bluuebunny/crossref_metadata_2025 huggingface dataset:
Global Warming Potentials of CO2 Uptake, CH4 Emissions, and Albedo Changes in a Restored Mangrove Ecosystem
Authors: Xu Zhe , Li Xianglan , Tian Pengpeng , Huang Yuting , Zhu Qingsong , Zou Huimin , Huang Ying , Zhang Zhao , Zhang Shumin , Chen Mengna , Chen Yahui
Published: June 2024

Restoration of mangrove forests has garnered increasing global prominence as a nature‐based solution for carbon (C) sequestration. However, it was unclear whether the radiation forcing induced by methane (CH4) emissions and albedo changes during mangrove restoration processes can offset the cooling effect resulting from the net carbon dioxide (CO2) uptake. In this study, we measured the CO2, CH4, and albedo during 2020–2022 using an open‐path eddy covariance system in an 8‐year restored mangrove ecosystem afforested in Zhejiang Province, China. Their integrated global warming potentials (GWPs) were calculated to assess the climatic impact of mangrove restoration. The results showed that the restored mangroves functioned as a CO2 sink and a CH4 source, with annual values of −656.75 to −465.41 and 5.54 to 9.07 g C m−2 yr−1, respectively. The albedo varied slightly with a range of 0.11–0.13. The integrated GWPs of CO2, CH4, and albedo were −1,354.00 and −1,875.70 g CO2‐eq m−2 yr−1 over the 20‐ and 100‐year time horizons, respectively. The negative values indicated that the mangrove restoration had a net cooling effect, mainly due to CO2 uptake. The warming effects caused by CH4 emissions and albedo changes had the potential to partially offset CO2 uptake by 12.55%–36.51% and 0.08%–0.42%, respectively. Random forest analysis showed that photosynthetically active radiation (PAR) was the dominant driver on integrated GWPs with feature importance values of 0.34. Our results revealed that the cooling benefit of 8‐year restored mangroves remained significant, even when it was partially offset by CH4 emissions and albedo changes.
Demonstrating a Hybrid Machine Learning Approach for Snow Characteristic Estimation Throughout the Western United States
Authors: Steele Hannah , Small Eric E. , Raleigh Mark S.
Published: June 2024

Snow is a critical component of global climate and provides water resources to over 1 billion people worldwide. Yet current measurement methods and modeling techniques lack the ability to fully capture snow characteristics such as snow water equivalent (SWE) and density across variable landscapes. In recent years, physics‐informed machine learning (ML) methods have demonstrated promise for combining data‐driven learning and physical information. However, this capability has not been widely explored within snow hydrology. Here, we develop a “hybrid” model that applies ML informed by outputs from a physical model and assess whether it provides more accurate estimations of SWE and snow density. We trained and evaluated models at 49 SNOw TELemetry locations spanning a range of snow climates in the western US using 9 years of daily data. The research addressed two questions. In the first, the performance of the hybrid model was compared against a plain neural network (long short‐term memory, Long‐Short Term Memory), a high‐quality physical model, and a statistical snow density model. The second question focused on how regionally trained hybrid models compared to a westwide model as well as their transferability between multiple snow regions. The results showed that combining physical information and ML reduced SWE Root Mean Square Error by 35% compared to a physical model and 51% compared to a neural network. Additionally, regional training only provided minimal benefits compared with a westwide model. These findings indicate that a hybrid approach can yield more accurate snowpack characterization than either physical snow models or ML alone.
Hydrological Research Evolution: A Large Language Model‐Based Analysis of 310,000 Studies Published Globally Between 1980 and 2023
Authors: Miao Chiyuan , Hu Jinlong , Moradkhani Hamid , Destouni Georgia
Published: June 2024

Hydrology plays a crucial role in understanding Earth's intricate water system and addressing water‐related problems, including against the backdrop of ongoing climate change. A retrospective review of the evolution of hydrology up to the current state of research is of great importance for understanding this role. While there have been some quantitative reviews of large numbers of hydrological publications, there still remains a lack of overarching hydrological research assessment, particularly with the focus on hydrological basins as fundamental spatial‐geographic units of hydrological analysis. Large language models, represented by OpenAI's ChatGPT, have demonstrated powerful textual understanding capabilities, making it possible to extract such overarching and basin information from hydrological publications. Here, we considered publications related to hydrology from Web of Science spanning January 1980 to October 2023, and parsed the information from this extensive body of literature by integrating a large language model and geocoding. These techniques enable quantitative analysis of research characteristics across different spatio‐temporal scales, focusing on hotspot topics, collaboration networks, and various basins worldwide. Our study revealed an increase in hydrological research since the 1990 s, with shifts in research priorities from groundwater and nutrients to climate change and ecohydrology. Some basins in North America and Europe have consistently been hotspots for hydrological research. Since the 2010s, there has been a noteworthy increase in interest toward basins in China and South Asia, but attention to many regions with frequent extreme rainfall remains insufficient. Geographical patterns show different preferred research topics for different basins, but climate change has emerged as the most prominent topic across all regions in the last decade. In conclusion, our study provides an effective approach to quantitative analysis of research trends, offering a fresh view on the evolution of hydrology as a research field, its focus on various hydrological basins around the world, and the emergence of overarching and basin‐specific hot topics over time.
Gender-Diverse Adolescents and Young Adults’ Experiences and Attitudes Toward Menstruation
Authors: Bear Benjamin , Gannon Meghan , Kazak Anne E. , Garrick Christopher , Eisenberg Julia , Alibabaee Yasaman , Schwartz Beth I.
Published: June 2024

Objective: Describe how menstruation affects the gender identity of gender-diverse adolescents and young adults who were assigned female at birth and now seek gender-affirming care. Method: Patients at a multidisciplinary pediatric gender program, ages 12–20 assigned female at birth and identified as gender diverse, and had reached menarche were recruited via purposive sampling. Thirty-six patients completed semistructured qualitative interviews about their experiences and attitudes toward menstruation. Open coding procedures, constant comparative method of ground theory, and inductive thematic analysis were used for analysis. Results: Four major themes were identified: (a) language, (b) first periods, (c) periods now, and (d) ways to cope. The association of menstruation with femininity was a source of discomfort. This was reinforced through language, menstrual products, and public bathrooms. Participants were uncomfortable with words related to menstruation but accepted their use with healthcare providers for menstrual management. Many participants noted that their discomfort with menstruation and its association with femininity confirmed their gender identity. A minority of participants expanded their definition of masculine to include people who menstruate. Participants coped with the discomfort of menstruation with distractions, avoidance, menstrual management, testosterone, mental reframing, gender-affirming clothing, and social support. Conclusions: Gender-diverse youth have a diversity of experiences and attitudes toward menstruation. Menstruation is not only a source of dysphoria; it can be a catalyst of exploration and confirmation of gender identity. Psychologists can help gender-diverse adolescents and young adults explore how menstruation influences their identity and identify strategies to cope with their discomfort.
Fifteen-year changes in health-related quality of life after bariatric surgery and non-surgical obesity treatment
Authors: Konttinen Hanna , Sjöholm Kajsa , Carlsson Lena M. S. , Peltonen Markku , Svensson Per-Arne
Published: June 2024

Background

Evidence on the long-term (≥10 years) development of health-related quality of life (HRQoL) following bariatric surgery is still limited and mainly based on small-scale studies. This study aimed to investigate (1) 15-year changes in mental, physical, social, and obesity-related HRQoL after bariatric surgery and non-surgical obesity treatment; and (2) whether sociodemographic factors and pre-operative health status are associated with 15-year HRQoL changes in the surgery group.

Methods

Participants were from the non-randomized, prospective, controlled Swedish Obese Subjects study. The surgery group (N = 2007, per-protocol) underwent gastric bypass, banding or vertical banded gastroplasty, and matched controls (N = 2040) received usual obesity care. Recruitment took place in 1987–2001 and measurements (including six HRQoL scales) were administered before treatment and after 0.5, 1, 2, 3, 4, 6, 8, 10 and 15 years. Multilevel mixed-effect regression models using all observations for estimation were conducted.

Results

Surgical patients experienced greater 15-year improvements in perceived health and overall mood, and greater reductions in depression, obesity-related problems, and social interaction limitations than controls (all p < 0.001, adjusted for baseline differences). Effect size (ES) was classified as large only for obesity-related problems (ES = 0.82). At the 15-year follow-up, surgical patients reported better perceived health (p < 0.001) and less obesity-related problems (p = 0.020) than controls. In the surgery group, patients with baseline diabetes had smaller 15-year reductions in social interaction limitations (p < 0.001) and depression (p = 0.049) compared to those without baseline diabetes. Although surgical patients with a history of psychiatric disorder reported lower HRQoL than those without such history over the 15-year follow-up, there were no significant differences in the long-term improvements between the two groups (p = 0.211–0.902).

Conclusions

Over 15 years, surgical patients experienced more positive development of HRQoL compared to those receiving usual care. This difference was large for obesity-related problems, but otherwise the differences were small. Patients with pre-operative diabetes might be at increased risk for smaller long-term HRQoL improvements.
Exosomal miR-17-5p derived from epithelial cells is involved in aberrant epithelium-fibroblast crosstalk and induces the development of oral submucosal fibrosis
Authors: Xie Changqing , Zhong Liang , Feng Hui , Wang Rifu , Shi Yuxin , Lv Yonglin , Hu Yanjia , Li Jing , Xiao Desheng , Liu Shuang , Chen Qianming , Tao Yongguang
Published: June 2024

Oral submucous fibrosis (OSF) is a chronic and inflammatory mucosal disease caused by betel quid chewing, which belongs to oral potentially malignant disorders. Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development. The epithelium, which is the first line of defense against the external environment, can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment. However, the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear. In this study, we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes. MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts, where it promoted cell secretion, contraction, migration and fibrogenic marker (α-SMA and collagen type I) expression. The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1 (TGFBR1) through the E3 ubiquitination ligase WWP1, thus facilitating downstream TGF-β pathway signaling. Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes. Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts. In conclusion, we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway, which provided a new perspective and strategy for the diagnosis and treatment of OSF.
Consensus definition and diagnostic criteria for neonatal encephalopathy—study protocol for a real-time modified delphi study
Authors: Branagan Aoife , Hurley Tim , Quirke Fiona , Devane Declan , Taneri Petek E. , Badawi Nadia , Sinha Bharati , Bearer Cynthia , Bloomfield Frank H. , Bonifacio Sonia L. , Boylan Geraldine , Campbell Suzann K. , Chalak Lina , D’Alton Mary , deVries Linda S. , El Dib Mohamed , Ferriero Donna M. , Gale Chris , Gressens Pierre , Gunn Alistair J. , Kay Sarah , Maeso Beccy , Mulkey Sarah B. , Murray Deirdre M. , Nelson Karin B. , Nesterenko Tetyana H. , Pilon Betsy , Robertson Nicola J. , Walker Karen , Wusthoff Courtney J. , Molloy Eleanor J. ,   Steering Group for DEFiNE (Definition of Neonatal Encephalopathy)
Published: June 2024

Background

‘Neonatal encephalopathy’ (NE) describes a group of conditions in term infants presenting in the earliest days after birth with disturbed neurological function of cerebral origin. NE is aetiologically heterogenous; one cause is peripartum hypoxic ischaemia. Lack of uniformity in the terminology used to describe NE and its diagnostic criteria creates difficulty in the design and interpretation of research and complicates communication with families. The DEFINE study aims to use a modified Delphi approach to form a consensus definition for NE, and diagnostic criteria.

Methods

Directed by an international steering group, we will conduct a systematic review of the literature to assess the terminology used in trials of NE, and with their guidance perform an online Real-time Delphi survey to develop a consensus diagnosis and criteria for NE. A consensus meeting will be held to agree on the final terminology and criteria, and the outcome disseminated widely.

Discussion

A clear and consistent consensus-based definition of NE and criteria for its diagnosis, achieved by use of a modified Delphi technique, will enable more comparability of research results and improved communication among professionals and with families.

Impact

The terms Neonatal Encephalopathy and Hypoxic Ischaemic Encephalopathy tend to be used interchangeably in the literature to describe a term newborn with signs of encephalopathy at birth. This creates difficulty in communication with families and carers, and between medical professionals and researchers, as well as creating difficulty with performance of research.

The DEFINE project will use a Real-time Delphi approach to create a consensus definition for the term ‘Neonatal Encephalopathy’.

A definition formed by this consensus approach will be accepted and utilised by the neonatal community to improve research, outcomes, and parental experience.
Bronchiolitis: evidence-based management in high-risk infants in the intensive care setting
Authors: Walsh Ruth , Costello Liam , DiCosimo Alexandria , Doyle Anne-Marie , Kehoe Laura , Mulhall Cormac , O’Hara Sean , Elnazir Basil , Meehan Judith , Isweisi Eman , Semova Gergana , Branagan Aoife , Roche Edna , Molloy Eleanor
Published: June 2024

Aim

Systematically review the management of infants with severe bronchiolitis in a paediatric intensive care unit (PICU) setting with a focus on high-risk infants to identify gaps in evidence-based knowledge.

Methods

This systematic review utilised Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) to examine the literature on the PICU management of bronchiolitis in infants <24 months old. Three databases, Embase, PubMed and Medline, were searched and higher levels of evidence I, II and III were included.

Results

There were 455 papers reviewed and 26 met the inclusion criteria. Furthermore, 19 of these studied respiratory interventions such as positive airway pressure and oxygen delivery. The remaining 7 examined: erythropoietin, caffeine, dexamethasone, protein supplementation, ribavirin, respiratory syncytial virus immune globulin, or diuretic therapy. Of the 26 studies, 20 excluded infants with high-risk conditions. Therapies showing favourable outcomes included Heliox, prophylactic dexamethasone pre-extubation, protein supplementation, and diuretic use.

Conclusions

Clinical trials for bronchiolitis management frequently exclude high-risk children. Innovative study design in the future may improve access to clinical trials for the management of bronchiolitis in high-risk infants in a PICU setting.

Impact

Clinical trials for bronchiolitis management frequently exclude high-risk children.

We review the evidence base for the management of an under-investigated patient demographic in the setting of acute bronchiolitis.

Randomised controlled trials are needed to determine the efficacy of management strategies for bronchiolitis in high-risk infants in a paediatric intensive care setting.
Late stage melanoma is hallmarked by low NLGN4X expression leading to HIF1A accumulation
Authors: Schörghofer David , Vock Laurenz , Mirea Madalina A. , Eckel Oliver , Gschwendtner Anna , Neesen Jürgen , Richtig Erika , Hengstschläger Markus , Mikula Mario
Published: June 2024

Background

Despite ongoing research and recent advances in therapy, metastatic melanoma remains one of the cancers with the worst prognosis. Here we studied the postsynaptic cell adhesion molecule Neuroligin 4X (NLGN4X) and investigated its role in melanoma progression.

Methods

We analysed histologic samples to assess the expression and predictive value of NLGN4X in human melanoma. The oncogenic role of NLGN4X was determined by loss or gain-of-function experiments in vitro as well as by analysis of tumorspheres, which were grafted to human skin organoids derived from pluripotent stem cells. Whole genome expression analysis and validation experiments were performed to clarify the molecular mechanism.

Results

We identified that suppression of NLGN4X down regulated the prefoldin member Von Hippel-Lindau binding protein 1 (VBP1). Moreover, loss of VBP1 was sufficient for accumulation of HIF1A and HIF1A signalling was further shown to be essential for the acquisition of migratory properties in melanoma. We re-established NLGN4X expression in late stage melanoma lines and observed decreased tumour growth after transplantation to human skin organoids generated from pluripotent stem cells. In line, we showed that high amounts of NLGN4X and its target VBP1 in human patient samples had a beneficial prognostic effect on patient survival.

Conclusion

In view of these findings, we propose that decreased amounts of NLGN4X are indicative of a metastatic melanoma phenotype and that loss of NLGN4X provides a novel mechanism for HIF induction.
Importations of SARS-CoV-2 lineages decline after nonpharmaceutical interventions in phylogeographic analyses
Authors: Goliaei Sama , Foroughmand-Araabi Mohammad-Hadi , Roddy Aideen , Weber Ariane , Översti Sanni , Kühnert Denise , McHardy Alice C.
Published: June 2024

During the early stages of the SARS-CoV-2 pandemic, before vaccines were available, nonpharmaceutical interventions (NPIs) such as reducing contacts or antigenic testing were used to control viral spread. Quantifying their success is therefore key for future pandemic preparedness. Using 1.8 million SARS-CoV-2 genomes from systematic surveillance, we study viral lineage importations into Germany for the third pandemic wave from late 2020 to early 2021, using large-scale Bayesian phylogenetic and phylogeographic analysis with a longitudinal assessment of lineage importation dynamics over multiple sampling strategies. All major nationwide NPIs were followed by fewer importations, with the strongest decreases seen for free rapid tests, the strengthening of regulations on mask-wearing in public transport and stores, as well as on internal movements and gatherings. Most SARS-CoV-2 lineages first appeared in the three most populous states with most cases, and spread from there within the country. Importations rose before and peaked shortly after the Christmas holidays. The substantial effects of free rapid tests and obligatory medical/surgical mask-wearing suggests these as key for pandemic preparedness, given their relatively few negative socioeconomic effects. The approach relates environmental factors at the host population level to viral lineage dissemination, facilitating similar analyses of rapidly evolving pathogens in the future.
Plasma cell differentiation is regulated by the expression of histone variant H3.3
Authors: Saito Yuichi , Harada Akihito , Ushijima Miho , Tanaka Kaori , Higuchi Ryota , Baba Akemi , Murakami Daisuke , Nutt Stephen L. , Nakagawa Takashi , Ohkawa Yasuyuki , Baba Yoshihiro
Published: June 2024

The differentiation of B cells into plasma cells is associated with substantial transcriptional and epigenetic remodeling. H3.3 histone variant marks active chromatin via replication-independent nucleosome assembly. However, its role in plasma cell development remains elusive. Herein, we show that during plasma cell differentiation, H3.3 is downregulated, and the deposition of H3.3 and chromatin accessibility are dynamically changed. Blockade of H3.3 downregulation by enforced H3.3 expression impairs plasma cell differentiation in an H3.3-specific sequence-dependent manner. Mechanistically, enforced H3.3 expression inhibits the upregulation of plasma cell-associated genes such as Irf4, Prdm1, and Xbp1 and maintains the expression of B cell-associated genes, Pax5, Bach2, and Bcl6. Concomitantly, sustained H3.3 expression prevents the structure of chromatin accessibility characteristic for plasma cells. Our findings suggest that appropriate H3.3 expression and deposition control plasma cell differentiation.
Electrically driven spin resonance of 4f electrons in a single atom on a surface
Authors: Reale Stefano , Hwang Jiyoon , Oh Jeongmin , Brune Harald , Heinrich Andreas J. , Donati Fabio , Bae Yujeong
Published: June 2024

A pivotal challenge in quantum technologies lies in reconciling long coherence times with efficient manipulation of the quantum states of a system. Lanthanide atoms, with their well-localized 4f electrons, emerge as a promising solution to this dilemma if provided with a rational design for manipulation and detection. Here we construct tailored spin structures to perform electron spin resonance on a single lanthanide atom using a scanning tunneling microscope. A magnetically coupled structure made of an erbium and a titanium atom enables us to both drive the erbium’s 4f electron spins and indirectly probe them through the titanium’s 3d electrons. The erbium spin states exhibit an extended spin relaxation time and a higher driving efficiency compared to 3d atoms with spin ½ in similarly coupled structures. Our work provides a new approach to accessing highly protected spin states, enabling their coherent control in an all-electric fashion.
DYRK1A signalling synchronizes the mitochondrial import pathways for metabolic rewiring
Authors: Marada Adinarayana , Walter Corvin , Suhm Tamara , Shankar Sahana , Nandy Arpita , Brummer Tilman , Dhaouadi Ines , Vögtle F.-Nora , Meisinger Chris
Published: June 2024

Mitochondria require an extensive proteome to maintain a variety of metabolic reactions, and changes in cellular demand depend on rapid adaptation of the mitochondrial protein composition. The TOM complex, the organellar entry gate for mitochondrial precursors in the outer membrane, is a target for cytosolic kinases to modulate protein influx. DYRK1A phosphorylation of the carrier import receptor TOM70 at Ser91 enables its efficient docking and thus transfer of precursor proteins to the TOM complex. Here, we probe TOM70 phosphorylation in molecular detail and find that TOM70 is not a CK2 target nor import receptor for MIC19 as previously suggested. Instead, we identify TOM20 as a MIC19 import receptor and show off-target inhibition of the DYRK1A-TOM70 axis with the clinically used CK2 inhibitor CX4945 which activates TOM20-dependent import pathways. Taken together, modulation of DYRK1A signalling adapts the central mitochondrial protein entry gate via synchronization of TOM70- and TOM20-dependent import pathways for metabolic rewiring. Thus, DYRK1A emerges as a cytosolic surveillance kinase to regulate and fine-tune mitochondrial protein biogenesis.
Increased vascular smooth muscle cell senescence in aneurysmal Fibulin-4 mutant mice
Authors: Stefens Sanne J. M. , van Vliet Nicole , IJpma Arne , Burger Joyce , Li Yunlei , van Heijningen Paula M. , Lindeman Jan H. N. , Majoor-Krakauer Danielle , Verhagen Hence J. M. , Kanaar Roland , Essers Jeroen , van der Pluijm Ingrid
Published: June 2024

Aortic aneurysms are dilatations of the aorta that can rupture when left untreated. We used the aneurysmal Fibulin-4R/R mouse model to further unravel the underlying mechanisms of aneurysm formation. RNA sequencing of 3-month-old Fibulin-4R/R aortas revealed significant upregulation of senescence-associated secretory phenotype (SASP) factors and key senescence factors, indicating the involvement of senescence. Analysis of aorta histology and of vascular smooth muscle cells (VSMCs) in vitro confirmed the senescent phenotype of Fibulin-4R/R VSMCs by revealing increased SA-β-gal, p21, and p16 staining, increased IL-6 secretion, increased presence of DNA damage foci and increased nuclei size. Additionally, we found that p21 luminescence was increased in the dilated aorta of Fibulin-4R/R|p21-luciferase mice. Our studies identify a cellular aging cascade in Fibulin-4 aneurysmal disease, by revealing that Fibulin-4R/R aortic VSMCs have a pronounced SASP and a senescent phenotype that may underlie aortic wall degeneration. Additionally, we demonstrated the therapeutic effect of JAK/STAT and TGF-β pathway inhibition, as well as senolytic treatment on Fibulin-4R/R VSMCs in vitro. These findings can contribute to improved therapeutic options for aneurysmal disease aimed at reducing senescent cells.
Effects of wall materials on the physicochemical properties of spray-dried bitter gourd (Momordica charantia L.) powders
Authors: Deng Yuanyuan , Liu Guang , Zhang Huimin , Zhou Pengfei , Tang Xiaojun , Li Ping , Zhao Zhihao , Zhang Yan , Wang Zhangying , Wei Zhencheng , Zhang Mingwei
Published: June 2024

Bitter gourd has numerous health-promoting effects on the human body. However, its use has been greatly limited due to its poor acceptance by consumers, resulting from its strong bitterness. This study investigated the effects of five wall materials, namely, soybean protein isolate, gum arabic, maltodextrin, resistant starch, and a soybean lecithin calcium caseinate mixture, on the physicochemical properties of spray-dried bitter gourd powders. The results showed that all five wall materials reduced the moisture content, water activity, browning degree, agglomeration, and bitterness of the spray-dried bitter gourd powder. Maltodextrin was found to be the most effective at reducing water activity, while soybean protein isolate was best at protecting the colour, and the soybean lecithin calcium caseinate mixture was best at reducing hygroscopicity and masking bitterness. Additionally, all five wall materials improved the preservation of flavonoids, saponins, and vitamin C, with soybean protein isolate being the most effective in improving the total flavonoid retention ratio and the soybean lecithin calcium caseinate mixture being the best in improving the retention ratios of total saponins and vitamin C. The spray-dried bitter gourd powder prepared with soybean protein isolate had the highest antioxidant activity and α-glucosidase inhibitory activity. These results are significant for understanding the relationship between wall materials and the physicochemical properties of spray-dried powder. Additionally, these materials provide bitter gourd product manufacturers with useful guidance for producing high-quality products. Furthermore, the results could provide useful insights for processing fruits with similar product characteristics, thus contributing to the enrichment of food processing knowledge.
The maintenance of oocytes in the mammalian ovary involves extreme protein longevity
Authors: Harasimov Katarina , Gorry Rebecca L. , Welp Luisa M. , Penir Sarah Mae , Horokhovskyi Yehor , Cheng Shiya , Takaoka Katsuyoshi , Stützer Alexandra , Frombach Ann-Sophie , Taylor Tavares Ana Lisa , Raabe Monika , Haag Sara , Saha Debojit , Grewe Katharina , Schipper Vera , Rizzoli Silvio O. , Urlaub Henning , Liepe Juliane , Schuh Melina
Published: June 2024

Women are born with all of their oocytes. The oocyte proteome must be maintained with minimal damage throughout the woman’s reproductive life, and hence for decades. Here we report that oocyte and ovarian proteostasis involves extreme protein longevity. Mouse ovaries had more extremely long-lived proteins than other tissues, including brain. These long-lived proteins had diverse functions, including in mitochondria, the cytoskeleton, chromatin and proteostasis. The stable proteins resided not only in oocytes but also in long-lived ovarian somatic cells. Our data suggest that mammals increase protein longevity and enhance proteostasis by chaperones and cellular antioxidants to maintain the female germline for long periods. Indeed, protein aggregation in oocytes did not increase with age and proteasome activity did not decay. However, increasing protein longevity cannot fully block female germline senescence. Large-scale proteome profiling of ~8,890 proteins revealed a decline in many long-lived proteins of the proteostasis network in the aging ovary, accompanied by massive proteome remodeling, which eventually leads to female fertility decline.
Non-stem cell lineages as an alternative origin of intestinal tumorigenesis in the context of inflammation
Authors: Verhagen Mathijs P. , Joosten Rosalie , Schmitt Mark , Välimäki Niko , Sacchetti Andrea , Rajamäki Kristiina , Choi Jiahn , Procopio Paola , Silva Sara , van der Steen Berdine , van den Bosch Thierry P. P. , Seinstra Danielle , de Vries Annemarie C. , Doukas Michail , Augenlicht Leonard H. , Aaltonen Lauri A. , Fodde Riccardo
Published: June 2024

According to conventional views, colon cancer originates from stem cells. However, inflammation, a key risk factor for colon cancer, has been shown to suppress intestinal stemness. Here, we used Paneth cells as a model to assess the capacity of differentiated lineages to trigger tumorigenesis in the context of inflammation in mice. Upon inflammation, Paneth cell-specificApcmutations led to intestinal tumors reminiscent not only of those arising in patients with inflammatory bowel disease, but also of a larger fraction of human sporadic colon cancers. The latter is possibly because of the inflammatory consequences of western-style dietary habits, a major colon cancer risk factor. Machine learning methods designed to predict the cell-of-origin of cancer from patient-derived tumor samples confirmed that, in a substantial fraction of sporadic cases, the origins of colon cancer reside in secretory lineages and not in stem cells.
Cu-nanoparticles enhance the sustainable growth and yield of drought-subjected wheat through physiological progress
Authors: Raza Muhammad Aown Sammar , Amin Jawad , Valipour Mohammad , Iqbal Rashid , Aslam Muhammad Usman , Zulfiqar Bilal , Muhammad Faqeer , Ibrahim Muhammad Arif , Al-Ghamdi Abdullah Ahmed , Elshikh Mohamed S. , Iqbal Javed , Toleikienė Monika , Elsalahy Heba H.
Published: June 2024

Drought stress (DS) is a significant abiotic stress that limits agricultural productivity worldwide. In semi-arid climates, one potential solution to alleviate the deleterious effects of drought is the use of soil amendments such as nanoparticles. The current research was conducted out to probe the sway of drought at critical growth stages (CGS) of wheat crop (D0: Control, D1: Drought at tillering stage, and D2: Drought at anthesis stage) and the application of Cu-nanoparticles (T0: 0 mg L−1, T1: 300 mg L−1, T2: 700 mg L−1, and T3: 950 mg L−1) in order to improve drought resilience. Results of the study revealed that DS considerably decreased the wheat growth and yield during CGS. However, Cu-nanoparticles application alleviated the detrimental backlash of DS and led to improvements in various aspects of wheat growth and yield, including plant height, spike length, 1000 grain weight, stomatal conductance, leaf chlorophyll content, water use efficiency, leaf turgor potential, relative water content, and ultimately the grain yield. The use of principal component analysis allowed us to integrate and interpret the diverse findings of our study, elucidating the impact of Cu-nanoparticle treatment on wheat growth and yield under drought. Overall, the study concluded that DS during the anthesis stage had the most significant negative impact on crop yield. However, applying Cu-nanoparticles at the rate of 300 mg L−1 proved to be an effective strategy for improving crop productivity by reducing the harmful effects of drought.
An improved gray wolf optimization algorithm solving to functional optimization and engineering design problems
Authors: Qiu Yihui , Yang Xiaoxiao , Chen Shuixuan
Published: June 2024

As a newly proposed optimization algorithm based on the social hierarchy and hunting behavior of gray wolves, grey wolf algorithm (GWO) has gradually become a popular method for solving the optimization problems in various engineering fields. In order to further improve the convergence speed, solution accuracy, and local minima escaping ability of the traditional GWO algorithm, this work proposes a multi-strategy fusion improved gray wolf optimization (IGWO) algorithm. First, the initial population is optimized using the lens imaging reverse learning algorithm for laying the foundation for global search. Second, a nonlinear control parameter convergence strategy based on cosine variation is proposed to coordinate the global exploration and local exploitation ability of the algorithm. Finally, inspired by the tunicate swarm algorithm (TSA) and the particle swarm algorithm (PSO), a nonlinear tuning strategy for the parameters, and a correction based on the individual historical optimal positions and the global optimal positions are added in the position update equations to speed up the convergence of the algorithm. The proposed algorithm is assessed using 23 benchmark test problems, 15 CEC2014 test problems, and 2 well-known constraint engineering problems. The results show that the proposed IGWO has a balanced E&P capability in coping with global optimization as analyzed by the Wilcoxon rank sum and Friedman tests, and has a clear advantage over other state-of-the-art algorithms.
Enhancing the electrical readout of the spin-dependent recombination current in SiC JFETs for EDMR based magnetometry using a tandem (de-)modulation technique
Authors: Gottscholl Andreas , Kraus Hannes , Aichinger Thomas , Cochrane Corey J.
Published: June 2024

Electrically detected magnetic resonance (EDMR) is a promising method to readout spins in miniaturized devices utilized as quantum magnetometers. However, the sensitivity has remained challenging. In this study, we present a tandem (de-)modulation technique based on a combination of magnetic field and radio frequency modulation. By enabling higher demodulation frequencies to avoid 1/f-noise, enhancing self-calibration capabilities, and eliminating background signals by 3 orders of magnitude, this technique represents a significant advancement in the field of EDMR-based sensors. This novel approach paves the way for EDMR being the ideal candidate for ultra-sensitive magnetometry at ambient conditions without any optical components, which brings it one step closer to a chip-based quantum sensor for future applications.
The impact of cognitive distraction on gustatory perception in volunteers with obesity
Authors: Ruda Iryna , Chellapandian Deepak Charles , Freiherr Jessica
Published: June 2024

Obesity, a global health challenge, is influenced by biological, behavioral, socioeconomical, and environmental factors. In our technology-driven world, distracted eating is prevalent, yet neurocognitive mechanisms behind it remain poorly understood. This study targets individuals with overweight and obesity, exploring taste perception under distraction comprehensively. Participants formed two distinct groups based on their Body Mass Index (BMI), lean and overweight/obese. During the experiment participants received gustatory stimuli while playing a Tetris game of various difficulty levels. Participants rated taste intensity and pleasantness, with linear mixed models analyzing distraction effects. Results confirmed that high distraction levels reduced perception of taste intensity (p = 0.017) and taste pleasantness (p = 0.022), with variations influenced by gender and weight status. Individuals in the overweight/obese group exhibited most profound intensity changes during distraction (p = 0.01). Taste sensitivity ratings positively correlated with BMI interacting with gender (male r = 0.227, p < 0.001; female r = 0.101, p < 0.001). Overall across both groups, female participants demonstrated higher taste sensitivity compared to male participants (p < 0.001). This study highlights the impact of cognitive distraction during consumption on taste perception, particularly in relation to weight status and gender, underscoring their significant roles in this interplay.
Machine learning for the prediction of in-hospital mortality in patients with spontaneous intracerebral hemorrhage in intensive care unit
Authors: Mao Baojie , Ling Lichao , Pan Yuhang , Zhang Rui , Zheng Wanning , Shen Yanfei , Lu Wei , Lu Yuning , Xu Shanhu , Wu Jiong , Wang Ming , Wan Shu
Published: June 2024

This study aimed to develop a machine learning (ML)-based tool for early and accurate prediction of in-hospital mortality risk in patients with spontaneous intracerebral hemorrhage (sICH) in the intensive care unit (ICU). We did a retrospective study in our study and identified cases of sICH from the MIMIC IV (n = 1486) and Zhejiang Hospital databases (n = 110). The model was constructed using features selected through LASSO regression. Among five well-known models, the selection of the best model was based on the area under the curve (AUC) in the validation cohort. We further analyzed calibration and decision curves to assess prediction results and visualized the impact of each variable on the model through SHapley Additive exPlanations. To facilitate accessibility, we also created a visual online calculation page for the model. The XGBoost exhibited high accuracy in both internal validation (AUC = 0.907) and external validation (AUC = 0.787) sets. Calibration curve and decision curve analyses showed that the model had no significant bias as well as being useful for supporting clinical decisions. XGBoost is an effective algorithm for predicting in-hospital mortality in patients with sICH, indicating its potential significance in the development of early warning systems.
Global ischemia induces stemness and dedifferentiation in human adult cardiomyocytes after cardiac arrest
Authors: Jinton Helen , Sopasakis Victoria Rotter , Sjölin Linnéa , Oldfors Anders , Jeppsson Anders , Oras Jonatan , Wernbom Mathias , Vukusic Kristina
Published: June 2024

Global ischemia has been shown to induce cardiac regenerative response in animal models. One of the suggested mechanisms behind cardiac regeneration is dedifferentiation of cardiomyocytes. How human adult cardiomyocytes respond to global ischemia is not fully known. In this study, biopsies from the left ventricle (LV) and the atrioventricular junction (AVj), a potential stem cell niche, were collected from multi-organ donors with cardiac arrest (N = 15) or without cardiac arrest (N = 6). Using immunohistochemistry, we investigated the expression of biomarkers associated with stem cells during cardiomyogenesis; MDR1, SSEA4, NKX2.5, and WT1, proliferation markers PCNA and Ki67, and hypoxia responsive factor HIF1α. The myocyte nuclei marker PCM1 and cardiac Troponin T were also included. We found expression of cardiac stem cell markers in a subpopulation of LV cardiomyocytes in the cardiac arrest group. The same cells showed a low expression of Troponin T indicating remodeling of cardiomyocytes. No such expression was found in cardiomyocytes from the control group. Stem cell biomarker expression in AVj was more pronounced in the cardiac arrest group. Furthermore, co-expression of PCNA and Ki67 with PCM1 was only found in the cardiac arrest group in the AVj. Our results indicate that a subpopulation of human cardiomyocytes in the LV undergo partial dedifferentiation upon global ischemia and may be involved in the cardiac regenerative response together with immature cardiomyocytes in the AVj.
Stronger Arctic amplification from anthropogenic aerosols than from greenhouse gases
Authors: Wu You-Ting , Liang Yu-Chiao , Previdi Michael , Polvani Lorenzo M. , England Mark R. , Sigmond Michael , Lo Min-Hui
Published: June 2024

Arctic amplification (AA), the greater Arctic surface warming compared to the global average, has been widely attributed to increasing concentrations of greenhouse gases (GHG). However, less is known about the impacts of other forcings - notably, anthropogenic aerosols (AER) - and how they may compare to the impacts of GHG. Here we analyze sets of climate model simulations, specifically designed to isolate the AER and GHG effects on global climate. Surprisingly, we find stronger AA produced by AER than by GHG during the 1955–1984 period, when the strongest global AER increase. This stronger AER-induced AA is due to a greater sensitivity of Arctic sea ice, and associated changes in ocean-to-atmosphere heat exchange, to AER forcing. Our findings highlight the asymmetric Arctic climate response to GHG and AER forcings, and show that clean air policies which have reduced aerosol emissions may have exacerbated the Arctic warming over the past few decades.
Development and validation of a smartphone-based deep-learning-enabled system to detect middle-ear conditions in otoscopic images
Authors: Dubois Constance , Eigen David , Simon François , Couloigner Vincent , Gormish Michael , Chalumeau Martin , Schmoll Laurent , Cohen Jérémie F.
Published: June 2024

Middle-ear conditions are common causes of primary care visits, hearing impairment, and inappropriate antibiotic use. Deep learning (DL) may assist clinicians in interpreting otoscopic images. This study included patients over 5 years old from an ambulatory ENT practice in Strasbourg, France, between 2013 and 2020. Digital otoscopic images were obtained using a smartphone-attached otoscope (Smart Scope, Karl Storz, Germany) and labeled by a senior ENT specialist across 11 diagnostic classes (reference standard). An Inception-v2 DL model was trained using 41,664 otoscopic images, and its diagnostic accuracy was evaluated by calculating class-specific estimates of sensitivity and specificity. The model was then incorporated into a smartphone app called i-Nside. The DL model was evaluated on a validation set of 3,962 images and a held-out test set comprising 326 images. On the validation set, all class-specific estimates of sensitivity and specificity exceeded 98%. On the test set, the DL model achieved a sensitivity of 99.0% (95% confidence interval: 94.5–100) and a specificity of 95.2% (91.5–97.6) for the binary classification of normal vs. abnormal images; wax plugs were detected with a sensitivity of 100% (94.6–100) and specificity of 97.7% (95.0–99.1); other class-specific estimates of sensitivity and specificity ranged from 33.3% to 92.3% and 96.0% to 100%, respectively. We present an end-to-end DL-enabled system able to achieve expert-level diagnostic accuracy for identifying normal tympanic aspects and wax plugs within digital otoscopic images. However, the system’s performance varied for other middle-ear conditions. Further prospective validation is necessary before wider clinical deployment.
Hetero-oligomerization of TDP-43 carboxy-terminal fragments with cellular proteins contributes to proteotoxicity
Authors: Kitamura Akira , Fujimoto Ai , Kawashima Rei , Lyu Yidan , Sasaki Kotetsu , Hamada Yuta , Moriya Kanami , Kurata Ayumi , Takahashi Kazuho , Brielmann Reneé , Bott Laura C. , Morimoto Richard I. , Kinjo Masataka
Published: June 2024

Carboxy terminal fragments (CTFs) of TDP-43 contain an intrinsically disordered region (IDR) and form cytoplasmic condensates containing amyloid fibrils. Such condensates are toxic and associated with pathogenicity in amyotrophic lateral sclerosis. However, the molecular details of how the domain of TDP-43 CTFs leads to condensation and cytotoxicity remain elusive. Here, we show that truncated RNA/DNA-recognition motif (RRM) at the N-terminus of TDP-43 CTFs leads to the structural transition of the IDR, whereas the IDR itself of TDP-43 CTFs is difficult to assemble even if they are proximate intermolecularly. Hetero-oligomers of TDP-43 CTFs that have recruited other proteins are more toxic than homo-oligomers, implicating loss-of-function of the endogenous proteins by such oligomers is associated with cytotoxicity. Furthermore, such toxicity of TDP-43 CTFs was cell-nonautonomously affected in the nematodes. Therefore, misfolding and oligomeric characteristics of the truncated RRM at the N-terminus of TDP-43 CTFs define their condensation properties and toxicity.
Dorsomorphin inhibits AMPK, upregulates Wnt and Foxo genes and promotes the activation of dormant follicles
Authors: Madsen Julie Feld , Ernst Emil Hagen , Amoushahi Mahboobeh , Dueholm Margit , Ernst Erik , Lykke-Hartmann Karin
Published: June 2024

AMPK is a well-known energy sensor regulating cellular metabolism. Metabolic disorders such as obesity and diabetes are considered detrimental factors that reduce fecundity. Here, we show that pharmacologically induced in vitro activation (by metformin) or inhibition (by dorsomorphin) of the AMPK pathway inhibits or promotes activation of ovarian primordial follicles in cultured murine ovaries and human ovarian cortical chips. In mice, activation of primordial follicles in dorsomorphin in vitro-treated ovaries reduces AMPK activation and upregulates Wnt and FOXO genes, which, interestingly, is associated with decreased phosphorylation of β-catenin. The dorsomorphin-treated ovaries remain of high quality, with no detectable difference in reactive oxygen species production, apoptosis or mitochondrial cytochrome c oxidase activity, suggesting safe activation. Subsequent maturation of in vitro-treated follicles, using a 3D alginate cell culture system, results in mature metaphase eggs with protruding polar bodies. These findings demonstrate that the AMPK pathway can safely regulate primordial follicles by modulating Wnt and FOXO genes, and reduce β-catenin phosphorylation.