bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Spatial Mismatches Between Marine Predators and Their Prey in the Southern Hemisphere in Response to Climate Change
Authors: Bas Maria , Ouled‐Cheikh Jazel , Fuster‐Alonso Alba , Julià Laura , March David , Ramírez Francisco , Cardona Luis , Coll Marta
Published: February 2025

Global change is rapidly reshaping species' habitat suitability ranges, hence leading to significant shifts in the distribution of marine life. Contrasting distributional responses among species can alter the spatial overlap between predators and prey, potentially disrupting trophic interactions and affecting food web dynamics. Here, we evaluate long‐term changes in the spatial overlap of habitat suitability ranges for trophically related species, including crustaceans, fish, penguins, and pinnipeds across 12 Large Marine Ecosystems from the Southern Hemisphere, merged into three primary regions: South America, Southern Africa, Australia and New Zealand. To this aim, we first use Boosted Regression Trees (BRTs) to hindcast and project species‐specific changes in suitable habitat from 1850 to 2100 under two future climate scenarios: SSP1‐2.6 (low climate forcing) and SSP5‐8.5 (high climate forcing). We then analyze changes in species habitat suitability and potential predator–prey spatial overlaps. Findings reveal that marine species generally exhibit changes in their suitable habitats, with pronounced shifts towards higher latitudes under the SSP5‐8.5 scenario. However, contrasting trends emerge among predators across functional groups and regions of South America, Southern Africa, Australia and New Zealand. These variations highlight the need for species and regional‐specific management responses. We also project contrasting spatial mismatches between predators and prey: predators experiencing declines in suitable habitat tend to exhibit greater overlap with their prey in future scenarios, whereas those with expanding suitable habitat show reduced spatial overlap with their prey. This study provides valuable insights that can inform spatial management strategies in response to climate change and illustrate how climate change may weaken species' ability to adapt to climate‐driven environmental changes due to trophic disruptions.
Combination of Biochar‐Based Fertilisers and Reactive Barriers Improved Soil Carbon Storage, Soil Moisture Retention, and Crop Yield in Short Term
Authors: Omidvar Negar , Joseph Stephen , Dissanayake Lakmini , Farrar Michael B. , Reverchon Frédérique , Burnett Russell , Rezaei Rashti Mehran , Amarasinghe Apsara , Tahery Sara , Xu Zhihong , Timms Wendy , Elliott Brittany , Liu Hongdou , Hosseini Bai Shahla
Published: February 2025

Climate change threatens long‐term soil health because of increased severity and frequency of drought periods. Applying biochar to soils before a drought can increase non‐biochar soil carbon (C) and water storage over the long term and sustain crop yield. However, the on‐farm benefit of buried solid biochar and applied liquid biochar at low rates remains uncertain. This study examined the effects of two novel biochar‐based soil amendments on soil C, water storage and crop yield. The biochar‐based amendments included a biochar reactive barrier (RB) made by layering wood‐based biochar, straw mulch and cow manure into a series of open surface trenches, and a liquid biochar mineral complex (BMC) applied twice, at low rate (200 kg ha−1) to one side of RB (fertilised area), while the other side of RB received no treatments (non‐fertilised area). Moisture concentration within the RB ranged from 6.76% up to 56.68% after large rainfall, more than double the surrounding soils and gradually started migrating from the RB outwards. Soil within 50 cm distance of the RB showed a 24.5% increase in non‐biochar soil C compared with soil at 600 cm distance of the RB, 2.54% versus 2.04%, respectively, in the non‐fertilised area, which was supported with lowering soil microbial activity. Pasture yield increase was associated with liquid BMC fertiliser rather than proximity to the RB. Pasture yield was 44% higher in the fertilised area compared with the non‐fertilised area 27.89 t ha−1 versus 19.31 t ha−1. Approximately 158 kg CO2e was removed from the atmosphere for each cubic meter of RB and an annual removal of 150 kg CO2e ha−1 was estimated by liquid BMC application. Income earned by increased yield was still profitable even though applied liquid BMC could cost between USD 400–520 ha−1 including shipping costs. Overall, our study suggested biochar‐based RB and BMC fertilisers can effectively increase soil moisture retention while building non‐biochar soil C storage in the surrounding soil. The adoption of biochar‐based techniques has the potential to improve drought resilience while increasing soil C in wide range of non‐irrigated cropping systems.
Development and validation of a new tool for simultaneous screening of malnutrition, sarcopenia and cachexia in older adults
Authors: Haroun Ahmed Mohammed Hassan , Mohamed Mona Hegazy , Gawad Marwa Abd El Azeem Abd EL , Rasheedy Doha
Published: February 2025

Introduction

The high prevalence of malnutrition, sarcopenia and cachexia among older adults presents a significant health care challenge, underscoring the need for effective screening tools. Given the frequent overlap of these conditions, a tool capable of simultaneously screening for all three conditions is imperative.

Methods

The development process included an extensive review of existing assessment instruments and data on risk factors, clinical presentations, and consequences of the three conditions. The tool underwent rigorous testing to evaluate its reliability and validity in a sample of 300 older adults. It was compared against standard diagnostic criteria and assessed alongside other screening tools, including the Mini Nutritional Assessment‐Short Form, the Short Nutritional Assessment Questionnaire and the Simple Questionnaire to Rapidly Diagnose Sarcopenia.

Results

Eighteen percent (n = 54) of participants were diagnosed with an overlap of the three conditions, 10% (n = 30) of cases presented with sarcopenia alone and 3% (n = 10) were diagnosed with malnutrition only. The new tool demonstrated Cronbach's alpha of 0.818 and high construct validity. The newly developed tool and Mini Nutritional Assessment–Short Form had the highest diagnostic accuracy for predicting the malnutrition and sarcopenia. The Short Nutritional Assessment Questionnaire had the highest diagnostic accuracy for predicting cachexia, whereas the Simple Questionnaire to Rapidly Diagnose Sarcopenia exhibited the lowest diagnostic accuracy across all conditions. The retention criteria for items were deemed valid for the 19 items included in the finalized version of the new tool.

Conclusions

Screening for malnutrition, sarcopenia and cachexia in older adults using a single tool was feasible. The new tool was easy to use and did not require anthropometric measurements or physical performance tasks. Geriatr Gerontol Int 2025; ••: ••–••.
Serum alpha‐fetoprotein/hepatocyte growth factor ratio as a novel biomarker predicting the prognosis of acute alcoholic hepatitis
Authors: Inada Hiroki , Nagaoka Katsuya , Hashimoto Kenyu , Toyota Toshinori , Narahara Satoshi , Kurano Sotaro , Tokunaga Takayuki , Tanaka Kentaro , Yoshimaru Yoko , Iio Etsuko , Watanabe Takehisa , Setoyama Hiroko , Tanaka Yasuhito
Published: February 2025

Aim

Acute alcoholic hepatitis (AAH) can be fatal, particularly when it progresses to severe alcoholic hepatitis. There are several prognostic markers, but none specifically reflects liver regenerative capacity. This study investigated the serum alpha‐fetoprotein (AFP)/hepatocyte growth factor (HGF) ratio as a novel prognostic indicator for AAH.

Methods

A single‐center retrospective analysis was conducted on 20 AAH patients, including 12 with severe alcoholic hepatitis, hospitalized between April 2007 and September 2023. Serum AFP and HGF levels were measured at diagnosis, and the AFP/HGF ratio was calculated. Prognostic performance was assessed using receiver operating characteristic analysis, Kaplan–Meier survival analysis, and a validation cohort of 67 non‐alcohol‐related liver failure cases.

Results

Receiver operating characteristic analysis demonstrated excellent prognostic performance for the AFP/HGF ratio, with an area under the curve of 0.97. Patients with high AFP/HGF ratios (≥1.86) had significantly longer overall survival than those with low ratios (<1.86; p < 0.001). The median survival time for the low‐ratio group was 55 days. In severe alcoholic hepatitis patients, a high AFP/HGF ratio was also associated with significantly longer overall survival (p = 0.013). At diagnosis, surviving patients had significantly higher AFP/HGF ratios when compared with subsequently deceased patients (p = 0.005). In the non‐AAH cohort, no significant difference was observed between groups, but survivors showed a trend toward higher AFP/HGF ratios.

Conclusion

The AFP/HGF ratio is a novel and highly specific prognostic marker for AAH, reflecting liver regenerative capacity. It may guide early therapeutic decisions and improve outcomes, particularly for high‐risk AAH patients.
The Interplay of Mind and Body: The Impact of Influencers' Body Size and Motivation Appeals
Authors: Cho Yoon‐Na , Taylor Charles Ray , Panteqi Mivena
Published: February 2025

Social media influencers have become increasingly prominent in advertising, and many play a role in shaping body image perceptions. This research proposes that disclosing influencers' body size through hashtags can help mitigate issues related to body image that have historically arisen from viewer exposure to idealized body images in advertising while promoting informed consumer decisions. Across two experiments, we investigate how body size hashtags and the type of motivation appealed to (intrinsic vs. extrinsic) influence social comparison, perceptions of influencer attractiveness, and purchase intention. Results reveal that individuals engage in more social comparisons when viewing an ad in which a larger‐sized influencer and an appeal to intrinsic motivations are used. We also identify social comparisons and perceived attractiveness as key mechanisms linking the effects of body size hashtags and motivation appeals to purchase intention. Managerial and societal implications are discussed.
The Online Presence During Synchronous Classes of Secondary Students in Chile: The Need to Incorporate Socio‐Emotional Knowledge and Teaching Strategies
Authors: Baeza Alfoncina , Hinostroza J. Enrique
Published: February 2025

Background

After the mandated closure and reopening of schools during and after the coronavirus pandemic, online synchronous teaching and learning has emerged as an opportunity to expand the reach of K‐12 education, however, there is a lack of understanding about the characteristics of the successful learning experiences during that period that could be transferred to the present. Therefore, students' experiences during that period constitute an opportunity to learn about the teaching strategies that enabled positive learning experiences under such conditions.

Objectives

Understand the experience of high‐school students during online classes and characterise the strategies that enabled positive learning perceptions.

Methods

Ten high‐school students were selected and asked to describe positive and negative episodes during online synchronous classes using a narrative research technique. Based on the Community of Inquiry (CoI) Framework, each presence (cognitive, social, and teaching) and its categories were investigated. The way that students experienced remote learning was defined using targeted content‐analysis techniques.

Results and Conclusions

The results show that students reported experiences in which cognitive, social and teaching presences from the original framework emerge, as well as learning and emotional presence, highlighting the key relevance of teaching presence in articulating the activities as well as the other presences. Also, they highlight the relevance of the structure, content and tone of the classes, the need to develop teachers' socio‐emotional knowledge and pedagogy, and their awareness and active consideration of the emotional consequences of their instructional strategies.
The Use of Gut Organoids: To Study the Physiology and Disease of the Gut Microbiota
Authors: Deng Ya , Yuan Xiaolu , Lu XianMin , Wu Jiangbo , Luo Chen , Zhang Ting , Liu Qi , Tang Siqi , Li Zhuo , Mu Xingyi , Hu Yanxia , Du Qian , Xu Jingyu , Xie Rui
Published: February 2025

The intestinal flora has attracted much attention in recent years. An imbalance in the intestinal flora can cause not only intestinal diseases but also cause a variety of parenteral diseases, such as endocrine diseases, nervous system diseases and cardiovascular diseases. Research on the mechanism of disease is likely to be hampered by sample accessibility, ethical issues, and differences between cellular animal and physiological studies. However, advances in stem cell culture have made it possible to reproduce 3D human tissues in vitro that mimic the cellular, anatomical and functional characteristics of real organs. Recent studies have shown that organoids can be used to simulate the development and disease of the gut and intestinal flora and have a wide range of applications in intestinal flora physiology and disease. Intestinal organoids provide a preeminent in vitro model system for cultivating microbiota that influence GI physiology, as well as for understanding how they encounter intestinal epithelial cells and cause disease. The mechanistic details obtained from such modelling may provide new avenues for the prevention and treatment of many gastrointestinal (GI) disorders. Researchers are now starting to take inspiration from other fields, such as bioengineering, and the rise of interdisciplinary approaches, including organoid chip technology and microfluidics, has greatly accelerated the development of organoids to generate intestinal organoids that are more physiologically relevant and suitable for gut microbiota studies. Here, we describe the development of organoid models of gut biology and the application of organoids to study the pathophysiology of diseases caused by intestinal dysbiosis.
The Overexpression of RTN4 Significantly Associated With an Unfavourable Prognosis in Patients With Lower‐Grade Gliomas
Authors: Feng Jing , Zhao Lin , Chen Huiyan , Lin Jianhai , Shang Mingchao , Xu Baoqing , Wang Xinpeng , Ma Danyu , Zhou Jinping , Zhao Hu
Published: February 2025

Gliomas, the most prevalent primary malignancy of the central nervous system, is characterised by its high mortality rates and unfavourable prognosis. Despite extensive research, the underlying mechanisms of glioma pathogenesis remain elusive. The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases provided the lower‐grade gliomas (LGG) transcriptome and related clinical data, which were downloaded separately. It was determined what the clinical data differences were between the two groups based on the median reticulon‐4 (RTN4) expression group. The R language's survminer tool was utilised to examine the variations in survival between the RTN4 high and low‐expression groups. The GeneMANIA database was searched for genes that might interact with RTN4, and these genes were then used to create extensive coexpression networks. Cox regression analysis, both univariate and multivariate, was used to filter out the independent prognostic factors influencing tumour growth. Based on independent prognostic parameters, a nomogram was created to predict prognosis. The model was assessed both internally and externally using receiver operating characteristic curve (ROC) and correcting curves. The R cibersort package was utilised to assess the level of immune infiltration abundance. We further validated our findings with clinical tissues using immunohistochemistry approaches. Statistical significance was determined using the Wilcoxon signed‐rank test, with a p value of < 0.05 considered significant. RTN4 expression in the tumour group was higher than in the normal group (p < 0.001), and a high‐expression level was linked to a poor prognosis (p = 0.028). Patients with elevated RTN4 expression exhibited significant differences from normal brain tissue samples when stratified analysis of LGG patients by sex or radiation treatment was performed (p < 0.001). The immune cell infiltration data demonstrated that the two groups' expressions of various immune cells differed, with pDC cells showing the greatest correlation (−0.421). Univariate and multivariate Cox regression study showed that RTN4, isocitrate dehydrogenase (IDH) mutation, 1p19q codeletion and nia age could be employed as independent prognostic factors for LGG, and the correction curve of the model fit well. Ultimately, clinical samples' immunohistochemistry revealed that RTN4 was markedly overexpressed in low‐grade gliomas. High RTN4 expression was strongly associated with a poor prognosis in LGG patients. RTN4 may serve as a prognostic biomarker for patients with LGG and represents a potential therapeutic target for immunotherapy in this patient population.
CBP/CREB Regulates the Proliferation and Apoptosis of Cardiomyocytes by Interacting With SERCA
Authors: Zhouguo Yiran , Yuan Zhiyong , Abdul Mannan , Xi Shun , Wei Tao , Yan Wei , Wang Yanan , Guo Rui , Xing Quansheng , Zhou Qing
Published: February 2025

Tetralogy of Fallot (TOF) is a common congenital heart disease. In this study, we proposed that cAMP response element‐binding protein (CREB)‐binding protein (CBP) regulates the proliferation and apoptosis in TOF by interacting with the sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA). To confirm this, we collected right ventricle tissue samples from TOF patients during surgery to correct the deformity and from the donors. We performed IHC, IF, RT‐qPCR, WB and ChIP experiments. The analysis of these experiments shows that the expression of CBP is higher in TOF patients than in healthy individuals. Further, the RT‐qPCR results indicated that the CBP and SERCA mRNA in TOF patients were significantly higher than in the healthy donors. Similarly, WB results suggested that the expression of CBP and SERCA was predominantly elevated in TOF patients compared to healthy individuals. Further, the AC16 cell line with CBP knockdown reveals high expression of the Edu compared to normal cells, and the percentage of the cell cycle in the M phase was elevated in the CBPi group. In addition, the CCK‐8 cell viability assay showed more proliferation in the CBPi group than in the control group at different time points. Moreover, the RT‐qPCR results indicated a lower expression of SERCA after the knockdown of CBP and CREB. Finally, the ChIP assay shows that CREB binds to the promoter of SERCA, and the CBP enrichment decreased after the CREB knockdown. In conclusion, these results suggest that CBP interacts with SERCA to regulate cell proliferation and apoptosis during heart development and that up‐regulation of CBP leads to TOF.
Aquaculture Equipment as a Fomite for Transmission of Red Sea Bream Iridovirus: Insights From a Case Study for Assessing Cross‐Contamination
Authors: Kawato Yasuhiko , Takada Yuzo , Matsuyama Tomomasa , Kurobe Tomofumi , Honryo Tomoki , Shirakashi Sho , Masuma Shukei
Published: February 2025

This is a case study that assessed risk factors for transmission of red sea bream iridovirus (RSIV) focused on cross‐contamination of aquaculture equipment in semi‐open system aquaculture. Our investigation during the RSIV outbreak in the fish farm demonstrated that equipment used for collecting dead fish, such as landing nets and gloves, was highly contaminated with RSIV. Based on the results, a daily operation for collecting dead fish was implemented, starting with net pens where no disease occurred, followed by the net pen where the RSIV outbreak occurred to prevent fomite transmission via RSIV‐contaminated equipment. In addition, the landing nets used for collecting dead fish were disinfected at the end of each day to avoid carryover of the virus to the following day. RSIV was not transmitted to the other net pens in the fish farm for more than 30 days. However, once an RSIV outbreak occurred in the net pen that was upstream in the operation for collecting dead fish, RSIV was transmitted to all net pens in approximately 1 week, implying that the transmission was caused by cross‐contamination. This study suggested that appropriate hygiene management is important to prevent fomite transmission between net pens, even in semi‐open system aquaculture.
Individualized Net Benefit of Intensive Blood Pressure Lowering Among Community‐Dwelling Older Adults in SPRINT
Authors: Jamshidian Mitra S. , Scherzer Rebecca , Estrella Michelle M. , Kravitz Richard L. , Boxer Rebecca S. , Tancredi Daniel J. , Berry Jarett D. , de Lemos James A. , Ginsberg Charles , Ix Joachim H. , Shlipak Michael G. , Ascher Simon B.
Published: February 2025

Background

The optimal blood pressure (BP) target for older adults with hypertension remains controversial, particularly among those with advanced age, frailty, or polypharmacy. This study estimated the individualized net benefit of intensive BP lowering among community‐dwelling older adults in the Systolic Blood Pressure Intervention Trial (SPRINT).

Methods

Among 5143 SPRINT participants age ≥ 65 years, Cox models were internally validated to predict an absolute difference in risk between treating to a systolic BP target of < 120 versus < 140 mm Hg for all‐cause death, cardiovascular outcomes, cognitive outcomes, and serious adverse events. Treatment effects were combined using simulated preference weights into individualized net benefits, representing the weighted sum of risk differences across outcomes. Net benefits were compared across categories of age (65–74 vs. ≥ 75 years), SPRINT‐derived frailty status (fit, less fit, and frail), and polypharmacy (≥ 5 medications).

Results

When simulating preferences for participants who view the benefits of BP lowering (reduction in death, cardiovascular events, and cognitive impairment) as much more important than treatment‐related harms (e.g., acute kidney injury and syncope), the median net benefit from intensive BP lowering was 4 percentage points (IQR: 3–6), and 100% had a positive net benefit favoring intensive BP lowering. When simulating benefits and harms to have similar, intermediate importance, the median net benefit was 1 percentage point (IQR: 0–2), and 85% had a positive net benefit. Participants with advanced age and frailty had greater net benefits from intensive BP lowering despite experiencing more harm in both simulations, and those with polypharmacy had greater net benefits when benefits were viewed as much more important than harms (p < 0.001 for all comparisons).

Conclusions

Among community‐dwelling older adults with hypertension in SPRINT, almost all participants had a net benefit that favored a systolic BP target of < 120 mm Hg, but the magnitude of net benefit varied according to estimated risks and simulated preferences.
Dietary Counselling Interventions in Malnutrition Research: Achieving an International Consensus on Best Practices Using an Amended Delphi Process
Authors: Weekes C. Elizabeth , de van der Schueren Marian A. E. , Keller Heather , Steiber Alison , Marshall Skye , Lim Su Lin , Baldwin Christine
Published: February 2025

Introduction

The evidence for the use of dietary counselling interventions in the management of malnutrition is inconsistent. Lack of consistency limits the ability to compare studies, impacting research, clinical practice and policy development.

Aims

To establish an international consensus on minimum requirements for dietary counselling interventions used for the prevention and management of malnutrition in adults in a clinical research context.

Methods

An international expert panel with seven members was formed. An amended Delphi study was conducted with 37 initial consensus statements generated from a targeted search of the literature. The agreement was assessed across two Delphi rounds and two online meetings. The full consensus was defined as the assignment of a score of 5 (strongly agree). A preliminary external validation was conducted with clinical and/or research dietetic professionals when delegates at the International Congress of Dietetics (ICD) 2021 voted during an online meeting on agreement with statements relating to patient assessment and delivery of a dietary counselling intervention.

Results

Consensus was achieved for 27 statements across four themes, with justifications and commentary. Minimum requirements included eight statements for ‘nutritional assessment’ (theme 1), seven for ‘nutritional intervention content’ (theme 2), five for ‘nutritional intervention delivery’ (theme 3) and seven for ‘monitoring and follow‐up’ (theme 4). The ICD delegates voted on elements of assessment (77 of 140 delegates in agreement) and delivery of the intervention (37 of 101 delegates in agreement), demonstrating that consensus on these aspects of nutritional support interventions was low to moderate in this delegate sample.

Conclusions

Consensus was achieved by an international group of experts to define the minimum essential factors for delivering dietary counselling interventions for the management of malnutrition in a research context; however, further external validation is required. The minimum requirements have the potential to influence research, clinical practice and policy development.
‘Smiling and Talking Slowly’: A Qualitative Study on the Ideal Ophthalmologist From the Perspective of Adults With Intellectual Disabilities
Authors: Chou Yueh‐Ching , Chen Bo‐Wei , Pu Christy , Hou Chiun‐Ho
Published: February 2025

Background

Health care accessibility and inequality for people with intellectual disabilities have long been subjects of discussion. Issues related to eye examinations and visits to ophthalmologists are particularly challenging for these people. However, disability studies and healthcare from the perspectives of people with intellectual disabilities remain scarce. The current study aims to explore the experiences and expectations of adults with intellectual disabilities during ophthalmologist visits, with a focus on their subjective viewpoints.

Methods

A qualitative study was conducted between 2021 and 2022 that involved semistructured interviews with 22 adults with intellectual disabilities who were users of day programs or residential services in Taiwan. The interviews, supplemented with pictures, were conducted using purposive sampling. Thematic analysis was used to analyse the data.

Findings

Four themes emerged regarding their experiences with ophthalmologists: ‘Because my eyes itched, I went to the doctor;’ the need for clear and slow explanations during vision screening; anxiety and discomfort during equipment use and focused examination; and ‘The doctor is good. She smiles and is gentle with me.’ In addition, two themes related to their expectations were identified:equipment use and pre‐examination instructions and ideal characteristics of ophthalmologists: smiling and talking slowly.

Conclusion

For people with intellectual disabilities, an ideal ophthalmologist is patient‐centred and provides individualised care—‘Smiling and Talking Slowly’; otherwise, fear of visiting eye doctors worsens their health inequalities. Integrating these considerations into ophthalmology training and practice is essential to enhance the quality of care for and the well‐being and dignity of people with intellectual disabilities.
Acute Epididymo‐Orchitis Caused by Escherichia coli in a Rhesus Monkey
Authors: Li Heling , Zhang Long , Wang Hong
Published: February 2025

Epididymo‐orchitis is characterized by painful swelling and inflammation of the epididymis and testes. A 4‐year‐old male rhesus monkey has clinical manifestations including anorexia, weakness, as well as redness and swelling of the right testis and epididymis. Bacterial culture of the urine was positive for Escherichia coli. Due to the antibiotic treatment being ineffective, the animal underwent a right orchiectomy. Postoperative histopathology confirmed necrosis and significant inflammatory cell infiltration, indicating severe acute epididymo‐orchitis (EO) caused by E. coli infection in the rhesus monkey. After surgical treatment and postoperative care, the animal survived. To our knowledge, this represents the first report of acute EO caused by E. coli in a rhesus monkey. These findings not only enhance our understanding of EO in NHPs but also provide a reference for further biomedical studies of EO induced by E. coli.
A Pharmacophore for Drugs Targeting the α4α4 Binding Site of the (α4)3(β2)2 Nicotinic Acetylcholine Receptor
Authors: Kusay Ali S. , Luo Yujia , O'Mara Megan L. , Balle Thomas
Published: February 2025

Neuronal nicotinic acetylcholine receptors (nAChRs) have an established role in pain pathways and devastating neurodegenerative diseases; however, few drugs have been successfully developed to target them. The most abundant nAChR in the brain, the α4β2 nAChR, is assembled from five subunits in a 3α:2β stoichiometry—(α4)3(β2)2. This receptor contains a unique agonist‐binding site at the α4α4 interface in addition to two classical agonist‐binding sites at α4β2 interfaces. Most known agonists target both α4α4 and α4β2 sites, however, a few compounds with selectivity for the α4α4 site have been identified. These α4α4 selective compounds have a modulator‐like effect akin to benzodiazepines in the γ‐aminobutyric acid type A receptor, which is desirable from a drug development perspective. The two most well characterised α4α4 selective compounds are CMPI and NS9283. Both are structurally very different from classical agonists, and it is puzzling how they occupy the same binding site. In the search for a common pharmacophore, we conducted extensive molecular dynamics simulations with both classical agonists and site‐selective non‐classical compounds. Analyses of the simulations revealed that the α4α4 binding site contains a unique pocket not found in the α4β2 binding site. CMPI and NS9283 were observed to bind in this pocket, thereby explaining why they are selective for the α4α4 binding site. The proposed binding mode featured a closed‐loop C conformation, which is strongly correlated with agonism in nAChRs and explained key site‐directed mutagenesis data for both compounds. Based on this binding mode, we proposed a pharmacophore for drugs targeting the α4α4 binding site. The proposed pharmacophore captures the essence of the original model, that is, nicotinic agonists act as a bridge between protein subunits. The pharmacophore model we propose is unique to the α4α4 binding site and provides a template for developing new site‐selective therapeutic agents.

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Safety and Cost Analysis of Immunoglobulin Cessation Trials in Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Authors: Koay Shiwen , Chen Yi‐Chun , Ransley George , Compton Laura , Lunn Michael P. , Carr Aisling S.
Published: February 2025

Background and Aims

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common chronic autoimmune neuropathy worldwide. A significant proportion of CIDP patients enter spontaneous or medication‐related remission, remaining stable without immunotherapy. Overtreatment of CIDP has clinical and financial implications. We examined performance of IVIg cessation trials in our CIDP cohort and report safety and cost analysis outcomes.

Methods

In individuals with CIDP on maintenance IVIg treatment, a cessation trial was proposed in clinically stable patients with a static IVIg regimen over a 12‐month period. We explored the proportion who were stable off treatment for 12 or more months and the time to recovery in those who declined and were re‐treated. We examined cost implications of this approach.

Results

45/125 individuals met criteria for clinical stability, with median age 58 years, I‐RODS 37/48, MRC‐SS 69/70 and annual treatment costs £107 000/person. Nine individuals had cessation trials resulting in decline within 2 years prior and were not re‐challenged, leaving 36 eligible individuals. 12 of 36 (33.3%) consented to cessation trial and eight of those (66.7%) remained stable off treatment for ≥ 12 months. The successful cessation trials resulted in a cost saving of £855 000/year, with a potential further saving of £1.7 million/year if all the eligible individuals had consented. All patients who deteriorated were rescued to previous baseline on retreatment.

Interpretation

Individuals with CIDP should be counselled about the natural history of the disease and future scheduled, targeted cessation trials. A dedicated clinical infrastructure is vital to safely perform cessation trials.
Skincare Benefits of a Postbiotic Ferment Produced Through Djon Djon Mushroom Fermentation by Saccharomyces
Authors: Pu Chunhong , Shi Doudou , Ingrassia Michael , Gedeon Harvey , Chu Tye , Zhang Jiachan , Wang Changtao
Published: February 2025

Background

Djon Djon is a particularly special black mushroom indigenous to Haiti that has a long history in both their cuisine and in traditional medicine. Centuries of folkloric utilization of theses “medicinal” botanicals tend to indicate the presence of a potentially efficacious western medicine entity.

Objectives

With the advantages afforded by both traditional medicines and fermentation, we endeavored to investigate if fermentation of Djon Djon mushrooms can provide skin care benefits.

Methods

In this study, active Djon Djon fermentation broth (DDF) was obtained using Saccharomyces, and anti‐inflammatory efficacy was assessed in cultured systems using human keratinocytes and fibroblasts, exposed to either UVB or H2O2 respectively. In addition, RNA‐Seq technology was employed to further characterize the mechanisms of DDF following ultraviolet irradiation.

Results

Characterization of the DDF displayed a high number of polysaccharides and peptides present following fermentation, that function to scavenge intracellular ROS, decrease MDA content, while increasing the levels of CAT, COL‐I, and HA in HSF induced by H2O2. In addition, levels of pro‐inflammatory factors (IL‐6, IL‐1β, and TNF‐α) were decreased in UVB irradiated HaCaT cells that had been treated with DDF. Analysis of cellular RNA indicated that DDF altered the DEGs involved in the AGE‐RAGE signaling pathway suggesting that this signaling cascade is inhibited by DDF. Additionally, DDF also influenced the metabolism of arachidonic acid, histidine, and phenylalanine, which are involved in inflammatory processes.

Conclusion

DDF can alleviate oxidative stress damage caused by hydrogen peroxide and photodamage caused by UVB, and the mechanism by which DDF protects skin cells is revealed, displaying the potential benefits of fermented DjonDjon in skincare.
Cosmetics Utilization Pattern, Perceived Adverse Effects and Identified Factors Among Final Year Under Graduate Female Students, University of Gondar, Ethiopia
Authors: Chanie Gashaw Sisay , Simegn Wudneh , Gedu Muhammed , Nega Tigist , Chekol Netsanet , Birhanu Zewdu
Published: February 2025

Objective

The current study aimed to assess the prevalence of cosmetics utilization and perceived adverse effects among female final‐year undergraduate students at the University of Gondar, northwest Ethiopia.

Methods

An institutional‐based cross‐sectional study was carried out from October 2023 to May 2024. We used stratified, simple random sampling techniques to select study participants. Data were collected by using a self‐administered questionnaire administered to trained graduate pharmacist students. EPI Info 7.1 was used for data entry, and SPSS version 26 was used for the data analysis. Descriptive statistics have been done for percentages and frequencies. We used bivariate and multiple logistic regressions to identify factors. Those variables with p < 0.05 were declared to be associated factors for the prevalence of cosmetics utilization and perceived adverse effects.

Results

A total of 403 study participants were included, with a response rate of (96%). In the current study, 81% of the students were using cosmetics, and 55.6% were exposed to cosmetics‐related adverse reactions, primarily skin rash (41%) and itching (38.3%). The most frequently used cosmetic products were toothpaste, lipstick, deodorant, and perfume, which accounted for 83.7%, 56.8%, and 24.7%, respectively. Lower age (20–25 years) AOR = 5.62, urban residence AOR = 1.97, health‐related department AOR = 2.46, economic income 501–1000 Ethiopian birr AOR = 4.05, not love engaged AOR = 3.65, and 3 and 4 years of study AOR = 2.96, with a 95% CI, were significantly associated with cosmetic usage for the students. Shampoos and conditioners AOR = 3.42; hair dye use AOR = 3.40; read information from the container AOR = 2.11; add water or other agents to cosmetics AOR = 2.26; and test Cosmetic adverse reactions AOR = 4.10, with a 95% CI, were significantly associated with cosmetics‐related adverse effects.

Conclusion

A significant proportion of the users suffered from cosmetic‐related adverse reactions. The health care system should be restructured to consider rational cosmetic utilization practices and prevent adverse health effects.
Resolution of pelvic postoperative spindle cell nodule with sarcomatous onset after 9 years of follow‐up
Authors: Matsuoka Ayumu , Mitsuhashi Akira , Usui Hirokazu , Otsuka Satoyo , Nishikimi Kyoko , Tate Shinichi , Okuya Rie , Yazawa Takuya , Shozu Makio , Koga Kaori
Published: February 2025

Introduction

Postoperative spindle cell nodules are benign and reactive lesions that occur at the previous surgical site. It often develops like a sarcoma and is resected via highly invasive procedures. To date, there have been no published reports on the natural progression of postoperative spindle cell nodules without surgical intervention.

Case

A 45‐year‐old woman underwent a total abdominal hysterectomy for leiomyoma. A 5‐cm pelvic mass exposed in the vaginal stump developed 7 weeks later, causing genital bleeding. Positron emission tomography–computed tomography revealed a pelvic mass and an enlarged pelvic lymph node with high uptake. We suspected an invasive sarcoma in the pelvis. However, through a transvaginal needle biopsy, the mass was diagnosed as a postoperative spindle cell nodule posthysterectomy. The nodule slowly reduced in size and completely disappeared 9 years posthysterectomy.

Conclusions

Correct diagnosis of this nodule with sarcomatous onset based on biopsy was important to avoid unnecessary surgeries. The lesion completely disappeared spontaneously after long‐term follow‐up.
Hippocampal Subfield Abnormalities in Patients With Primary Trigeminal Neuralgia
Authors: Filimonova Elena , Pashkov Anton , Moysak Galina , Martirosyan Azniv , Rzaev Jamil
Published: February 2025

Background and Purpose

Primary trigeminal neuralgia (PTN) is a prevalent chronic pain disorder whose pathogenesis is not solely confined to the trigeminal system. Although substantial progress has been made in understanding the underlying mechanisms, comprehensive and consistent data concerning the involvement of the hippocampal formation in this process are lacking. The aim of this study was to evaluate structural changes in hippocampal subfields in patients with PTN.

Methods

Fifty‐nine individuals who were diagnosed with PTN and 28 healthy controls matched for age and sex underwent high‐resolution 3 Tesla MRI. HippUnfold software was used for the segmentation of hippocampal subfields and the extraction of features. Covariance analyses were performed to analyze changes in the volume, thickness, and gyrification index of different subfields in patients with PTN compared to controls. Furthermore, the relationships between MR morphometry data and the severity of nerve root compression, as well as the intensity and duration of pain, were examined in patients with PTN.

Results

Our analysis demonstrated a decrease in the volume of the right cornu ammonis subfield 1 (CA1)–CA3 and left CA2 hippocampal subfields in patients with PTN compared to healthy controls (adjusted p < 0.05 for all comparisons). No statistically significant associations were found between hippocampal MR morphometry data and clinical metrics.

Conclusions

Our results suggest the existence of bilateral structural abnormalities in the hippocampal subfields in individuals with PTN, which could contribute to the development and progression of this condition.
Contractual Requirements and Bidding Behavior in Public Procurement With Entry
Authors: Drake Samielle , Xu Fei
Published: February 2025

We combine theoretical and empirical analyses to investigate the impacts of contractual requirements on bidding behavior and competition in procurement auctions with endogenous entry. Our analysis demonstrates that contractual requirements affect expected payoffs, influencing the equilibrium number of bidders and their bids under zero‐profit conditions. Specifically, in equilibrium, increased contractual requirements enhance competition by raising bidders' expected payoffs, while higher entry costs reduce competition. Overall, a rise in entry costs results in elevated equilibrium bids. Under certain conditions, an increase in contractual requirements raises equilibrium bids. Additionally, we emphasize the significance of enforceability in shaping bidding behavior and, thus, in policy implementation. Empirical evidence from public cleaning services procurement in Sweden supports the implications of our model.
Testing the Mediating Role of Zero‐Sum Beliefs in the Effect of Resource Scarcity on Out‐Group Exclusion/Un‐inclusion
Authors: Takebe Masataka , Nakashima Ken'ichiro
Published: February 2025

When resources are scarce, people often exclude/un‐include others. However, the psychological process underlying this phenomenon is unclear. We tested the mediating role of zero‐sum beliefs using vignette (Studies 1, 2, and 3) and priming (Study 4) experiments. In Studies 1, 2a, and 2b (n = 94, 206, and 508, respectively), via increased zero‐sum beliefs, resource scarcity reduced the number of new employees to be hired (Study 1), increased opposition to accepting more foreign workers (Study 2a), and strengthened support for the return of foreign workers (Study 2b). In Study 3 (n = 132), suggesting that resources are non‐zero‐sum reduced the opposition to accepting more foreign workers via decreased zero‐sum beliefs under resource scarcity. However, in Studies 1, 2a, and 3, zero‐sum beliefs only had a partial mediating role; that is, the direct effects remained. In Studies 4a and 4b (n = 232 and 583, respectively), resource scarcity priming did not affect attitudes toward accepting more foreign workers via zero‐sum beliefs. Future research directions are discussed.
Monitoring of Rivaroxaban Therapy in Hypercoagulable Dogs
Authors: Phillips Erin M. , Blois Shauna L. , Abrams‐Ogg Anthony C. G. , Wood R. Darren , Monteith Gabrielle , Cuq Benoît
Published: February 2025

Background

Measurement of rivaroxaban efficacy using the rivaroxaban‐specific anti‐Xa assay (raXa) can be used for monitoring in veterinary medicine. Detection of rivaroxaban efficacy using other hemostatic tests would make monitoring timelier and more accessible.

Objectives

Compare results of raXa with prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, tissue factor (TF) and kaolin‐activated thromboelastography (TEG), and thrombin generation (TG) in hypercoagulable dogs.

Animals

Twelve client‐owned dogs, diagnosed with hypercoagulability or thromboembolic disease, and prescribed rivaroxaban, were recruited from a tertiary referral hospital from 2020 to 2022.

Methods

Prospective clinical trial. Jugular vein blood samples were collected before treatment, and 1 week and 1–3 months after initiation of rivaroxaban therapy. Hemostatic tests were performed at each visit (3 h after rivaroxaban dosing). TG curve parameters lag time, endogenous thrombin potential (ETP), peak, and time to peak (ttpeak) were assessed.

Results

There was a significant linear relationship between raXa and PT (r2 = 0.74, p < 0.001), ETP (r2 = 0.83, p < 0.001), lag time (r2 = 0.87, p < 0.001), peak (r2 = 0.86, p < 0.001), and ttpeak (r2 = 0.86, p < 0.001). There was a weak linear relationship between raXa and kaolin‐activated TEG parameter reaction time (R) (r2 = 0.49, p = 0.026). There was no significant relationship between raXa and aPTT, fibrinogen concentration and the remainder of the TEG variables (p > 0.05).

Conclusion and Clinical Importance

PT and TG correlated with raXa. PT performed at a reference laboratory appeared to be a convenient method to monitor a small cohort of dogs receiving rivaroxaban therapy.
Can Copepods Feed on Kelp Detritus? A Laboratory Study With Calanus finmarchicus
Authors: Kvile Kristina Ø. , d'Auriac Marc Anglès , Altin Dag , Olsen Rolf Erik , Hancke Kasper
Published: February 2025

Kelp forests are dynamic coastal habitats that generate large amounts of carbon‐rich detritus. The fate of this detritus is largely unknown and considered a missing link in global carbon budgets. Kelp detritus can serve as food for benthic invertebrates and pelagic invertebrate larvae, but we know close to nothing about the role of kelp detritus as food for other zooplankton. We conducted feeding experiments to test if the highly abundant pelagic copepod Calanus finmarchicus can feed on fragments of two dominant kelp species, Saccharina latissima and Laminaria hyperborea. A series of experiments including particle ingestion, fecal pellet production, and DNA tracing tended to support the hypothesis that C. finmarchicus can feed on kelp particles of both species, but at a reduced rate relative to when on a regular phytoplankton diet. Moreover, the results provide initial evidence that L. hyperborea contains substances that are toxic to copepods, an observation that warrants further research. Pelagic copepods consuming kelp detritus would constitute a largely undescribed pathway of carbon from benthic primary producers to the pelagic food web, and a trajectory for deep‐sea carbon sequestration. We hope these preliminary results will inspire future studies on the role of pelagic filter feeders in carbon transport and turnover from macroalgae habitats.
Polyphosphate: The “Dark Matter” of Bacterial Chromatin Structure
Authors: Racki Lisa R. , Freddolino Lydia
Published: February 2025

Polyphosphate (polyP), broadly defined, consists of a chain of orthophosphate units connected by phosphoanhydride bonds. PolyP is the only universal inorganic biopolymer known to date and is present in all three domains of life. At a first approximation polyP appears to be a simple, featureless, and flexible polyanion. A growing body of evidence suggests that polyP is not as featureless as originally thought: it can form a wide variety of complexes and condensates through association with proteins, nucleic acids, and inorganic ions. It is becoming apparent that the emergent properties of the condensate superstructures it forms are both complex and dynamic. Importantly, growing evidence suggests that polyP can affect bacterial chromatin, both directly and by mediating interactions between DNA and proteins. In an increasing number of contexts, it is becoming apparent that polyP profoundly impacts both chromosomal structure and gene regulation in bacteria, thus serving as a rarely considered, but highly important, component in bacterial nucleoid biology.