bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive factors of development of dysthyroid optic neuropathy among individuals with thyroid-eye disease
Authors: Kemchoknatee Parinee , Thongsawangchai Nicha , Srisombut Thansit , Tangon Duanghathai , Chantra Somporn
Published: September 2023

Purpose

Dysthyroid optic neuropathy (DON) is a severe visual loss condition in thyroid eye disease (TED). This study aimed to identify factors affecting moderate-to-severe TED or DON in Thai populations.

Methods

We retrospectively reviewed the records of 230 TED patients at Rajavithi Hospital between January 1, 2017, and October 31, 2022.

Results

Mild, moderate-to-severe TED, and DON were found in 60.43%, 22.61%, and 16.96% of participants, respectively. Female predominance was noted in all groups. The proportion of older age, hyperthyroidism, current smokers, and type 2 diabetes mellitus (T2DM) participants were significantly higher in the DON group. Multivariable logistic-regression analysis revealed that hyperthyroidism and current smoking significantly increased the risk of developing moderate-to-severe TED (OR = 3.001, p = 0.010, and OR = 4.153, p = 0.015, respectively). Exophthalmos was the strongest predictor (OR = 6.834, p < 0.001). Regarding DON risk factors, older age (≥55 years) had OR = 3.206 ( p = 0.003), hyperthyroidism had OR = 3.228 ( p = 0.005), and being a current smoker had OR = 3.781 ( p = 0.011). T2DM posed the greatest risk of DON development (OR = 4.111, p = 0.004).

Conclusions

Hyperthyroidism and current smoking are significant risk factors for moderate-to-severe TED and DON. TED patients with diabetes mellitus or older age should be closely monitored and informed about their risk of developing DON.
Food is fuel for tourism: Understanding the food travelling behaviour of potential tourists after experiencing ethnic cuisine
Authors: Aziz Sadia , Khan Niazi Muhammad Abdullah , Zafar Shandana
Published: September 2023

Food or culinary tourism has become a field of interest for scholars, and food tourism is considered a vital part of tourism research. The study aims to understand how value creation at ethnic cuisine influences the travelling behaviour of potential tourists. The study has considered potential tourists’ ethnocentrism/cosmopolitanism behaviour affecting the intention to consume food at the destination. The influence of destination image as a mediator and food neophilia as a moderating is considered to understand the behavioural patterns of ethnic food consumer and their intention to visit a destination. This study used the cross-sectional descriptive research design. A field survey was conducted, and data were gathered from visitors of Chinese cuisines in four major cities of Pakistan. The study results are divided into four categories. First, the direct effect shows that consumers’ cosmopolitan positive and ethnocentric behaviour has a negative effect on the intention to consume ethnic food at the destination. Second, the mediation results show that consumption value significantly mediates the relationship between consumer cosmopolitan and intention to consume ethnic food at the destination while insignificantly mediates between consumer ethnocentrism and intention to consume ethnic food at the destination. Experiential value significantly mediates the relationship between consumer cosmopolitan/ethnocentrism. Third, results for serial mediation showed that destination image with the experiential and consumption value significantly serially mediated the relationships. Finally, results showed that food neophilia has significantly moderated the relationship. The study is a unique effort in the field of culinary tourism and will help researchers and destination management officers (DMOs) to understand the role of local ethnic cuisine in shaping the intentions of potential tourists to travel and consume food at destinations.
Music therapy in paediatric palliative care: A scoping review
Authors: Overå Monika
Published: September 2023

The aim of this scoping review is to summarise the existing empirical evidence and produce an overview of the ways in which music therapy in paediatric palliative care is described in the literature, with a specific focus on hospital-at-home. It was performed through searches undertaken in eight databases and completed using the methodological framework proposed by Arksey and O’Malley. The findings of the scoping review indicate the following: (1) there is no clear definition of music therapy in paediatric palliative care; (2) there is limited research on paediatric palliative care; (3) music therapy in hospital-at-home offers isolated patients and families a feeling of connectedness; (4) both expressive and receptive music therapy approaches are included in the existing studies, emphasising the need to adapt to the patient’s age, abilities, interests and energy levels; and (5) the outcomes of the music therapy discussed in the literature focus on enhancing the quality of life. Overall, music therapy appears to be an asset for the interdisciplinary team working to improve quality of life, but research methods which respond specifically to the voices of the children and adolescents must be developed to improve paediatric palliative care further.
Predicting the financial wellbeing of autistic adults: Part I
Authors: Cai Ru Ying , Hall Gabrielle , Pellicano Elizabeth
Published: September 2023

Many autistic adults are likely to experience poor financial wellbeing and hardship due to unemployment and under-employment. Research in the general population demonstrates that subjective financial wellbeing—how people perceive their financial situation—influences quality of life. There is no research, however, examining the subjective financial wellbeing of autistic people. This study therefore aimed to (1) understand the subjective financial wellbeing of a sample of autistic adults living in Australia compared to a general Australian population sample and (2) identify the predictors of subjective financial wellbeing in this sample of autistic adults. To this end, 191 autistic adults aged 18–83 years (mean = 39.28, standard deviation = 11.74) completed an online survey about their economic status, financial wellbeing, financial behaviors, confidence in money management skills, and anxiety and depression symptoms. Almost half of our sample felt it was a struggle to make ends meet, whereas only one-third of the general Australian population felt this way. Similar to the general population, autistic people’s income and their financial behaviors (specifically, saving and not borrowing for everyday expenses) predicted their sense of financial wellbeing. Our findings have implications for both research and practice.

Lay abstract

Researchers have found the way people feel about their financial situation is related to their quality of life. We know that many autistic people find it hard to find a job. And for those autistic people who have a job, they are often underpaid. Not having a job or being underpaid often means having low income. Having low income is likely to influence how autistic people feel about their financial situation. However, no research has looked at these issues for autistic people. This is the first study that helps us learn more about what autistic adults think about their financial situation. We looked at autistic people’s thoughts on this issue compared to people from the general Australian population. We also looked at what things might impact how autistic people feel about their financial situation—which might be how much money they earn, what they do with that money, and their mental health. Many autistic adults felt they were struggling with financial wellbeing and this was connected both to the level of their income and how they said they managed their money. Those who were able to save and not borrow for everyday expenses reported feeling a greater sense of financial wellbeing. Concrete changes might help to improve autistic people’s financial wellbeing. We need to investigate how we can help autistic people find and keep well-paying jobs. And we need to work out the best ways of equipping autistic people with the skills they need in financial matters.
Sensemaking and evidence in criminal investigations of organised crime: A literature review
Authors: Visser Coen , Markus Arjan , de Poot Christianne , Kop Nicolien , Weggeman Mathieu
Published: September 2023

Producing evidence that can be used in court is a central goal of criminal investigations. Forensic science focuses with considerable success on the production of pieces of evidence from specific sources. However, less is known about how a team of investigating police officers progressively produces a body of evidence during the course of a criminal investigation. This literature review uses Weickian sensemaking to analyse what is known about this process in criminal investigations into organised crime. Focusing on the criminal investigation team, collective sensemaking is used as a lens through which to place the reasoning processes used in constructing evidence in a social context. In addition to describing three constituent parts of collective sensemaking relevant for criminal investigations, six factors are identified that influence the quality of collective sensemaking. Building on these results, nine focal points are presented for analysing the sensemaking processes in a criminal investigation team, aimed at advancing knowledge about the production of evidence in criminal investigations of organised crime. Furthermore, a definition of evidence is developed that is suitable for studying sensemaking in the context of an ongoing criminal investigation.
China’s metaphorically “othered” image in The New York Times (1949-2020)
Authors: Shi Linfei , Jiang Yajun , Ma Junjie
Published: September 2023

This study investigates, within the framework of Critical Metaphor Analysis, how The New York Times ( NYT) has been metaphorically formulating China as an “other” from 1949 to 2020. Metaphors were identified with reference to Pragglejaz Group’s (2007) Metaphor Identification Procedure. WAR and GAME were detected as dominant concepts, and LIQUID, DISEASE, ANIMAL, MACHINE, and OBSTACLE secondary imagery. It is found that the newspaper’s journalistic values in foreign news reporting and judging criteria toward political leadership have remained radically unchanged. Having been influenced by changes in China-U.S. relations and America’s domestic socio-political ideals, the NYT has been othering China from the civilized world, which tends to be particularly prominent when China’s performance is short of the values and norms preached by the US, and became inconspicuous during China-U.S. alliance. Running counter to its commitment to “truth,” the newspaper employed discursive strategies to balance between America’s moral self-identity and its China policy, and vindicate behaviors identical to those it has been criticizing China for.
Introducing the PFxEU tracker dataset: Tracking political financing in the European Union
Authors: Katsaitis Alexander
Published: September 2023

A rich literature examines the links between politics, money and corruption across the globe. Somewhat surprisingly, this topic has not found much attention in European Union studies. This article presents the PFxEU tracker, an open-access dataset that tracks the financial donations received by European Union political parties. It systematically codes (a) each donation received; (b) its amount; (c) the type of donor; and (d) its region of origin. Analysing the dataset, a cleavage can be observed. On one side are parties that have Eurosceptic and nationalist agendas and individual donors. On the opposite side are federalist agendas and international-business donors. Moreover, individuals form the largest donor category, and nearly half of all donations come from Central and Eastern Europe. PFxEU aims to encourage further research into European Union political financing, supports research collaboration devoted to the analysis of corruption and European Union politics and makes basic political information part of the public domain.
“Dogs on Call”: A Community-Engaged Human Subjects Training with Hospital Based Therapy Dog Teams
Authors: Townsend Lisa , Towsley Nyssa , Gee Nancy R.
Published: September 2023

Problem: As community-engaged research (CER) methods evolve, Institutional Review Boards (IRBs) must adapt policies to facilitate CER research. This paper describes a novel collaboration between hospital-based therapy dog volunteer teams (CERs), academic faculty, and an IRB. Subjects: CER volunteers delivered a canine-assisted intervention to hospitalized adults in a clinical trial. Methods: IRB members and faculty developed a human subjects protections training tailored to the volunteer handlers’ role as study interventionists including an interactive video- and discussion-based training with a knowledge assessment. Findings: Fourteen volunteer handlers were trained. The expedited IRB review period was similar to national average rates (18 days.) Volunteer handlers have conducted 107 research visits with little patient attrition. Conclusion: Tailored human subjects trainings facilitate research with interventions delivered by people who are not typically involved in research. Bespoke CER human subjects training requires collaboration between researchers and IRBs and flexibility in IRB policy regarding CER.
Recurrence of cervical artery dissection: A systematic review and meta-analysis
Authors: Lounsbury Elizabeth , Niznick Naomi , Mallick Ranjeeta , Dewar Brian , Davis Alexandra , Fergusson Dean A , Dowlatshahi Dar , Shamy Michel
Published: September 2023

Background and Purpose:

Cervical artery dissection (CAD) involving the carotid or vertebral arteries is an important cause of stroke in younger patients. The purpose of this systematic review is to assess the risk of recurrent CAD.

Methods:

A systematic review and meta-analysis was conducted on studies in which patients experienced radiographically confirmed dissections involving an extracranial segment of the carotid or vertebral artery and in whom CAD recurrence rates were reported.

Results:

Data were extracted from 29 eligible studies (n = 5898 patients). Analysis of outcomes was performed by pooling incidence rates with random effects models weighting by inverse of variance. The incidence of recurrent CAD was 4% overall (95% confidence interval (CI) = 3–7%), 2% at 1 month (95% CI = 1–5%), and 7% at 1 year in studies with sufficient follow-up (95% CI = 4–13%). The incidence of recurrence associated with ischemic events was 2% (95% CI = 1–3%).

Conclusions:

We found low rates of recurrent CAD and even lower rates of recurrence associated with ischemia. Further patient-level data and clinical subgroup analyses would improve the ability to provide patient-level risk stratification.
Objectivity, practicality, and significance of practice guidelines for the practicing neurologists: What we learnt from consensus criteria in CIDP, Myasthenia Gravis and Inflammatory Myopathies
Authors: Dalakas Marinos C.
Published: September 2023

The value of practice guidelines in the three most common autoimmune neuromuscular disorders, namely Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Myasthenia Gravis (MG) and Autoimmune Inflammatory Myopathies (AIM), has been extensively debated regarding their usefulness in clinical practice, objectivity and universal value considering that guidelines are also established regionally in certain countries. This commentary highlights common concerns on how guidelines are presently generated, pointing out: (a) non-sufficient diversity among Task-Force members to identify and address not only routine clinical and electrophysiology issues but also immunology, imaging, pathology, biomarkers, epidemiology or treatment economics; (b) Task-Force being often comprised by the same or seemingly like-minded members conveying the erroneous impression that experts with opposing views might have been excluded, even if this is clearly not the case; and (c) relying on web-based registries or retrospective data collections from heterogeneous sources. As a result, the existing practice guidelines in CIDP, MG and AIM remain an unfinished business but an excellent base for further enhancement. Guidelines can be extremely helpful not only for clinical trials but also in clinical practice if viewed as a living document with continuously updated versions by experts even with opposing views with precise information on diagnostics, pathomechanisms, therapeutic schemes, evolving biomarkers and economics of new therapies with validation of the post-guidelines criteria. Geographic diversity should be taken into consideration because the availability of biomarker testing, and therapies differ among countries. Patient preferences need to be also considered in therapeutic guidelines because newly marketed drugs offer more options steadily changing the therapeutic algorithms in autoimmune neuromuscular diseases generating also questions as to whether they also influence decisions on insurance coverage. Collectively, these startup considerations are aimed to make practice guidelines more objective, widely acceptable worldwide and more practical or easier to follow in clinical practice.
Cutaneous presentation of cryptococcal infection with subclinical central nervous system involvement secondary to fingolimod therapy
Authors: Chey Shin Yee , O’Sullivan Niamh-Anna , Beer Trevor , Leong Wai K , Kermode Allan G
Published: September 2023

Fingolimod is a multiple sclerosis disease-modifying therapy which sequestrates lymphocytes in the lymph nodes, thereby reducing peripheral blood lymphocytes. Cryptococcal infection is an important adverse effect which should be recognised. We report a case of cutaneous and central nervous system infection who presented with isolated cutaneous symptoms in the absence of neurological or systemic manifestations.
Grace, Inspiration, Fulfillment, Timeless, Soulful (GIFTS): The Why and How of Podcasts for Recognition and Mentoring of Faculty in Medicine
Authors: Croghan Ivana T. , Ghosh Amit K. , Fratianni Amy M. , Kuhle Carole L. , Johnson Ruth E. , Hays James Taylor , Cassmann James A. , Andresen Richard T. , Bhagra Anjali
Published: September 2023

This commentary offers the reader an alternative to mentoring through the use of PODCASTS. By providing the listener with an understanding of the challenges and opportunities for self-reflection and sharing of experiences by the interviewees, we are impacting the listener attitudes and future goals through lessons learned.
Self-Assessment of Patient Safety Reporting and Learning System in Private Hospitals in Indonesia
Authors: Rachmawati Emma , Umniyatun Yuyun , Imanda Rahmi , Listiowati Ekorini , Nurmansyah Mochamad Iqbal
Published: September 2023

Introduction

Hospitals are required to implement patients safety incident (PSI) reporting, analysis, and problem-solving. Self-assessment is important for exploring gaps and strengthening PSI reporting and learning system.

Objectives

This study examined PSI reporting and learning systems through self-assessment based on WHO guidance, analysis of section scores by hospital class, and analysis of section relationships.

Method

This cross-sectional study was conducted on 193 health workers from 47 Indonesian non-profit private hospitals selected using non-probability sampling. Samples in each hospital consisted of seven hospital staff, including quality and patients’ safety committee, infectious diseases control committee, manager/head of nursing, as well as functional staff comprising doctors, nurses, pharmacists, and nutritionists. Six aspects based on WHO guidance were measured in this study namely 1) environment for reporting, 2) reporting rules and content, 3) analysis and investigation, 4) governance, 5) action and learning, as well as 6) patients’ and family engagement. The data obtained were analyzed using univariate and bivariate analysis.

Results

The results showed that the total average score was 64.7 ± 3.3, and the average score on all components of PSI reporting and learning system was minimum 59.3 and maximum 69.6 of a total score of 100. The lowest average score was found in patients’ and family engagement component at 59.3 ± 8.4. Class B hospitals had higher average scores on each component than class C and D hospitals, except on the action and learning and patients’ and family engagement section. There was a significant positive linear correlation between each section of PSI reporting and learning system ( p-value < 0.01).

Conclusion

The PSI reporting and learning system in hospitals is in need of improvement across all aspects. One specific area that requires attention is the implementation of mechanisms for patient and family engagement, which can play an important role in promoting safety programs.
Stable and Shifting Sexualities among American High School Students, 2015 to 2021
Authors: Mittleman Joel
Published: September 2023

In a context of widespread attacks on lesbian, gay, bisexual, transgender, and queer (LGBTQ+) youth, statistics on rising LGBTQ+ identification need to be addressed with precision and care. In this visualization, the author presents nationally representative sexuality data from the Centers for Disease Control and Prevention’s Youth Risk Behavior Survey. Using stacked horizontal bar graphs, the author summarizes American high school students’ reported sexual identities and same-sex sexual contacts from 2015 to 2021. In contrast to sensationalistic reporting claiming that these data show “explosive” and “skyrocketing” growth, this visualization illustrates that most measures of American adolescent sexuality have been fairly stable. Since 2015, the only substantial changes that have occurred are in female students’ reports of being bisexual or “not sure.” These changes in sexual identity have been accompanied only by very modest changes in female students’ same-sex sexual contacts. Among male students, sexual identities and contacts have been almost entirely stable since 2015.
Governing pathological markets: Microbes, banana export markets, and speculative farming practices
Authors: Wang Chi-Mao , Chien Ker-Hsuan
Published: September 2023

This paper examines the making and remaking of Taiwan's banana export market in response to the devastation caused by an outbreak of a novel infectious plant disease, Fusarium wilt disease Tropical Race 4 (TR4, Fusarium oxysporum f. sp. Cubense) . Taiwan was the world's fourth-largest exporter of bananas in the 1960s before the collapse of the market in the early 1970s. While scholars have drawn on actor-network theory-inspired performativity approach to understand the role of non-human actants in market-making, insufficient attention has been given to the distinct impacts of microbes on cases such as that of Taiwan's banana export market. Microbes’ creative and ever-evolving qualities constantly present challenges related to the control and containment of such non-human entities, for which no pre-existing or universally applicable solutions exist. Consequently, there is a lack of research that provides useful frameworks to understand such disease-plagued markets. To bridge this gap in the literature, we examine the remaking of Taiwan's banana export market in the aftermath of the TR4 crisis using a case study approach and develop the notion of pathological markets. Inspired by recent scholarship on biosecurity and related care practices, we outline two characteristics that shape pathological markets: (a) speculative and probiotic care practices and (b) the rescaling of market organisations. The results of the fieldwork conducted as part of the present study in laboratories, government offices and on banana farms lead us to contend that the growth and development of particular microbes in multispecies environments such as Taiwan's banana farms constantly pose significant challenges for market farming. Moreover, to co-exist with the threats posed by the growth and development of microbes such as those which cause Fusarium wilt disease TR4, growers in Taiwan's banana export market rely heavily on probiotic and speculative care practices.
Developing a practice-driven research agenda in implementation science: Perspectives from experienced implementation support practitioners
Authors: Jensen Todd M. , Metz Allison J. , Disbennett Mackensie E. , Farley Amanda B.
Published: September 2023

Background

Attention is being placed on the “ironic gap” or “secondary” research-to-practice gap in the field of implementation science. Among several challenges posited to exacerbate this research-to-practice gap, we call attention to one challenge in particular—the relative dearth of implementation research that is tethered intimately to the lived experiences of implementation support practitioners (ISPs). The purpose of this study is to feature a qualitative approach to engaging with highly experienced ISPs to inform the development of a practice-driven research agenda in implementation science. In general, we aim to encourage ongoing empirical inquiry that foregrounds practice-driven implementation research questions.

Method

Our analytic sample was comprised of 17 professionals in different child and family service systems, each with long-term experience using implementation science frameworks to support change efforts. Data were collected via in-depth, semi-structured interviews. Our analysis followed a qualitative content analysis approach. Our focal conceptual category centered on the desired areas of future research highlighted by respondents, with subcategories reflecting subsets of related research question ideas.

Results

Interviews yielded varying responses that could help shape a practice-driven research agenda for the field of implementation science. The following subcategories regarding desired areas for future research were identified in respondents’ answers: (a) stakeholder engagement and developing trusting relationships, (b) evidence use, (c) workforce development, and (d) cost-effective implementation.

Conclusions

There is significant promise in bringing implementation research and implementation practice together more closely and building a practice-informed research agenda to shape implementation science. Our findings point not only to valuable practice-informed gaps in the literature that could be filled by implementation researchers, but also topics for which dissemination and translation efforts may not have yielded optimal reach. We also highlight the value in ISPs bolstering their own capacity for engaging with the implementation science literature to the fullest extent possible.
Risk of ovarian hyperstimulation syndrome in women with malignancies undergoing treatment with long-acting gonadotropin-releasing hormone agonist after controlled ovarian hyperstimulation for fertility preservation: a systematic review
Authors: Ingold Caroline , Navarro Paula Andrea , de Oliveira Renato , Barbosa Caio Parente , Bedoschi Giuliano
Published: September 2023

Background:

Fertility preservation is an important quality of life issue for women of reproductive age undergoing gonadotoxic treatment. The possibility of administering an adjuvant long-acting gonadotropin-releasing hormone agonist (GnRHa) with the aim of reducing the number of follicles susceptible to the effects of chemotherapy and thus reducing the risk of ovarian damage is considered in some international society guidelines, particularly in certain cancers such as breast cancer. Nowadays, the administration of long-acting GnRHa after controlled ovarian hyperstimulation (COH) for fertility preservation by cryopreservation of oocytes or embryos is increasingly used. However, cases of ovarian hyperstimulation syndrome (OHSS) have been reported following the use of long-acting GnRHa after COH for fertility preservation, indicating that the potential adverse effects of this treatment need to be further investigated.

Objectives:

The aim of this systematic review was to comprehensively characterize patients who developed OHSS after treatment with long-acting GnRHa following COH for fertility preservation.

Methods:

A comprehensive search of major electronic databases through January 2023 was performed. Studies reporting the use of long-acting GnRHa after COH for fertility preservation and the development of OHSS were included. Risk of bias was assessed using a modified version of the Newcastle-Ottawa scale. Results were synthesized qualitatively.

Results:

Three studies with five patients met the eligibility criteria. The majority of patients were diagnosed with breast cancer and all patients underwent COH for oocyte cryopreservation. OHSS occurred in all patients after administration of long-acting GnRHa. The interval between ovulation induction and administration of long-acting GnRHa thereafter ranged from 3 to 5 days. All patients were treated conservatively and recovered without complications.

Conclusion:

Current evidence suggests that the use of long-acting GnRHa after COH for fertility preservation may be associated with OHSS. Healthcare providers should thoroughly discuss the benefits and risks of this intervention with their patients before making a decision. Further studies are needed to fully elucidate the causal relationship between long-acting GnRHa and OHSS in this population.
Sexual signals and behavior in children: Building hypotheses about the function of sexuality in childhood
Authors: Crittenden Patricia M , Landini Andrea
Published: September 2023

Increasingly children have been referred for assessment and treatment because they used sexual behavior including “sexually harmful behavior.” Such children are often treated as a source of danger to others rather than as neglected or abandoned children who used sexualized behavior to protect themselves. In this exploratory paper, we present a series of case examples, arranged developmentally from infancy to puberty. All had standardized assessments of attachment from which detailed descriptions of behavior were derived. In addition, we have information about the parents that we used to help explain their behavior. We also review briefly the scientific basis for understanding how smell and touch affect sexualized behavior involving children. We conclude that children’s sexualized behavior and sexualized behavior from parents to young children is usually not sexually motivated. Instead, the behavior appears to serve attachment functions for both children and parents when their needs for protection and comfort have not been met. We note that sexual bonds are formed very rapidly whereas attachment bonds are formed slowly. Under urgent and dangerous conditions, sexuality may make bonds more quickly than slower attachment processes could do, thus providing the advantages of attachment (protection and comfort) quickly. Of course, this short-cut comes at a developmental cost. We close with recommendations for research and for professional practice.
Direct Oral Anticoagulants for the Treatment of Venous Thromboembolism in Obesity
Authors: Hattaway Quinn , Starr Jessica A. , Pinner Nathan A.
Published: September 2023

Background: Direct oral anticoagulants (DOACs) are known to have similar efficacy with a decreased risk of bleeding when compared to warfarin for the treatment of venous thromboembolism (VTE). In patients with obesity, there are limited data regarding the safety and efficacy of DOACs. Despite concerns for both under- and over-dosing patients with extremes of body weight, there are no dose adjustment recommendations in the package inserts for any of the DOACs. Objective: To evaluate the safety and efficacy of DOACs versus warfarin for the treatment of VTE in patients with obesity. Methods: This single-center, retrospective cohort study included obese patients initiated on DOAC or warfarin therapy for VTE from January 2015 to January 2022. Patients with cancer, hypercoagulable disorders, end-stage kidney disease, or pregnancy were excluded. The primary endpoint was VTE recurrence. Secondary endpoints included major and minor bleeding. Results: A total of 120 patients met criteria for inclusion. Ninety-two received DOAC therapy and 28 received warfarin. The primary endpoint occurred in 4 patients in the DOAC group and 3 patients in the warfarin group ( P = 0.35). Major bleeding occurred in 2 patients. Minor bleeding events occurred in 10 (8.33%) patients. Of those, 6 (6.5%) events occurred in patients receiving a DOAC and 4 (14.3%) events occurred in patients receiving warfarin ( P = 0.28). Limitations of this study include the retrospective single-center study design. Conclusions: There was a comparable risk of bleeding and recurrent VTE between DOACs and warfarin in patients initiated on therapy for VTE.
HMGB1 and Toll-like receptors: potential therapeutic targets in autoimmune diseases
Authors: Ren Wenxuan , Zhao Lei , Sun Ying , Wang Xichang , Shi Xiaoguang
Published: September 2023

HMGB1, a nucleoprotein, is expressed in almost all eukaryotic cells. During cell activation and cell death, HMGB1 can function as an alarm protein (alarmin) or damage-associated molecular pattern (DAMP) and mediate early inflammatory and immune response when it is translocated to the extracellular space. The binding of extracellular HMGB1 to Toll-like receptors (TLRs), such as TLR2 and TLR4 transforms HMGB1 into a pro-inflammatory cytokine, contributing to the occurrence and development of autoimmune diseases. TLRs, which are members of a family of pattern recognition receptors, can bind to endogenous DAMPs and activate the innate immune response. Additionally, TLRs are key signaling molecules mediating the immune response and play a critical role in the host defense against pathogens and the maintenance of immune balance. HMGB1 and TLRs are reported to be upregulated in several autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, and autoimmune thyroid disease. The expression levels of HMGB1 and some TLRs are upregulated in tissues of patients with autoimmune diseases and animal models of autoimmune diseases. The suppression of HMGB1 and TLRs inhibits the progression of inflammation in animal models. Thus, HMGB1 and TLRs are indispensable biomarkers and important therapeutic targets for autoimmune diseases. This review provides comprehensive strategies for treating or preventing autoimmune diseases discovered in recent years.
Exendin-4 ameliorates tau hyperphosphorylation and cognitive impairment in type 2 diabetes through acting on Wnt/β-catenin/NeuroD1 pathway
Authors: Kang Xiaonan , Wang Dan , Zhang Lu , Huang Teng , Liu Siyue , Feng Xiaohui , Guo Yaoyao , Zhang Ziyin , Wang Zhongjing , Ren Huihui , Yuan Gang
Published: September 2023

Background

 Type 2 diabetes (T2D) is an independent risk factor for Alzheimer's disease (AD). Exendin-4 (Ex-4), a widely used glucagon-like peptide-1 receptor agonist drug in the treatment of T2D, has been demonstrated the therapeutic effects on diabetic encephalopathy (DE). Especially, the Ex-4 ameliorates the tau hyperphosphorylation and cognitive impairment in DE. And these crucial alterations are also important bridge between T2D and AD. However, its unique mechanism is unclear.

Methods

 The db/db mice, high-fat-diet (HFD) / streptozotocin (STZ)—induced diabetic (HF-diabetic) mice, and high-glucose-damaged (HGD) HT-22 hippocampal cells were enrolled to examine the effects of Ex-4 on AD-like changes in T2D. The Novel object recognition test (NORT) and Morris water maze test (MWMT) were conducted to evaluate the cognitive impairment. The Dickkopf-1 (DKK1) was employed to weaken the activation of the Wnt/β-catenin pathway to explore the mechanism of Ex-4 in protecting the brain functions. The JASPAR was based to predict the interaction between NeuroD1 and the promoter region of Ins2. Moreover, the chromatin immunoprecipitation coupled with quantitative polymerase chain reaction (ChIP-qPCR) and luciferase reporter assays were performed.

Results

 Ex-4 alleviated the tau hyperphosphorylation, increased the brain-derived insulin, and improved the PI3K/AKT/GSK3-β signalling in db/db mice, HF-diabetic mice, and HGD HT-22 hippocampal neuronal cells. The NORT and MWMT indicated that Ex-4 alleviated the learning and memory deficits in HF-diabetic mice. The inhibitor Dickkopf-1 (DKK1) of the Wnt/β-catenin pathway significantly blocked the protective effects of Ex-4. Regarding further molecular mechanisms, NeuroD1 was affected by Ex-4 in vivo and in vitro, and the knockdown or overexpression of NeuroD1 suggested its crucial role in promoting the brain insulin by Ex-4. Meanwhile, the ChIP‒qPCR and luciferase reporter assays confirmed the combination between NeuroD1 and the promoter region of the insulin-encoding gene Ins2. And this interaction could be promoted by Ex-4.

Conclusions

Our study proposes that Ex-4 alleviates tau hyperphosphorylation and cognitive dysfunction by increasing Ins2-derived brain insulin through the Wnt/β-catenin/NeuroD1 signaling in T2D. And its also show new lights on part of the progress and mechanism on treatment targets for the DE in T2D.
Land use of energy supply for carbon neutral mobility: a well-to-wheel analysis
Authors: Bakker Stefan , Moorman Saeda , Knoope Marlinde , Terwindt Maurits
Published: September 2023

Background

The transition to carbon neutral mobility will require a lot of carbon neutral energy, but a lot of space
as well. In many countries, it will be a challenge to find this space or to import enough energy. Land use indicators related to sustainable mobility usually focus on space for transport infrastructure and parking, i.e. direct land use, and do not include energy supply. Existing literature on the emerging research field of ‘energy landscapes’ has not covered the transport sector.

Objective

The aim of this paper is to estimate the order of magnitude of land or sea area required for carbon neutral mobility.

Method

In a well-to-wheel analysis, we investigate the land use for the production, transport, storage, distribution, and charging/refuelling of carbon neutral energy carriers for various modes of transport. The analysis focuses on the Netherlands, but part of the results are expected to be broadly applicable to other countries as well.

Findings

The results show that electricity from wind or solar energy supplied to electric vehicles is the most space efficient. Use of hydrogen and synthetic fuels in vehicles takes 2–5 times more land, while use of biofuels from energy crops takes 100 times more land compared to the electricity route. We also conclude that the indirect land use for energy supply for carbon neutral road transport in the Netherlands is in the same order of magnitude as the current direct land use of road mobility.
Gene-based burden scores identify rare variant associations for 28 blood biomarkers
Authors: Aldisi Rana , Hassanin Emadeldin , Sivalingam Sugirthan , Buness Andreas , Klinkhammer Hannah , Mayr Andreas , Fröhlich Holger , Krawitz Peter , Maj Carlo
Published: September 2023

Background

A relevant part of the genetic architecture of complex traits is still unknown; despite the discovery of many disease-associated common variants. Polygenic risk score (PRS) models are based on the evaluation of the additive effects attributable to common variants and have been successfully implemented to assess the genetic susceptibility for many phenotypes. In contrast, burden tests are often used to identify an enrichment of rare deleterious variants in specific genes. Both kinds of genetic contributions are typically analyzed independently. Many studies suggest that complex phenotypes are influenced by both low effect common variants and high effect rare deleterious variants. The aim of this paper is to integrate the effect of both common and rare functional variants for a more comprehensive genetic risk modeling.

Methods

We developed a framework combining gene-based scores based on the enrichment of rare functionally relevant variants with genome-wide PRS based on common variants for association analysis and prediction models. We applied our framework on UK Biobank dataset with genotyping and exome data and considered 28 blood biomarkers levels as target phenotypes. For each biomarker, an association analysis was performed on full cohort using gene-based scores (GBS). The cohort was then split into 3 subsets for PRS construction and feature selection, predictive model training, and independent evaluation, respectively. Prediction models were generated including either PRS, GBS or both (combined).

Results

Association analyses of the cohort were able to detect significant genes that were previously known to be associated with different biomarkers. Interestingly, the analyses also revealed heterogeneous effect sizes and directionality highlighting the complexity of the blood biomarkers regulation. However, the combined models for many biomarkers show little or no improvement in prediction accuracy compared to the PRS models.

Conclusion

This study shows that rare variants play an important role in the genetic architecture of complex multifactorial traits such as blood biomarkers. However, while rare deleterious variants play a strong role at an individual level, our results indicate that classical common variant based PRS might be more informative to predict the genetic susceptibility at the population level.
A long-read sequencing and SNP haplotype-based novel preimplantation genetic testing method for female ADPKD patient with de novo PKD1 mutation
Authors: Peng Cuiting , Chen Han , Ren Jun , Zhou Fan , Li Yutong , Keqie Yuezhi , Ding Taoli , Ruan Jiangxing , Wang He , Chen Xinlian , Liu Shanling
Published: September 2023

The autosomal dominant form of polycystic kidney disease (ADPKD) is the most common hereditary disease that causes late-onset renal cyst development and end-stage renal disease. Preimplantation genetic testing for monogenic disease (PGT-M) has emerged as an effective strategy to prevent pathogenic mutation transmission rely on SNP linkage analysis between pedigree members. Yet, it remains challenging to establish reliable PGT-M methods for ADPKD cases or other monogenic diseases with de novo mutations or without a family history. Here we reported the application of long-read sequencing for direct haplotyping in a female patient with de novo PKD1 c.11,526 G > C mutation and successfully established the high-risk haplotype. Together with targeted short-read sequencing of SNPs for the couple and embryos, the carrier status for embryos was identified. A healthy baby was born without the PKD1 pathogenic mutation. Our PGT-M strategy based on long-read sequencing for direct haplotyping combined with targeted SNP haplotype can be widely applied to other monogenic disease carriers with de novo mutation.
Higher plasma interleukin − 6 levels are associated with lung cavitation in drug-resistant tuberculosis
Authors: Maseko Thando Glory , Ngubane Slindile , Letsoalo Marothi , Rambaran Santhuri , Archary Derseree , Samsunder Natasha , Perumal Rubeshan , Chinappa Surie , Padayatchi Nesri , Naidoo Kogieleum , Sivro Aida
Published: September 2023

Background

Lung cavitation is associated with heightened TB transmission and poor treatment outcomes. This study aimed to determine the relationship between systemic inflammation and lung cavitation in drug-resistant TB patients with and without HIV co-infection.

Methods

Plasma samples were obtained from 128 participants from the CAPRISA 020 Individualized M(X)drug-resistant TB Treatment Strategy Study (InDEX) prior to treatment initiation. Lung cavitation was present in 61 of the 128 drug-resistant TB patients with 93 being co-infected with HIV. The plasma cytokine and chemokine levels were measured using the 27-Plex Human Cytokine immunoassay. Modified Poisson regression models were used to determine the association between plasma cytokine/chemokine expression and lung cavitation in individuals with drug-resistant TB.

Results

Higher Interleukin-6 plasma levels (adjusted risk ratio [aRR] 1.405, 95% confidence interval [CI] 1.079–1.829, p = 0.011) were associated with a higher risk of lung cavitation in the multivariable model adjusting for age, sex, body mass index, HIV status, smoking and previous history of TB. Smoking was associated with an increased risk of lung cavitation (aRR 1.784, 95% CI 1.167–2.729, p = 0.008). An HIV positive status and a higher body mass index, were associated with reduced risk of lung cavitation (aRR 0.537, 95% CI 0.371–0.775, p = 0.001 and aRR 0.927, 95% CI 0.874–0.983, p = 0.012 respectively).

Conclusion

High plasma interleukin-6 levels are associated with an increased risk of cavitary TB highlighting the role of interleukin-6 in the immunopathology of drug-resistant TB.
Whole genome analysis of Bacillus amyloliquefaciens TA-1, a promising biocontrol agent against Cercospora arachidicola pathogen of early leaf spot in Arachis hypogaea L
Authors: Wang Chen , Ahsan Taswar , Ding Ao , Han Di , Zang Chao-Qun , Huang Yu-Qian , Hussain Khalid
Published: September 2023

Background

Early leaf spot disease, caused by Cercospora arachidicola, is a devastating peanut disease that has severely impacted peanut production and quality. Chemical fungicides pollute the environment; however, Bacillus bacteria can be used as an environmentally friendly alternative to chemical fungicides. To understand the novel bacterial strain and unravel its molecular mechanism, De novo whole-genome sequencing emerges as a rapid and efficient omics approach.

Results

In the current study, we identified an antagonistic strain, Bacillus amyloliquefaciens TA-1. In-vitro assay showed that the TA-1 strain was a strong antagonist against C. arachidicola, with an inhibition zone of 88.9 mm. In a greenhouse assay, results showed that the TA-1 strain had a significant biocontrol effect of 95% on peanut early leaf spot disease. De novo whole-genome sequencing analysis, shows that strain TA-1 has a single circular chromosome with 4172 protein-coding genes and a 45.91% guanine and cytosine (GC) content. Gene function was annotated using non-redundant proteins from the National Center for Biotechnology Information (NCBI), Swiss-Prot, the Kyoto Encyclopedia of Genes and Genomes (KEGG), clusters of orthologous groups of proteins, gene ontology, pathogen-host interactions, and carbohydrate-active enZYmes. antiSMASH analysis predicted that strain TA-1 can produce the secondary metabolites siderophore, tailcyclized peptide, myxochelin, bacillibactin, paenibactin, myxochelin, griseobactin, benarthin, tailcyclized, and samylocyclicin.

Conclusion

The strain TA-1 had a significant biological control effect against peanut early leaf spot disease in-vitro and in greenhouse assays. Whole genome analysis revealed that, TA-1 strain belongs to B. amyloliquefaciens and could produce the antifungal secondary metabolites.