bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanistic target of rapamycin signaling activity in the human placenta across gestation and in maternal obesity
Authors: Bidne Katie L , Erickson Kathryn E , Powell Theresa L , Jansson Thomas
Published: January 2025

The mechanistic target of rapamycin system is vital to placental development, formation, and function. Alterations in this system in the placenta have been associated with altered fetal growth. However, changes in placental mechanistic target of rapamycin signaling across gestation are poorly understood. We collected 81 human placental samples from 4 to 40 weeks gestation to test the hypothesis that placental mechanistic target of rapamycin signaling activity increases over gestation and is activated in maternal obesity in early gestation. Proteins involved in upstream mechanistic target of rapamycin regulation and mTORC1/2 downstream signaling were quantified using immunoblotting in placentas of male or female fetuses. Readouts of mTORC1 activation, phospho-rpS6, and phospho-4EBP1 were highest in first trimester and decreased across gestation. Phosphorylation of AKT (308 and 473) increased over gestation. Interestingly, abundance of cytochrome c oxidase I and mitochondrial ATP synthase, key subunits of mitochondrial complexes III/IV and V, respectively, were elevated in first trimester obese placentas compared to control, but only in placenta from female fetuses. We suggest that the high placental mechanistic target of rapamycin signaling activity in early pregnancy may be related to the high anabolism and active trophoblast proliferation and invasion in the second half of the first trimester. In addition, we conclude that maternal obesity has only limited impact on this key placental signaling pathway across gestation in women.
MRI versus relapse: optimal activity monitoring for management of progressive multiple sclerosis
Authors: Giovannoni Gavin , Hetherington Suzannah , Jones Eddie , Dominguez Castro Patricia , Karu Himanshu , Ansari Soudeh , Karlsson Goeril , de las Heras Virginia , Lines Carol
Published: January 2025

Secondary progressive multiple sclerosis is often categorized as ‘active’/‘non-active’ based on inflammatory activity on MRI, or relapse; however, the value of MRI/relapse as indicators of disease activity in real-world and clinical trial settings merits further investigation. We separately analysed retrospective data from patients with clinically diagnosed secondary progressive multiple sclerosis in the Adelphi Real-World Disease Specific Programme (a cross-sectional survey) in multiple sclerosis (Adelphi: n = 2554) and the placebo group of the Phase III EXploring the efficacy and safety of siponimod in PAtients with secoNDary progressive multiple sclerosis (EXPAND) trial, [EXPAND-PBO (placebo group of the EXPAND): n = 546] to assess: differences between active/non-active disease in the real-world (characteristics; monitoring); the value of MRI and relapse to indicate disease activity; and the number and characteristics of non-active patients with disease activity in the clinical study. In Adelphi, 1889 patients had ‘active’ disease (≥1 relapse in the year before index date and/or ≥1 new lesion on most recent MRI) versus 665 with ‘non-active’ disease (no relapses in the previous year and no new lesions on MRI); median age was 48 versus 53 years; 73.5 versus 87.8% had moderate-to-severe disease; 75.7 versus 54.3% were taking disease-modifying treatment; 87.7 versus 58.7% had received an MRI in the past year. Most active cases (n = 1116; 59.1%) were identified by MRI versus 239 (12.7%) by relapse and 534 (28.3%) by MRI plus relapse. In EXPAND-PBO, 263 patients were classified ‘active’ (≥1 relapse in 2 years before screening and/or ≥1 gadolinium-enhancing lesion) and 270 ‘non-active’ (no relapse in the 2 years before screening and no gadolinium-enhancing lesion[s]) at baseline; similar proportions of these groups had received disease-modifying treatment prior to placebo: 77.2 and 80.7%. Of non-active patients, 53.0% had disease activity on study; in these patients, 74.1% had disease activity identified by MRI, 8.4% by relapse, and 17.5% by MRI plus relapse. In patients classified non-active at baseline: age and percentage with Expanded Disability Status Scale score 6.0–6.5 were similar between patients with disease activity on study versus patients who remained non-active: 48 versus 52 years; 49.7 versus 56.7%, respectively. In real-world and clinical trial settings, MRI could be a better option than relapse for the identification of disease activity. However, in the real-world, fewer non-active patients had received an MRI in the last year than active patients, which is concerning given that most disease activity in EXPAND-PBO was identified via MRI. We highlight difficulties in consistently identifying disease activity and the negative implications of infrequent monitoring of non-active disease.
Going ‘meta’: a systematic review of metacognition and functional neurological disorder
Authors: Sadnicka Anna , Strudwick Ann-Marie , Grogan John P , Manohar Sanjay , Nielsen Glenn
Published: January 2025

In functional neurological disorder (FND), there is a fundamental disconnect between an apparently intact nervous system and the individuals’ ability to consistently perform motor actions, perceive sensory signals, and/or access effective cognition. Metacognition, the capacity to self-evaluate cognitive performance, appears highly relevant to FND pathophysiology. Poor metacognition is a potential mechanism via which abnormal models of self and the state of the world could arise and persist unchecked. There is therefore a justified enthusiasm that studies of metacognition may give substance to FND’s intangible nature. However, many assume an impairment in metacognition even though experimental studies are still in their infancy. This systematic review provides an analytical checkpoint of the evidence after the first five years of experimental work. We firstly summarise current methods for testing metacognition, prerequisite knowledge that allows readers to independently evaluate the evidence. Using preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) approach we then screened the 21 articles on this topic and review the experimental data of the eight studies that specifically tested metacognition in subjects with FND. Questionnaire metrics used to estimate global metacognition and general confidence in FND revealed a mixed picture of low or normal confidence. Of the five studies that used performance-controlled metrics, the gold-standard to estimate local metacognition in FND, four found metacognition to be equivalent to healthy controls and one paper supported impaired metacognition. We consequently try and broaden the debate and discuss alternative headline scenarios. We review how positive studies may offer insight and debate whether null studies could represent false negatives. However, since most studies find equivalent metacognition to controls, we also discuss whether metacognition could be intact and how this could inform mechanistic models of FND and have potential clinical utility. In summary, this review highlights signal of interest within the data, exposes current limitations and flags the many open questions.
Mesoporous materials 2.0: innovations in metals and chalcogenides for future applications
Authors: Han Minsu , Nagaura Tomota , Kim Jeonghun , Alshehri Saad M , Ahamad Tansir , Bando Yoshio , Alowasheeir Azhar , Asakura Yusuke , Yamauchi Yusuke
Published: January 2025

Incorporating mesoporous structures into various materials can provide abundant active sites and facilitate smooth diffusion, and their effectiveness has been demonstrated across a range of material types. However, despite the development of numerous mesoporous materials, first-generation mesoporous materials (e.g., silica-based compositions) have limited applications due to their poor electrical conductivity and limited compositional diversity, necessitating additional processing for widespread utilization. Our group first proposed the synthesis of mesoporous metals using a solution-based soft-templating method based on self-assembly of micelles, marking a significant advancement in mesoporous materials. This effective process has recently been extended to the synthesis of mesoporous metals and chalcogenides. Chalcogenides have garnered significant attention due to their intriguing optical, electrical, and electrochemical properties arising from their distinctive electronic structures. Mesoporous chalcogenides have been found to effectively enhance these properties. This paper provides a comprehensive review of the synthesis of mesoporous metals and chalcogenides—representing second-generation mesoporous materials (mesoporous materials 2.0)—with specific examples. Our goal is to inform readers about second-generation mesoporous materials and provide insights for further research.
Improvement in serum eosinophilia is observed in clinical responders to ustekinumab but not adalimumab in inflammatory bowel disease
Authors: Wong Emily C L , Dulai Parambir S , Marshall John K , Jairath Vipul , Reinisch Walter , Narula Neeraj
Published: January 2025

Introduction

In inflammatory bowel disease (IBD), the number of eosinophils increases in the lamina propria of the intestinal tract, but their specific patho-mechanistic role remains unclear. Elevated blood eosinophil counts in active IBD suggest their potential as biomarkers for predicting response to biological therapies. This study evaluates blood eosinophil count trends and their predictive value for clinical response and endoscopic improvement in patients with IBD receiving ustekinumab or adalimumab induction therapy.

Methods

Participant-level data from phase 3 and 4 clinical trials (UNIFI, SEAVUE, VARSITY) evaluating ustekinumab and adalimumab for moderate–severe Crohn’s disease (CD) and ulcerative colitis (UC) were used. The primary outcome was clinical response, defined by reductions in disease activity scores. Eosinophil counts were compared between responders and non-responders at multiple time points using t-tests. Logistic regression assessed the odds of achieving a clinical response based on baseline eosinophil counts.

Results

Among patients treated with ustekinumab for UC, responders had significantly higher baseline eosinophil counts compared to non-responders (0.21 × 109/L vs 0.18 × 109/L, P = .042). By week 8, responders showed a greater absolute (−0.07 × 109/L vs −0.01 × 109/L, P < .001) and percent decline (−33.33% vs −5.55%, P = .027) in eosinophil counts. In CD, ustekinumab responders also had higher baseline eosinophil counts and showed significant reductions by week 8. However, no significant differences in eosinophil counts were observed among CD patients treated with adalimumab or UC patients treated with vedolizumab.

Conclusion

Eosinophil reduction was identified as a marker for early response to ustekinumab in both UC and CD, but not adalimumab. No difference was observed among UC patients treated with vedolizumab either. Targeting the IL-12/IL-23 pathway may be more effective in managing eosinophil-associated inflammation in IBD.
Lung ultrasound in neonates and children with cardiac diseases with focus on post cardiac surgical period: time for systematic use—an expert opinion report by the Association for European Paediatric and Congenital Cardiology Imaging Working Group
Authors: Cantinotti Massimiliano , Di Salvo Giovanni , Voges Inga , Raimondi Francesca , Greil Gerald , Garrido Almudena Ortiz , Grotenhuis Heynric B , McMahon Colin J
Published: January 2025

Background

Despite lung ultrasound (LUS) gaining consensus for the diagnosis of pulmonary complication in paediatric acute care setting and in adult cardiology, its use in paediatric cardiology remains limited.

Aim

The aim of the present investigation is to provide an expert opinion on the applications of LUS in neonates and children with congenital heart disease, with a special focus on the post-surgical period.

Methods and Results

A complete guide for identification of landmarks and major signs (A and B lines) and their characteristics is provided. Diagnostic criteria, tips, and tricks for the diagnosis, and differential diagnosis of common pulmonary diseases such as pleural effusion, pneumonia, and consolidation are provided. To perform diagnosis of pneumothorax is illustrated. Applications of LUS for evaluation of hemidiaphragm motility and for a comprehensive assessment of retrosternal area are also discussed. The use of LUS for guidance of minor, common interventional procedures such as lung recruitment and drainage insertion is also described. The report also highlights current gaps of knowledge, including the difficulty for quantitative estimation of pleural effusion and atelectasis, and future prospective.

Conclusion

There is sufficient evidence to support a systematic use of LUS for the diagnosis and follow-up of neonates and children with cardiac disease especially those undergoing paediatric cardiac surgery. LUS is an easy, accurate, fast, cheap, and radiation-free tool that should become a routine in daily practice.
Impact of sex hormones on pheochromocytomas, paragangliomas, and gastroenteropancreatic neuroendocrine tumors
Authors: Wang Katharina , Fischer Alessa , Maccio Umberto , Zitzmann Kathrin , Robledo Mercedes , Lauseker Michael , Bauer Jana , Bechmann Nicole , Gahr Simon , Maurer Julian , Peischer Lea , Reul Astrid , Nieß Hanno , Zimmermann Petra , Ilmer Matthias , Schilbach Katharina , Knösel Thomas , Kroiss Matthias , Fassnacht Martin , Müller Simon A , Morand Gregoire B , Huber Alexander , Vetter Diana , Lehmann Kuno , Kulcsar Zsolt , Mohr Hermine , Pellegata Natalia S , Hantel Constanze , Reincke Martin , Beuschlein Felix , Pacak Karel , Grossman Ashley B , Auernhammer Christoph J , Nölting Svenja
Published: January 2025

Objective

The effects of sex hormones remain largely unexplored in pheochromocytomas and paragangliomas (PPGLs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Methods

We evaluated the effects of estradiol, progesterone, Dehydroepiandrosterone sulfate (DHEAS), and testosterone on human patient-derived PPGL/GEP-NET primary culture cell viability (n = 38/n = 12), performed next-generation sequencing and immunohistochemical hormone receptor analysis in patient-derived PPGL tumor tissues (n = 36).

Results

In PPGLs, estradiol and progesterone (1 µm) demonstrated overall significant antitumor effects with the strongest efficacy in PPGLs with NF1 (cluster 2) pathogenic variants. Estrogen receptor alpha (ERα) positivity was detected in 11/36 PPGLs, including 4/4 head-and-neck paragangliomas (HNPGLs). ERα–positive tumors responded with a significant cell viability decrease to estradiol. DHEAS and testosterone (1 µm) displayed no effects, but higher doses of testosterone (10 µm) demonstrated significant antitumor effects, including a pheochromocytoma lung metastasis with strong androgen receptor positivity (30%). Driven by the antitumor effects of estrogen, we evaluated G-protein-coupled estrogen receptor (GPER) agonist G-1 as a potential therapeutic option for PPGLs and found strong significant antitumor potential, with the strongest efficacy in tumors with NF1 pathogenic variants. Moreover, we detected sex-related differences—tumors from male patients showed significantly stronger responsivity to G-1 compared with tumors from female patients. In GEP-NETs, sex hormones showed overall no effects, especially no tumor growth-promoting effects.

Conclusion

We provide novel data on the effects of elevated sex hormone levels, potentially seen during pregnancy or hormone replacement therapy, on PPGL/GEP-NET tumor growth. G-1 might offer a novel therapeutic approach for some PPGLs depending on patient’s sex and the individual tumor’s genetic/molecular background. All HNPGLs showed ERα positivity.
Tumour necrosis factor alpha-induced protein 3-interacting protein 3 overexpression protects against arrhythmogenic remodelling in the heart failure mice
Authors: Yang Hongjie , Shen Xiaoyan , Wang Huibo , Shuai Wei
Published: January 2025

Aims

Ventricular arrhythmias (VAs), which can lead to sudden cardiac death, are the primary cause of mortality in patients with heart failure (HF). However, the precise mechanisms underlying these arrhythmias are not well understood. Recent studies have implicated tumour necrosis factor alpha-induced protein 3-interacting protein 3 (TNIP3) in pathological cardiac hypertrophy. Nevertheless, its role in isoproterenol (ISO)-associated VAs remains elusive.

Methods and results

We overexpressed TNIP3 in the myocardium using an adeno-associated virus 9 system, administered via tail vein injection. C57BL/6 mice received daily subcutaneous injections of ISO for two consecutive weeks to establish an HF model. We performed histopathology and electrophysiological studies to assess ventricular structural remodelling, electrical remodelling, and susceptibility to VAs. Additionally, RNA sequencing (RNA-Seq) and western blot analysis were conducted to elucidate the underlying mechanisms. The expression of TNIP3 was up-regulated following ISO treatment. TNIP3 overexpression significantly reversed ISO-induced cardiac dysfunction, fibrosis, electrical remodelling, and VAs susceptibility. Accordingly, RNA-Seq identifies that the inflammatory response takes an important role in ISO-induced Vas, and TNIP3 overexpression could alleviate ISO-induced cardiac proinflammatory response by promoting M1 to M2 macrophage polarization. Mechanistically, PI3K/Akt/NF-κB signalling is responsible for the protective effect of TNIP3 overexpression on ISO-induced HF. And PI3K/Akt signalling activation offset the protective effect of TNIP3 overexpression on ISO-induced cardiac inflammation and VAs.

Conclusion

The findings of this study highlight the critical role of TNIP3 in ISO-associated cardiac remodelling and VAs, which are induced by the inhibited activation of the PI3K/Akt/NF-κB signalling pathway.
Isolation and characterization of the midgut microbiota of Aedes albopictus to identify suitable candidates for paratransgenesis
Authors: Darbandsari Mersa , Asgari Majid , Abaei Mohammad R , Ghorbanzadeh Zahra , Derikvand Maryam , Okwarah Patrick , Djadid Navid Dinparast , Raz Abbasali
Published: January 2025

Aedes albopictus is a widely recognized carrier of various pathogens. Its resilient characteristics enable it to easily spread across diverse climates. The microbiota in the midgut of mosquitoes plays a crucial role in the interactions between the host and pathogens and can either enhance or reduce the ability of the insect to transmit diseases. Hence, determining the microorganisms present in the mosquito’s digestive system could be a promising approach to developing an effective method of controlling them. Hence, the aim of this study was to investigate the microbial compositions in the midguts of Ae. albopictus mosquitoes collected from the fields of Sistan and Baluchestan Province. The midguts of 60 female mosquitoes were dissected, and their related bacteria were determined using the culture-dependent method. Different colonies were differentiated using the biochemical tests followed by 16S rRNA gene sequencing. The isolated bacteria were identified as belonging to the Asaia, Delftia, Serratia, Aeromonas, Paracoccus, and Planomicrobium genera based on biochemical and molecular analysis. The findings obtained in this study were largely consistent with earlier studies conducted on mosquitoes gathered from different regions throughout the world. Overall, the findings could enhance our understanding of the microbial diversity in Ae. albopictus and aid in the identification of a potent and widespread bacterium for the development of a paratransgenesis tool to combat Aedes-borne infectious diseases.
Epidemiology, transmission dynamics, risk factors, and future directions of rabies in the Arabian Peninsula using one health approach: a review
Authors: Islam Md Mazharul , Naeem Aisha , Mshelbwala Philip P , Dutta Pronesh , Hassan Mohammad Mahmudul , K. Elfadl Ahmed , Kodama Chiori , Zughaier Susu M , Farag Elmoubashar , Bansal Devendra
Published: January 2025

Despite global initiatives to eliminate dog-mediated human rabies by 2030, the Arabian Peninsula faces challenges due to insufficient data. This review addresses the current rabies situation and knowledge gaps in the region and proposes One Health interventions. Employing a mixed-method approach combining scoping and systematic review, the study commenced with a Delphi discussion to identify knowledge gaps and set objectives. The literature search encompassed published articles and grey literature. The spatial and temporal distribution of rabies was analysed, alongside quantitative meta-analyses to assess prevalence. Rabies virus gene sequences from the NCBI database were examined for reservoir hosts and evolutionary patterns. The final Delphi discussion with experts focused on addressing knowledge gaps and formulating One Health interventions. The first reported human rabies case in this region occurred in Saudi Arabia in 1980. Yemen reported the highest number of cases (439), followed by Iraq (249), Saudi Arabia (91), Jordan (14), and Oman (9). Fox bites accounted for the most cases (47.4%), followed by dog (36.8%) and wild animal (15.8%) bites. The virus was detected in at least 21 animal species. Phylogenetic analysis detected a single strain with two clades, with foxes being the primary virus reservoir. However, the experts expressed scepticism about the accuracy of rabies reports in scientific literature. To achieve the 2030 goal of eliminating dog-mediated human rabies, a stepwise approach towards rabies elimination assessment is crucial in the region. Enhanced surveillance, awareness campaigns, and access to post exposure prophylaxis are essential to address the disease burden.
Evaluating the burden and transmission dynamics of chikungunya virus infections in the Eastern Mediterranean Region: a systematic review and meta-analysis
Authors: Shaik Riyaz Ahamed , Ahmad Mohammad Shakil , Miraj Mohammad , Sami Waqas , Azam Alashjaee Ahmed , Okwarah Patrick
Published: January 2025

The Chikungunya virus (CHIKV) presents substantial public health challenges in the Eastern Mediterranean Region (EMR), with its prevalence and interaction with other arboviruses (ABVs) remaining poorly understood. This systematic review and meta-analysis aimed to assess the prevalence of CHIKV and its association with other ABVs, such as dengue virus (DENV), Rift Valley fever virus (RVFV), malaria, and yellow fever virus (YFV), in the EMR. We systematically searched databases including PubMed, Embase, Web of Science, Scopus, Cochrane Library, CINAHL, PsycINFO, and ScienceDirect to identify epidemiological studies that report CHIKV prevalence and provide odds ratios (ORs) for CHIKV compared to other ABVs. Data analysis was performed using a random-effects model. Heterogeneity was evaluated using the χ2 test and I2 statistic. The GRADE approach was used to evaluate the quality of the studies while the AXIS tool, NOS tool, and AHRQ checklist assessed the risk of bias. The meta-analysis revealed a significant prevalence of CHIKV in the EMR. However, the studies exhibited heterogeneity, indicating variability in the results. A comparison of CHIKV with other ABVs did not show any statistically significant differences in prevalence. The meta-analysis found a notable prevalence of CHIKV in the EMR. The results also indicated that the prevalence of CHIKV is comparable to that of other ABVs in the region. These findings provide an overview of the burden of CHIKV in the EMR.
A new Drosophila melanogaster research resource: CRISPR-induced mutations for clonal analysis of fourth chromosome genes
Authors: Weasner Bonnie M , Weasner Brandon P , Cook Kevin R , Stinchfield Michael J , Kondo Shu , Saito Kuniaki , Kumar Justin P , Newfeld Stuart J
Published: January 2025

As part of an ongoing effort to generate comprehensive resources for the experimental analysis of fourth chromosome genes in Drosophila melanogaster, the Fourth Chromosome Resource Project has used CRISPR mutagenesis with single guide RNAs to isolate mutations in 62 of the 80 fourth chromosome, protein-coding genes. These mutations were induced on a fourth chromosome bearing a basal FRT insertion to facilitate experimental approaches involving FLP recombinase-induced mitotic recombination. To permit straightforward comparisons among mutant stocks, most of the mutations were generated on isogenic fourth chromosomes, which were then crossed into a common genetic background. Of the 119 mutations, 84 are frameshift mutations likely to be null alleles, 29 are small, in-frame deletions, and 6 have yet to be characterized molecularly. The mutations were tested for recessive lethal, female-sterile, and visible phenotypes. Stable stocks for most of the mutations have been submitted to repositories in the United States and Japan for public distribution.
A high-quality assembly revealing the PMEL gene for the unique plumage phenotype in Liancheng ducks
Authors: Wang Zhen , Guo Zhanbao , Liu Hongfei , Liu Tong , Liu Dapeng , Yu Simeng , Tang Hehe , Zhang He , Mou Qiming , Zhang Bo , Cao Junting , Schroyen Martine , Hou Shuisheng , Zhou Zhengkui
Published: January 2025

Background

Plumage coloration is a distinctive trait in ducks, and the Liancheng duck, characterized by its white plumage and black beak and webbed feet, serves as an excellent subject for such studies. However, academic comprehension of the genetic mechanisms underlying duck plumage coloration remains limited. To this end, the Liancheng duck genome (GCA_039998735.1) was hereby de novo assembled using HiFi reads, and F2 segregating populations were generated from Liancheng and Pekin ducks. The aim was to identify the genetic mechanism of white plumage in Liancheng ducks.

Results

In this study, 1.29 Gb Liancheng duck genome was de novo assembled, involving a contig N50 of 12.17 Mb and a scaffold N50 of 83.98 Mb. Beyond the epistatic effect of the MITF gene, genome-wide association study analysis pinpointed a 0.8-Mb genomic region encompassing the PMEL gene. This gene encoded a protein specific to pigment cells and was essential for the formation of fibrillar sheets within melanosomes, the organelles responsible for pigmentation. Additionally, linkage disequilibrium analysis revealed 2 candidate single-nucleotide polymorphisms (Chr33: 5,303,994A>G; 5,303,997A>G) that might alter PMEL transcription, potentially influencing plumage coloration in Liancheng ducks.

Conclusions

Our study has assembled a high-quality genome for the Liancheng duck and has presented compelling evidence that the white plumage characteristic of this breed is attributable to the PMEL gene. Overall, these findings offer significant insights and direction for future studies and breeding programs aimed at understanding and manipulating avian plumage coloration.
Fecal fermentation of lentinan and its effect on gut microbiota and metabolites
Authors: Yang Yuhan , Zhou Xu , Wang Botao , Wei Li , Zhang Yuyan , Wang Xuemin , Bai Junying , Suo Huayi
Published: January 2025

Lentinan (LNT) is a polysaccharide from Shiitake mushrooms that has significant effects regarding antioxidant, hypoglycemic, anti-inflammatory activities, etc., and this effect is influenced by the human intestinal flora. However, the interactions between LNT and human intestinal microorganisms, and their metabolic processes, remain unclear. In this study, the fermentation characteristics of LNT and its effects on intestinal flora and metabolites were studied by in vitro fermentation. Our results indicated that LNT was effectively utilised by intestinal microbiota, and the utilisation rate was 62.7 ± 3.0% after fermentation for 48 hr. The concentrations of short-chain fatty acids (mainly acetic acid and propionic acid) were increased to 4.157 ± 0.197 and 5.847 ± 0.283 mM, respectively. LNT also increased the relative abundance of beneficial bacteria, such as Bifidobacterium and Parabacteroides, while reducing harmful bacteria like Veillonella and Klebsiella. Metabolomics and microbial correlation analysis revealed that the catabolism of LNT was also accompanied by amino acid catabolism, especially alanine, aspartic acid, glutamate, and the biosynthesis of adenosine 5’-monophosphate, etc. These findings suggest that LNT can support gut health and demonstrates potential as a prebiotic.
Use of Intravaginal Cooling to Provide Symptom Relief in Women With Vulvovaginal Candidiasis and Reduce Immunopathology in an Accompanying Mouse Model
Authors: Yano Junko , Langdon Kimberly , Swor Michael , Noverr Mairi C , Fidel Paul L
Published: January 2025

Background

Vulvovaginal candidiasis (VVC), caused primarily by Candida albicans, is treated with anti-fungal drugs, often with variable efficacy and relapses. New therapeutic strategies, including drug-free alternatives, are needed. Upon overgrowth or environmental triggers, C. albicans commensal yeast transitions into hyphae resulting in an aberrant immunopathologic neutrophil response that contributes to the characteristic signs and symptoms of vaginitis. The purpose of this study was to evaluate the efficacy of an intravaginal cooling device (Vlisse) in women with VVC to provide symptom relief via putative reversal of C. albicans hyphae to yeast, with additional proof of principle in an animal model.

Methods

Five women with VVC were instructed to use the device twice daily for 3 days. Vulvovaginal symptoms were monitored and scored for each use, followed by pelvic examination at 30 days. A mouse model of VVC employed cooled micro stir rods to evaluate the cooling effect on fungal morphology and vaginal immunopathology.

Results

Clinical cure was achieved in all women. In the mouse model, the insertion of pre-cooled magnetic rods intravaginally for short periods over 3 days, reduced the immunopathogenic neutrophil infiltration and hyphae.

Conclusions

Intravaginal cooling provides clinical cure for VVC and proof of principle in an animal model.
Addressing water scarcity to support climate resilience and human health
Authors: Zimmermann Karl , Abadi Azar M , Brauman Kate A , Maestu Josefina , Oude Essink Gualbert , Schuster-Wallace Corinne , Smith Ryan , Madani Kaveh , Adeel Zafar , Gribble Matthew O
Published: January 2025

Water scarcity is projected to affect half of the world’s population, gradually exacerbated by climate change. This article elaborates from a panel discussion at the 2023 United Nations Water Conference on “Addressing Water Scarcity to Achieve Climate Resilience and Human Health.” Understanding and addressing water scarcity goes beyond hydrological water balances to also include societal and economic measures. We consider five categories of health impacts resulting from deteriorating water qualities and quantities: (1) water-related diseases and water for hygiene, (2) malnutrition and water for food, (3) livelihoods, income, development, and water for energy, (4) adverse air quality from drought-induced dust and wildfire smoke, and (5) mental health effects from water scarcity-related factors. A discussion on the barriers and opportunities for resilient water systems begins by reframing water scarcity as a “pathway to water bankruptcy” and introducing Water Partnerships to empower local water leaders with the awareness, education, and resources to devise and implement locally appropriate water management strategies. Other barriers include the (1) lack of tools to consider the socioeconomic implications of water scarcity, (2) lack of water information being in actionable formats for decision-makers, (3) lack of clarity in the application of water scarcity modeling to gain policy-relevant findings, and (4) inadequate drought adaptation planning. The article includes recommendations for local governments, national governments, international actors, researchers, nongovernmental organizations, and local constituents in addressing these barriers. The predominant theme in these recommendations is collaborative, multidisciplinary Water Partnerships, knowledge-sharing in accessible formats, and empowering participation by all. This article’s central thesis is that addressing water scarcity must focus on people and their ability to lead healthy and productive lives.
Beyond the baseline: quantification of two phosphatidylethanol homologues in whole blood by LC–MS-MS and retrospective data analysis from a National Reference Laboratory
Authors: Mathewson Nicole J , Okoye Nkemakonam C , Nelson Heather A , Pandya Vrajesh , Moore Chad , Johnson-Davis Kamisha L
Published: January 2025

Alcohol is the most abused substance in Western society, resulting in major economic losses and negative health consequences. Therefore, there is a need for a selective and robust detection method for alcohol consumption in various clinical and forensic settings. This study aimed to validate a mass spectrometry method for quantifying phosphatidylethanol (PEth) and perform retrospective data analysis from the patient population of a national reference laboratory. Quantification of PEth in whole blood was accomplished using an LC–MS-MS assay. Isotopically labeled internal standard for the two PEth homologues was added to the whole-blood specimen, followed by protein precipitation with a mixture of acetonitrile and isopropyl alcohol. After centrifugation, an aliquot of the supernatant was buffered with ammonium acetate before LC–MS–MS analysis on an Agilent 6470 triple quadrupole mass spectrometer coupled to an Agilent 1260 Infinity II LC system. This LC–MS-MS assay was validated for clinical use in accordance with Clinical & Laboratory Standards Institute guidelines. The analytical measurement range, 10–2000 ng/mL, was linear with R2 of 0.999. The within-run and total imprecision was < 5% CV for the low (20 ng/mL), medium (200 ng/mL), and high QC (1000 ng/mL). Results from accuracy and method comparison experiments met the bias criteria of ±15%. Retrospective data analysis showed ∼27% of patients had PEth concentrations <20 ng/mL. Males and females had similar positivity rates for PEth and the positivity rate of women of reproductive age (15–44 years old) was 35% in comparison to 25% in women 45–89 years old. This study’s LC–MS-MS method showed acceptable analytical performance in quantifying PEth as a sensitive and specific biomarker for evaluating alcohol consumption. Results from this study may provide an opportunity to educate women of reproductive age on drinking during pregnancy and the long-term effects of alcohol use.
Serratia Infections in Burn Care
Authors: Wallace David L , Rogers Alan D
Published: January 2025

Serratia marcescens is an opportunistic nosocomial pathogen with significant implications for burn care due to its multidrug resistance, virulence, and ability to colonize hospital environments. This retrospective study, conducted at an American Burn Association Verified Burn Centre, reviewed 22 cases of S. marcescens infections from 2015 to 2020. Patients exhibited a mean total body surface area (TBSA) burned of 28% (range: 2%-71%), with 68% sustaining burns >20% TBSA and 40.9% presenting with inhalation injuries.

The pathogen was most commonly isolated from sputum (36%) and burn wound tissue (50%), with a mean time to positive culture of 8.7 days. Early-onset infections were associated with increased mortality, particularly in patients with major burns, as five out of seven such individuals succumbed to infection. The overall mortality rate was 23%, despite timely antibiotic administration.

Targeted topical antimicrobials, such as Dakin’s solution, nanocrystalline silver, and polyhexamethylene biguanide, offer potential benefits but lack robust evidence for optimal use. Stronger clinical data are needed to guide their application and improve outcomes. These findings underscore the need for enhanced surveillance, refined treatment strategies, and research into S. marcescens management in burn care.
Short INDELs and SNPs as markers of evolutionary processes in hybrid zones
Authors: Perini Samuel , Johannesson Kerstin , Butlin Roger K , Westram Anja M
Published: January 2025

Polymorphic short insertions and deletions (INDELs ≤ 50 bp) are abundant, although less common than single nucleotide polymorphisms (SNPs). Evidence from model organisms shows INDELs to be more strongly influenced by purifying selection than SNPs. Partly for this reason, INDELs are rarely used as markers for demographic processes or to detect divergent selection. Here, we compared INDELs and SNPs in the intertidal snail Littorina saxatilis, focussing on hybrid zones between ecotypes, in order to test the utility of INDELs in the detection of divergent selection. We computed INDEL and SNP site frequency spectra using capture sequencing data. We assessed the impact of divergent selection by analyzing allele frequency clines across habitat boundaries. We also examined the influence of GC-biased gene conversion because it may be confounded with signatures of selection. We show evidence that short INDELs are affected more by purifying selection than SNPs, but part of the observed site frequency spectra difference can be attributed to GC-biased gene conversion. We did not find a difference in the impact of divergent selection between short INDELs and SNPs. Short INDELs and SNPs were similarly distributed across the genome and so are likely to respond to indirect selection in the same way. A few regions likely affected by divergent selection were revealed by INDELs and not by SNPs. Short INDELs can be useful (additional) genetic markers helping to identify genomic regions important for adaptation and population divergence.
Life table study of sublethal concentrations of emamectin benzoate against Spodoptera frugiperda (Lepidoptera, Noctuidae)
Authors: Chen Chengyu , Tang Yiting , Zhao Yunxia , Zhang Xuefeng , Zhang Kai
Published: January 2025

The fall armyworm, Spodoptera frugiperda J.E. Smith (Lepidoptera: Noctuidae), is a well-known agricultural pest in North and South America and has invaded Africa, the Far East, and Australia in the past decade. To investigate the integrated management of S. frugiperda, the sublethal impacts of emamectin benzoate were studied. Leaf-dipping bioassays were used to investigate the effects of sublethal (LC10 and LC30) concentrations of emamectin benzoate on S. frugiperda demographic parameters, and data were interpreted based on the age-stage, two-sex life table theory. The results showed that the developmental time of larvae was prolonged while the fecundity decreased after sublethal concentration treatment. Furthermore, the intrinsic and finite rates of increase, as well as the net reproductive rate, significantly declined following LC30 concentration exposure, whereas the average generation time was extended in comparison to the control group. The intrinsic rate of increase (rm) dropped to 0.14 (LC10) and 0.13 (LC30)/day, compared to the control group (0.18/day). The net reproductive rate (R0) dropped from 775.40 to 303.10 and 193.30 after the LC10 and LC30 concentration treatment, respectively. In this study, sublethal concentrations of emamectin benzoate adversely affected the developmental time, fecundity, and life table parameters of S. frugiperda.
The construction of thematic platforms for Chinese old maps: a global overview
Authors: Dang Ying , Hu Qi , Li Shuang
Published: January 2025

As a significant historical resource in cartography, humanities, and social science research, old maps possess exceptional research value and have garnered extensive attention from various fields and researchers. However, there is currently a lack of comprehensive understanding regarding the construction of old map platforms both domestically and internationally, and even a lack of familiarity with how and where to search old maps online. Given this context, we have fully investigated and systematically sorted out the thematic platforms of old maps from around the world, analyzed the construction of each platform, reviewed them in terms of visualization, map interaction, and shared services. Subsequently, this study proposed the direction of the construction of old map platforms from multiple dimensions, with a focus on the points where artificial intelligence can empower historical map research. We advocate for the further integration and sharing of old maps to support multidisciplinary research in fields such as historical geography, cartography, digital humanities, and art.
Lattice Multislice Algorithm for Fast Simulation of Scanning Transmission Electron Microscopy Images
Authors: Doberstein Christian , Binev Peter
Published: January 2025

We introduce a new approach to the numerical simulation of Scanning Transmission Electron Microscopy images. The Lattice Multislice Algorithm takes advantage of the fact that the electron waves passing through the specimen have limited bandwidth and therefore can be approximated very well by a low-dimensional linear space spanned by translations of a well-localized function. Just like in the PRISM algorithm recently published by C. Ophus, we utilize the linearity of the Schrödinger equation but perform the approximations with functions that are well localized in real space instead of Fourier space. This way, we achieve a similar computational speedup as PRISM, but at a much lower memory consumption and reduced numerical error due to avoiding virtual copies of the probe waves interfering with the result. Our approach also facilitates faster recomputations if local changes are made to the specimen such as changing a single atomic column.
A Novel Self-Opening Transfer Shuttle for the Transfer of Air-Sensitive Sample to Scanning Electron Microscopy
Authors: Wan Peng , Wang Xuri , Zhang Qiang , Xu Zhou , Cai Rui , Zhou Yumeng
Published: January 2025

A self-opening transfer shuttle has been designed and fabricated for the transfer of air-sensitive samples to scanning electron microscopy (SEM). Delayed push out of an airtight sample cabin sealed inside the shuttle allows the protection of the sample from air exposure during the pumping of SEM chamber. A compressed spring is employed to automatically drive the push out of the cabin. Once the cabin is fully pushed out, the sample contained inside is revealed for SEM investigation through a hollow window created on the shuttle. The O-rings that are fixed at both ends of the sample cabin not only serve as sealing parts that make the cylinder airtight but also act as resistance elements that provide sufficient friction force to slow down the push out of the sample cabin. With the advantages of self-opening without the need for external control or force, and its reasonably small size, this low-cost and easy-to-use transfer shuttle has wide compatibility with different SEMs and holds a promising application prospect in numerous research areas.
Retrieval of Phase Information from Low-Dose Electron Microscopy Experiments: Are We at the Limit Yet?
Authors: Vega Ibáñez Francisco , Verbeeck Jo
Published: January 2025

The challenge of imaging low-density objects in an electron microscope without causing beam damage is significant in modern transmission electron microscopy. This is especially true for life science imaging, where the sample, rather than the instrument, still determines the resolution limit. Here, we explore whether we have to accept this or can progress further in this area. To do this, we use numerical simulations to see how much information we can obtain from a weak phase object at different electron doses. Starting from a model with four phase values, we compare Zernike phase contrast with measuring diffracted intensity under multiple random phase illuminations to solve the inverse problem. Our simulations have shown that diffraction-based methods perform better than the Zernike method, as we have found and addressed a normalization issue that, in some other studies, led to an overly optimistic representation of the Zernike setup. We further validated this using more realistic 2D objects and found that random phase illuminated diffraction can be up to five times more efficient than an ideal Zernike implementation. These findings suggest that diffraction-based methods could be a promising approach for imaging beam-sensitive materials and that current low-dose imaging methods are not yet at the quantum limit.
Morphological and Anatomical Deformities of Hirudo verbana, Carena 1820 (Annelida, Hirudinea) After Feeding: Light and Electron Microscopic Analysis
Authors: Ülger Özmen , Ayhan Huseyin
Published: January 2025

Leeches are widely used as model organisms in scientific studies and medical treatments. Medical leeches are hematophagous parasites that usually feed on the blood of their hosts. Some leeches show deformities, usually after feeding. This causes both medical and economic losses as it reduces the effectiveness of leeches in cultivation and medical treatment. The aim of this study was to investigate the effects of morphological deformations after feeding in Hirudo verbana, Carena 1820 (Annelida, Hirudinea), an important species in medical leech treatments. For this purpose, both histopathological and scanning electron microscopy examinations of starved and fed leeches were performed. The causes of deformities in medical leeches were found to be due to overfeeding, which caused cracks on the intestinal surface and therefore deterioration of the tissues. It is also thought that the immunological agents in the fed blood destroyed the medical leech tissue in these regions. In addition, it was determined that the cellular structure of the shaped blood elements stored in the cavity after feeding was preserved for a long time (months) without deterioration. It is certain that revealing the mechanism by which this occurs will inspire the preservation of blood for a long time in blood transfusion.
Disease activity and glucocorticoid tapering patterns in Japanese patients with systemic lupus erythematosus treated with anifrolumab: post hoc analysis of the Japanese subpopulation of the TULIP-2 study
Authors: Tanaka Yoshiya , Atsumi Tatsuya , Okada Masato , Miyamura Tomoya , Ishii Tomonori , Nishiyama Susumu , Matsumura Ryutaro , Morishima Yosuke , Yamaguchi Yoshiyuki , Abreu Gabriel , Lindholm Catharina , Morand Eric F , Takeuchi Tsutomu
Published: January 2025

Objectives: To investigate the efficacy of anifrolumab on disease activity and glucocorticoid tapering patterns in Japanese patients with systemic lupus erythematosus (SLE).

Methods: We analysed disease activity and glucocorticoid tapering in the Japanese subpopulation (anifrolumab, n = 24; placebo, n = 19) of the TULIP-2 trial, which showed the efficacy and safety of anifrolumab in patients with moderate-to-severe active SLE.

Results: The percentage of patients who achieved a British Isles Lupus Assessment Group–based Composite Lupus Assessment response at Week 52 was greater in the anifrolumab group than placebo [50.0% (12/24) vs. 15.8% (3/19); p = 0.014]. Lupus low disease activity state (LLDAS) was achieved at Week 52 by 9/24 (37.5%) and 3/19 (15.8%) patients receiving anifrolumab and placebo, respectively. During the 52-week study period, in the anifrolumab vs. placebo groups, 5/24 (20.8%) patients were in LLDAS ≥50% of observed time vs. 0/19 (0.0%), and 14/24 (58.3%) vs. 6/19 (31.6%) patients were classified into favourable glucocorticoids tapering pattern. Anifrolumab had an acceptable tolerability profile, consistent with the overall population.

Conclusions: In the Japanese subpopulation of the TULIP-2 trial, anifrolumab resulted in an improvements in disease activity to those reported for the overall population, suggesting a beneficial effect for disease control.