvétius: ali, é o próprio Leibniz que se torna uma máquina de reflexão, similar ao “tear de meias”. A opção materialista do homem máquina retoma uma tradição que assimila o texto ao tecido. Encontramos a mesma imagem no Fausto de Goethe, que é citado por Freud em A interpretação dos sonhos, e na novela de Henry James O motivo no tapete. A invenção é sempre cruzamento, tecelagem e mestiçagem, numa interação entre criação técnica e representação da atividade intelectual. O sistema de programação dos teares foi posteriormente adaptado às primeiras máquinas analíticas, ancestrais de nossos computadores atuais. A Enciclopédia teorizou esta interação, reabilitando os teares e concebendo o pensamento como um trabalho.
Consciência e reflexão no Ensaio de Locke
Authors: Freitas Vinícius França
Published: April 2023

O artigo discute as noções de ‘consciência’ e ‘reflexão’ no Ensaio sobre o entendimento humano de John Locke. Apresentam-se dois critérios para se distinguir entre ambas as atividades mentais. Primeiramente, a consciência é uma atividade passiva, involuntária e não depende de atenção para ser exercida, diferentemente da reflexão, que, ao menos em um de seus graus – pois Locke concebe a existência de dois graus de reflexão –, é uma atividade ativa, voluntária e atenciosa da mente. Em segundo lugar, a consciência se distingue da reflexão na medida em que ela é uma atividade mental geradora de juízos / crenças, diferentemente da reflexão, cujas atividades apenas produzem ideias. Enquanto a consciência permite ao ser humano conhecer – julgar sobre e acreditar em suas atividades e estados mentais –, a reflexão é apenas uma capacidade mental de ter ideias e, enquanto tal, não é passível de ser verdadeira ou falsa.
Sensação inerte e sensação ativa em Diderot
Authors: Castro Clara
Published: April 2023

Este artigo pretende estudar quatro princípios do movimento da matéria (força viva, força morta, força íntima da molécula e força vital) que aparecem no Sonho de d’Alembert (1769), nos Princípios filosóficos sobre a matéria e o movimento (1770) e nos Elementos de fisiologia (1782) de Diderot. Com tal estudo, gostaríamos de mostrar a possibilidade daquilo que chamamos de sensação inerte e de sensação ativa, com base num quinto princípio: a força neural. Nossa hipótese é que o raciocínio que fundamenta a teoria de Diderot sobre a sensibilidade universal da matéria desemboca nas ideias de sensação inerte e de sensação ativa.
Clastres contra Rousseau: a filosofia à luz da etnologia
Authors: Bandera Mauro Dela
Published: April 2023

Leitor atento de Rousseau, embora raramente o citasse em seus textos, Clastres emprega o mesmo vocabulário que ganhou fama sob a pluma do cidadão de Genebra, tomando por vezes distância de suas reflexões: 1) alusão à vontade geral; 2) a encenação do gesto fundador da sociedade civil de cercar um terreno e o discurso possessivo que inaugura a propriedade privada e a acompanha (“isto é meu”); 3) e, por fim e mais importante, a crítica direcionada às duas frentes que compõem a narrativa de Rousseau sobre a origem do Estado: de um lado, a associação entre desejo de prestígio e vontade de poder; de outro, o fundamento econômico do poder político. Se é certo afirmar que a Arqueologia da violência é contra Hobbes ou uma inversão do argumento de Hobbes – pois aí Clastres politiza a guerra –, por sua vez, a Sociedade contra o Estado é em certa medida contra Rousseau ou, ainda, uma inversão do argumento de Rousseau, visto que se coloca contra a narrativa hipotética da história ocidental: não mais da economia e do prestígio para a política, mas da política para a economia, pois aí Clastres politiza a economia.
Dois casos de cerceamento à circulação de livros no Brasil no ano de 2021: o expurgo da Fundação Palmares e a falsificação de postagens do Padre Lancelotti
Authors: Reimão Sandra , Nery Joao Elias , Maues Flamarion
Published: April 2023

Este estudo discute a questão da censura a livros enfocando especificamente dois casos de tentativa de cerceamento à circulação de livros ocorridos no Brasil no ano de 2021, terceiro ano do governo federal de extrema direita de Jair Bolsonaro. Estes casos utilizaram diferentes estratégias: no primeiro deles, o da fundação Palmares, houve a censura a livros pelo impedimento de circulação dos mesmos através da realização do expurgo dos exemplares de uma biblioteca pública; e no segundo, o caso da postagem do padre Júlio Lancellotti, houve manipulação eletrônica de uma informação em que a indicação de um livro foi eliminada e substituída por outra indicação portadora de um sentido antagônico à proposição inicial. Em ambos os casos – um de cerceamento físico e outro de adulteração digital - a intenção autoritária é explícita: o objetivo das ações é e eliminar os livros e as ideias neles defendidas do espaço público, para que as ideias que os autoritários antidemocráticos propagam sejam as únicas difundidas.
Precision Medicine in Neurocritical Care for Cerebrovascular Disease Cases
Authors: Petersen Nils H. , Sheth Kevin N. , Jha Ruchira M.
Published: April 2023

Scientific advances have informed many aspects of acute stroke care but have also highlighted the complexity and heterogeneity of cerebrovascular diseases. While practice guidelines are essential in supporting the clinical decision-making process, they may not capture the nuances of individual cases. Personalized stroke care in ICU has traditionally relied on integrating clinical examinations, neuroimaging studies, and physiologic monitoring to develop a treatment plan tailored to the individual patient. However, to realize the potential of precision medicine in stroke, we need advances and evidence in several critical areas, including data capture, clinical phenotyping, serum biomarker development, neuromonitoring, and physiology-based treatment targets. Mathematical tools are being developed to analyze the multitude of data and provide clinicians with real-time information and personalized treatment targets for the critical care management of patients with cerebrovascular diseases. This review summarizes research advances in these areas and outlines principles for translating precision medicine into clinical practice.
Flight from Urban Blight: Lead Poisoning, Crime, and Suburbanization
Authors: Curci Federico , Masera Federico
Published: April 2023

In this paper we study the effect of violent crime on residential and firms location decisions and their implications for segregation in cities. We do so by proposing a new instrument to exogenously predict violent crime in city centers. We base our instrument on chemical and medical evidence that links local characteristics of the soil to lead poisoning and aggression. We show that the increase in violent crime between 1960 and 1990 due to lead poisoning moved almost 8 million people to the suburbs. Firms followed by leaving the city centers. We then show that the suburbanization process was characterized by “white flight”.
Family Support during Hard Times: Dynamics of Intergenerational Exchange after Adverse Events
Authors: Schaller Jessamyn , Eck Chase
Published: April 2023

We use event studies to examine changes in intergenerational financial transfers and informal care within families following wealth loss, job exit, widowhood, and health shocks. We find sharp reductions in giving to adult children following negative shocks to parents' wealth and earned income, particularly in low-wealth households. Giving also decreases with some health shocks and increases following spousal death. Meanwhile, children of low-wealth households increase financial transfers to parents following adverse shocks in parental households and children of both high- and low-wealth households sharply increase their provision of informal care to parents following a wide range of adverse shocks.
Strategies of self-presentation in author’s texts of professionals with di6erent professional backgrounds
Authors: Abdullaeva Mehirban M.
Published: April 2023

Background. Xe article is devoted to the features of self-presentation, expressed in the author’s texts, considered in the context of evaluation of professionals. Referring to the group of methods based on the “personality-text” relation is conditioned by the change in management paradigms and importance of employee’s creative potential as well as independence in modern economic conditions. Objective. Xe aim of this study was to determine the features of self-presentation of specialists with diYerent professional experience by analyzing the texts through the selection of formal and substantive attributions that reZect the individual characteristics of the author. We assumed that the texts created by specialists of diYerent age, gender, job level will diYer in terms of formal and content-related criteria, explicit and underlying semantic structures. Sample. Xe sample consisted of 83 employees of a manufacturing company. Methods. Xe participants were asked to give seven self-descriptions, answering the question “Who am I?” and to continue 10 un[nished sentences on the topic “My profession”. Xe resulting texts were subjected to a content analysis procedure based on the statistical processing of the selected categories (relative frequencies, correlations and signi[cant diYerences between them). Results. Xe results obtained made it possible to single out two strategies for writing texts on the same topic, which reveal the author’s experience: “detached, passive” and “included, active”. Xese strategies are tracked both at the level of explicit, formal characteristics of the text and at the level of deep semantic structures — semantic roles and metaprograms. Psychosemantic correlates of experience are indicators of emotional valence (positive, negative, neutral) and indicators of the frequency of adjectives, nouns and verbs in the text. Conclusion. Xese data demonstrate the diagnostic capabilities of psychosemantic methods in assessing the individual characteristics of employees when it is impossible to calculate the social desirability of answers, as well as in obtaining important information for building correct communications with them.