bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morale, performance and disclosure
Authors: Jiang Xu , Xue Ying 
Published: January 2023

AbstractWe study the optimal disclosure policy in a sender–receiver communication game where the receiver's morale, defined as his expected state of the world, affects his performance. The sender observes the state and chooses whether to disclose it to the receiver, who then decides whether to participate in a task. The receiver wins if his performance in the task meets a target. No disclosure is optimal if the receiver wins with average morale in each state. Otherwise, in the threshold disclosure equilibrium that Pareto‐dominates full disclosure, the receiver quits as the sender discloses the worst states and wins as the sender withholds the rest. The receiver wins in more states in the Pareto‐optimal equilibrium as the sender chooses a non‐monotonic disclosure policy. Our theory reveals a trade‐off between transparency and efficiency when morale affects performance. It has applications in a broad range of areas including military, family, education and business.
Development of drugs targeting hypoxia‐inducible factor against tumor cells with VHL mutation: Story of 127 years
Authors: Takamori Hajime , Yamasaki Toshinari , Kitadai Rui , Minamishima Yoji Andrew , Nakamura Eijiro 
Published: January 2023

AbstractIntratumoral hypoxia is associated with tumor progression and therapeutic resistance. The VHL tumor suppressor gene was identified in 1993, and later studies revealed that the gene product pVHL interacts with other proteins to form the VBC complex. The VBC complex functions as an E3 ubiquitin ligase and regulates the abundance of the α‐subunit of the transcription factor hypoxia‐inducible factor (HIF). Hypoxia‐inducible factor regulates thousands of genes required for cells to adapt and survive in hypoxic conditions, and thus pVHL plays a major role in oxygen‐sensing pathways. Patients with von Hippel–Lindau (VHL) disease, harboring a germline mutation of the VHL gene, develop renal cell carcinomas and a series of tumors showing hypervascular phenotypes. The extensive findings that have clarified the function of VHL have contributed to the development of novel first‐in‐human drugs, including belzutifan, a HIF‐2α inhibitor. The 2019 Nobel Prize in Physiology or Medicine was awarded to Dr. William G. Kaelin Jr., Dr. Peter J. Ratcliffe, and Dr. Gregg L. Semenza as researchers contributing to clarifying the mechanism of the oxygen‐sensing pathway of cells. The first report of VHL disease was in 1894, meaning the development of a specific drug for this disease took almost 125 years. In this article, we describe how researchers and clinician scientists successfully clarified the function of VHL and achieved a preclinical proof of concept to apply for clinical trials, key requirements for drug development.
High therapeutic efficacy of 5‐Fluorouracil‐loaded exosomes against colon cancer cells
Authors: Shekh Rafia , Ahmad Afza , Tiwari Rohit Kumar , Saeed Mohd , Shukla Ratnakar , Al‐Thubiani Wafa Safar , Ansari Irfan Ahmad , Ashfaque Mohd. , Bajpai Preeti 
Published: January 2023

AbstractThe successful chemotherapeutic regime required for the clinical management of different cancers largely depends on the efficient drug delivery within the cancer cells. Exosomes have emerged as an enticing candidate for exploring their role as delivery vehicles. Exosomes are reported to be intrinsically nanosized vesicles competent for efficient delivery across the cellular membrane. In the present study, we assessed the feasibility of an autologous exosome‐based drug delivery platform for delivering 5‐Fluorouracil (5‐FU) against human colon cancer HCT116 cells. Autologous exosomes have shown probable tropism toward the tumor microenvironment, which makes them the most competitive vehicle for drug delivery. It was observed that the autologous exosomes loaded with 5‐FU showed an enhanced rate of drug release under acidic conditions. The result of the cell viability assay showed that treatment of 5‐FU‐loaded exosomes (equivalent to 5 μg 5‐FU) resulted in enhanced cytotoxic effect in HCT116 cells as compared to an equivalent amount of free 5‐FU (5 μg), which elucidated the efficient delivery of the 5‐FU by exosomes inside the cancer cells. Subsequently, 5‐FU‐loaded exosomes led to increased nuclear condensation and fragmentation along with increased ROS production. In addition, 5‐FU‐loaded exosomes caused enhanced dissipation of mitochondrial membrane potential and caspase‐3 activation, resulting in increased apoptosis induction. Our study also revealed that 5‐FU‐loaded exosomes upsurged the arrest in the cell cycle at the G0/G1 stage in HCT‐116 cells and it was found to be associated with decreased CDK4 and Cyclin D1 expression concomitantly with the upregulation of CDK inhibitor, p21Cip1 expression. Thus, the findings from the present study highlight the advantages of autologous exosomes as a natural drug carrier which could efficiently deliver chemotherapeutic drugs to cancer cells.
The influence of NQO2 on the dysfunctional autophagy and oxidative stress induced in the hippocampus of rats and in SH‐SY5Y cells by fluoride
Authors: Ran Long‐Yan , Xiang Jie , Zeng Xiao‐Xiao , He Wen‐Wen , Dong Yang‐Ting , Yu Wen‐Feng , Qi Xiao‐Lan , Xiao Yan , Cao Kun , Zou Jian , Guan Zhi‐Zhong 
Published: January 2023

AbstractIntroductionFor investigating the mechanism of brain injury caused by chronic fluorosis, this study was designed to determine whether NRH:quinone oxidoreductase 2 (NQO2) can influence autophagic disruption and oxidative stress induced in the central nervous system exposed to a high level of fluoride.MethodsSprague–Dawley rats drank tap water containing different concentrations of fluoride for 3 or 6 months. SH‐SY5Y cells were either transfected with NQO2 RNA interference or treated with NQO2 inhibitor or activator and at the same time exposed to fluoride. The enrichment of gene signaling pathways related to autophagy was evaluated by Gene Set Enrichment Analysis; expressions of NQO2 and autophagy‐related protein 5 (ATG5), LC3‐II and p62, and mammalian target of rapamycin (mTOR) were quantified by Western‐blotting or fluorescent staining; and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) assayed biochemically and reactive oxygen species (ROS) detected by flow cytometry.ResultsIn the hippocampal CA3 region of rats exposed to high fluoride, the morphological characteristics of neurons were altered; the numbers of autophagosomes in the cytoplasm and the levels of NQO2 increased; the level of p‐mTOR was decreased, and the levels of ATG5, LC3‐II and p62 were elevated; and genes related to autophagy enriched. In vitro, in addition to similar changes in NQO2, p‐mTOR, ATG5, LC3 II, and p62, exposure of SH‐SY5Y cells to fluoride enhanced MDA and ROS contents and reduced SOD activity. Inhibition of NQO2 with RNAi or an inhibitor attenuated the disturbance of the autophagic flux and enhanced oxidative stress in these cells exposed to high fluoride.ConclusionOur findings indicate that NQO2 may be involved in regulating autophagy and oxidative stress and thereby exerts an impact on brain injury caused by chronic fluorosis.
Hypermethylation of HIC2 is a potential prognostic biomarker and tumor suppressor of glioma based on bioinformatics analysis and experiments
Authors: Luo Feifei , Liao Yifu , Cao Endong , Yang Yong , Tang Kai , Zhou Dexiang , Zhou Dong , Cai Haiping 
Published: January 2023

AbstractIntroductionGlioma is the most common primary tumor in the central nervous system, and prognostic biomarkers are still lacking. HIC ZBTB transcriptional repressor 2 (HIC2) is a hypermethylated gene that plays an important functional role in cardiac development. However, the actual role of HIC2 in glioma progression remains unclear. This study aimed to investigate the function of HIC2 and whether it could be a prognostic biomarker in glioma.MethodsThe DNA methylation and mRNA expression profiles of HIC2 were downloaded from public databases. The prognostic prediction ability and mechanism research of HIC2 were evaluated.ResultsWe found that HIC2 was hypermethylated and expressed at low levels in glioma samples. Hypermethylation and low expression of HIC2 predicted poor prognosis. Multivariate Cox regression analysis suggested that HIC2 was an independent prognostic factor for gliomas. Co‐IP assays demonstrated that HIC2 interacts with RNF44, and dual‐luciferase reporter assays and ChIP assays revealed that HIC2 transcriptionally inhibits PTPRN2 expression.ConclusionsOur findings suggest that HIC2 represents a tumor suppressor gene and prognostic biomarker for glioma progression and that overexpression of HIC2 inhibits the proliferation of glioma in vitro and in vivo by interacting with RNF44 and PTPRN2.
Patient‐reported outcomes after Tixagevimab and Cilgavimab pre‐exposure prophylaxis among solid organ transplant recipients: Safety, effectiveness, and perceptions of risk
Authors: Alejo Jennifer L. , Kim Jake D. , Chiang Teresa P.Y. , Avery Robin K. , Karaba Andrew H. , Jefferis Alexa , Warren Daniel S. , Massie Allan B. , Tobian Aaron A.R. , Segev Dorry L. , Werbel William A. 
Published: January 2023

AbstractBackgroundTixagevimab and Cilgavimab (T + C) is authorized for pre‐exposure prophylaxis (PrEP) against Coronavirus Disease 2019 (COVID‐19) in solid organ transplant recipients (SOTRs), yet patient‐reported outcomes after injection are not well described. Furthermore, changes in risk tolerance after T + C PrEP have not been reported, of interest given uncertain activity against emerging Omicron sublineages.MethodsWithin a national prospective observational study, SOTRs who reported receiving T + C were surveyed for 3 months to ascertain: (1) local and systemic reactogenicity, (2) severe adverse events with focus on cardiovascular and alloimmune complications, and (3) breakthrough COVID‐19, contextualized through (4) changes in attitudes regarding COVID‐19 risk and behaviors.ResultsAt 7 days postinjection, the most common reactions were mild fatigue (29%), headache (20%), and pain at injection sites (18%). Severe adverse events were uncommon; over 3 months of follow‐up, 4/392 (1%) reported acute rejection and one (.3%) reported a myocardial infarction. Breakthrough COVID‐19 occurred in 9%, 16–129 days after receiving full dose (300/300 mg) T + C, including two non‐ICU hospitalizations. Most surveyed SOTRs (65%) felt T + C PrEP was likely to reduce their COVID‐19 risk, and 70% reported increased willingness to engage in social activities such as visiting friends. However, few felt safe to return to in‐person work (20%) or cease public mask‐wearing (15%).ConclusionsIn this prospective study of patient‐reported outcomes, T + C was well tolerated with few serious events. Several COVID‐19 breakthroughs were reported, notable as most SOTRs reported changes in risk tolerance after T + C. These results aid counseling of SOTRs regarding real‐world safety and effectiveness of T + C.
International consortium for innovation and quality: An industry perspective on the nonclinical and early clinical development of intravitreal drugs
Authors: Pruimboom‐Brees Ingrid M. , Gupta Swati , Chemuturi Nagendra , Booler Helen S. , Nimz Erik , Ferrell Ramos Meg , Caruso Antonello , Maass Katie F. , Bantseev Vladimir , Huang Qihong , Choules Mary P. , Nussbaum Jesse C. , Kanodia Jitendra , Thompson Christopher , Durairaj Chandrasekar 
Published: January 2023

AbstractThe eye, which is under constant exposure to environmental pathogens, has evolved various anatomic and immunological barriers critical to the protection of tissues lacking regenerative capacity, and the maintenance of a clear optic pathway essential to vision. By bypassing the ocular barriers, intravitreal (IVT) injection has become the mainstay for the delivery of drugs to treat conditions that affect the back of the eye. Both small molecules and biotherapeutics have been successfully administered intravitreally, and several drugs have been approved for the treatment of (wet) age‐related macular degeneration and diabetic macular edema. However, IVT injection is an invasive procedure, which requires sufficient technical expertise from the healthcare professional administering the drug. Potential side effects include bleeding, retinal tear, cataracts, infection, uveitis, loss of vision, and increased ocular pressure. Pharmaceutical companies often differ in their drug development plan, including drug administration techniques, collection of ocular tissues and fluids, ophthalmology monitoring, and overall conduct of nonclinical and clinical studies. The present effort, under the aegis of the Innovation & Quality Ophthalmic Working Group, aims at understanding these differences, identifying pros and cons of the various approaches, determining the gaps in knowledge, and suggesting feasible good practices for nonclinical and early clinical IVT drug development.
Teaching Against Omnipotence: Mussolini's Racial Laws and the Ethics of Memory in Times of Neofascism
Authors: Salvio Paula M. 
Published: January 2023

AbstractThis essay opens on the streets of Rome in 2019 among displays of fascist relics, architecture, and memorial sites. Each display speaks to Italy's violent colonial and fascist history, one that continues to be entangled with and to overdetermine Italy's contemporary restrictive citizenship laws and anti‐immigrant policies. Here, Paula M. Salvio turns to a psychoanalytic understanding of omnipotence, and to Michael Rothberg's concept of multidirectional memory, in order to pursue the half‐spoken history of Italian fascism that is hauntingly absent from Italy's public school curriculum, as well as from sites of public pedagogy such as museums, cinema, memorials, and social media platforms. This absence raises important questions about the ethical obligation education has to teach against omnipotence in conventional classroom settings and sites of public pedagogy. Salvio concludes with a reading of a socially engaged project, the Holocaust Memorial located in the Milan Central Railway Station on Platform 21, that is aimed at teaching against omnipotence. The memorial stands as a site of conscience that is committed to making visible what was hidden for years — the deportation between 1943 and 1945 of Italian Jews from the Milan Central Railway Station to Auschwitz‐Birkenau and Bergen‐Belsen.
Role of herbivore‐induced maize volatiles in the chemotactic behaviour of Telenomus podisi and Diceraeus melacanthus
Authors: Nascimento Izabela N. , Michereff Mirian F. F. , Pereira Walter E. , Villas‐Boas Paulino R. , Gusmão Marcos Rafael , Caufield John , Laumann Raúl A. , Borges Miguel , Blassioli‐Moraes Maria Carolina 
Published: January 2023

AbstractPlants respond indirectly to herbivore injury in a species‐specific way and emit a specific blend of volatiles that are attractive to the enemies of herbivores. We evaluated whether maize plants, Zea mays L. (Poaceae), can recognize herbivory damage from a generalist stink bug, Diceraeus melacanthus Dallas (Hemiptera: Pentatomidae). This species is not a common pest in maize, but is currently found on maize crops in Brazil. We aimed to answer the following questions: (1) does D. melacanthus use maize plant volatiles for host location? (2) Do maize plant chemical volatile profiles change due to feeding by D. melacanthus? And (3) do herbivore‐induced plant volatiles (HIPVs) emitted by maize plants play a role in the foraging behaviour of the generalist stink bug egg parasitoid Telenomus podisi Ashmead (Hymenoptera: Scelionidae)? The results show that females of D. melacanthus do not use constitutive volatiles or HIPVs as host location cues. However, feeding by D. melacanthus activates maize indirect defence, inducing emission of HIPVs and attracting the herbivore's enemy. Thus, strengthening indirect defence of plants can be a strategy to protect crops in the field by recruiting natural enemies through chemical information, as an additional approach to control D. melacanthus within an integrated pest management program.
Predictors of treatment attrition of cognitive health interventions in first episode psychosis
Authors: Au‐Yeung Christy , Bowie Christopher R. , Montreuil Tina , Baer Larry H. , Lecomte Tania , Joober Ridha , Abdel‐Baki Amal , Jarvis G. Eric , Margolese Howard C. , De Benedictis Luigi , Schmitz Norbert , Thai Helen , Malla Ashok K. , Lepage Martin 
Published: January 2023

AbstractAimDropping out of psychological interventions is estimated to occur in up to a third of individuals with psychosis. Given the high degree of attrition in this population, identifying predictors of attrition is important to develop strategies to retain individuals in treatment. We observed a particularly high degree of attrition (48%) in a recent randomized controlled study assessing cognitive health interventions for first‐episode psychosis participants with comorbid social anxiety. Due to the importance of developing interventions for social anxiety in first episode psychosis, the aim of the present study was to identify putative predictors of attrition through a secondary analysis of data.MethodsParticipants (n = 96) with first episode psychosis and comorbid social anxiety were randomized to receive cognitive behavioural therapy for social anxiety or cognitive remediation. Differences between completers and non‐completers (<50% intervention completed) were compared using t‐tests or chi‐square analyses; statistically significant variables were entered into a multivariate logistic regression model.ResultsNon‐completers tended to be younger, had fewer years of education and had lower levels of social anxiety compared to completers. Lower baseline social anxiety and younger age were statistically significant predictors of non‐completion in the logistic regression model.ConclusionsAge and social anxiety were predictors of attrition in cognitive health interventions in first episode psychosis populations with comorbid social anxiety. In the ongoing development of social anxiety interventions for this population, future studies should investigate specific engagement strategies, intervention formats and outcome monitoring to improve participant retention in treatment.
Political connections of Chinese fund management companies and fund performance
Authors: He Chao , Kryzanowski Lawrence , Zhao Yunfei 
Published: January 2023

AbstractThis study uses hand‐collected information on shareholders’ backgrounds of mutual funds and their fund management companies (FMCs), and administrative and criminal penalties for insider trading as the proxy of government regulation intensity. We fill a gap in the literature by identifying a positive relationship between funds’ performance and the proportion of state‐owned FMC ownership that becomes negative when the Chinese government increased its regulatory effort to reduce informational advantages from political connections obtained through this ownership channel. Results are robust using DiD and IV analyses, placebo tests, propensity score matching, Oster test for missing covariates, channel tests, and alternate ownership classifications.
Thalamic subfield iron accumulation after acute mild traumatic brain injury as a marker of future post‐traumatic headache intensity
Authors: Chong Catherine D. , Nikolova Simona , Dumkrieger Gina , Wu Teresa , Berisha Visar , Li Jing , Ross Katherine , Schwedt Todd J. 
Published: January 2023

AbstractObjectiveTo explore alterations in thalamic subfield volume and iron accumulation in individuals with post‐traumatic headache (PTH) relative to healthy controls.BackgroundThe thalamus plays a pivotal role in the pathomechanism of pain and headache, yet the role of the thalamus in PTH attributed to mild traumatic brain injury (mTBI) remains unclear.MethodsA total of 107 participants underwent multimodal T1‐weighted and T2* brain magnetic resonance imaging. Using a clinic‐based observational study, thalamic subfield volume and thalamic iron accumulation were explored in 52 individuals with acute PTH (mean age = 41.3; standard deviation [SD] = 13.5), imaged on average 24 days post mTBI, and compared to 55 healthy controls (mean age = 38.3; SD = 11.7) without history of mTBI or migraine. Symptoms of mTBI and headache characteristics were assessed at baseline (0–59 days post mTBI) (n = 52) and 3 months later (n = 46) using the Symptom Evaluation of the Sports Concussion Assessment Tool (SCAT‐5) and a detailed headache history questionnaire.ResultsRelative to controls, individuals with acute PTH had significantly less volume in the lateral geniculate nucleus (LGN) (mean volume: PTH = 254.1, SD = 43.4 vs. controls = 278.2, SD = 39.8; p = 0.003) as well as more iron deposition in the left LGN (PTH: T2* signal = 38.6, SD = 6.5 vs. controls: T2* signal = 45.3, SD = 2.3; p = 0.048). Correlations in individuals with PTH revealed a positive relationship between left LGN T2* iron deposition and SCAT‐5 symptom severity score at baseline (r = −0.29, p = 0.019) and maximum headache intensity at the 3‐month follow‐up (r = −0.47, p = 0.002).ConclusionRelative to healthy controls, individuals with acute PTH had less volume and higher iron deposition in the left LGN. Higher iron deposition in the left LGN might reflect mTBI severity and poor headache recovery.
Developing multivariable models for predicting headache improvement in patients with acute post‐traumatic headache attributed to mild traumatic brain injury: A preliminary study
Authors: Mao Lingchao , Dumkrieger Gina , Ku Dohyun , Ross Katherine , Berisha Visar , Schwedt Todd J. , Li Jing , Chong Catherine D. 
Published: January 2023

AbstractObjectives/BackgroundPost‐traumatic headache (PTH) is a common symptom after mild traumatic brain injury (mTBI). Although there have been several studies that have used clinical features of PTH to attempt to predict headache recovery, currently no accurate methods exist for predicting individuals’ improvement from acute PTH. This study investigated the utility of clinical questionnaires for predicting (i) headache improvement at 3 and 6 months, and (ii) headache trajectories over the first 3 months.MethodsWe conducted a clinic‐based observational longitudinal study of patients with acute PTH who completed a battery of clinical questionnaires within 0–59 days post‐mTBI. The battery included headache history, symptom evaluation, cognitive tests, psychological tests, and scales assessing photosensitivity, hyperacusis, insomnia, cutaneous allodynia, and substance use. Each participant completed a web‐based headache diary, which was used to determine headache improvement.ResultsThirty‐seven participants with acute PTH (mean age = 42.7, standard deviation [SD] = 12.0; 25 females/12 males) completed questionnaires at an average of 21.7 (SD = 13.1) days post‐mTBI. The classification of headache improvement or non‐improvement at 3 and 6 months achieved cross‐validation area under the curve (AUC) of 0.72 (95% confidence interval [CI] 0.55 to 0.89) and 0.84 (95% CI 0.66 to 1.00). Sub‐models trained using only the top five features still achieved 0.72 (95% CI 0.55 to 0.90) and 0.77 (95% CI 0.52 to 1.00) AUC. The top five contributing features were from three questionnaires: Pain Catastrophizing Scale total score and helplessness sub‐domain score; Sports Concussion Assessment Tool Symptom Evaluation total score and number of symptoms; and the State‐Trait Anxiety Inventory score. The functional regression model achieved for modeling headache trajectory over the first 3 months.ConclusionQuestionnaires completed following mTBI have good utility for predicting headache improvement at 3 and 6 months in the future as well as the evolving headache trajectory. Reducing the battery to only three questionnaires, which assess post‐concussive symptom load and biopsychosocialecologic factors, was helpful to determine a reasonable prediction accuracy for headache improvement.