bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance evaluation of CXCL10 ELISA “cosmic” kit to measure CXCL10 in cerebrospinal fluid of patients with HTLV‐1‐associated myelopathy
Authors: Ko Riyoko , Takahashi Katsunori , Kunitomo Yasuo , Tanabe Kenichiro , Yagishita Naoko , Yamauchi Junji , Araya Natsumi , Nakashima Makoto , Horibe Erika , Shimizu Takahiro , Sato Tomoo , Yamano Yoshihisa
Published: December 2024

Objectives

This study aimed to validate the clinical utility of cerebrospinal fluid (CSF) CXCL10 measurements in HTLV‐1‐associated myelopathy (HAM) using a CXCL10 ELISA “Cosmic” kit, a more widely applicable method than cytometric bead array (CBA).

Methods

CSF CXCL10 levels were measured in 165 samples from 111 patients with HAM and 18 controls using a CXCL10 ELISA “Cosmic” kit. We assessed the following: (1) CSF CXCL10 concentrations by HAM activity level (high, moderate, and low) versus controls; (2) correlation with CBA; (3) cutoff values, sensitivity, and specificity for differentiating among HAM activity levels; (4) changes in HAM activity after steroid therapy; and (5) relationship between HAM activity and prognosis in patients undergoing steroid therapy. A correlation coefficient of ≥0.9 with CBA was the primary endpoint.

Results

The median CSF CXCL10 levels in the high, moderate, low, and control groups were 4016.0, 841.0, 112.8, and 102.5 pg/mL, respectively. The ELISA findings were highly correlated with the CBA findings (r = 0.99). Cutoff values were set at 2500 pg/mL (sensitivity, 93.3%; specificity, 100%) to distinguish between high and moderate activity and 180 pg/mL (sensitivity, 81.8%; specificity, 100%) for low to moderate activity comparable to CBA. The new cutoffs enabled the detection of HAM activity changes and prediction of motor disability progression under steroid therapy.

Conclusion

CXCL10 ELISA “Cosmic” kit findings were strongly correlated with CBA findings, meeting the primary endpoint and demonstrating comparable sensitivity and specificity for distinguishing HAM activity. This product shows a promising ability to determine the therapeutic strategy.
Split Hand‐Foot Malformations—Unveiling Unique Molecular Diagnosis From a Brazilian Cohort
Authors: Cás Eduardo Da , Ceroni José Ricardo Magliocco , Yamamoto Guilherme Lopes , Castro Matheus Augusto Araújo , Bisneto Edgard França , Jorge Alexander Augusto de Lima , Filho Joao Bosco Oliveira , Kim Chong Ae , Krepischi Ana Cristina Vitorino , Bertola Débora Romeo
Published: December 2024

Split hand‐foot malformation (SHFM) is a congenital limb malformation affecting primarily the central rays of the hands and/or feet, with variable expressivity, incomplete penetrance and syndromic forms. It is genetically heterogeneous, including point mutations and structural variants in different loci. Five individuals with SHFM were clinically evaluated in a Tertiary Center in Brazil: four of them presented additional, nonskeletal findings, including one individual with split foot, hand syndactyly, and ectodermal findings. Structural variants and point mutations in genes associated with SHFM were identified in all individuals. Our results highlight genetic heterogeneity observed in this group of skeletal disorders, alongside incomplete penetrance, a challenging task imposed on genetic counseling. Of note, an individual harboring a recurrent heterozygous variant in MAP3K20 presented a phenotype reminiscent of TP63‐related disorders, contrary to the one recently reported in the literature with prominent facial dysmorphisms, expanding the phenotypic spectrum of this newly recognized syndromic form of SHFM.
Utilizing Centromedian Thalamus Connectivity to Personalize Noninvasive Neuromodulation Targets
Authors: Fu Cong , Feng Zijian , Ge Qiu , Yue Juan , Zang Yu‐Feng , Luan Guoming
Published: December 2024

Introduction

The centromedian nucleus (CM) of the thalamus is essential for arousal, attention, sensory processing, and motor control. Neuromodulation targeting CM dysfunction has shown efficacy in various neurological disorders. However, its individualized precise transcranial magnetic stimulation (TMS) remains unreported. Using resting‐state functional MRI, we mapped CM‐based functional connectivity (CM‐FC) to develop a personalized TMS scheme for neurological conditions.

Methods

We first analyzed the CM‐FC patterns of healthy subjects via 10 scanning sessions in three MRI scanners spanning two subject groups: one from the Human Connectome Project (n = 20, four sessions) dataset and the other from Hangzhou Normal University (n = 20, three sessions of 3 T MRI and three sessions of 1.5 T MRI). Pearson's correlation was used for CM‐FC evaluation. Then, we proposed an overlapping index ranging from 1 to 10, and group‐level clusters with the highest overlapping index located 4 cm beneath the scalp were identified. In the individual CM‐FC map, watershed image segmentation was used to obtain an individual cluster. The peak voxel with the highest FC value within the individual cluster was defined as a potential individualized target for future TMS.

Results

The spatial FC patterns were remarkably similar between the left and right CMs. CMs have widespread positive connectivity with cortical areas, including the sensorimotor cortex, supplementary motor area, middle frontal cortex, medial temporal cortex, and middle cingulate. Among the group‐level FC patterns of the left and right CMs, only the left CM had a group cluster in the left primary sensorimotor cortex (PSMC, cluster size = 51) with an overlapping index of 10, that is, 10 sessions showed significant CM‐FC.

Conclusions

The left PSMC exhibited reproducible FC with the left CM. The individual peak FC location in the left PSMC could be used as a TMS target for indirect modulation of CM activity and aid in the treatment of CM‐related neurological disorders.
The Circadian Clock Gene Bmal1 Regulates Microglial Pyroptosis After Spinal Cord Injury via NF‐κB/MMP9
Authors: Li Dachuan , Liu Siyang , Lu Xiao , Gong Zhaoyang , Wang Hongli , Xia Xinlei , Lu Feizhou , Jiang Jianyuan , Zhang Yuxuan , Xu Guangyu , Zou Fei , Ma Xiaosheng
Published: December 2024

Background

The treatment of spinal cord injury (SCI) is usually ineffective, because neuroinflammatory secondary injury is an important cause of the continuous development of spinal cord injury, and microglial pyroptosis is an important step of neuroinflammation. Recently, Bmal1, a core component of circadian clock genes (CCGs), has been shown to play a regulatory role in various tissues and cells. However, it is still unclear whether Bmal1 regulates microglial pyroptosis after SCI.

Methods

In this study, we established an in vivo mouse model of SCI using Bmal1 knockout (KO) mice and wild‐type (WT) mice, and lipopolysaccharide (LPS)‐induced pyroptosis in BV2 cells as an in vitro model. A series of molecular and histological methods were used to detect the level of pyroptosis and explore the regulatory mechanism in vivo and in vitro respectively.

Results

Both in vitro and in vivo results showed that Bmal1 inhibited NLRP3 inflammasome activation and microglial pyroptosis after SCI. Further analysis showed that Bmal1 inhibited pyroptosis‐related proteins (NLRP3, Caspase‐1, ASC, GSDMD‐N) and reduced the release of IL‐18 and IL‐1β by inhibiting the NF‐κB /MMP9 pathway. It was important that NF‐κB was identified as a transcription factor that promotes the expression of MMP9, which in turn regulates microglial pyroptosis after SCI.

Conclusions

Our study initially identified that Bmal1 regulates the NF‐κB /MMP9 pathway to reduce microglial pyroptosis and thereby reduce secondary spinal cord injury, providing a new promising therapeutic target for SCI.
Influence of TyG Index on Large Vascular Occlusive Stroke Following Endovascular Treatment
Authors: Sun Wei , Shen Huixin , Wu Xiao , He Aini , Yao Xuefan , Chen Fei , Song Haiqing , Huang Xiaoqin
Published: December 2024

Aims

This study aimed to investigate the impact of the triglyceride‐glucose index (TyG index) on clinical consequences in individuals with large vascular occlusion (LVO)‐induced acute ischemic stroke (AIS) following endovascular treatment (EVT).

Methods

We conducted a single‐center retrospective cohort study, including AIS with LVO who underwent EVT. Patients were categorized into TyG index groups, calculated as “(fasting triglyceride [mg/dL] × fasting blood glucose [mg/dL]/2).” Clinical outcomes were assessed, including poor outcome (modified Rankin Scale [mRS] > 2 [3–6]) at 90 days, early neurological deterioration (END), symptomatic intracranial hemorrhage (sICH), and 90‐day mortality after EVT. Logistic regression and restricted cubic splines (RCS) were used to examine the relationship between the TyG index and clinical outcomes. Receiver operating characteristic (ROC) curve was constructed to evaluate the prognostic capacity of the TyG index.

Results

A total of 424 patients were included. Higher TyG levels were associated with worse functional outcome at 90 days (per unit: p = 0.006), sICH (per unit: p = 0.002, T3 versus T1: p = 0.004), and 90‐day mortality (T2 versus T1: p = 0.011, T3 versus T1: p = 0.029) in logistic regression. A RCS model revealed a linear association between the TyG index and poor outcome at 90 days, sICH, and 90‐day mortality (p for nonlinearity > 0.05). In ROC curve analysis, the traditional risk factors model (area under the curve [AUC]: 0.824, 95% CI: 0.784–0.859) was outperformed by the conventional risk factors + TyG index model (AUC: 0.845, 95% CI: 0.807–0.878) in predicting poor outcome (p = 0.021).

Conclusion

A higher TyG index is associated with worse clinical outcomes in LVO‐induced AIS patients after EVT. Additionally, the TyG index enhances risk prediction of traditional risk factors for poor outcome.
Nitrogen Application Stimulates Methane Emissions
Authors: Fang Kaikai
Published: December 2024

Nitrogen fertilizer plays a vital role in rice cultivation, yet its excessive application significantly intensifies methane emissions from rice paddies. Therefore, the urgent adoption of effective agronomic interventions is crucial to mitigate methane emissions resulting from nitrogen fertilizer application.
Cumulative Heat Stress in Fluctuating Temperatures and Implications for the Distribution of Freshwater Fish
Authors: Rezende Enrico L. , Carter Mauricio J.
Published: December 2024

Predicting how rising temperatures will impact different species and communities is imperative and increasingly urgent with ongoing global warming. Here, we describe how thermal–death time curves obtained in the laboratory can be combined with an envelope model to predict the mortality of freshwater fish under field conditions and their distribution limits. We analyze the heat tolerance and distribution of 22 fish species distributed across North America and demonstrate that high temperatures imposed a distribution boundary for 11 of them, employing a null model. Importantly, predicted thermal boundaries closely match the warmest suitable locality of the envelope model. Simulated warming suggests that the distribution of fish species with lower heat tolerances will be disproportionately affected by rising temperatures, and the rate of local extinctions will be higher across fish communities in warmer localities. Ultimately, our analyses illustrate how physiological information can be combined with distribution models to forecast how warming temperatures are expected to impact different species and ecological communities.
Contrasting Approaches in the Implementation of GRADE Methodology in Guidelines for Haemophilia and Von Willebrand Disease
Authors: Skinner Mark W. , Albisetti Manuela , Ardila Jesús , Astermark Jan , Blatny Jan , Carcao Manuel , Chowdary Pratima , Connell Nathan T. , Crato Miguel , Dargaud Yesim , d'Oiron Roseline , Dunn Amy L. , Escobar Miguel A. , Escuriola‐Ettingshausen Carmen , Gouider Emna , Harroche Annie , Hermans Cedric , Jimenez‐Yuste Victor , Kaczmarek Radoslaw , Kenet Gili , Khoo Liane , Klamroth Robert , Langer Florian , Lillicrap David , Mahlangu Johnny , Male Christoph , Matsushita Tadashi , Meunier Sandrine , Miesbach Wolfgang , Nolan Beatrice , Oldenburg Johannes , O'Mahony Brian , Ozelo Margareth , Pierce Glenn F. , Ramos Gloria , Recht Michael , Romero‐Lux Olivia , Rotellini Dawn , Santoro Rita C. , Singleton Tammuella C. , Srivastava Alok , Susen Sophie , Talks Kate , Tran Huyen , Valentino Leonard A. , Windyga Jerzy , Yang Renchi , Mancuso Maria Elisa ,   also on behalf of AICE, AHAD‐AP, AHCDC, ATHN, CLAHT, EHC, French CRH & MHEMO, HTCCNC, NBDF, PEDNET, UKHCDO, WFH
Published: December 2024

Introduction

The 2024 ISTH clinical practice guideline (CPG) for treatment of congenital haemophilia, the NBDF‐McMaster Guideline on Care Models for Haemophilia Management, and ASH ISTH NBDF WFH guidelines on the diagnosis and management of VWD all utilised GRADE methodology.

Aim

Discuss missed opportunities and the methodological approach of the ISTH Guideline in contrast to how GRADE was previously applied in rare diseases.

Methods

Critically analyse the methodology of each guideline along with best practices in the use of GRADE. Where applicable, the WFH Guidelines for the Management of Haemophilia were analysed.

Results

Important differentiating features in applying GRADE were identified. Where a strong evidence base is lacking, data other than those from randomized controlled trials, which may not always be justified, need to be considered, including incorporation of outcomes important to people living with the disease. Justification and stakeholder input to prioritize questions requiring a new guideline, panel composition with necessary patient participation and content expertise were also found to be significant differentiating features.

Conclusion

The puristic approach taken in the ISTH Guideline development process, without consideration of accepted adaptations to GRADE implementation, created a missed opportunity for progressing haemophilia care, leading to guideline recommendations that have been widely deemed invalid and obsolete by expert healthcare professionals and by those living with the condition, the very people who are expected to implement or bear the impact of the recommendations. Lessons learnt from this comparative analysis should guide future guideline development and encourage collaboration to further advance haemophilia.
Patient and Public Involvement Work With Parents of Children With Life‐Limiting Conditions and Bereaved Parents: A Rapid Systematic Review
Authors: Holder Pru , Page Bethan , Hackett Julia , Mitchell Sarah , Fraser Lorna K.
Published: December 2024

Background

Guidance and principles for involving the public in research or service planning exist but are not specific to the needs of parents of children with life‐limiting conditions or bereaved parents.

Aim

Review the evidence on involving parents of children with life‐limiting conditions and bereaved parents in research, service planning and advocacy, and use this to develop best practice guidance.

Methods

Rapid review following the Cochrane Rapid Reviews Methods Group Guidance. MEDLINE and EMBASE were searched for primary studies of any design and literature/systematic reviews, and grey literature searching was conducted. Sources reporting on involving parents of children with life‐limiting conditions or bereaved parents in healthcare, research, or charity work in any setting, were included. Data were charted using the UK standards for public involvement in research (PPI). Two PPI consultation workshops were conducted with parents (n = 13) and healthcare professionals/charity representatives (n = 7).

Results

Six sources were included. Four reported benefits of parental involvement and two reported burdens. In relation to best practice, two reported on the importance of inclusive opportunities, three on working together, four on support and learning, three on communications, one on impact, and one on governance. PPI consultation workshops highlighted new factors which were not present in the literature around communication and understanding the impact of involvement.

Conclusion

Organisations working with this group should consider offering inclusive approaches to improve diversity, levelling power imbalances, ensuring flexibility of approach, and appropriate communication and impact.

Patient or Public Contribution

The study was conducted in collaboration with 13 parents of children with life‐limiting conditions and bereaved parents, and seven palliative care professionals. The group were involved at key stages of the review and contributed to the development of the findings and conduct of the review.
More Than Knowledge: Consumer Financial Capability and Saving Behavior
Authors: Núñez‐Letamendia Laura , Sánchez‐Ruiz Patricia , Silva Ana C.
Published: December 2024

This paper explores the association between financial capability, defined broadly through different constituents, and households' savings behavior. Using a survey conducted to a sample of 1501 consumers, the results, correcting for endogeneity, indicate that in order to explain savings behavior: (i) knowledge about investment products (funds, stocks, bonds, etc.) is more important than knowledge about concepts of an economic‐financial nature (simple and compound interest rate, inflation, and diversification); (2) self‐confidence in financial knowledge is more relevant than actual financial knowledge; (3) budgeting skills are strongly relevant; and (4) some of the elements proposed by the Theory of Planned Behavior, in particular control or self‐efficacy, are valid predictors of savings behavior. In sum, a broad conception of financial capability, beyond financial knowledge, is needed to understand savings behavior. Our study has implications for policy decision makers, consumers, and educational and financial institutions and sheds light on future lines of research.
Editor's Highlights—January 2025
Authors: Kemény Lajos
Published: December 2024

Immune‐mediated inflammatory skin diseases (IMIDs) frequently result in chronic and debilitating health conditions that significantly diminish patients' quality of life. In the past 10 years, we have seen a huge breakthrough in treating IMIDs by blocking cytokines or cytokine receptors through monoclonal antibodies and by blocking the signaling pathway using Janus kinase (JAK) inhibitors. Nowadays, an increasing number of patients with different immune‐mediated skin diseases are being treated with systemic and topical JAK inhibitors. Dermatologists frequently use these new medications in an off‐label way to treat various skin diseases. Thus, in the January issue of the Journal, we show the efficacy of JAK inhibitors in treating erythema nodosum leprosum, silicone‐induced foreign body reactions in a patient with chronic graft‐versus‐host disease, but also cover the potential side effects of JAK inhibitors in treating skin diseases.
Transient Anti‐TCRβ mAb Treatment Induces CD4+T Cell Exhaustion and Prolongs Survival in a Mouse Model of Systemic Lupus Erythematosus
Authors: Gonzalez Nancy Mize , Zou Dawei , Zeng Zihua , Feng Frances Xiuyan , Zhang Xiaolong , Sannes Caitlin , Gu Andy , Zu Youli , Chen Wenhao
Published: December 2024

T cells play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). Chronic T cell receptor (TCR) signalling induces T cell exhaustion, characterised by reduced capacity to induce tissue damage. Here, we investigated the therapeutic potential of the anti‐TCRβ (H57‐597) monoclonal antibody (mAb) in a mouse model of SLE. Four‐month‐old MRL/lpr mice exhibiting SLE phenotypes received 5 weekly doses of anti‐TCRβ mAb or phosphate‐buffered saline (PBS) vehicle control. Subsequently, mouse survival was monitored daily. On day 1 post the final dose of treatment, SLE pathogenesis was determined using histological staining and spot urine test. T and B cell states in the brain, kidney, and secondary lymphoid organs were determined by flow cytometry. Transient treatment of anti‐TCRβ mAb significantly prolonged the survival of MRL/lpr mice. Accordingly, MRL/lpr mice in the anti‐TCRβ mAb group exhibited decreased proteinuria scores and minimal renal pathological damage compared to the PBS control group. Flow cytometric analysis revealed that anti‐TCRβ mAb treatment resulted in a reduction in the frequencies of CD4+ T cells and CD138+B220lo/− plasma cells, plus an increase in Foxp3+ regulatory T cell frequency. Furthermore, CD4+ T cells from anti‐TCRβ mAb treated mice exhibited elevated expression levels of PD‐1 and TIM‐3, with reduced IFN‐γ production, indicative of an exhaustion‐like phenotype. Therefore, transient administration of anti‐TCRβ mAb treatment induces an exhaustion‐like phenotype in CD4+ T cells, resulting in prolonged survival of MRL/lpr mice. Inducing autoreactive T‐cell exhaustion holds promise as an attractive therapeutic approach for SLE.
Patients' Experiences of Healthcare Professionals' Competence in Digital Counselling in Healthcare Settings—A Qualitative Systematic Review
Authors: Kaihlaniemi Juulia , Suonnansalo Petra , Kääriäinen Maria , Kaakinen Pirjo , Litendahl Maija , Paukkonen Leila , Laukkonen Kirsi , Oikarinen Anne
Published: December 2024

Aim

To critically appraise and synthesise qualitative evidence about patients' experiences of healthcare professionals' competence in digital counselling in healthcare settings.

Design

A qualitative systematic review.

Methods

The review followed the Joanna Briggs Institute methodology for systematic reviews of qualitative evidence. The review included studies that focused on patient experiences of healthcare professionals' competence in digital counselling and were published in English, Finnish or Swedish, with no time limits. Study selection, quality appraisal and data extraction were performed by two independent reviewers. Findings from the studies included were pooled using the meta‐aggregation method.

Data Sources

Eight databases (Web of Science, CINAHL, Scopus, PsycArticles, Medic, Medline (Ovid), EBSCO Open Dissertations and MedNar) were systematically searched on 25 September 2023.

Results

Sixteen studies (published between 2009 and 2023) were included in the review, from which 42 findings were extracted and organised into eight categories based on their meaning. Three synthesised findings were identified: (1) Competence to provide efficient digital counselling, (2) competence to support patient self‐management during digital counselling and (3) competence in establishing a reciprocal relationship in digital counselling.

Conclusion

The evidence from the review can be used to support healthcare professionals' competence in digital counselling. It was found that competence in digital counselling includes the competence to provide digital counselling that is efficient and enables counselling to be implemented in health care, supports patients to self‐manage and establishes a reciprocal counselling relationship in a digital environment.

Implications for the Profession and Patient Care

Recognising healthcare professionals' competence in digital counselling can enhance their motivation and professional growth, potentially improving the quality of services and patient outcomes. These findings can inform the development of healthcare education, fostering the training of more competent healthcare professionals and digital counsellors.

Reporting Method

The review was undertaken and reported using the PRISMA guidelines.

Protocol Registration

PROSPERO CRD42024499509.

No Patient or Public Contribution.
Clinical impact of endogenous luteinizing hormone in frozen–thawed embryo transfer during hormone replacement cycle without gonadotropin‐releasing hormone analog coadministration: Effects on pregnancy outcomes
Authors: Sakata Akiko , Matsuda Shigeru , Kuwabara Yoshimitsu , Kato Ryoko , Nakao Kimihiko , Ichikawa Tomoko , Suzuki Shunji
Published: December 2024

Purpose

To assess the correlation between serum luteinizing hormone (LH) levels preceding luteal replacement initiation and outcomes of frozen–thawed embryo transfer (FET) cycles during hormone replacement therapy (HRT) without co‐administration of gonadotropin‐releasing hormone (GnRH) analog.

Methods

We retrospectively enrolled 490 FET cycles performed between March 2018 and May 2023. Patients were categorized into quartiles based on their serum LH levels preceding luteal replacement. Multivariate logistic regression analysis was performed, with clinical pregnancy and live birth rates as dependent variables. The independent variables included women's mean age, serum LH, and estradiol levels preceding luteal replacement, and endometrial thickness during transfer.

Results

Mean age, serum estradiol, and LH levels preceding luteal replacement were 36.8 ± 0.2 years, 306.5 ± 7.7 pg/mL, and 10.3 ± 0.3 mIU/mL, respectively. The clinical pregnancy and live birth rates were 46.8% and 31.9%, respectively, and varied significantly between quartiles. Multivariate analysis revealed that younger age and higher LH levels were significantly associated with increased clinical pregnancy and live birth rates.

Conclusions

Endogenous LH may facilitate pregnancy within FET cycles under HRT without GnRH analogs by preparing the endometrium for implantation.
Agreement between clinical criteria and quantitative polymerase chain reaction for diagnosing scabies in Auckland children
Authors: Nambiar Tarun , Zaveri Sanskruti , Thornley Simon , Selak Vanessa , Sundborn Gerhard , Pasay Cielo , Morris Arthur J
Published: December 2024

Aim

We sought to determine the degree of agreement between clinical and laboratory methods for diagnosing scabies in school‐aged children.

Methods

Clinical information and samples were collected from children aged 7 months to 14 years attending educational institutions in Auckland, New Zealand. Two methods determined scabies status: the International Alliance for the Control of Scabies clinical criteria (IACS) and quantitative polymerase chain reaction (qPCR). Sensitivity and specificity of each method, as the reference or index standard, were estimated and agreement was determined using Cohen's kappa statistic.

Results

Sixteen of 145 children were positive based on IACS criteria and 15 of 64 with a suspicious skin lesion returned a positive qPCR test. IACS sensitivity and specificity were 66.7% (95% confidence interval (CI): 39.9–93.3) and 94% (95% CI: 89.9–98.0), respectively (with qPCR as the reference). For qPCR, sensitivity and specificity were 50% (95% CI: 25.5–74.5) and 96.9% (95% CI: 94.0–100.0), respectively (with IACS as the reference). The kappa value was 0.53.

Conclusion

Agreement between clinical and laboratory methods in the identification of scabies diagnosis was moderate. Both methods had low sensitivity but high specificity. Scabies diagnosis might be improved, thereby enhancing control measures, by relaxing the IACS criteria (as some IACS‐negative participants returned positive qPCR tests, indicating mite DNA was present) and conversely supplementing clinical assessment with qPCR testing.
Parkin‐TLR4‐NLRP3 Axis Directs Melatonin to Alleviate Atrazine‐Induced Immune Impairment in Splenic Macrophages
Authors: Liu Shuo , Yang Tian‐Ning , Wang Yu‐Xiang , Ma Xiang‐Yu , Shi Yu‐Sheng , Zhao Yi , Li Jin‐Long
Published: December 2024

Atrazine (ATR) is a widespread environmental herbicide that seriously affects agricultural work and human safety. Melatonin (MLT) as an endogenous neuroendocrine hormone is widely found in animals and plants, which have antioxidant and anti‐inflammatory effects. Pink1/Parkin‐mediated mitophagy keeps normal physiological processes by degrading damaged mitochondria in cells. Therefore, we investigated the potential role and mechanism of MLT in ATR‐induced toxic injury of the spleen. The results showed that MLT alleviated ATR‐induced unclear boundary between the white pulp and the red pulp of the spleen. It is also shown that ATR resulted in swollen mitochondria, partial extinction of mitochondrial membranes and cristae, and increased mitophagy under the action of MLT. ATR‐induced reactive oxygen species (ROS) activates the Pink1/Parkin pathway, which guides mitophagy development and then causes the activation of TLR4/NF‐κB inflammatory pathway. Meanwhile, these damages further exacerbated the production of NLRP3 inflammasomes, leading to spleen necrosis. Interestingly, these changes were improved after MLT treatment. Collectively, we found that MLT alleviates ATR‐induced immune impairment in splenic macrophages via regulating Parkin‐TLR4‐NLRP3 axis which elucidates the effect of melatonin on the spleen and provides a novel perspective on melatonin in splenic inflammatory injury treatment.
Dynamics of Selected Milk Quality Parameters and Expression Patterns of miR‐26a, miR‐27a, and miR‐148a During Transition From Colostrum to Mature Milk in Awassi Sheep
Authors: Özkan Hüseyin , Sarıbay Mustafa Kemal , Keçeli Hasan Hüseyin , Kaya Ufuk , Sertkol Ramazan
Published: December 2024

This study investigated expressions of microRNA (miR)‐26a, miR‐27a, and miR‐148a in plasma, colostrum and milk collected on different days (0th, 4th, 7th, 14th, and 28th days) during transition from colostrum to milk in Awassi sheep. Relationships between miRNAs and quality parameters were also explored. During transition, Somatic Cell Count, Fat‐free dry matter, protein, lactose decreased, pH, freezing point (FP), electrical conductivity (EC) increased. Malondialdehydes (MDA) were tended to decrease in plasma and milk. Compared to 0th day, miR‐26a was upregulated approximately 27‐folds and 17‐folds in 14th and 28th days, in milk. On 14th day, miR‐27a showed almost 18‐folds upregulation, while miR‐148a was downregulated more than fivefolds on 7th and 14th days. In plasma, miR‐26a was upregulated almost 40‐folds and sevenfolds on 7th and 14th days. Additionally, miR‐27a was upregulated by approximately fivefolds on 4th day, around 20‐folds on 7th day, and about fourfolds on 14th day. miR‐148a was upregulated approximately 11‐folds on 7th day. While miR‐26a positively correlated with miR‐27a, pH, fat, and EC, it was negatively correlated with MDA in plasma. miR‐27a was positively correlated with miR‐148a and pH. Plasma miR‐148a and milk miR‐148a were negatively correlated. miR‐26a and miR‐27a were positively correlated in milk. Milk miR‐26a was positively correlated with pH, FP, and EC, while it was negatively correlated with fat, milk and plasma MDA. Milk miR‐27a was negatively correlated with fat and MDA, but positively with EC. The results obtained for the first‐time during transition indicate potentials of miR‐26a and miR‐27a to act as biomarkers for sheep milk quality.
Event‐based supervisor control for a cyber‐physical waterway lock system
Authors: Fragkoulis D. G. , Koumboulis F. N. , Tzamtzi M. P. , Totomis P. G.
Published: December 2024

An event‐based supervisory control scheme, in the Ramdage–Wonham framework, will be proposed for the cyber‐physical Waterway Lock system, known as Lock III, in Tilburg, the Netherlands. The proposed control scheme imposes desired behavior, by appropriately disabling controllable events, so as to avoid activation of actuator commands that may lead to undesired and potentially hazardous operating states. The discrete event model of the total Waterway Lock system, comprising 54 actuator and sensor automata, will be presented in analytic 6‐tuple forms of its subsystems. The system's desired behavior, which is expressed using six rules, will be formulated as 84 regular and prefix closed languages that will be realized as appropriate supervisor automata. All supervisors are developed by a general two‐state supervisor form, which facilitates their implementation. A distributed control architecture will be proposed, which organizes all supervisors in distinct groups, each of which controls one and only one distinct command event. The complexity of the proposed control scheme will be computed to be equal to (168,324,564), being reasonable, as compared to the large number of subsystems and the restrictive design requirements. The physical realizability of the 84 supervisors, with respect to the 54 subsystems of the waterway lock system, will be proved analytically. Also, it will be proved analytically that the proposed supervisor architecture guarantees the nonblocking property of the controlled automaton, including all subsystems. The establishment of these analytic proofs supports the extendibility of the results to other applications. To demonstrate the resulting large‐scale controlled automaton's good performance, its marked behavior and simulation results will be presented.
Functional Lumen Imaging Probe Panometry Findings in Obese Patient Populations
Authors: Nguyen Anh D. , Bhatt Anjali , Merchant Ambreen , Cipher Daisha J. , Ellison Ashton , Reddy Chanakyaram A. , Davis Dan , Souza Rhonda F. , Konda Vani J. A. , Spechler Stuart J.
Published: December 2024

Background

Few data are available on functional lumen imaging probe (FLIP) findings specifically in obese patients. We aimed to evaluate FLIP metrics in obese patients who had not undergone bariatric surgery and in those who had sleeve gastrectomy (SG) or Roux‐en‐Y gastric bypass (RYGB). We also sought correlations of FLIP abnormalities with esophageal symptoms and HRM findings.

Methods

We identified obese patients who had FLIP performed during workups either for a first bariatric operation (surgery‐naïve patients), or for surgical revision of SG and RYGB operations that resulted in inadequate weight loss. We recorded esophageal symptoms, HRM data, and FLIP metrics.

Key Results

We identified 228 eligible patients (87 surgery‐naïve, 90 SG, 51 RYGB). Dysphagia and chest pain were frequent symptoms in all groups. Median EGJ diameter and EGJ‐DI were similar in surgery‐naïve and postsurgical patients, but subgroup analysis of symptomatic patients with no HRM diagnosis revealed reduced EGJ opening in 12%. Abnormal FLIP response patterns were common (69% surgery‐naïve, 74% SG, 65% RYGB) with higher ACR rates in SG (46.7% vs. 29.9%, p = 0.026) and RYGB (41.2% vs. 29.9%, p = 0.189) and lower SRCR rates in SG (11.1% vs. 24.1%, p = 0.021) and RYGB (5.9% vs. 24.1%, p = 0.006) compared to surgically naïve patients. There were no significant associations between FLIP contractile response patterns and symptoms or HRM diagnoses.

Conclusions

Dysphagia and chest pain are common in obese patients, and most obese patients (with or without bariatric surgery) have FLIP contractile response abnormalities that do not correlate with HRM findings. FLIP findings appear to be especially valuable in obese patients who have esophageal symptoms with no HRM diagnosis.
Molecular fingerprints of cell size sensing and mating type differentiation in pennate diatoms
Authors: Belišová Darja , Bilcke Gust , Audoor Sien , D'hondt Sofie , De Veylder Lieven , Vandepoele Klaas , Vyverman Wim
Published: December 2024

A unique cell size‐sensing mechanism is at the heart of the life cycle of diatoms. During population growth, cell size decreases until a sexual size threshold (SST) is reached, below which cells become sexually competent. In most pennate diatoms, the two mating types undergo biochemical and behavioral differentiation below the SST, although the molecular pathways underlying their size‐dependent maturation remain unknown.

Here, we developed a method to shorten the generation time of Cylindrotheca closterium through single‐cell microsurgery, enabling the transcriptomic comparison of genetically identical large and undifferentiated cells with small, sexually competent cells for six different genotypes.

We identified 21 genes upregulated in small cells regardless of their mating type, revealing how cells undergo specific transcriptional reprogramming when passing the SST. Furthermore, we revealed a size‐regulated gene cluster with three mating type‐specific genes susceptible to sex‐inducing pheromones. In addition, comparative transcriptomics confirmed the shared mating type specificity of Mating‐type Related Minus 2 homologs in three pennate diatoms, suggesting them to be part of a conserved partner recognition mechanism.

This study sheds light on how diatoms acquire sexual competence in a strictly size‐dependent manner, revealing a complex machinery underlying size‐dependent maturation, mating behavior, and heterothally in pennate diatoms.
Extracellular Vesicles From LPS‐Treated PDLSCs Induce NLRP3 Inflammasome Activation in Periodontitis
Authors: Wu Yeke , Li Jiawei , Liu Min , Gao Ranran , Zhou Hongling , Hu Qiongying , Zhao Lixing , Xie Yunfei
Published: December 2024

Objective

This study aimed to investigate the effects of lipopolysaccharide (LPS)‐pretreated primary periodontal ligament stem cell (PDLSC)‐derived extracellular vesicles (EVs) (L‐PDLSC‐EVs) on periodontitis.

Materials and Methods

PDLSCs were obtained from mouse periodontal ligaments via enzymatic digestion. An in vitro inflammatory microenvironment for PDLSCs was established using LPS, and L‐PDLSC‐EVs were isolated through ultracentrifugation and identified. EVs from different treatments were co‐incubated with RAW264.7 macrophages (Mφs) or periodontal ligament fibroblasts (PLFs) and their co‐cultures, whereafter the biological behaviors in Mφs and PLFs were evaluated. Periodontitis mouse models were established to verify the role of L‐PDLSC‐EVs and the mechanisms involved.

Results

There were no significant changes in the characteristics of L‐PDLSC‐EVs compared with control EVs. L‐PDLSC‐EVs promoted M1‐type Mφ polarization and activated the nucleotide‐binding oligomerization domain, leucine‐rich repeat, and pyrin domain‐containing protein 3 (NLRP3) inflammasome. Furthermore, L‐PDLSC‐EVs promoted PLF cytotoxicity and apoptosis by enhancing the M1 polarization of Mφs. In periodontitis mouse models, L‐PDLSC‐EVs facilitated alveolar bone loss, PLF injury, and inflammatory responses, accompanied by an increased proportion of M1‐type Mφs and reinforced NLRP3 inflammasome activation.

Conclusions

L‐PDLSC‐EVs promoted PLF injury and exacerbated periodontitis through activating the NLRP3 inflammasome and promoting the polarization of M1‐type Mφs, providing novel insights for the periodontitis progression.
TAM‐Derived Exosomes Promote EMT by Upregulating lncRNA MIR4435‐2HG in Head and Neck Cancer
Authors: Liu Junjiang , Mu Jingtian , Liang Zhi , Zhang Yizhi , Hu Tao , Wu Fanglong , Zhou Hongmei
Published: December 2024

Objective

This study aimed to investigate the impact of tumor‐associated macrophage (TAM)‐derived exosomes on epithelial–mesenchymal transition (EMT) in head and neck squamous cell carcinoma (HNSCC) and the underlying mechanisms involved.

Subjects and Methods

Exosomes were isolated and characterized using transmission electron microscopy, nanoparticle size analysis, and western blotting. The effect on EMT in HNSCC cells was assessed using wound healing, transwell invasion, and EMT marker assays. Bioinformatics analysis was conducted to predict key TAM‐related long noncoding RNAs and evaluate their relationship with EMT in HNSCC.

Results

We observed that treatment with TAM‐derived conditioned medium (CM) promoted EMT in HNSCC cells. Within the CM, we observed abundant exosomes that were taken up by HNSCC cells. Furthermore, TAM‐derived exosomes promoted EMT in HNSCC cells. Mechanistically, high MIR4435‐2HG expression levels were observed in TAM‐derived exosomes and in HNSCC cells after treatment with TAM‐derived exosomes. Notably, high MIR4435‐2HG expression levels may be closely related to molecules that promote EMT in HNSCC.

Conclusions

TAM‐derived exosomes promote EMT in HNSCC cells by upregulating MIR4435‐2HG expression, suggesting that MIR4435‐2HG is a candidate target for HNSCC therapy.
Reduced content of gamma‐aminobutyric acid enhances resistance to bacterial wilt disease in tomato
Authors: Zhao Achen , Li Qiuyi , Meng Pengfei , Liu Ping , Wu Siqun , Lang Zhaobo , Song Yi , Macho Alberto P.
Published: December 2024

Bacteria within the Ralstonia solanacearum species complex cause devastating diseases in numerous crops, causing important losses in food production and industrial supply. Despite extensive efforts to enhance plant tolerance to disease caused by Ralstonia, efficient and sustainable approaches are still missing. Before, we found that Ralstonia promotes the production of gamma‐aminobutyric acid (GABA) in plant cells; GABA can be used as a nutrient by Ralstonia to sustain the massive bacterial replication during plant colonization. In this work, we used CRISPR‐Cas9‐mediated genome editing to mutate SlGAD2, which encodes the major glutamate decarboxylase responsible for GABA production in tomato, a major crop affected by Ralstonia. The resulting Slgad2 mutant plants show reduced GABA content, and enhanced tolerance to bacterial wilt disease upon Ralstonia inoculation. Slgad2 mutant plants did not show altered susceptibility to other tested biotic and abiotic stresses, including drought and heat. Interestingly, Slgad2 mutant plants showed altered microbiome composition in roots and soil. We reveal a strategy to enhance plant resistance to Ralstonia by the manipulation of plant metabolism leading to an impairment of bacterial fitness. This approach could be particularly efficient in combination with other strategies based on the manipulation of the plant immune system, paving the way to a sustainable solution to Ralstonia in agricultural systems.
Beyond Security: The Compliance Dimension of National Security Reviews in Singapore and Taiwan
Authors: Chen Weitseng
Published: December 2024

Growing concerns over Chinese investment have spurred stricter national security reviews globally, yet compliance and enforcement within these reviews remain understudied. This paper examines the enforcement mechanisms of national security review in Singapore and Taiwan, key trade partners with China. It contrasts Singapore's emphasis on rigorous ex post monitoring with Taiwan's focus on restrictive ex ante screening. To strengthen public enforcement, Singapore relies on privatized monitoring while Taiwan incorporates private enforcement. This study argues that robust state oversight through public enforcement is critical for compliance, but underscores the importance of extending enforcement beyond the initial investment stage to include post‐entry monitoring. Additionally, incorporating market intermediaries as enforcement agents presents a promising approach. This comparative analysis contributes to a richer understanding of national security review enforcement beyond traditional US‐centric framework.
Participation Disenchants: How Online Political Participation Decreases Online Political Efficacy in China
Authors: Bogs Anton
Published: December 2024

Existing literature largely agrees that authoritarian regimes establish channels for political participation to gather valuable information on citizens' anti‐regime sentiments and policy preferences and to supervise lower‐level bureaucrats and firms. However, we lack knowledge of how citizens—key actors behind this informational function—actually experience these channels. I investigate citizens' experiences in the context of online political participation in China, drawing on survey data and online fieldwork. I find evidence suggesting that initial online political participation significantly decreases feelings of online political efficacy through a “disenchantment” process in which participating citizens gather sobering first‐hand experience and subsequently lower their assessment of the regime's responsiveness. On this basis, I develop a theory of an “information‐propaganda trade‐off” that authoritarian regimes face: to obtain more information, authoritarian regimes can encourage more citizens to participate. Once citizens participate, however, they grow disillusioned, and the regime's propaganda becomes less convincing.
Exhaustion Disorder in Primary Care: A Comparison With Major Depressive Disorder and Adjustment Disorder
Authors: Sennerstam Victoria , Hedman‐Lagerlöf Erik , Nilsonne Gustav , Lekander Mats , Rück Christian , Wallert John , Axelsson Erland , Lindsäter Elin
Published: December 2024

Exhaustion disorder (ED) was introduced to the Swedish version of the International Classification of Diseases, 10th edition (ICD‐10) 2005. Primarily characterized by general fatigue and cognitive deficits, ED has become one of the most common mental health diagnoses in Sweden. Little is still known regarding the discriminative validity of the ED diagnosis and how it relates to other diagnostic constructs. The study aimed to investigate the discriminative validity of ED compared with two similar diagnoses, major depressive disorder (MDD) and adjustment disorder (AD). Using data from a sample of patients with a principal diagnosis of either ED (n = 352), MDD (n = 99), or AD (n = 302), we compared demographic and clinical variables and scores on self‐report symptom scales. Results showed that ED patients were of a higher age and had a higher frequency of sickness absence than MDD and AD patients. There was a substantial overlap of symptoms between ED and MDD, only differing on two of nine self‐report symptom scales, with ED patients rating lower work ability d = −0.37 and alcohol consumption d = −0.57. Compared with AD patients, ED patients reported more severe symptoms in every symptom domain. Given the prevalent use of ED diagnosis, its diagnostic validity and clinical usefulness merit further attention.
A bioassay of crop response to fertilizer nutrients in soils from a chronosequence of reclaimed natural gas pipeline rights‐of‐way
Authors: Muitire Clemence , Zvomuya Francis , Amarakoon Inoka , Adesanya Theresa , Mante Afua
Published: December 2024

Construction of underground pipelines on cropland impacts the soil ecosystem, resulting in crop yield losses persisting for several years after right‐of‐way (ROW) reclamation. Information on whether higher than recommended fertilizer application rates could improve productivity of reclaimed ROWs is scarce. The objective of this growth room bioassay was to determine the productivity response of a chronosequence of reclaimed ROW soils to differential fertilizer rates. Bulk soil samples were collected from the 0 to 20 cm soil layer on two ROWs of different ages (i.e., time since reclamation, TSR). The experiment was laid out in a completely randomized design with a 3 × 3 factorial treatment structure with three replications per treatment. The factors were TSR (4 and 10 year plus undisturbed (off‐ROW) sites) and fertilizer application rates (no fertilizer (Check); recommended rate (100%) of nitrogen (N), phosphorus (P), potassium (K), and sulphur (S); and 150% of the recommended N, P, K, and S rates). The recommended nutrient rates produced 66% lower canola dry matter yield (DMY) and 45% lower wheat DMY in the 4‐year ROW soil relative to the off‐ROW soil. Increasing the rate to 150% of the recommended rate significantly increased canola and wheat DMY in the 4‐year ROW soil to levels similar to those in the off‐ROW soil receiving the recommended rate. Nitrogen uptake by canola and wheat was 30%–45% lower, while P uptake was 40%–55% lower in the ROW soils than in the off‐ROW soil. These results indicate incomplete recovery of the ROW soils within at least the first 4 year following completion of reclamation. However, crop yields were not significantly different between the 10 year ROW and the off‐ROW at 100% fertilizer rate suggesting that productivity had been restored to off‐ROW levels by year 10 following reclamation. Findings from this study will contribute towards the formulation of strategies for improving the productivity of reclaimed ROWs on cropland.