bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinicopathological analysis of NEK1 variants in amyotrophic lateral sclerosis
Authors: Rifai Olivia M. , Waldron Fergal M. , Sleibi Danah , O'Shaughnessy Judi , Leighton Danielle J. , Gregory Jenna M.
Published: July 2024

Many genes have been linked to amyotrophic lateral sclerosis (ALS), including never in mitosis A (NIMA)‐related kinase 1 (NEK1), a serine/threonine kinase that plays a key role in several cellular functions, such as DNA damage response and cell cycle regulation. Whole‐exome sequencing studies have shown that NEK1 mutations are associated with an increased risk for ALS, where a significant enrichment of NEK1 loss‐of‐function (LOF) variants were found in individuals with ALS compared to controls. In particular, the p.Arg261His missense variant was associated with significantly increased disease susceptibility. This case series aims to understand the neuropathological phenotypes resulting from NEK1 mutations in ALS. We examined a cohort of three Scottish patients with a mutation in the NEK1 gene and evaluated the distribution and cellular expression of NEK1, as well as the abundance of phosphorylated TDP‐43 (pTDP‐43) aggregates, in the motor cortex compared to age‐ and sex‐matched control tissue. We show pathological, cytoplasmic TDP‐43 aggregates in all three NEK1‐ALS cases. NEK1 protein staining revealed no immunoreactivity in two of the NEK1‐ALS cases, indicating a LOF and corresponding to a reduction in NEK1 mRNA as detected by in situ hybridisation. However, the p.Arg261His missense mutation resulted in an increase in NEK1 mRNA molecules and abundant NEK1‐positive cytoplasmic aggregates, with the same morphologic appearance, and within the same cells as co‐occurring TDP‐43 aggregates. Here we show the first neuropathological assessment of a series of ALS cases carrying mutations in the NEK1 gene. Specifically, we show that TDP‐43 pathology is present in these cases and that potential NEK1 LOF can either be mediated through loss of NEK1 translation or through aggregation of NEK1 protein as in the case with p.Arg261His mutation, a potential novel pathological feature of NEK1‐ALS.
Synthesis of sexual selection: a systematic map of meta‐analyses with bibliometric analysis
Authors: Pollo Pietro , Lagisz Malgorzata , Yang Yefeng , Culina Antica , Nakagawa Shinichi
Published: July 2024

Sexual selection has been a popular subject within evolutionary biology because of its central role in explaining odd and counterintuitive traits observed in nature. Consequently, the literature associated with this field of study became vast. Meta‐analytical studies attempting to draw inferences from this literature have now accumulated, varying in scope and quality, thus calling for a synthesis of these syntheses. We conducted a systematic literature search to create a systematic map with a report appraisal of meta‐analyses on topics associated with sexual selection, aiming to identify the conceptual and methodological gaps in this secondary literature. We also conducted bibliometric analyses to explore whether these gaps are associated with the gender and origin of the authors of these meta‐analyses. We included 152 meta‐analytical studies in our systematic map. We found that most meta‐analyses focused on males and on certain animal groups (e.g. birds), indicating severe sex and taxonomic biases. The topics in these studies varied greatly, from proximate (e.g. relationship of ornaments with other traits) to ultimate questions (e.g. formal estimates of sexual selection strength), although the former were more common. We also observed several common methodological issues in these studies, such as lack of detailed information regarding searches, screening, and analyses, which ultimately impairs the reliability of many of these meta‐analyses. In addition, most of the meta‐analyses' authors were men affiliated to institutions from developed countries, pointing to both gender and geographical authorship biases. Most importantly, we found that certain authorship aspects were associated with conceptual and methodological issues in meta‐analytical studies. Many of our findings might simply reflect patterns in the current state of the primary literature and academia, suggesting that our study can serve as an indicator of issues within the field of sexual selection at large. Based on our findings, we provide both conceptual and analytical recommendations to improve future studies in the field of sexual selection.
No one really plans to have multiple sclerosis: Transition readiness and quality of life in paediatric multiple sclerosis
Authors: Thoby Estherline , Veras Julissa , Nallapati Spandana , Jimenez Manuel E. , Bhise Vikram
Published: July 2024

Aim

We sought to explore the experiences and perceptions of the quality of life of adolescents with pediatric‐onset multiple sclerosis and assess their readiness for academic, employment and/or health care‐related transitions.

Background

Adolescents with pediatric‐onset multiple sclerosis face unique challenges in managing a chronic illness while navigating future scholastic, social and occupational goals. We conducted a qualitative study with in‐depth, semi‐structured interviews from July 2017 to March 2019. Adolescents with pediatric‐onset multiple sclerosis were recruited from a pediatric neurology subspeciality practice until reaching data saturation. A total of 17 interviews were completed via telephone with participants ages 15 through 26.

Results

Through content analysis of the interviews, we identified five major themes: (1) receiving a new diagnosis; (2) adapting to life with pediatric‐onset multiple sclerosis; (3) evaluating education/career transition preparedness; (4) adjusting within family life and establishing support systems; and (5) assessing current medical services and preparedness for adult medical care.

Conclusions

Autonomy in health care management, adequate control of physical symptoms and sufficient family support impacted perceptions of quality of life. Implementing a dedicated transition visit, including the parent(s) of those with pediatric‐onset multiple sclerosis, early in adolescence may provide an avenue for appropriate anticipatory guidance regarding available services, independent medical management and continuity of care.
Children's Perspective on Social Workers' Questioning Practices
Authors: Sørensen Kresta Munkholt , Jacobsen Charlotte Bredahl , Koustrup Cecilie
Published: July 2024

Three tendencies currently influence social workers' questioning practices at statutory meetings with children in out‐of‐home care: an awareness that the children may have unmet needs that social workers should detect and react upon the introduction of screening instruments to social work and changes in questioning practices due to a quest for greater child participation. This project explores children's preferences about social workers' questioning practices given these trends. A total of 18 Danish children aged 10–13 participated in three separate panels in 2020 and 2021. Each panel met up on three Saturday afternoons to discuss and offer opinions on subjects that included social workers' questioning practices with or without the use of screening questionnaires. According to the children, social workers need to reach a better balance between children's right to privacy and their need for help. They want fewer people ‘meddling in their lives’, more privacy and to be questioned only when social workers can act very concretely to help them solve a problem. Children's preferences indicate that we should adjust social work questioning practices with children placed in out‐of‐home care in general and our use of screening instruments in social work in particular.
Streamlined two‐step fragment analysis PCR and exome sequencing of RFC1 for diagnostic testing of suspected CANVAS patients
Authors: Jaklič Helena , Božović Ivana Babič , Peterlin Borut , Kovanda Anja
Published: July 2024

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is caused by biallelic pathogenic expansions, or compound heterozygosity with other pathogenic variants in the RFC1 gene. CANVAS is estimated to be underdiagnosed, both because of the lack of formal diagnostic criteria and molecular challenges that translate to lesser access and high cost of routine testing. Our aim was to address the need for making CANVAS genetic testing routine, by designing a streamlined two‐step PCR consisting of a short‐allele screening PCR and a confirmatory PCR with fragment capillary electrophoresis detection. Exome sequencing of RFC1 was additionally foreseen to resolve potential compound heterozygosity cases. Specificity of our approach was evaluated using ataxia patients with known non‐CANVAS diagnoses, and optimized using Southern blot confirmed CANVAS patients. We evaluated our approach by testing patients consecutively referred for clinically suspected CANVAS using first the two‐step PCR, followed by exome sequencing. Our approach was able to accurately identify negative and confirm positive cases in prospectively collected suspected CANVAS patients presenting with at least three typical clinical signs. The proposed testing approach provides an alternative method able to clearly distinguish between CANVAS negative and positive cases and can be easily incorporated into the genetic diagnostic laboratory workflow.
Evaluation of Triglyceride‐Glucose Index Elevation as a Biomarker and Risk Factor in Laryngeal Squamous Cell Carcinoma
Authors: Dogan Remzi , Kucuk Ramazan Bahadir , Tugrul Selahattin , Yenigun Alper , Calim Omer Faruk , Dogan Elif Ece , Polat Emre , Ozturan Orhan
Published: July 2024

Objectives

Insulin resistance is associated with increased levels of IGF‐1. IGF‐1 has been shown to increase the risk of laryngeal squamous cell carcinoma. The Triglyceride‐glucose index (TyG index) is a marker of insulin resistance. Our study aimed to investigate the relationship between the TyG index and laryngeal squamous cell carcinoma.

Design

Retrospective cohort study.

Setting

Two tertiary care academic hospitals.

Methods

The study included 53 patients with laryngeal squamous cell carcinoma (Group 1) and 48 healthy volunteers (Group 2). Laryngeal cancer patients were divided into two groups according to their stage. Stages I and II were named Group 1A, and Stages III and IV were called Group 1B. The TyG index was calculated as ln [fasting Triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. The effect of the TyG index on laryngeal cancer was investigated on the parameters of sex, age, body mass index, and stage of the disease.

Results

There were no significant differences in age, sex, and BMI between the groups. The TyG index of group 1 (4.75 ± 0.33) was significantly higher than that of group 2 (4.59 ± 0.15). The TyG index value of group 1B (4.84 ± 0.31) was significantly higher than both group 1A (4.61 ± 0.32) and group 2 (4.59 ± 0.15). There was no significant difference between the TyG index values of group 1A (4.61 ± 0.32) and group 2 (4.59 ± 0.15).

Conclusion

The TyG index may be a promising laryngeal squamous cell carcinoma biomarker. People with a higher TyG index may have a higher incidence of laryngeal squamous cell carcinoma and a higher risk of progression.
PRRX1‐fused mesenchymal neoplasm: A novel PRRX1::NCOA1 fusion transcript
Authors: Cheng Xiao , Wang Jian , Fang Rong , Xu Jiayun , Wang Suying , Zhao Ming
Published: July 2024

PRRX1‐fused mesenchymal neoplasm is a recently identified, rare subcutaneous soft tissue neoplasm that is characterized by fusion of PRRX1 (exon 1) with NCOA1 (exon 13) in the majority of reported cases. Although initially considered to be fibroblastic, a possibility of neural or neuroectodermal differentiation has been suggested in a subset of cases. We report a 26‐year‐old female with a 4.0 cm painless mass located in the subcutis of the left thigh. Microscopically, the tumor was well‐circumscribed and multinodular and was composed of relatively monomorphic ovoid to spindle cells arranged in loose fascicles, trabeculae, and cords within alternating myxoid and fibrous matrix, and vascularized stroma. Mitotic figures were scarce and necrosis was not observed. By immunohistochemistry, the neoplastic cells demonstrated focal co‐expression of S100 protein and SOX10 and were negative for epithelial membrane antigen, smooth muscle actin, desmin, CD34, STAT6, HMB45, Melan‐A, and MUC4. The expression of Rb1 was retained. Targeted RNA‐sequencing identified a novel transcript fusion of PRRX1 (exon 1)::NCOA1 (exon 15), which was further confirmed by reverse transcription polymerase chain reaction and Sanger sequencing. The tumor was narrowly excised and no tumor recurrence or metastasis was identified after 13 months of follow‐up. In summary, we report a new case of PRRX1‐fused mesenchymal neoplasm, expanding the molecular genetic spectrum and providing further support for possible neural or neuroectodermal differentiation of this emerging soft tissue tumor entity.
Toxic epidermal necrolysis‐like cutaneous toxicity following chimeric antigen receptor T‐cell therapy in recurrent large B‐cell lymphoma
Authors: Bhullar Puneet K. , Motaparthi Kiran , Zieman Daniel P. , Johnson Cassandra , Gurnani Pooja , Sokumbi Olayemi
Published: July 2024

Chimeric antigen receptor (CAR) T‐cell therapy has demonstrated remarkable success in treating various B‐cell malignancies, redirecting T‐cell cytotoxicity toward cancer cells. Despite its efficacy, CAR‐T therapy is associated with potential risks, including cytokine release syndrome (CRS) and cytopenia. We present a case of a 69‐year‐old man with diffuse large B‐cell lymphoma treated with axicabtagene‐ciloleucel CAR‐T therapy, who developed a rare and severe cutaneous toxicity resembling toxic epidermal necrolysis (TEN). The patient exhibited persistent fevers, CRS, and subsequent development of a widespread erythematous macular eruption, progressing to vesiculation with bullae. Notably, allopurinol‐induced TEN was considered with the patient's recent exposure to allopurinol, although the onset and minimal mucosal involvement did not align with typical presentations of allopurinol‐induced cases. The cutaneous reaction, distinct from typical SJS/TEN, showed minimal mucosal involvement and coincided with the cytokine release storm, differing from allopurinol‐induced TEN. Despite the absence of guidelines, the patient was managed with systemic steroids, achieving significant improvement. This case expands the spectrum of CAR‐T therapy‐related cutaneous toxicities, highlighting the need for early recognition of histopathology and tailored management by dermatologists. Further understanding of these reactions is crucial for optimizing the safety profile of this groundbreaking immunotherapy.
Improving assessment and management of suicide risk among people who inject drugs: A mixed methods study conducted at the Medically Supervised Injecting Centre, Sydney
Authors: Hocknull Kate , Geiger Brennan , Bartlett Mark , Colledge‐Frisby Samantha , Shand Fiona , Day Carolyn A. , Jauncey Marianne , Roxburgh Amanda
Published: July 2024

Introduction

People who inject drugs are 13 times more likely to die by suicide than the general population. Guidelines for responding to risk in this population are limited. Harm reduction services attended by people who inject drugs require targeted strategies to address the complexities of suicide risk among this population.

Methods

Co‐design, engaging health professionals and people with lived experience informed the study. Mixed methods were used to understand the experience of managing suicide risk among clients attending the Medically Supervised Injecting Centre (MSIC) in Sydney. A survey was administered to assess staff confidence in managing risk. Focus groups were conducted with health professionals and MSIC clients to explore experiences of suicide management, response and opportunities for improvement.

Results

Half (N = 17) the MSIC staff surveyed reported over 10 years' experience working with this population. Confidence in managing suicide risk was low. Three key themes emerged from focus groups (N = 17): (i) Autonomy and the need to involve clients in the assessment process; (ii) Trust between clients and health professionals, and transparency in decision‐making; and (iii) System barriers, described by health professionals as inadequate referral pathways for clients in distress, and by clients as negative experiences of care, including involuntary admission and not receiving medication (e.g. methadone).

Discussion and Conclusions

Revised assessment guidelines and a tailored safety plan were developed. These resources are also suitable for other alcohol and other drug services. The challenge in managing suicide risk in harm reduction services is balancing duty of care with staff–client relationships and client engagement.
Harm from others' drinking among young adults in Taiwan: Predictors and deteriorating quality of life
Authors: Chen Ren‐Hao , Chang Hsing‐Yi , Hsu Yi‐Tien , Chen Wei J. , Chen Chuan‐Yu
Published: July 2024

Introduction

This study aimed to investigate the prevalence of different forms of harm from others’ drinking (HFOD), predictors and the relationship with multi‐dimensional quality of life among young adults in an emerging alcohol market in Asia—Taiwan.

Methods

Data were extracted from a 2018 household survey with national representativeness on substance use experiences. The analytic sample comprised 4901 participants aged 18–34. Eight items were used to measure HFOD experiences. Five‐dimensional quality of life was assessed by the EQ‐5D‐5L. Multivariable regressions with complex survey analyses were performed to estimate the prevalence and risk association.

Results

Almost 4.2% of young adults experienced any form of HFOD; psychological harm occurred more prevalently than physical harm (3.7% and 1.5%, respectively). Those aged 25–29 and 30–34 had a two‐ to three‐fold risk of HFOD compared with those aged 18–24. Both non‐drunk drinking and drunk drinking were associated with an increased risk of psychological HFOD (adjusted odds ratio 2.36 and 5.89, respectively), whereas the risk of physical HFOD was related only to drunk drinking (adjusted odds ratio 7.8). Psychological HFOD victimisation emerged as the strongest predictor for deteriorated quality of life (adjusted b −0.14; 95% confidence interval −0.24, −0.04), especially in the dimensions of pain/discomfort and anxiety/depression. Among HFOD victims, only 33% sought help.

Discussion and Conclusions

The HFOD among young adults, commonly exhibited in psychological form, was linked with deteriorated quality of life; nonetheless, young HFOD victims are under‐recognised. When devising interventions for alcohol harm, developmental perspectives should be integrated into policies implemented in healthcare and community settings.
Fat bodies, diet culture, and human flourishing: How did we get it so wrong?
Authors: Bowden Jennifer , Habets Myk
Published: July 2024

Contemporary diet culture is detrimental to many Western men and women, though women are disproportionately impacted. This results in poor body image, low self‐esteem, and unhealthy lifestyles. Christian discourse is not immune to the influence of diet culture, with many popular Christian pastors and authors adopting this paradigm and seeking to align it with a Christian worldview. When an understanding of a human being as an anthropological duality is brought to bear on the issue of diet culture, a more consistently Christian anthropology can resource a healthier view of the embodied self and provide resources for a robust Christian response to diet culture.
Circulating small non‐coding RNAs are associated with the insulin‐resistant and obesity‐related type 2 diabetes clusters
Authors: de Klerk Juliette A. , Beulens Joline W. J. , Bijkerk Roel , van Zonneveld Anton Jan , Elders Petra J. M. , ’t Hart Leen M. , Slieker Roderick
Published: July 2024

Aim

To uncover differences in small non‐coding RNAs (sncRNAs) in individuals with type 2 diabetes (T2D) categorized into five clusters based on individual characteristics, which may aid in the identification of those prone to rapid progression.

Materials and Methods

In the Hoorn Diabetes Care System (DCS) cohort, participants were clustered by age, body mass index (BMI), and glycated haemoglobin, C‐peptide and high‐density lipoprotein (HDL) cholesterol levels, yielding severe insulin‐deficient diabetes, severe insulin‐resistant diabetes (SIRD), mild obesity‐related diabetes (MOD), mild diabetes, and mild diabetes with high HDL cholesterol clusters (n = 412). Utilizing plasma sncRNA‐sequencing, we identified distinct cluster‐specific sncRNAs. Validation was performed in a smaller DCS Hoorn dataset (n = 138). To elucidate their potential functions, we examined tissue expression, identified potential targets or (co‐)regulated proteins, conducted gene set enrichment analyses on the targets through Reactome, and examined tissue expression of the (co‐)regulated proteins.

Results

The insulin‐resistant cluster exhibited aberrant expression of 10 sncRNAs, while the high BMI cluster featured eight differentially expressed sncRNAs. Multiple (co‐)regulated proteins were identified for sncRNAs associated with both clusters. Proteins associated with both clusters showed enrichment for metabolism. Proteins that specifically and only associated with the SIRD cluster showed enrichment for immune‐related signalling. Furthermore, MOD cluster‐specific associated proteins showed enrichment for the complement system.

Conclusions

Our research showed differential sncRNA levels among type 2 diabetes clusters. This may reflect and could deepen our understanding of molecular mechanisms, in development, progression, and risk factors for each cluster.
Common ant species dominate morphospace: unraveling the morphological diversity in the Brazilian Amazon Basin
Authors: Andrade‐Silva Joudellys , Baccaro Fabrício B. , Prado Lívia P. , Guénard Benoit , Kass Jamie M. , Warren Dan L. , Economo Evan P. , Silva Rogério R.
Published: July 2024

Rare plant and vertebrate species have been documented to contribute disproportionately to the total morphological structure of species assemblages. These species often possess morphologically extreme traits and occupy the boundaries of morphological space. As rare species are at greater risk of extinction than more widely distributed species, human‐induced disturbances can strongly affect ecosystem functions related to assemblage morphology. Here, we assess to what extent the distributions of ant morphological traits are supported by morphologically extreme species and how they are distributed among habitats in a global biodiversity hotspot, the Brazilian Amazon. We used a morphological database comprising 15 continuous morphological traits and 977 expert‐validated ant species distributed across the Brazilian Amazon. We produced species range estimates using species distribution models or alpha hulls (when few records were available). Next, we conducted a principal components analysis to combine traits into a space with reduced dimensionality (morphospace). Then, we identified morphologically extreme species in this space and quantified their contributions to morphological diversity across different habitat types in the Brazilian Amazon Basin. We identified 114 morphologically extreme ant species across the Amazon ant morphospace. These species also accounted for a large percentage of morphospace filling, exceeding 99% representation in the most disturbed habitats in the Amazon. Our results suggest that a few morphologically extreme species capture most of the variation in ant morphology and, therefore, the spectrum of ecosystem functions performed by ants in the Brazilian Amazon Basin. Further, unlike in many other groups, these extreme morphologies were represented by the set of most common species. These results suggest greater functional redundancy and resilience in Brazilian Amazon ants, but more broadly, they contribute to our understanding of ecological processes that sustain ecosystem functions.
The myth of federal reserve de facto independence
Authors: Pittaluga Giovanni B. , Seghezza Elena , Morelli Pierluigi
Published: July 2024

In the literature on central banks independence these institutions are considered as being apolitical. In reality, central banks are political actors and their de facto independence changes over time even if their de jure independence remains unvaried. An example of this is the Federal Reserve Bank (Fed), whose de facto independence in the past decades has fluctuated significantly because of the pressures of Congress and the President. To counter these pressures, the Fed seeks support from certain interest groups. The success of this behavior is more likely when the President and Congress represent different political parties.
CRP and sCD25 help distinguish between adult‐onset Still's disease and HLH
Authors: Beckett Madelaine , Spaner Caroline , Goubran Mariam , Wade John , Avina‐Zubieta Juan Antonio , Setiadi Audi , Tucker Lori , Shojania Kam , Au Sheila , Mattman Andre , Lee Agnes Y. Y. , Fajgenbaum David C. , Chen Luke Y. C.
Published: July 2024

Objective

Adult‐onset Still's disease (AOSD) and secondary hemophagocytic lymphohistiocytosis (sHLH) are both hyperferritinemic cytokine storm syndromes that can be difficult to distinguish from each other in hospitalized patients. The objective of this study was to compare the inflammatory markers ferritin, D‐dimer, C‐reactive protein (CRP), and soluble CD25 (sCD25) in patients with AOSD and sHLH. These four markers were chosen as they are widely available and represent different aspects of inflammatory diseases: macrophage activation (ferritin); endothelialopathy (D‐dimer); interleukin‐1/interleukin‐6/tumour necrosis factor elevation (CRP) and T cell activation (sCD25).

Methods

This was a single‐center retrospective study. Patients diagnosed by the Hematology service at Vancouver General Hospital for AOSD or sHLH from 2009 to 2023 were included.

Results

There were 16 AOSD and 44 sHLH patients identified. Ferritin was lower in AOSD than HLH (median 11 360 μg/L vs. 29 020 μg/L, p = .01) while D‐dimer was not significantly different (median 5310 mg/L FEU vs. 7000 mg/L FEU, p = .3). CRP was higher (median 168 mg/L vs. 71 mg/L, p <.01) and sCD25 was lower (median 2220 vs. 7280 U/mL, p = .004) in AOSD compared to HLH. The combined ROC curve using CRP >130 mg/L and sCD25< 3900 U/mL to distinguish AOSD from HLH had an area under the curve (AUC) of 0.94 (95% confidence interval 0.93–0.97) with sensitivity 91% and specificity 93%.

Conclusions

These findings suggest that simple, widely available laboratory tests such as CRP and sCD25 can help clinicians distinguish AOSD from HLH in acutely ill adults with extreme hyperferritinemia. Larger studies examining a wider range of clinically available inflammatory biomarkers in a more diverse set of cytokine storm syndromes are warranted.
Enhanced stabilisation and reduced fibril forming potential of an amyloidogenic light chain using a variable heavy domain to mimic the homodimer complex
Authors: Maerivoet Alana , Price Rebecca , Galmiche Cécile , Scott‐Tucker Anthony , Kennedy Jeff , Crabbe Tom , Antonyuk Svetlana , Madine Jillian
Published: July 2024

Light chain amyloidosis (AL), is classified as a plasma cell dyscrasia, whereby a mutant plasma cell multiplies uncontrollably and secretes enormous amounts of immunoglobulin‐free light chain (FLC) fragments. These FLCs undergo a process of misfolding and aggregation into amyloid fibrils, that can cause irreversible system‐wide damage. Current treatments that focus on depleting the underlying plasma cell clone are often poorly tolerated, particularly in patients with severe cardiac involvement, meaning patient prognosis is poor. An alternative treatment approach currently being explored is the inhibition of FLC aggregation by stabilisation of the native conformer. Here, we aimed to identify and characterise antibody fragments that target FLC domains and promote their stabilisation. Using phage‐display screening methods, we identified a variable heavy (VH) domain, termed VH1, targeted towards the FLC. Using differential scanning fluorimetry and surface plasmon resonance, VH1 was characterised to bind and kinetically stabilise an amyloidogenic FLC, whereby a > 5.5 °C increase in thermal stability was noted. This improved stability corresponded to the inhibition of fibril formation, where 10 : 1 LC : VH1 concentration reduced aggregation to baseline levels. X‐ray crystallographic structures of the LC : VH1 complex at atomic resolution revealed binding in a 1 : 1 ratio, mimicking the dimeric antigen binding sites of the native immunoglobulin molecule and the native LC homodimer.
Fire impacts on the biology of stream ecosystems: A synthesis of current knowledge to guide future research and integrated fire management
Authors: Erdozain Maitane , Cardil Adrián , de‐Miguel Sergio
Published: July 2024

Freshwater ecosystems host disproportionately high biodiversity and provide unique ecosystem services, yet they are being degraded at an alarming rate. Fires, which are becoming increasingly frequent and intense due to global change, can affect these ecosystems in many ways, but this relationship is not fully understood. We conducted a systematic review to characterize the literature on the effects of fires on stream ecosystems and found that (1) abiotic indicators were more commonly investigated than biotic ones, (2) most previous research was conducted in North America and in the temperate evergreen forest biome, (3) following a control‐impact (CI) or before‐after (BA) design, (4) predominantly assessing wildfires as opposed to prescribed fires, (5) in small headwater streams, and (6) with a focus on structural and not functional biological indicators. After quantitatively analyzing previous research, we detected great variability in responses, with increases, decreases, and no changes being reported for most indicators (e.g., macroinvertebrate richness, fish density, algal biomass, and leaf decomposition). We shed light on these seemingly contradicting results by showing that the presence of extreme hydrological post‐fire events, the time lag between fire and sampling, and whether the riparian forest burned or not influenced the outcome of previous research. Results suggest that although wildfires and the following hydrological events can have dramatic impacts in the short term, most biological endpoints recover within 5–10 years, and that detrimental effects are minimal in the case of prescribed fires. We also detected that no effects were more often reported by BACI studies than by CI or BA studies, raising the question of whether this research field may be biased by the inherent limitations of CI and BA designs. Finally, we make recommendations to help advance this field of research and guide future integrated fire management that includes the protection of freshwater ecosystems.
Predicting emergent animal biodiversity patterns across multiple scales
Authors: Johnston Alice S. A.
Published: July 2024

Restoring biodiversity‐based resilience and ecosystem multi‐functionality needs to be informed by more accurate predictions of animal biodiversity responses to environmental change. Ecological models make a substantial contribution to this understanding, especially when they encode the biological mechanisms and processes that give rise to emergent patterns (population, community, ecosystem properties and dynamics). Here, a distinction between ‘mechanistic’ and ‘process‐based’ ecological models is established to review existing approaches. Mechanistic and process‐based ecological models have made key advances to understanding the structure, function and dynamics of animal biodiversity, but are typically designed to account for specific levels of biological organisation and spatiotemporal scales. Cross‐scale ecological models, which predict emergent co‐occurring biodiversity patterns at interacting scales of space, time and biological organisation, is a critical next step in predictive ecology. A way forward is to first capitalise on existing models to systematically evaluate the ability of scale‐explicit mechanisms and processes to predict emergent patterns at alternative scales. Such model intercomparisons will reveal mechanism to process transitions across fine to broad scales, overcome approach‐specific barriers to model realism or tractability and identify gaps which necessitate the development of new fundamental principles. Key challenges surrounding model complexity and uncertainty would need to be addressed, and while opportunities from big data can streamline the integration of multiple scale‐explicit biodiversity patterns, ambitious cross‐scale field studies are also needed. Crucially, overcoming cross‐scale ecological modelling challenges would unite disparate fields of ecology with the common goal of improving the evidence‐base to safeguard biodiversity and ecosystems under novel environmental change.
Increased crossing of thermal stress thresholds of vegetation under global warming
Authors: Li Xiangyi , Huntingford Chris , Wang Kai , Cui Jiangpeng , Xu Hao , Kan Fei , Anniwaer Nazhakaiti , Yang Hui , Peñuelas Josep , Piao Shilong
Published: July 2024

Temperature extremes exert a significant influence on terrestrial ecosystems, but the precise levels at which these extremes trigger adverse shifts in vegetation productivity have remained elusive. In this study, we have derived two critical thresholds, using standard deviations (SDs) of growing‐season temperature and satellite‐based vegetation productivity as key indicators. Our findings reveal that, on average, vegetation productivity experiences rapid suppression when confronted with temperature anomalies exceeding 1.45 SD above the mean temperature during 2001–2018. Furthermore, at temperatures exceeding 2.98 SD above the mean, we observe the maximum level of suppression, particularly in response to the most extreme high‐temperature events. When Earth System Models are driven by a future medium emission scenario, they project that mean temperatures will routinely surpass both of these critical thresholds by approximately the years 2050 and 2070, respectively. However, it is important to note that the timing of these threshold crossings exhibits spatial variation and will appear much earlier in tropical regions. Our finding highlights that restricting global warming to just 1.5°C can increase safe areas for vegetation growth by 13% compared to allowing warming to reach 2°C above preindustrial levels. This mitigation strategy helps avoid exposure to detrimental extreme temperatures that breach these thresholds. Our study underscores the pivotal role of climate mitigation policies in fostering the sustainable development of terrestrial ecosystems in a warming world.
Potato flour‐based film: Effect of gelatine on the rheological, thermal, mechanical and barrier properties
Authors: Fu Zong‐qiang , Zheng Zi‐xu , Li Yi , Guo Shao‐xiang , Gao Dong‐ming , Li Fei‐fei
Published: July 2024

Potato flour/gelatine films in different ratios (6:0, 5:1, 4:1, 3:1, 2:1 and 1:1) were prepared and their properties were examined in this study. Potato flour film‐forming dispersion without gelatine showed the highest particle size and apparent viscosity. As the gelatine concentration increased, the composite films became smoother and more transparent. Gelatine incorporated with potato flour films reduced the retrogradation enthalpy and glass transition temperature, leading to the low tensile strength and high elongation at break. Although water content and water solubility index increased with the higher gelatine concentration, water vapour permeability of composite films decreased from 14.59 × 10−13 gm−1s−1Pa−1 to 5.83 × 10−13 gm−1s−1Pa−1. In addition, it was noted that water contact angle increased from 24.50° to 102.33° as gelatine concentration increased from 0% (6:0) to 50% (1:1). According to these findings, potato flour film with the presence of gelatine showed the better moisture barrier properties.
UNCovering new causes of monogenic systemic lupus erythematosus
Authors: Ellyard Julia I , Gantier Michael P
Published: July 2024

UNC93B1 is essential for the stability and endosomal trafficking of nucleic‐acid sensing Toll‐like receptors (TLRs) including TLR7 and TLR8. Increased TLR7 responses are associated with lupus autoimmunity in both mice and humans. In a recent article, Al‐Azab et al. demonstrate the role of a variant of UNC93B1 (p.V117L) in the induction of pediatric systemic lupus erythematosus in patients and in mice through TLR7/8 hyperresponsiveness. They also highlight a potential role for the pharmacological inhibition of interleukin‐1 receptor–associated kinase (IRAK) 1 and/or 4 in ameliorating disease.
Combining Desulfurisation Gypsum and Polyacrylamide to Reduce Soil Salinity and Promote Buckwheat Photosynthesis
Authors: Tao Wanghai , Zhao Xue , Ning Songrui , Ji Meiyue , Wang Quanjiu
Published: July 2024

Soil salinisation poses a significant threat to global agricultural production and food security. China is among the countries most severely impacted by soil salinisation. To investigate the improvement technology for saline–alkali stress in buckwheat, a typical multigrain crop in northwest China, a coupling regulation study using desulfurisation gypsum and polyacrylamide (PAM) was conducted in 2019 and 2020. Desulfurisation gypsum was applied at 0, 5.5, 11, 16.5 and 22 kg·ha−1, while PAM was applied at 0, 15, 30, 45 and 60 kg·ha−1. The results demonstrated that applying 11 t·ha−1 desulfurisation gypsum and 30 kg·ha−1 PAM effectively reduces soil salinity and pH, averaging 81.79% and 6.07%, respectively. Furthermore, it did not cause soil heavy metal pollution and created the best soil environment for buckwheat growth. Among the models tested, the nonrectangular hyperbolic model was the most accurate in describing buckwheat's photosynthetic light response. The optimal treatment for achieving the best photosynthetic performance—measured by apparent quantum efficiency, maximum net photosynthetic rate, light compensation point, light saturation point, dark respiration rate, stomatal conductance, intercellular CO2 concentration, transpiration rate, leaf water use efficiency and yield—was achieved through applying 11 t·ha−1 desulfurisation gypsum and 30 kg·ha−1 PAM. Therefore, desulfurised gypsum and PAM should be applied at 11 t·ha−1 and 30 kg·ha−1, respectively, to improve buckwheat's adaptability to different light intensities while promoting its photosynthetic response in saline–alkali soils. This study provides an effective technical scheme for reducing salt and promoting the growth of crops under salinity stress, which is of great significance for improving salinity land in arid areas.
Modeling phase separation mechanisms in oxy‐fluoride glass‐ceramics containing SrF2:Ln3+ and ZnAl2O4:Cr3+ nanocrystals
Authors: Wadhwa Abhishek , Xu Xiuxia , Huang Yiping , Qiao Xvsheng , Du Jincheng , Fan Xianping , Wang Zhiyu , Qian Guodong
Published: July 2024

It is imperative to develop a comprehensive understanding of phase separation mechanisms in multi‐phase oxy‐fluoride glass ceramics (GCs) to customize their structural and optical characteristics for particular applications in photonics. The manuscript utilizes molecular dynamics (MD) simulations to examine the phase separation mechanisms in SiO2–Al2O3–SrF2–ZnF2–LnF3‐CrF3 (where Ln represents the lanthanide elements) GCs during the simultaneous precipitation of SrF2: Ln3+ and ZnAl2O4: Cr3+ nanocrystals. Insights into the atomic‐level interactions that regulate the separation and formation of distinct phases rich in fluoride and oxide are obtained through MD simulations. The results reveal that Sr2+ and Ln3+ ions partition preferentially into the fluoride phase, whereas Zn2+ and Cr3+ associate with the oxide aluminosilicate network. Remarkably, the separated fluoride and oxide phases bear structural similarities with the existing experimental outcomes. The introduction of SrF2 facilitates phase separation in oxy‐fluoride glass system by causing the formation of SrF2: Ln3+ nanocrystals in regions abundant in fluoride, while the substitution of ZnF2 for SrF2 results in the formation of ZnAl2O4: Cr3+ nanocrystals originating from the separated oxide phase. Therefore, the reported simulations offer molecular‐level insights into the mechanisms underlying phase separation and the functions of various glass components, thereby facilitating the development of customized oxy‐fluoride GCs with tailored properties.
Upregulation of circ‐IGF1R increased therapeutic effect of hypoxia‐pretreated ADSC‐derived extracellular vesicle by regulating miR‐503‐5p/HK2/VEGFA axis
Authors: Shi Rongfeng , Jia Pengfei , Zhao Suming , Yuan Hongxin , Shi Jiahai , Zhao Hui
Published: July 2024

Diabetes mellitus is a major cause of blindness and chronic ulcers in the working‐age population worldwide. Wound healing is deeply dependent on neovascularization to restore blood flow. Former research has found that differentially expressed circular RNAs (circRNAs) are associated with hyperglycaemia‐induced endothelial cell damage, and hypoxia‐pretreated adipose‐derived stem cells (ADSCs)‐extracellular vesicle (HEV) transplants have a more therapeutic effect to enhance wound healing in diabetic mice by delivery circRNA. The current investigation employed high‐throughput sequencing to identify circRNAs that are abnormally expressed between EV and HEV. The regulatory mechanism and predicted targets of one differentially expressed circRNA, circ‐IGF1R, were investigated utilizing bioinformatics analyses, luciferase reporter assays, angiogenic differentiation assays, flow cytometric apoptosis analysis and RT‐qPCR. Circ‐IGF1R expression increased in HEV, and downregulation of circ‐IGF1R suppressed and reversed the promotion effect of HEV on angiogenesis in ulcerated tissue. Bioinformatics analyses and luciferase reporter assays confirmed that miR‐503‐5p was the downstream target of circ‐IGF1R, and inhibiting miR‐503‐5p restored the promotion effect of HEV on angiogenesis after circ‐IGF1R silence. The study also found that miR‐503‐5p can interact with 3'‐UTR of both HK2 and VEGFA. Overexpression of HK2 or VEGFA restored the promotion effect of HExo on angiogenesis after circ‐IGF1R silence. Overexpression miR‐503‐5p or silence HK2/VEGFA reversed the protective effect of circ‐IGF1R to MLMECs angiogenic differentiation. Overexpression of circ‐IGF1R increased the protective effect of HEV on the promotion of wound healing in mice with diabetes. Circ‐IGF1R promotes HIF‐1α expression through miR‐503‐5p sponging. Our data demonstrate that circ‐IGF1R overexpression EVs from ADSCs suppress high glucose‐induced endothelial cell damage by regulating miR‐503‐5p/HK2/VEGFA axis.
Identification of SLC7A11‐AS1/SLC7A11 pair as a ferroptosis‐related therapeutic target for hepatocellular carcinoma
Authors: Yuan Xiao , Wang Yida , Jiao Sitong , Gao Huanhuan , Zhang Mengqian , Wang Xin , Zhou Xunyu , Wu Chuanfang , Bao Jinku
Published: July 2024

Hepatocellular carcinoma (HCC), a prevalent malignancy worldwide, poses significant challenges in terms of prognosis, necessitating innovative therapeutic approaches. Ferroptosis offers notable advantages over apoptosis, holding promise as a novel therapeutic approach for HCC complexities. Moreover, while the interaction between long non‐coding RNAs (lncRNAs) and mRNAs is pivotal in various physiological and pathological processes, their involvement in ferroptosis remains relatively unexplored. In this study, we constructed a ferroptosis‐related lncRNA‐mRNA correlation network in HCC using Pearson correlation analysis. Notably, the SLC7A11‐AS1/SLC7A11 pair, exhibiting high correlation, was identified. Bioinformatics analysis revealed a significant correlation between the expression levels of this pair and key clinical characteristics of HCC patients, including gender, pathology, Ishak scores and tumour size. And poor prognosis was associated with high expression of this pair. Functional experiments demonstrated that SLC7A11‐AS1, by binding to the 3′UTR region of SLC7A11 mRNA, enhanced its stability, thereby promoting HCC cell growth and resistance to erastin‐ induced ferroptosis. Additionally, in vivo studies confirmed that SLC7A11‐AS1 knockdown potentiated the inhibitory effects of erastin on tumour growth. Overall, our findings suggest that targeting the SLC7A11‐AS1/SLC7A11 pair holds promise as a potential therapeutic strategy for HCC patients.
Epimedium‐Curculigo herb pair enhances bone repair with infected bone defects and regulates osteoblasts through LncRNA MALAT1/miR‐34a‐5p/SMAD2 axis
Authors: Miao Maomao , Li Mengying , Sheng Yunjie , Tong Peijian , Zhang Yang , Shou Dan
Published: July 2024

Infected bone defects (IBDs) are the common condition in the clinical practice of orthopaedics. Although surgery and anti‐infective medicine are the firstly chosen treatments, in many cases, patients experience a prolonged bone union process after anti‐infective treatment. Epimedium‐Curculigo herb pair (ECP) has been proved to be effective for bone repair. However, the mechanisms of ECP in IBDs are insufficiency. In this study, Effect of ECP in IBDs was verified by micro‐CT and histological examination. Qualitative and quantitative analysis of the main components in ECP containing medicated serum (ECP‐CS) were performed. The network pharmacological approaches were then applied to predict potential pathways for ECP associated with bone repair. In addition, the mechanism of ECP regulating LncRNA MALAT1/miRNA‐34a‐5p/SMAD2 signalling axis was evaluated by molecular biology experiments. In vivo experiments indicated that ECP could significantly promote bone repair. The results of the chemical components analysis and the pathway identification revealed that TGF‐β signalling pathway was related to ECP. The results of in vitro experiments indicated that ECP‐CS could reverse the damage caused by LPS through inhibiting the expressions of LncRNA MALAT1 and SMAD2, and improving the expressions of miR‐34a‐5p, ALP, RUNX2 and Collagen type І in osteoblasts significantly. This research showed that ECP could regulate the TGF‐β/SMADs signalling pathway to promote bone repair. Meanwhile, ECP could alleviate LPS‐induced bone loss by modulating the signalling axis of LncRNA MALAT1/miRNA‐34a‐5p/ SMAD2 in IBDs.
The effects of simvastatin‐loaded nanoliposomes on human multilineage liver fibrosis microtissue
Authors: Parsa Shima , Dousti Maryam , Mohammadi Nasim , Abedanzadeh Mozhgan , Dehdari Ebrahimi Niloofar , Dara Mahintaj , Sani Mahsa , Nekouee Muhammad , Abolmaali Samira Sadat , Sani Farnaz , Azarpira Negar
Published: July 2024

In this in vitro study, for the first time, we evaluate the effects of simvastatin‐loaded liposome nanoparticles (SIM‐LipoNPs) treatment on fibrosis‐induced liver microtissues, as simvastatin (SIM) has shown potential benefits in the non‐alcoholic fatty liver disease process. We developed multicellular liver microtissues composed of hepatic stellate cells, hepatoblastoma cells and human umbilical vein endothelial cells. The microtissues were supplemented with a combination of palmitic acid and oleic acid to develop fibrosis models. Subsequently, various groups of microtissues were exposed to SIM and SIM‐LipoNPs at doses of 5 and 10 mg/mL. The effectiveness of the treatments was evaluated by analysing cell viability, production of reactive oxygen species (ROS) and nitric oxide (NO), the expression of Kruppel‐like factor (KLF) 2, and pro‐inflammatory cytokines (interleukin(IL)‐1 α, IL‐1 β, IL‐6 and tumour necrosis factor‐α), and the expression of collagen I. Our results indicated that SIM‐LipoNPs application showed promising results. SIM‐LipoNPs effectively amplified the SIM‐klf2‐NO pathway at a lower dosage compatible with a high dosage of free SIM, which also led to reduced oxidative stress by decreasing ROS levels. SIM‐LipoNPs administration also resulted in a significant reduction in pro‐inflammatory cytokines and Collagen I mRNA levels, as a marker of fibrosis. In conclusion, our study highlights the considerable therapeutic potential of using SIM‐LipoNPs to prevent liver fibrosis progress, underscoring the remarkable properties of SIM‐LipoNPs in activating the KLF2‐NO pathway and anti‐oxidative and anti‐inflammatory response.