bluuebunny/crossref_metadata_2025 huggingface dataset:
An analysis of the use of visual elements in workplace diversity disclosure
Authors: Momin Mahmood , Chong Sabrina
Published: January 2023

Purpose

The purpose of this study is to examine how visual elements along with textual narratives are used to disclose workplace diversity-related information in corporate social and environmental reports.

Design/methodology/approach

A qualitative content analysis is used to examine the workplace diversity-related information in the 2016 standalone sustainability/corporate responsibility reports of 47 Fortune companies. A total of 539 tables, figures and photographs and their related textual narratives are analysed through an impression management lens.

Findings

The study finds that multiple types of visual elements are used to supplement textual narratives to communicate workplace diversity-related messages. The positive and often non-verifiable workplace diversity-related information is symbolically suggestive of the companies’ workplace diversity commitment and success. While tables and figures are typically presented using numbers, percentages and words to enhance and promote the positive information, the “feel-good” photographs are used to arouse positive feelings in the readers. These visual elements are presented in either a single-visual or mixed-visual presentation form.

Practical implications

This study has the potential to inform and assist preparers in the use of multiple visual elements and textual narratives to promote an impartial and substantive reporting of workplace diversity-related information. Understanding the motivation behind the usage and presentation of visual elements can be useful for the promulgation of guidelines for workplace diversity disclosure, and make readers aware that the visual elements can be exploited for impression management and symbolic legitimacy.

Originality/value

This study provides empirical evidence on the use of multiple types of visual elements in the reporting of workplace diversity-related information. It demonstrates how these visual elements are strategically used and presented to deliver an impression of workplace diversity to the readers.
Effects of precipitated and ground calcium carbonate coating on mechanical properties of fluting paper
Authors: Çiçekler Mustafa , Üzüm Velican , Çopurkuyu Emrullah
Published: January 2023

Purpose

The purpose of this study is to investigate the effects of a pigment coating on the mechanical properties of fluting paper.

Design/methodology/approach

Two different calcium carbonate pigments were used in the preparation of the coated color, precipitated calcium carbonate (PCC) and ground calcium carbonate (GCC). Fluting paper produced by recycling waste paper was used as base paper. The effects of PCC and GCC pigments on mechanical properties were compared. Ring crush test (RCT), corrugating medium test (CMT), corrugating crush test (CCT), tensile and burst strength tests were applied to the coated papers, and the results were compared to the mechanical properties of base paper.

Findings

The tensile and burst indices of the coated papers were found to be higher than base papers about 13.9% and 6.05%, respectively. While the coating process positively affected the RCT and CCT values, it did not show a significant impact on the CMT values. GCC, one of the pigments used in coating colors, had a more effective effect on the mechanical properties of fluting papers compared to PCC.

Originality/value

These results suggest that coating of fluting papers has a positive effect on mechanical properties and the use of GCC as a pigment is more effective than PCC.
Airline brand image, passenger perceived value and loyalty towards full-service and low-cost carriers
Authors: Fu Yan-Kai
Published: January 2023

Purpose

This study aims to examine the mediating and moderating processes that link airline brand image to passenger loyalty through perceived value.

Design/methodology/approach

The research participants were Taiwanese passengers with experience travelling abroad by air. Structural equation modelling and multigroup analysis were used to investigate the effect of airline brand image and perceived value on the loyalty of passengers using full-service and low-cost carriers.

Findings

For both airline types, airline brand image had a significant and positive effect on passenger perceived value. Perceived value had a significant and positive effect on passenger loyalty, perceived value was a crucial mediator and airline type was not a key moderator in the model.

Originality/value

In this study, focusing on the perspective of Taiwanese passengers, a conceptual model of the factors that lead to passenger loyalty, with a focus on brand image, was developed. This paper contributes to the literature and application field by examining the mediating effect of perceived value and the moderating role of airline type in the aviation industry; on the basis of the results, potential recovery strategies for airlines in the post-COVID-19 era are provided.
Association between the first exposure to general anesthesia and alopecia areata
Authors: Lee Heera , Choi Young Woong , Kim You Chan , Choi Jee Woong
Published: January 2023

Alopecia areata (AA) is an autoimmune cutaneous disorder reported to be related to various immunologic diseases and psychiatric disorders. Some AA patients report the onset of patchy hair loss after surgeries under general anesthesia (GA). However, no large‐scale studies have been conducted on the relationship between AA and GA. Thus, we aimed to evaluate whether exposure to GA is associated with an increased risk of AA. In this retrospective study, we analyzed a population exposed to GA. These individuals were compared to unexposed controls, matched by age, sex, income level, and comorbidities (propensity score matching, 1:2 ratio), from the national sample cohort from January 1, 2002, to December 31, 2015. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for the risk of AA associated with GA using Cox proportional hazard regression. As a result, the risk of AA occurrence was significantly higher in the GA‐exposed group after adjusting confounding factors (adjusted HR 1.22, 95% CI 1.07–1.43, P = 0.005). The cumulative incidence of AA was higher in the GA‐exposed group (log‐rank P = 0.005). The risk of AA increased with GA exposure time. However, the type of surgery and the method of anesthesia did not impact the risk of developing AA. Thus, in conclusion, exposure to GA was associated with a higher risk of developing AA.
IL‐31 and IL‐31 receptor alpha in pemphigus: Contributors to more than just itch?
Authors: Okuno Satoshi , Hashimoto Takashi , Yamazaki Yuki , Okuzawa Manami , Satoh Takahiro
Published: January 2023

Pemphigus is an autoimmune blistering disorder with four major subtypes: pemphigus vulgaris (PV), pemphigus vegetans (PVe), pemphigus foliaceus (PF), and pemphigus herpetiformis (PH). Among them, PF and PH present itching as a clinical feature; however, the mechanisms behind the pruritus are still unclear. In this report, we sought to investigate the expression of a type 2 inflammation‐related pruritogenic cytokine IL‐31 and its receptor subunit IL‐31RA through immunofluorescence staining analysis. The number of eosinophils, basophils, and mast cells, and the expression levels of thymic stromal lymphopoietin (TSLP) and periostin were also investigated. Evaluation showed an increase in the number of dermal IL‐31+ cells and IL‐31RA+ cells in PH and PVe. Epidermal expression of IL‐31RA increased in PV, PF, and PVe, but not in PH, compared to healthy individuals. The number of dermal eosinophils and basophils was also increased in PVe and PH. The number of dermal mast cells and expression levels of TSLP and periostin did not change among pemphigus subtypes and healthy controls. Collectively, enhanced IL‐31/IL‐31RA signaling and the increased numbers of dermal eosinophils and basophils may participate in itching in PH. On the other hand, IL‐31/IL‐31RA signaling seemed unable to provoke itching in PVe, a non‐pruritic subtype of pemphigus, although it might contribute to epidermal thickening and dermal fibrosis.
Gender targets and trickle‐down effects: Avoiding the ‘decoupling dynamics’ that limit female representation in senior roles
Authors: Gould Jill A. , Kulik Carol T. , Sardeshmukh Shruti R.
Published: January 2023

Women constitute the majority of the Australian public sector workforce, but their representation in senior roles is not proportional. Australian public services have gender targets to improve the representation of women in senior roles. Based on previous research, targets are expected to first increase female representation at the target's focal level, such as executive level. Then they should initiate a trickle‐down effect (TDE), increasing female representation at the level immediately below the target's focal level, such as the executive feeder level. However, the TDE observed in a state public service decelerated after a gender target was imposed. We identified whether individual departments had a consistent or inconsistent TDE and conducted 13 semi‐structured interviews with key stakeholders. Too many service‐wide targets with low prioritisation of a gender target, as well as missing and ineffective practices, generated decoupling dynamics. Only departments with gender champions who had visible backing from the Chief Executive were able to keep the gender target coupled with practice to achieve its intended outcomes.

Points for practitioners

Gender targets in Australian public services may not be achieving intended outcomes due to decoupling—a response to policies in which the policies are ignored and/or ineffective practices are implemented.

Too many competing targets and limited accountability for achieving a gender target create a potential for decoupling by allowing individuals and groups to ignore or weakly adopt the policy.

Integrated bundles of top‐down (e.g. requiring at least two women on shortlists) and bottom‐up practices (e.g. mentoring) can help avoid decoupling by ensuring women are appointed to senior roles and supported to progress through an organisation.

Chief Executives are key to ensuring a gender target remains coupled with its implementation; Chief Executives must provide visible support to internal champions to make gender targets effective.
Increasing livelihood vulnerabilities to coastal erosion and wastewater intrusion: The political ecology of Thai aquaculture in peri‐urban Bangkok
Authors: Marks Danny , Bayrak Mucahid Mustafa , Connell John
Published: January 2023

Most livelihood research focuses on micro‐level decisions affecting occupations but fails to examine wider scale processes that shape markets, institutions, and thus livelihood choices. A political ecology framework can help address this gap by providing ways to analyse how multi‐scalar and extra‐local practices, policies, and discourses affect local‐level socio‐environmental outcomes. In the qualitative research reported here, that framework is applied to Tha Kam, a peri‐urban coastal sub‐district of Bangkok, where most residents are small‐scale aquaculture farmers. These farmers have experienced precipitous drops in incomes because of two major environmental changes: coastal erosion and wastewater intrusion. The causes are multiple and complex, and many originate not from practices within Tha Kham but from challenges present at a larger scale or that start upstream. The political and economic drivers of these problems stem from Thailand’s fragmented vertical and horizontal governance structure, unequal class relations in which smallholder farmers and peri‐urban residents are marginalised, and lack of accountability and representation. This combination of multi‐scalar factors and power imbalances has contributed to evolving injustices of peri‐urbanisation, all of which are profoundly geographical in their significance.
Quantification of phytochemicals, and compounds’ identification in functional tea from Ficus capensis and Justicia secunda
Authors: Uchegbu Nneka Nkechi , Fasuan Temitope Omolayo , Onuoha Nchekwube Love
Published: January 2023

This work evaluated the development of beverage from Ficus capensis and Justicia secunda leaves composite using response surface methodology three‐level factorial design gas chromatography–mass spectrophotometry. Fresh leaves of F. capensis and J. secunda were processed into tea. The results indicated the optimal extracts blends of 48% of F. capensis and 52% of J. secunda. The iron content was 489.11 mg/g; flavonoid content, 83.64 mg QE/100 g; vitamin C content, 1003.14 mg/100 g; and pyridoxine content, 357.31 mg/100 g. Alkaloid profile showed tetrahydrorhombiofoline (35%), columbamine (20.10%), laudanosine (11.50%), salsoline (8.22%), methylcobalamin (7.98%), quinine (5.89%), and quinidine (3.21%). Other phytocompounds with bioactive characteristics include 11‐octadecenoic acid, methyl ester (32.43 g/100 g); hexadecanoic acid, methyl ester (16.69 g/100 g); 9,12‐octadecadienoic acid (Z,Z)‐, methyl ester (12.81 g/100 g); (E)‐9‐octadecenoic acid, ethyl ester (9.71 g/100 g); hexadecanoic acid, ethyl ester (5.86 g/100 g); methyl stearate (4.62); linoleic acid, ethyl ester (4.62 g/100 g), octadecanoic acid, ethyl ester (1.84 g/100 g); and octasiloxane, 1,1,3,3,5,5,7,7,9,9,11,11,13,13,15,15‐hexadecamethyl (0.19 g/100 g) with good sensory attributes. The optimized tea from F. capensis and J. secunda is rich in health‐supporting substances and could be employed in promoting healthy living.
Change of stream network connectivity under polder‐type flood control measure
Authors: Gao Yuqin , Liu Yunping , Gao Li , Wu Ming , Intriago Gordillo Jhandre Ronald , Xue Zheng , Chen Shuning
Published: January 2023

Polder is usually used for flood control in the river delta area. With the rapid development of urbanization, the dikes or pumps cut the original stream network system, and the stream network connectivity (SNC) and the river system pattern have changed. The dikes or pumps generally force up the river's water level, and regional flood formation mechanisms and processes have changed. In order to quantitatively describe the characteristics of polder‐type flood control measure (PFCM) and the change law of SNC, firstly, the streams inside polders were generalized as virtual streams, a hydrological‐hydrodynamic model was constructed by connecting Hydrologic Engineering Center‐Hydrologic Modeling System and MIKE11 model. Secondly, an SNC evaluation model was constructed based on flow resistance and hydrological process. Finally, the SNC under different scenarios was simulated and evaluated to reveal the influence of the PFCM on SNC. And the dominance analysis method obtained the main control factors of SNC changes. The results showed that the pumps as the main drainage facility under the PFCM, SNC after the opening of the pumps were increased by 0.060, 0.103, and 0.311 for 50%, 30%, and 3% frequency flood scales compared with the pumps closed, respectively. However, compared with the natural stream (without the PFCM), the SNC decreased by 0.391, 0.456, and 0.487, respectively, at the same time of the same flood scale. The PFCM negatively impacted the SNC, and the number of pumps was the main control factor of the SNC.
Investigating the role of delayed contrast magnetic resonance imaging (MRI) to differentiate radiation necrosis from tumour recurrence in brain metastases after stereotactic radiosurgery
Authors: Admojo Lorenztino , Korte James , Anderson Nigel , Phillips Claire , Caspersz Lauren , Lasocki Arian
Published: January 2023

Introduction

The incidence of radionecrosis (RN) after stereotactic radiosurgery (SRS) to brain metastases is increasing. An overlap in the conventional MRI appearances of RN and tumour recurrence (TR) is diagnostically challenging. Delayed contrast MRI compares contrast enhancement over two time periods to create treatment response assessment maps (TRAMs). We aim to assess the utility of TRAMs in brain metastases patients.

Methods

Delayed contrast MRI scans were performed on ten brain metastases patients, previously treated with SRS, who developed equivocal lesion(s) on routine MRI follow‐up. T1‐weighted images were obtained five minutes and 60–75 min after contrast injection, followed by Brain Lab software analysis to create TRAMs. TRAMs patterns were then compared with the patient's clinical status, subsequent imaging, and histology results.

Results

We identified three regions on TRAMs: central, peripheral, and surrounding. Each region could be described either as contrast accumulation (red colour and representing non‐tumour tissue) or contrast clearance (blue colour and representing tumour tissue). Our analysis demonstrated similarities in the TRAMs pattern between TR and RN, though to varying degrees.

Conclusion

In conclusion, the TRAMs appearances of RN and TR overlap. Our findings suggest that the previously‐described correlation between contrast clearance and TR is at least partially attributable to more solid initial enhancement, rather than convincingly a difference in the underlying tissue properties, and the additional diagnostic value of TRAMs may be limited. Thus, further research on TRAMs is necessary prior to incorporating it into routine clinical management after SRS for brain metastases.
Intestinal morphometry and cell density features in tropical farmed fish: A methodological approach
Authors: Bellinate Bruna Karla Assad , Farias Karine Nathiele Nogueira , do Nascimento Silva André Luiz , Siqueira Mayara Schueroff , Povh Jayme Aparecido , Franco‐Belussi Lilian , Fernandes Carlos Eurico
Published: January 2023

The digestive tract of fish has many morphological adaptations related to habitat and nutrition. Intestinal biometry may reflect these adaptations. Here, we aimed to describe histometric patterns in farmed fish and their relationship with feeding by using a standardized protocol considering cell density by tissue area. Five juvenile specimens of each species (Pseudoplatystoma corruscans, Piaractus mesopotamicus, and Oreochromis niloticus) were used. O. niloticus possessed higher intestinal weight and length besides higher intestinal quotient and intestinal somatic index than the other species. The general histological composition was similar between species. However, P. corruscans showed differences in thickness between the anterior and posterior segments. O. niloticus had thinner serosa and muscularis layers than the other species. The cell density was distinct in both species and segments. Comparing the intestinal segments, O. niloticus displayed the lowest count of granulocytes. Goblet cell density was lower in P. mesopotamicus in all segments. However, the volume of these cells was higher in the anterior and middle anterior segments. Our data demonstrated that intestinal structural plasticity is associated with the difference in feeding habits. Here, we used quantitative standardized histometric criteria to understand the morphophysiological diversity of the fish digestive tract, and this technique can be applied in future studies to evaluate changes in the digestive tracts of vertebrates.
What are Sertoli cells? Historical, methodological, and functional aspects
Authors: Thumfart Kristina M. , Mansuy Isabelle M.
Published: January 2023

Sertoli cells are somatic cells that are in close contact with germ cells in the mammalian testes. They have multiple functions and fulfill key roles for the development and proper maturation of spermatogenic cells into functional spermatozoa. One of their most important properties is to release trophic factors and supply nutrients to germ cells. But they are also involved in the regulation of the immune system in testis, and provide an immunologically privileged environment for developing germ cells. Because they are so essential for reproductive cells, their alterations can have detrimental consequences for fertility. Many environmental factors and exposures such as high caloric diet, toxins, and pollutants are thought to compromise Sertoli cells physiology. This review describes the discovery of Sertoli cells and the methods used for their study, summarizes their major properties and functions, and describes their dysfunctions in pathologies, particularly associated with environmental stressors.
“Addressing the core trait of bipolar disorder”: A concept analysis of mood‐stabilizing drugs
Authors: Marchionatti Lauro Estivalete , Blaya‐Rocha Paula , Magalhães Pedro VS
Published: January 2023

Objective

The term “mood stabilizer” is controversial in the literature and criticized for being imprecise and overly inclusive, having its retirement suggested to avoid misuse. Nevertheless, it continues to be employed as it may still carry important meaning.

Methods

We employed document analysis for reviewing relevant definitions of mood stabilizer employed in the literature. Then, we clarify the meanings associated with the term by employing evolutionary concept analysis. Based on its results, we present a theoretical model for a mood stabilizer and further match it with evidence gathered from published meta‐analyses and other sources for drugs used in the treatment of bipolar disorder.

Results

Concept analysis unearthed four attributes of a mood stabilizer that were nested into the following ascending hierarchy: “not worsening,” “acute effects,” “prophylactic effects,” and “advanced effects.” “Prophylactic effects” were often considered the core aspect of a legitimate mood stabilizer.

Conclusion

The proposed model uses a hierarchy of attributes that take into account the complexity of the term and help to determine whether a drug is a mood stabilizer. Prophylaxis is pivotal to the concept, whose utility lies in implying a drug able to truly treat bipolar disorder, as opposed to merely targeting symptoms. Consistent use of the term could encourage investigation of drugs that modify long‐term outcomes and illness trajectory, instead of simply approaching symptom clusters.
Quality of laboratory biomarker monitoring during treatment with lithium in patients with bipolar disorder
Authors: Bosi Alessandro , Ceriani Laura , Elinder Carl‐Gustaf , Bellocco Rino , Clase Catherine M. , Landen Mikael , Carrero Juan‐Jesus , Runesson Björn
Published: January 2023

Background

Clinical guidelines recommend monitoring of creatinine and lithium throughout treatment with lithium. We here assessed the extent to which this occurs in healthcare in Sweden.

Methods

This is an observational study of all adults with bipolar disorder starting lithium therapy in Stockholm, Sweden, during 2007–2018. The main outcome was monitoring of blood lithium and creatinine at therapy initiation and/or once annually. The secondary outcome was monitoring of calcium and thyroid‐stimulating hormone (TSH). Patients were followed up until therapy cessation, death, out‐migration, or to the end of 2018.

Results

We identified 4428 adults with bipolar disorder who started lithium therapy and were followed up for up to 11 years. Their median age was 39 years, and 63% were women. The median duration on lithium therapy was 4.3 (IQR: 1.9–7.45) years, and the majority who discontinued therapy started another mood stabilizer soon after. Overall, 21% started lithium therapy without assessing the serum/plasma concentration of creatinine. The proportion of people who did not have both lithium and creatinine measured increased from 21% in the first year to 33% in the eleventh year. The proportion with annual testing for TSH or calcium was slightly lower. As few as 16% of patients had both lithium and creatinine tested once annually during their complete time on lithium.

Conclusions

In a Swedish community sample, lithium and creatinine monitoring was inconsistent with guideline recommendations that call for measurement of annual biomarker levels.
Gut microbiome in allogeneic HCT survivors: The insults are gone but the damage lingers
Authors: van Lier Yannouck , Hazenberg Mette D.
Published: January 2023

The gut microbiome is an important regulator of health and disease. The report by Hino et al. suggests that damage to the microbiome, inflicted before and soon after allogeneic haematopoietic progenitor cell transplantation, does not heal by itself, most likely with consequences for late transplantation outcomes.

Commentary on: Hino et al. Prolonged gut microbial alterations in post‐transplant survivors of allogeneic haematopoietic stem cell transplantation. Br J Haematol 2023;200:725‐737.
Plant–treehopper convergence may trick butterflies into trophic oviposition mistakes
Authors: Lima Luan Dias , Ceballos‐González Amalia Victoria , Prato Amanda , Kaminski Lucas Augusto , do Nascimento Fábio Santos
Published: January 2023

Our research aimed to compare the chemical cues of treehoppers and host plants in two rare cases of herbivorous myrmecophilous butterflies laying eggs on treehoppers. Our hypothesis that the cuticular hydrocarbon (CHC) profiles of the treehoppers would resemble those of their host plants was confirmed.
Morale, performance and disclosure
Authors: Jiang Xu , Xue Ying
Published: January 2023

We 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

Intratumoral 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

The 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

Introduction

For 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.

Methods

Sprague–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.

Results

In 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.

Conclusion

Our 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

Introduction

Glioma 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.

Methods

The DNA methylation and mRNA expression profiles of HIC2 were downloaded from public databases. The prognostic prediction ability and mechanism research of HIC2 were evaluated.

Results

We 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.

Conclusions

Our 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

Background

Tixagevimab 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.

Methods

Within 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.

Results

At 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%).

Conclusions

In 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

The 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

This 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

Plants 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

Aim

Dropping 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.

Methods

Participants (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.

Results

Non‐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.

Conclusions

Age 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.
Current advances in antiviral RNA interference in mammals
Authors: Wang Jiaxin , Li Yang
Published: January 2023

Mammals have potent innate immune systems that work together to fight against a variety of distinct viruses. In addition to interferon (IFN) response, which has been intensively studied, antiviral RNA interference (RNAi) is gradually being studied. However, previous studies indicated low Dicer activity on double‐stranded RNA (dsRNA) substrates in vitro and that IFN response masks or inhibits antiviral RNAi in mammals. Therefore, whether or not the RNAi is functional for antiviral response in mammalian somatic cells is still an ongoing area of research. In this review, we will present the current advances in antiviral RNAi in mammals and focus on three fundamental questions critical to the intense debate about whether RNAi can function as an innate antiviral immunity in mammals.
Political connections of Chinese fund management companies and fund performance
Authors: He Chao , Kryzanowski Lawrence , Zhao Yunfei
Published: January 2023

This 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

Objective

To explore alterations in thalamic subfield volume and iron accumulation in individuals with post‐traumatic headache (PTH) relative to healthy controls.

Background

The 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.

Methods

A 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.

Results

Relative 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).

Conclusion

Relative 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.