bluuebunny/crossref_metadata_2025 huggingface dataset:
The future of geography field course pedagogy in UK higher education
Authors: Woodley Ewan , Barr Stewart , Batty Lesley , Bickerstaff Karen , Darvill Christopher , Ferdous Raihana , Holmes Naomi , Jon Ihnji , Lynch Kenny , Martin Julian , Marvell Alan , McDougall Derek , Pitt Hannah , Singleton Aled , Souch Catherine , Yorke Lynda
Published: November 2024

Field courses are widely regarded as integral to geography degree programmes, providing students with opportunities for experiential learning, often in unfamiliar international environments. Yet, this key area of pedagogy appears increasingly unsustainable and complex for Higher Education Institutions (HEIs) within the context of the urgent need for decarbonisation, increasing financial costs, and the institutional challenges of comprehensively embedding necessary Equality, Diversity and Inclusion (EDI) considerations into these activities. Here, we report on a national‐level workshop (April 2024) that brought together a wide range of HE practitioners to discuss the future of UK field course pedagogy, using the fieldwork principles adopted by the Royal Geographical Society (with the Institute of British Geographers) (RGS‐IBG) in 2020 as a basis for framing future discourse. Using a Three Horizons approach to guide our conversations, we critically explored the (un)sustainability of current academic and institutional practices, alongside future directions and ‘disrupting’ (innovative) practices for promoting transformative change in this area of education. Here, we argue for two sector‐wide discussions that require collaborative engagement with practitioners, institutions and students. Firstly, we highlight the urgent need for transparent and critical reflection on the challenges and hypocrisy of aeromobility in academia and the need for more widespread adoption of low‐carbon (‘slower’) modes of travel. Secondly, we call for the immediate reconceptualization of field course pedagogy to place EDI considerations at the core of field course design and practice, aiding a transition towards Universal Design for Learning (UDL). As such, we call on the geography community in higher education to engage in critical reflection on how we take meaningful and urgent action to address the disconnect between our stated educational values around environmental sustainability and EDI, and our actual educational practices.
Feldversuche zu Geogitter stabilisierten Tragschichten mit gebundenem Oberbau über weichem Untergrund mit hohem Quellvermögen
Authors: Klompmaker Jörg , Shahkolahi Amir , Gallage Chaminda
Published: November 2024

Um die Stabilisierungs‐ und Bewehrungswirkung von Geogittern in ungebundenen Tragschichten mit gebundenem Oberbau zu untersuchen, wurde 2018 in einem ländlich gelegenen Wohngebiet südlich der Metropole Brisbane, Australien, ein großmaßstäblicher Feldversuch über weichem, hoch quellfähigem Ton durchgeführt. Im Zuge einer Straßensanierung wurden verschiedene Testfelder mit variablen Geogitteranordnungen angelegt, um eine quantitative Bewertung der Stabilisierungs‐ und Bewehrungswirkung durch den Einfluss der verwendeten gelegten und gereckten Geogitter aus monolithischen Stäben zu ermöglichen: sowohl im Hinblick auf ihren anfänglichen Beitrag zur Tragfähigkeitserhöhung als auch auf ihren langfristigen Nutzen hinsichtlich der Verlängerung der Gebrauchstauglichkeit der Asphaltdeckschichten. Während der Bauphase wurden in allen Testfeldern umfangreiche Baugrunduntersuchungen durchgeführt, sodass der anfängliche Zustand des Untergrunds und der ungebundenen Tragschicht ausführlich charakterisiert wurde. Nach Fertigstellung wurden die Testfelder im Rahmen eines Monitorings durch eingebaute Messtechnik fortlaufend überwacht. Der Beitrag beschreibt die Baugrunduntersuchungen, den Bau der Testfelder sowie die Ergebnisse des Monitorings drei Jahre nach Verkehrsfreigabe der Straße.
Getting started with the graded response model: An introduction and tutorial in R
Authors: Zein Rizqy Amelia , Akhtar Hanif
Published: November 2024

This tutorial introduces the graded response model (GRM), a tool for testing measurement precision within the item response theory (IRT) paradigm, which is useful for informing researchers about the item and person properties of their measurement. The tutorial aims to guide applied researchers through a unidimensional GRM analysis in the R environment, using the psych, mirt and ggmirt packages. GRM is specifically designed to examine the psychometric properties of psychological scales with polytomous (Likert‐style) items. The tutorial illustrates the procedure using data from the Open Psychometrics Database on the right‐wing authoritarianism (RWA) scale, outlining the theoretical underpinnings of GRM and steps for data preparation, testing model assumptions, model fitting, plotting item parameters and interpretation of results.
An enterprise technical architecture for the implementation of the South African National Health Insurance
Authors: Iyamu Tiko , Chitsa Farirai
Published: November 2024

The South African National Health Insurance (NHI) faces challenges due to a lack of an enterprise technical architecture (ETA) solution, for the implementation. This study aims to propose an ETA, to enable and support the implementation of the South African ETA. The qualitative method was employed in the data collection. Actor‐network theory (ANT) was applied as a lens to examine the data. The findings reveal several critical influencing factors, including readiness assessment, geographical locations of stakeholders; diversity of healthcare facilities; flexibility of technology solutions; and synchronization of processes and patients' data. The study highlights the need to provide governance for the technologies that influence the implementation of NHI. Based on the influencing factors, a framework was developed. The framework is intended to provide architectural governance (principles, standards, and policies), to efficiently and effectively, facilitate, support, and enable the implementation of the South African NHI.
Adolescent mental time travel predicting meaning in life: The potential mediating role of self‐continuity
Authors: Yuan Muzi , Yin Yue , Liu Junsheng , Sang Biao
Published: November 2024

Introduction

Knowing who we are and what we are living for helps us to better adjust in everyday life and confront negative life events, especially for adolescents who are going through critical developmental periods when changes in life could bring both psychopathology risk yet opportunity to achieve a better self. The current study focused on mental time travel, the mental visit to the past or future, and examined the impact on adolescents' perceived meaning in life, with the potential mediating factor of self‐continuity.

Methods

A total of 1543 high school students aged 12 to 18 years old (Mage = 15.02, SDage = 1.58, 52% girls) from Jiangsu Province, China were recruited in a two‐wave longitudinal survey that separated by an interval of 6 months. Participants reported their proneness to engage in nostalgia or future prospection at T1 and sense of self‐continuity at T2, while the perceived meaning in life were reported at both time points. The latent structural equation models were established with items as indicators for all study variables.

Results

Mental time travel, including both nostalgia and future prospection, facilitated adolescent meaning in life via increased self‐continuity, except that future prospection showed only positive indirect effect, while nostalgia demonstrated direct yet negative impact on meaning in life after accounting for the positive mediation effect.

Conclusions

Findings highlighted the distinct effects of the past‐ and future‐oriented mental time travel on adolescent meaning in life, and provided insights for promoting adolescent psychological adjustment.
Therapeutic Plasma Exchange for the Symptomatic Treatment of Scleromyxedema: A Case Report and Literature Review
Authors: Lanehart Matthew H. , Johnson Erika S. , Aqui Nicole A.
Published: November 2024

Scleromyxedema is a rare skin mucinosis often associated with systemic involvement and monoclonal gammopathy (MG). No formal recommendation for management with therapeutic plasma exchange (TPE) has been published due to rarity. This paper reports a 42‐year‐old male with progressive scleromyxedema. The patient was treated with glucocorticoids, immunosuppressants, and intravenous immunoglobulin (IVIG) therapy, but the disease progressed. Ultimately, the patient was referred for TPE, which resulted in decreased skin stiffness, improved extremity range of motion, and decreased visibility of papules on the hands. The patient's debilitating dysphagia gradually improved. A review of the literature focusing on clinical response identified five cases of scleromyxedema patients treated with TPE. Three of the five cases reported significant improvement in cutaneous symptoms and range of motion for at least 12 months. Overall, we propose that TPE should be considered an effective supportive treatment for symptomatic relief in severe or refractory scleromyxedema.
Structural and Functional Insight Into YefM–YoeB Complex of Toxin–Antitoxin System From Streptococcus pneumoniae
Authors: Kim Do‐Hee , Lee Yong‐Chan , Jin Chenglong , Kang Sung‐Min , Kang Su‐Jin , Kang Hoon‐Seok , Lee Bong‐Jin
Published: November 2024

Streptococcus pneumonia is a Gram‐positive and facultative anaerobic bacterium that causes a number of diseases, including otitis media, community‐acquired pneumonia, sepsis, and meningitis. With the emergence of antibiotic‐resistant strains, there is an urgent need to develop antibiotics with a novel mechanism. The toxin–antitoxin (TA) system, which is primarily found in prokaryotes, consists of a toxin and its equivalent antitoxin genes. The YefM–YoeB module is a Type II TA system, where the YoeB toxin functions as a putative mRNA interferase upon activation, while the YefM antitoxin acts as a transcription repressor by binding to its promoter region along with YoeB. In this study, we determined the crystal structure of the YefM–YoeB complex from S. pneumoniae TIGR4 to comprehend the binding mechanism of the TA system. Furthermore, an in vitro ribonuclease activity assay was conducted to identify the ribonuclease activity of the YoeB toxin. Additionally, furthermore, the oligomeric state of the YefM–YoeB complex in solution was investigated, and a DNA‐binding mode was proposed. These structural and functional insights into the YefM–YoeB complex could provide valuable information for the development of novel antibiotics targeting S. pneumonia‐associated diseases.
The Role of Contact and Emotional Intelligence in the Attitudes of General Population Towards Individuals Living With Mental Illness
Authors: Andreopoulou Alexia , Vasiou Aikaterini , Mastrothanasis Konstantinos
Published: November 2024

Mental illness stigma is still a widespread phenomenon with damaging psychological and social consequences. This study is of relevance to the design of appropriate psychiatric services which reinforce the social integration of individuals living with mental illness. It investigates the relationship between contact, emotional intelligence (EI) and attitudes of the general population towards people with mental illness. This study utilized a random sampling method to collect data from 183 participants. Measures included the EI Scale for assessing EI, the level of contact (LOC) Report to examine the LOC with mental illness, and the Attitudes towards Mental Illness Scale to evaluate attitudes towards mental illness. Each of these instruments has been validated in previous research. Data analysis involved Pearson's correlation analysis, multiple linear regression, and mediation analysis to explore the relationships between variables. EI and particularly the abilities of use of emotion and other's emotional appraisal were associated with more positive attitudes towards mental illness. conversely, lower levels of contact were associated with higher levels of social care, indicating a complicated relationship between contact and attitudes. The findings highlight that a deeper understanding of the association between contact with individuals living with mental illness and attitudes towards them is needed, focusing on potential mechanisms that might modify this association. Additionally, a focal point that is underlined in this research is the important role of EI in affecting attitudes as it seems to offer promising directions in planning educational programs and stigma reduction interventions.
Estrogen Regulates Mitochondrial Activity Through Inducing Brain‐Derived Neurotrophic Factor Expression in Skeletal Muscle
Authors: Tse Margaret Chui Ling , Pang Brian Pak Shing , Bi Xinyi , Ooi Teresa Xinci , Chan Wing Suen , Zhang Jiangwen , Chan Chi Bun
Published: November 2024

Estrogen is an essential hormone for the development and functional activities of reproductive organs. Recent studies showed that estrogen signaling is also an important regulator of lipid and glucose metabolism in a number of tissues, but the molecular mechanism is not fully understood. We report here that estrogen is a stimulator of brain‐derived neurotrophic factor (BDNF) synthesis in the skeletal muscle. Estradiol (E2), but not testosterone, induces a dose‐ and time‐dependent BDNF production in cultured myotubes. Estrogen depletion in ovariectomized mice significantly reduced Bdnf expression in the glycolytic myofibers, which could be rescued after E2 administration. Mechanistically, E2 stimulation triggered the tethering of estrogen receptor (ER) α, but not ERβ, to the estrogen‐responsive element on promoter VI of the Bdnf gene in skeletal muscle. When Bdnf production was inhibited by shRNA in C2C12 myotubes, E2‐induced mitochondria activation and pyruvate dehydrogenase kinase 4 expressions were jeopardized. Collectively, our results demonstrate that BDNF is an underrecognized effector of estrogen in regulating mitochondrial activity and fuel metabolism in the skeletal muscle.
Sarcopenia Is a Prognostic Factor of Adverse Effects and Mortality in Patients With Tumour: A Systematic Review and Meta‐Analysis
Authors: Zhang Yujie , Zhang Jingjing , Zhan Yunfan , Pan Zhe , Liu Qiaohong , Yuan Wei'an
Published: November 2024

Background

The relationship between sarcopenia and the prognosis of patients with tumours who received radio‐ and/or chemotherapy still needs to be determined. In this study, we aim to investigate the relationship between sarcopenia and adverse effects and mortality in patients with tumours that received radio‐ and/or chemotherapy, stratified by study design, tumour category, the method sarcopenia assessed, treatment options, study location and among other factors.

Methods

PubMed, Web of Science and Embase were searched from inception to 15 August 2024, without language restrictions and with a manual search of references for additional articles retrieval. Cohort studies of ≥ 100 patients with tumours that evaluated the association between sarcopenia or muscle mass and the adverse effects or overall survival induced by radio‐ and/or chemotherapy were included.

Results

Thirty‐nine studies were included, involving 8966 patients with tumours, including 3383 patients with sarcopenia. The pooled prevalence of sarcopenia in patients with tumours was 0.42 (95% CI 0.36–0.48, p < 0.001) overall. The prevalence of sarcopenia is higher in Oceania patients 0.60 (95% CI 0.28–0.89, p < 0.001), those with reproductive tumour 0.57 (95% CI 0.30–0.83, p < 0.001), and sarcopenia assessed by the lumbar‐skeletal muscle index 0.46 (95% CI 0.39–0.53, p < 0.001) than in other subgroups, but not show significant differences in sex. Sarcopenia was associated with an increased risk of adverse effects in patients who received radio‐ and/or chemotherapy, with a relative risk (RR) of 1.44 (95% CI 1.21–1.71, p < 0.001). Retrospective studies (RR = 1.49; 95% CI 1.24–1.79; p < 0.001), sarcopenia assessed by other methods (RR = 2.98; 95% CI 1.52–5.87; p < 0.001), and patients in Europe (RR = 1.92; 95% CI 1.15–3.22; p = 0.013), received chemoradiotherapy (RR = 1.47; 95% CI 1.23–1.76; p < 0.001), and with head and neck tumours (RR = 1.54; 95% CI 1.17–2.01; p = 0.010) had higher relative risk than other subgroups. Sarcopenia was also associated with reduced overall survival in patients with tumours, with a pooled hazard ratio (HR) of 1.66 (95% CI 1.40–1.96, p < 0.001). Prospective studies (HR = 1.72; 95% CI 0.97–3.07; p = 0.065), sarcopenia assessed by the cervical‐skeletal muscle index (HR = 2.66; 95% CI 1.73–4.09; p < 0.001), and patients in Asia (HR = 1.91; 95% CI 1.50–2.42; p < 0.001), received chemoradiotherapy (HR = 1.85; 95% CI 1.46–2.45; p < 0.001) and with head and neck tumours (HR = 2.35; 95% CI 1.88–2.95; p < 0.001) had higher HR than other subgroups.

Conclusions

Sarcopenia was associated with a higher risk of adverse effects and mortality in patients with tumours received radio‐ and/or chemotherapy.
Comprehensive data of 5085 patients newly diagnosed with colorectal liver metastasis between 2013 and 2017: Fourth report of a nationwide survey in Japan
Authors: Sakamoto Katsunori , Beppu Toru , Honda Goro , Kotake Kenjiro , Yamamoto Masakazu , Takahashi Keiichi , Endo Itaru , Hasegawa Kiyoshi , Itabashi Michio , Hashiguchi Yojiro , Kotera Yoshihito , Kobayashi Shin , Yamaguchi Tatsuro , Kawai Kazushige , Natsume Soichiro , Tabuchi Ken , Kobayashi Hirotoshi , Yamaguchi Kensei , Tani Kimitaka , Morita Satoshi , Ajioka Yoichi , Miyazaki Masaru , Sugihara Kenichi
Published: November 2024

The Joint Committee for Nationwide Survey on colorectal liver metastasis (CRLM) was established to improve treatment outcomes in patients with CRLM. The aim of this study was to evaluate the transition in the characteristics and treatment strategies of patients with CRLM and to analyze the prognostic factors. The data of 5085 patients newly diagnosed between 2013 and 2017 were compared with those of 3820 patients from 2005 and 2007. In patients who underwent hepatectomy (n = 2759 and 2163), the number of CRLMs was significantly higher and in the 2013–2017 data than in the 2005–2007 data (median 2 vs. 1; p = .005). Overall survival (OS) rates after diagnosis of CRLM after hepatectomy were better in the 2013–2017 data than that in the 2005–2007 data (5‐year OS, 62.4% vs. 56.7%, p < .001). Recurrence‐free survival (RFS) after hepatectomy was comparable between the groups (5‐year RFS, 30.5% vs. 30.7%; p = .068). Multivariate analyses identified age at diagnosis of CRLM ≥70 years, lymph node metastasis of primary lesion, preoperative carbohydrate antigen (CA) 19–9 value >100 U/mL, number of CRLM 2–4, and R2 resection as independent predictors of OS. Synchronous CRLM, concomitant extrahepatic metastasis, lymphatic invasion, lymph node metastasis of primary lesion, preoperative CA19‐9 value >100 U/mL, number of CRLM 5–, and nonlaparoscopic approach were selected as that of RFS. Despite having a higher prevalence of advanced stage CRLM in the 2013–2017 patient population compared to the 2005–2007 cohort, prognostic outcomes demonstrably improved in the later period.
In‐utero exposure to tenofovir‐containing pre‐exposure prophylaxis and bone mineral content in HIV‐unexposed infants in South Africa
Authors: Reddy Kerusha , Naidoo Kimesh L. , Lombard Carl , Godlwana Zukiswa , Desmond Alicia C. , Clark Richard , Rooney James F. , Gray Glenda , Moodley Dhayendre
Published: November 2024

Introduction

Tenofovir disoproxil fumarate (TDF) is a common drug of choice for pre‐exposure prophylaxis (PrEP) or as a combination HIV treatment for pregnant women. In‐utero exposure to TDF was found to be associated with lower bone mineral content (BMC) in HIV‐exposed uninfected neonates. Data for infants born to women taking TDF‐PrEP are lacking. The CAP016 randomized control trial was conducted in South Africa between September 2017 and August 2021 and pregnant women either initiated TDF/FTC PrEP in pregnancy (Immediate PrEP arm‐IP) or at cessation of breastfeeding (Deferred PrEP arm‐DP). In a secondary data analysis, we evaluated BMC in HIV‐unexposed infants in the CAP016 trial in the first 18 months of life in association with maternal TDF‐PrEP use during pregnancy.

Methods

Infants born to women randomized to the IP arm or DP arm in the CAP016 clinical trial had BMC measurements of the whole body with head (WBH) and lumbar spine (LS) by dual energy X‐ray absorptiometry (DXA) at 6, 26, 50 and 74 weeks.

Results

Of 481 infants born to women enrolled in the CAP016 clinical trial, 335 (69.6%) infants had a minimum of one DXA scan of the WBH and LS between 6 and 74 weeks of age (168 IP and 167 DP). Women in the IP arm received TDF‐FTC PreP for a median of 19 weeks between initiation in pregnancy and delivery. Using a mixed linear regression model and adjusted for gestational age, sex and ever‐breastfed, the mean difference (95% CI) for BMC of the WBH between IP and DP arms were −0.74 (−8.69 to 7.20), −1.26 (−10.75 to 8.23), −9.17 (−20.02 to 1.69) and 5.02 (−6.74 to 16.78) g at 6, 26, 50 and 74 weeks (p = 0.283). Mean differences in BMC of the LS were 0.07 (−0.10 to 0.23), 0.02 (−0.18 to 0.22), −0.14 (−0.36 to 0.09) and 0.14 (−0.11 to 0.38) g at 6, 26, 50 and 74 weeks, respectively (p = 0.329).

Conclusions

In a randomized controlled trial, there were no differences in BMC of the WBH and LS between infants exposed to in‐utero TDF‐FTC PrEP and unexposed infants in the first 18 months of life.
Current global vitamin and cofactor prescribing practices for primary mitochondrial diseases: Results of a European reference network survey
Authors: Neugebauer Julia , Reinson Karit , Bellusci Marcello , Park Julien H. , Hikmat Omar , Bertini Enrico , Schiff Manuel ,   MetabERN PM‐MD Consortium authors, Rahman Shamima
Published: November 2024

Primary mitochondrial diseases (PMD) account for a group of approximately 400 different genetic disorders with diverse clinical presentations and pathomechanisms. Although each individual disorder is rare, collectively they represent one of the largest groups in the field of inherited metabolic disorders. The complexity of PMD results in a continued lack of therapeutic options, necessitating a predominantly symptomatic treatment approach for affected patients. While a subset of diseases responds exceptionally well to treatment with specific vitamins or cofactors, for most PMD systematic reviews were not able to show significant benefit. This is in discrepancy to their continued frequent use among specialists. To gain further insight into the current clinical practice of vitamin and cofactor supplementation among clinicians treating children and adults affected by PMD, we conducted a worldwide cross‐sectional questionnaire study exploring the choice of substances and the specific diseases where they are applied. To our knowledge, this is the first global study exploring this topic and featuring a high response rate from paediatricians. The vast majority (95%, 106/112) of responding specialists recommended the use of vitamins and cofactors, either in an agnostic approach irrespective of the specific PMD or directed to the treatment of specific diseases or phenotypes. Our study highlights significant regional and specialty‐specific differences in supplementation practices. We provide some preliminary insights into specialist‐based opinions regarding the use of vitamins and cofactors in PMD and highlight the need for more rigorous clinical and preclinical investigations and/or clear consensus statements.
Leader(ship) Identity Development and Meaning Making: A Scoping Review
Authors: Sunderman Hannah M. , Orsini Jonathan
Published: November 2024

Despite a growing body of scholarship on leader and leadership (i.e., leader[ship]) identity development (LID), there has been surprisingly little systematic attention devoted to the connection between LID and meaning making, which is notable because meaning making has been regarded as foundational to the LID process. Accordingly, the current scoping review explores the scholarship and key characteristics at the intersection of LID and meaning making. Specifically, the year of publication, research method and design, country of participants, and theories central to author justification are analyzed. After sharing the results, contributions, and implications for the constructs of LID and meaning making are outlined, with attention given to theoretical and methodological areas for future research. Finally, an integrated constructivist model of LID is proposed that urges leadership scholars and practitioners to incorporate developmental, identity, learning, and meaning‐making theories into their discussions of LID.
Ultrastructure and Function of the Stalk Gland Complex of Pompholyx faciemlarva (Rotifera: Monogononta)
Authors: Araújo Thiago Quintão , Hochberg Rick
Published: November 2024

Many planktonic rotifers carry their oviposited eggs until hatching. In some species, the eggs are attached to the mother via secretions from her style gland, which forms a thread that extends from her cloaca. In species of Pompholyx, the mother possesses the rare ability to change the tension on the secreted thread, which alters the proximity of the egg with respect to her body. In this study, we used behavioral observations, confocal microscopy, and transmission electron microscopy to study the functional morphology of the stalk gland, which secretes a similar thread to the style gland. Our observations reveal that six longitudinal muscles insert on a stalk‐gland complex, which is a combination of a two‐headed gland and an epithelial duct that connects to the posterior cloaca. The gland secretes a single, long, electron‐dense thread that traverses the duct and attaches to the egg surface through the cloaca. Three retractor muscles insert on the stalk gland and function to pull the entire complex anteriorly, thereby increasing tension on the thread and moving the egg close to the mother's body. A set of three (two pairs and a single dorsal) protractor muscles antagonize these actions, and their contraction pulls the gland complex close to the cloaca, thereby releasing tension on the thread and allowing the egg to distance itself from the mother. The stalk gland complex does not appear to be homologous to the style glands of other rotifers, but we hypothesize that it functions as a form of maternal protection as is the case with style glands.
Application of mPEG‐PCL‐mPEG Micelles for Anti‐Zika Ribavirin Delivery
Authors: M. R. Blahove , J. A. Saviskas , J. Rodriguez , B. G. Santos‐Villalobos , M. A. Wallace , J. A. Culmer , J. R. Carter
Published: November 2024

Nanoparticles are rapidly becoming the method of choice for a number of nanomedicine applications, especially drug delivery. Many current nanoparticle models for drug delivery include a metal base with a drug conjugated to its surface. However, this raises concerns regarding toxicity since the conjugated drug and metal‐based center of the nanoparticle are generally not biocompatible. A novel approach to solve this dilemma is the development of nanosized biocompatible polymer‐based micellar nanoparticles (MNPs), created from methoxy poly(ethylene‐glycol) poly(ɛ‐caprolactone)‐methoxy poly(ethylene glycol) (i.e., mPEG‐PCL‐mPEG) triblock polymers formed around an antiviral drug of choice, ribavirin. The goal is to create a drug carrier triblock nanoparticle system that is labile at a specific intercellular pH resulting in drug release, leading to the suppression of viral pathogens, and without undue toxicity to the cell. Through this approach we created a drug‐loaded nanoparticle that dissociates when exposed to pH of 5.49 (endosomal pH), releasing ribavirin intercellularly, resulting in effective suppression of the mosquito‐borne virus, Zika, in JEG‐3 cells (gestational choriocarcinoma cells), in comparison to untreated and unencapsulated ribavirin controls as shown by plaque reduction assays and confirmation by RT‐PCR. The level of suppression observed by ribavirin‐loaded MNPs was achieved while requiring approximately 90% less ribavirin than in experiments utilizing unencapsulated ribavirin. The drug delivery system that is described here has shown significant suppression of Zika virus and suggests a role for this drug delivery system as an antiviral platform against additional viral pathogens.
EZH2 Activates HTLV‐1 bZIP Factor‐Mediated TGF‐β Signaling in Adult T‐Cell Leukemia
Authors: Zhang Xu , Yi Kaining , Wang Bingbing , Chu Kaifei , Liu Jie , Zhang Jie , Fang Jiaqi , Zhao Tiejun
Published: November 2024

Adult T‐cell leukemia (ATL) is an aggressive malignancy caused by human T‐cell leukemia virus type 1 (HTLV‐1) infection. Enhancer of zeste homolog 2 (EZH2) has been implicated in the development and progression of multiple cancers, including virus‐induced malignancies. However, the potential function of EZH2 in HTLV‐1‐induced oncogenesis has not been clearly elucidated. In the present study, we showed that EZH2 was overexpressed and activated in HTLV‐1‐infected cell lines, potentially due to the activation of EZH2 promoter by HTLV‐1 Tax and NF‐κB p65 subunit. In addition, we found that EZH2 enhanced the HBZ‐induced activation of TGF‐β signaling in a histone methyltransferase‐independent manner. As a mechanism for these actions, we found that EZH2 targeted Smad3/Smad4 to form a ternary complex, and the association between Smad3 and Smad4 was markedly enhanced in the presence of EZH2. Knockdown of EZH2 in ATL cells indeed repressed the expressions of the TGF‐β target genes. In particular, EZH2 synergistically enhanced the HBZ/TGF‐β‐induced Foxp3 expression. Treatment of 3‐Deazaneplanocin A, a specific inhibitor of EZH2 significantly inhibited the Foxp3 expression. Taken together, our results suggest that EZH2 may be involved in the differentiation of regulatory T cells through activating the HBZ‐Smad3‐TGF‐β signaling axis, which is considered to be a key strategy for viral persistence.
Associations of Lipid Profiles With the Onset of HEV‐Related Acute Liver Failure: A Multicenter Cohort Study
Authors: Dong Rui , Xue Hong , Chen Lin , Jin Wenjuan , Luo Zhenghan , Shen Chao , Huang Lili , Shao Jianguo , Wang Jie
Published: November 2024

Hepatitis E virus (HEV) is one of the major etiologies for acute liver failure. This multicenter retrospective cohort study aimed to investigate the associations of lipid profiles with the risk of HEV‐related acute liver failure (HEV‐ALF) among hospitalized patients with acute hepatitis E. A total of 1061 participants were obtained from three tertiary medical centers in Jiangsu, China, between February 2018 and May 2024. Univariate and multivariate Cox regression models were constructed to assess the associations between lipid profiles and the risk of HEV‐ALF onset. The time‐dependent area under the receiver‐operating‐characteristic curve (AUROC) and decision curve analysis were used to further evaluate the predictive value of blood lipids. After adjusting for potential confounders, total cholesterol (HR = 0.535, 95% CI: 0.437–0.656, p < 0.001), high‐density lipoprotein‐cholesterol (HR = 0.065, 95% CI: 0.027–0.154, p < 0.001), low‐density lipoprotein‐cholesterol (HR = 0.653, 95% CI: 0.512–0.833, p = 0.001), and apolipoprotein A (ApoA) (HR = 0.006, 95% CI: 0.002–0.020, p < 0.001) were significantly associated with a reduced risk of HEV‐ALF. Moreover, blood ApoA exhibited excellent discrimination ability and net benefit for predicting 7‐day (AUROC = 82.47%, 95% CI: 77.92–87.02) and 14‐day (AUROC = 78.81%, 95% CI: 74.13–83.49) HEV‐ALF onset. The findings may provide further evidence on the progression of HEV infection and future risk prediction.
Transmission Network and Phylogenetic Analysis Highlight the Role of Suburban Population in HIV‐1 Transmission Among Older Adults in Nanjing, Jiangsu Province, China
Authors: Li Xin , Shi Hui , Shi Hongjie , Xu Yuanyuan , Wu Sushu , Wu Rong , Yuan Xin , Wang Jingwen , Zhu Zhengping
Published: November 2024

Describing the transmission characteristics among older adults is essential for designing tailored interventions. An epidemiological investigation combined with phylogenetic analysis was conducted to reveal potential transmission linkages among older adults in Nanjing. Between 2018 and 2022, 188 pol sequences were successfully amplified. Multiple genotypes were identified, including CRF07_BC (55.3%), CRF01_AE (30.3%), CRF08_BC (8.0%), B (3.2%), CRF55_01B (1.1%), CRF67_01B (0.5%), CRF68_01B (0.5%), and unique recombinant forms (URF) (1.1%). Transmission network analysis identified 120 genetically linked patients forming 23 clusters, ranging from 2 to 26 individuals. Multivariable logistic regression analysis showed that compared with farmers and heterosexuals, patients with other occupations (OR = 0.404, 95% CI: 0.173−0.945) and MSM (OR = 0.193, 95% CI: 0.050−0.738) were less likely to have high linkage. Subjects who lived in suburban areas were more likely to have high linkage (OR = 10.932, 95% CI: 3.335−35.830). The Sankey diagram suggested that patients living in suburban areas primarily transmitted the disease within the local district (χ2 = 24.192, p < 0.001). Among the 188 pol sequences, the prevalence of pretreatment drug resistance was 8%. In suburban areas with a rising HIV‐1 epidemic, improving early detection and timely treatment is critical. More tailored interventions for this subgroup are urgently needed.
Memory B Cells Provide Long‐Term Protection to Vaccinated Kidney Transplant Recipients Against SARS‐CoV‐2 Variants
Authors: Espi Maxime , Charmetant Xavier , Benotmane Ilies , Lefsihane Katia , Barateau Véronique , Gallais Floriane , Boulenouar Hafsa , Ovize Anne , Barbry Alexia , Bouz Christine , Morelon Emmanuel , Defrance Thierry , Fafi‐Kremer Samira , Caillard Sophie , Thaunat Olivier
Published: November 2024

Kidney transplant recipients (KTRs) are highly vulnerable to COVID‐19. An intensified scheme of vaccination offers short‐term protection to the 50%–75% of KTRs able to develop a germinal center reaction, required for the generation of neutralizing titers of antibodies (NAbs). However, the duration of this vaccinal protection is unknown. In‐depth longitudinal analysis of the immune response to vaccination of 33 KTRs demonstrates that the low peak of IgGs, the progressive decline in antibody titers, and the emergence of a variant of concerns (VOC) of SARS‐CoV2, synergize to let 2/3 of responders to vaccine without NAbs after only a few months. Yet, a retrospective study of an independent cohort of 274 KTRs, revealed that the risk of severe COVID‐19 in the latter was low, similar to that of patients with serum neutralizing capacity against VOC. Our work links this late vaccine protection with the presence of memory B cells, which are generated during the initial vaccine‐induced germinal center reaction, have a wide repertoire directed against conserved spike epitopes, and rapidly differentiate into IgG‐producing plasma cells upon antigenic rechallenge. We conclude that in contrast with a serological layer that goes fading rapidly, the cellular layer of humoral memory provides an efficient long‐term protection against VOC to KTRs. This illustration of the complementary roles of the two layers of the humoral memory has implications in immunopathology beyond the COVID‐19 in KTRs.
Systemic Immune‐Inflammation‐Based Biomarker and Fragility Fractures in People Living With HIV: A 10‐Year Follow‐Up Cohort Study in China
Authors: Liu Bo , Zhang Qiang
Published: November 2024

Fragility fractures are a significant concern among people living with HIV(PLWH) due to the combined effects of chronic inflammation, immune dysregulation, and antiretroviral therapy. Traditional biomarkers have limited predictive value for fragility fractures in this population. This study aims to evaluate the systemic immune inflammation‐based scores as novel biomarkers for predicting fragility fractures in PLWH in China. We conducted a cohort study of PLWH in the orthopedic department of Beijing Ditan Hospital from January 2011 to September 2023. We monitored fragility fractures and collected data on demographics, clinical characteristics, and laboratory parameters. Multivariate Cox and logistic regression models were used to assess the predictive value of the neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), monocyte‐to‐lymphocyte ratio (MLR), systemic immune‐inflammation index (SII), and systemic inflammation response index (SIRI) for fragility fractures. Restricted cubic splines (RCS) were employed to explore potential nonlinear relationships, and subgroup analyses were conducted to examine the stability of these associations. During a median follow‐up of 5.5 years, our study included 1148 PLWH patients, and 204 patients (17.8%) experienced fragility fractures. After adjusting for all covariates, SII and SIRI were identified as independent risk factors for fragility fractures in PLWH, whereas NLR, PLR, and MLR were not. Patients with higher levels of SII and SIRI had a significantly increased risk of fragility fractures compared to those with lower levels (HR: 1.96, 95% CI: 1.24–3.10, p = 0.004; HR: 1.83, 95% CI: 1.16–2.88, p = 0.009). RCS analysis indicated a stable linear relationship between SIRI and fragility fractures. Furthermore, KM curves demonstrated that patients with higher SII and SIRI scores had a higher likelihood of experiencing fragility fractures. Our research shows that SII and SIRI are promising biomarkers for predicting fragility fractures in PLWH. Clinicians should consider incorporating SIRI into clinical practice to improve fracture risk stratification and guide preventive strategies for this vulnerable population.
Highly Sensitive and Specific Diagnosis of Enterovirus A71 by Reverse Transcription Multiple Cross‐Displacement Amplification‐Labeled Nanoparticles Biosensor
Authors: Cheng Jinzhi , Zhou Yuhong , Tang Xiaomin , Lu Jingrun , Wang Yu
Published: November 2024

Enterovirus A71 (EVA71) is a leading causative agent of hand, foot, and mouth disease, posing a significant threat to the health of young children, particularly in the Asia‐Pacific region. Currently, there is no specific antiviral drug for EVA71 infection; therefore, early and rapid diagnosis is critical for disease prevention and control. Here, we report the development of a simple, rapid, and sensitive detection method for EVA71 infection using reverse transcription‐multiple cross displacement amplification (RT‐MCDA) combined with nanoparticle‐based lateral flow biosensors (LFB). In the RT‐MCDA system, a set of 10 primers was designed to target the highly conserved region of the VP1 gene of EVA71 and amplify the genes in an isothermal amplification device. The RT‐MCDA amplification reaction products could then be identified by visual detection reagent (VDR) and LFB without the need for specialized equipment. The results demonstrated that the optimal reaction condition for the EVA71‐RT‐MCDA assay was 65℃ for 40 min. The EVA71‐RT‐MCDA assay could detect as low as 40 copies of plasmid and 50 copies of pseudotyped virus in a reaction. No cross‐reaction was found between EVA71 strains and non‐EVA71 strains. For 125 clinical anal swab samples, with EVA71‐RT‐MCDA assay, 30 samples were positive, which was in consistent with the the conventional real‐time quantitative reverse transcription polymerase chain reaction assays. The entire procedure, including a 15‐min specimen processing step, a 40‐min MCDA reaction, and result reporting within 2 min, was completed in less than 60 min. In conclusion, the EVA71‐RT‐MCDA‐LFB assay targeting the VP1 gene is a rapid, highly sensitive, simple, and specific test that could be widely applied in point‐of‐care settings and basic medical facilities in rural areas.
Numerical Technique Based on Operational Matrices of Fractional Integration Using ψ$$ \psi $$‐Shifted Chebyshev Polynomials
Authors: Sadiq Shazia , ur Rehman Mujeeb
Published: November 2024

In this paper, we present a numerical scheme based on a modified form of shifted Chebyshev polynomials to find the numerical solution of a class of fractional differential equations. For this purpose, we work out operational matrices of fractional integration of ‐shifted Chebyshev polynomials obtained from shifted Chebyshev polynomials. Finally, the solution to the problem under consideration is obtained by solving a system of algebraic equations that results from the use of operational matrices of integration. The analysis of integer and non‐integer order differential equations is presented to show the convergence of the solution of fractional order differential equation to the corresponding solution of the integer order differential equation. At the end, we present some linear and non‐linear examples to validate the theoretical analysis. Non‐linear examples are solved using Quasilinearization and proposed numerical technique.
Frequency‐Specific Alternations in the Amplitude of Fluctuations in Tension‐Type Headache: A Machine Learning Study
Authors: Jia Xize , Li Mengting , Zhang Shuxian , Antwi Collins Opoku , Zhan Linlin , Zhao Mengqi , Wen Jianjie , Hu Su , Hao Zeqi , Ren Jun
Published: November 2024

Brain neural signal at different frequency bands relates to different functions. However, the frequency‐specific properties of spontaneous brain activity in tension‐type headache (TTH)—the most rampant primary headache—remain largely unknown. We investigated the local neural activity of 33 TTH patients and 31 healthy controls (HCs) in the conventional frequency band and two sub‐frequency bands (slow‐4 and slow‐5 frequency band), employing fractional amplitude of low‐frequency fluctuations (fALFF), percent amplitude fluctuations (PerAF) and Wavelet‐ALFF analytic methods. Using age as covariate, we performed two sample t‐test to compare the between‐group differences of each metrics in each frequency band. Support vector machine (SVM) was conducted to classify TTH patients and HCs on the basis of altered spontaneous brain activities. TTH patients showed lower fALFF values in the left cerebellar lobule X, left parahippocampal gyrus, and right supplementary motor area in slow‐5 band. TTH patients showed lower PerAF in the left fusiform and cerebellar regions in three bands. Altered Wavelet‐ALFF values in the right thalamus, left anterior cingulum gyrus, superior parietal gyrus and middle and parietal frontal regions in three frequency bands were detected. And the SVM classifier obtained an overall accuracy of 77.38%, 82.38%, and 95% based on fALFF, PerAF, and Wavelet ALFF values, respectively. TTH patients exhibited abnormal neural activity in various brain regions. The abnormal brain activities serve as powerful features for distinguishing TTH patients. This preliminary exploration provides a novel insight into the underlying mechanism of TTH.
Building Narratives Through Empathy: The Role of Empathy Mechanisms and Associative Thinking in Creative Writing
Authors: Golab Dominik , Barbot Baptiste
Published: November 2024

Empathy emerges as a pivotal skill in creative writing, yet previous studies lack an understanding of empathy's multidimensionality and specific impact of its facets on the capacity to generate narrative stories. This cross‐sectional study delved into the various cognitive and affective empathy facets—that is, perspective‐taking, online simulation, emotion contagion, proximal responsivity, and peripheral responsivity—and their contributions to creative writing. Further, it examined the mediating effects of associative thinking—conceptualized as a common empathy‐creativity resource—on the relationship between empathy facets and creative writing. Two‐hundred twenty participants (university students) completed performance‐based tasks and self‐report measures of creative writing, associative thinking, and empathy. A latent mediation model implemented in Structural Equation Modeling indicated two effects of empathy facets on creative writing, with perspective‐taking emerging as a positive predictor. Additionally, peripheral responsivity (i.e., affect sharing in indirect contexts) exhibited an indirect positive influence on creative writing, mediated by associative thinking. In summary, associative thinking appears to be an important ingredient in both empathy and creative writing, while cognitive empathy, specifically intuitive perspective‐taking, contributes significantly to creative writing skills. Future studies should further explore these connections and their causalities, possibly using experimental or longitudinal approaches.
Preoperative Anemia and Iron Deficiency in Elective Gastrointestinal Cancer Surgery Patients
Authors: Skorupski Clarissa P. , Cheung Matthew C. , Hallet Julie , Kaliwal Yosuf , Nguyen Lena , Pavenski Katerina , Zuckerman Jesse S. , Lin Yulia
Published: November 2024

Background and Objectives

Preoperative anemia can impact postoperative outcomes, but its importance in gastrointestinal cancer patients, and significance of anemia etiology remains unclear. We aimed to characterize the frequency and impact of preoperative anemia, and iron‐deficiency anemia (IDA), on perioperative outcomes.

Methods

We performed a retrospective cohort study of adult patients undergoing elective gastrointestinal cancer surgery. The primary outcome was the incidence of perioperative RBC transfusion. Secondary outcomes included 90‐day postoperative major morbidity, ICU admission, and 90‐day hospital readmission. Multivariable analyses were performed to assess the association between preoperative anemia and IDA and outcomes.

Results

Preoperative anemia was present in 55.5% of patients (n = 15 414), and 58.3% of anemic patients were iron deficient. Preoperative anemia was independently associated with increased risk of RBC transfusion (RR 2.88, 95% CI 2.60–3.20), and secondary outcomes. For every preoperative hemoglobin decrease of 1 g/dL, the adjusted risk of perioperative RBC transfusion increased by 40% (RR 1.39, 95% CI 1.37–1.42).

Conclusion

Preoperative anemia is prevalent, and an independent risk factor for adverse postoperative outcomes. Decreases in preoperative hemoglobin levels elevate the risk of transfusion and adverse outcomes, supporting further study to optimize management of treatable causes of preoperative anemia including IDA.
Reducing ACL injury risk: A meta‐analysis of prevention programme effectiveness
Authors: Clar Clemens , Fischerauer Stefan F. , Leithner Andreas , Rasic Laura , Ruckenstuhl Paul , Sadoghi Patrick
Published: November 2024

Purpose

The aim of this study was to conduct a meta‐analysis of the literature regarding anterior cruciate ligament (ACL) injury prevention programmes (IPPs) in order to assess the effectiveness of ACL prevention programmes based on current high‐quality studies. The hypothesis was that the implementation of ACL IPPs significantly reduces the incidence of ACL ruptures compared to standard practice.

Methods

A meta‐analysis of the literature was conducted using the databases PubMed, EMBASE, MEDLINE, CINHAL and Cochrane Central Register of Controlled Trials. The search terms utilized were ACL, injury, knee, control and prevention. The collected data and reported clinical outcomes were independently gathered by three different individuals. After evaluating the heterogeneity of the studies, the DerSimonian–Laird random effects models were employed to determine the pooled risk ratios (RRs) and the risk differences (RDs) regarding ACL Injuries. The RD was utilized to ascertain the number needed to treat.

Results

The search strategy identified 743 studies, of which 11 met all inclusion and quality criteria for pooled analysis. The total number of study participants was 16,316. The overall RR of sustaining an ACL injury in the intervention group was 0.36 (95% confidence interval [CI]: 0.23 to 0.57) of the control group, showing a significant reduction in the ACL injury risk of the intervention group (p < 0.001). We identified an RD of −1.4% (95% CI: −2.4% to −0.4%) in favour of the intervention group. The number needed to treat in preventing one ACL rupture was 71.

Conclusion

In conclusion, the study clearly demonstrates a significant positive preventive effect of training programmes concerning ACL injuries (p < 0.001). The pooled estimates indicate that such programmes result in a significant reduction of ACL injury risks (p < 0.001). Despite the moderate quality of the included literature, the results exhibit robustness. However, based on the literature examined, no definitive superior training programme could be identified.

Level of Evidence

II.