bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving human sperm motility via red and near-infrared laser irradiation: in-vitro study
Authors: Ahmed Rasha , Hamdy Omnia , Elattar Shaimaa , Soliman Amany Ahmed 
Published: January 2024

AbstractImproved sperm motility is necessary for successful sperm passage through the female genital system, efficacious fertilization, and a greater probability of pregnancy. By stimulating the mitochondrial respiratory chain, low-level laser photobiomodulation has been shown to increase sperm motility and velocity. The respiratory chain in mitochondria is the primary site of action for cytochrome c oxidase because it can absorb light in the visible and infrared ranges. The present study aimed to investigate the effects of red laser 650 nm, near infrared laser (NIR) 980 nm, and combination of both on human spermatozoa motility and DNA integrity at different doses. An in-vitro controlled trial was performed in Al Zahraa university hospital laboratory using thirty fresh human semen specimens. Samples were exposed to red laser 650 nm, near infrared laser (NIR) 980 nm, and combination of both for various irradiation times. Sperm motility for the test and control aliquots was assessed as recommended in the manual of WHO-2021. Sperm chromatin integrity was evaluated using the Sperm Chromatin Structure Assay. Results revealed almost 70%, 80% and 100% increase in the total motility after 3 min of the 650-nm, 980-nm and the combined laser irradiation, respectively. Additionally, the Sperm Chromatin Dispersion assay was carried out on sperm heads utilizing human sperm DNA fragmentation, demonstrating that none of the three laser types had any discernible effects.
Graphical abstract
Sicily and the Hellenistic Mediterranean World
Authors: Walthall D. Alex 
Published: January 2024

In Sicily and the Hellenistic Mediterranean World, D. Alex Walthall investigates the royal administration of Hieron II (r. 269-215 BCE), the Syracusan monarch who leveraged Sicily's agricultural resources to build a flourishing kingdom that, at one time, played an outsized role in the political and cultural affairs of the Western Mediterranean. Walthall's study combines an historical overview with the rich archaeological evidence that traditionally has not been considered in studies of Hellenistic kingdoms. Exploring the Hieronian system of agricultural taxation, he recasts the traditional narrative of the island's role as a Roman imperial 'grain basket' via analysis of monumental granaries, patterns of rural land-use, standardized grain measures, and the circulation of bronze coinage— the material elements of an agricultural administration that have emerged from recent excavations and intensive landscape survey on the island. Combining material and documentary evidence, Walthall's multi-disciplinary approach offers a new model for the writing of economic and social history of ancient societies.
Quantifying Interseismic Volume Strain from Chemical Mass‐Balance Analysis in Tectonic Mélanges
Authors: Chen T.‐W. , Smye A. , Fisher D. , Hashimoto Y. , Raimbourg H. , Famin V. 
Published: January 2024

AbstractEstimating interseismic deformation in subduction fault zones can offer insights into the frequency and magnitude of megathrust earthquakes. Diffusive mass transfer is a significant mechanism of strain during interseismic periods along the plate interface, observed through the pervasive scaly fabrics and mineral veins in tectonic mélanges of ancient accretionary prisms. The dissolution of fluid‐mobile elements (e.g., Si and Large‐Ion Lithophile Elements) along scaly folia and subsequent reprecipitation as veins lead to the enrichment of fluid‐immobile elements (e.g., Ti and High Field Strength Elements) in scaly fabrics. The kinetics of dissolution‐precipitation is temperature‐dependent, suggesting depth‐dependent mass transfer along subduction interfaces. Here, we evaluate the magnitudes of volume strain in a suite of mélange samples that span peak metamorphic temperatures of 130–340°C. Micro‐chemical analysis shows that the depletion of fluid‐mobile elements and enrichment of fluid‐immobile elements in scaly fabrics increases with temperature. Assuming the conservation of Ti, we apply mass balance constraints to calculate the volumetric strain in scaly fabrics. Results indicate average volumetric strain of 28% and 95% in the individual scaly fabrics of the Lower Mugi and Makimine mélanges in Japan, which record temperatures near the updip and downdip isotherms bounding the seismogenic zone, respectively. To determine the total volume strain within an area of interest, we integrate the amount of volume loss along individual microstructures across the network using image analyses, which ranges from 3% to 14% for the mélanges. Our approach demonstrates the potential to fully describe the deformation related to mass transfer by connecting characterization in different scales with geochemical analyses.
Long‐Term Landslide Evolution and Restoration After the Wenchuan Earthquake Revealed by Time‐Series Remote Sensing Images
Authors: Wang Xin , Fan Xuanmei , Fang Chengyong , Dai Lanxin , Zhang Wei , Zheng Hongrui , Xu Qiang 
Published: January 2024

AbstractA powerful earthquake, particularly in mountainous regions, has the ability to trigger an immense number of landslides, resulting in severe damages. However, effectively assessing their recoveries in the years following the mainshocks has not yet been attempted due to the lack of continuously updated landslide inventories. Therefore, we proposed a novel detection framework utilizing time‐series Landsat images from 2000 to 2021, which enabled us to achieve a long‐term landslide inventory in the seismic zone for the first time. The response patterns of landslide development under different conditions were explored in detail. The restoration models were quantitatively established, revealing that the recoveries of post‐earthquake landslide activity and vital environmental indicators require a range from ∼5.29 to ∼25.00 years. This pioneering research is highly beneficial in comprehending the impact of earthquake‐induced hazards on short‐term land surface damage and long‐term ecological equilibrium.
The Response of Surface Temperature Persistence to Arctic Sea‐Ice Loss
Authors: Lewis Neil T. , Seviour William J. M. , Roberts‐Straw Hannah E. , Screen James A. 
Published: January 2024

AbstractWe investigate the response of surface temperature persistence, quantified using a lagged autocorrelation, to imposed Arctic sea‐ice loss in coupled model experiments. Sea‐ice loss causes increases in persistence over ocean in midlatitudes and the low‐Arctic, which are of a similar magnitude to the total response to climate change in these regions. Using an idealized model, we show that sea‐ice loss induces a slowing of meridional wind anomalies, which can drive the midlatitude persistence increase obtained in coupled models. Sea‐ice loss should induce persistence increases in the Arctic, through its effect on the surface heat capacity. However, in coupled models with imposed sea‐ice loss, persistence increase in the Arctic is essentially absent. We suggest that methods used to constrain sea‐ice in coupled models may spuriously reduce the effects of sea‐ice loss on persistence.
Time‐Dependent Role of Multiyear La Niña in Impacting the Pacific Tropical Instability Waves
Authors: He Wei‐Bang , Yang Yang , Liang X. San 
Published: January 2024

AbstractPrevious studies have shown that the tropical instability waves (TIWs) in the Equatorial Pacific are enhanced during La Niña and suppressed during El Niño. Unlike El Niño which tends to decay quickly, La Niña often persists through the subsequent one or 2 years, becoming a multiyear La Niña. Using a time‐dependent and space‐localized energetics formalism and a suite of observational and reanalysis data, we found that the eddy kinetic energy (EKE) associated with TIWs only peaks during the first‐year La Niña and decreases significantly during the second‐year La Niña. This is caused, to the first order, by the weaker equatorial cold tongue near the equator and anomalous cooling in the off‐equator regions during the second‐year La Niña, as compared to the first‐year La Niña, which leads to a significant decrease in meridional density shear, and thus a reduction in baroclinic instability. Meanwhile, the weakened South Equatorial Current during the second‐year La Niña also contribute to EKE decrease by transferring less kinetic energy to the TIWs via barotropic instability. The meridionally broad spatial pattern of negative temperature anomalies during the second‐year La Niña is the major reason for the weakened TIW activity.
Novel exosomal circEGFR facilitates triple negative breast cancer autophagy via promoting TFEB nuclear trafficking and modulating miR-224-5p/ATG13/ULK1 feedback loop
Authors: Song Huachen , Zhao Zitong , Ma Liying , Zhao Weihong , Hu Yi , Song Yongmei 
Published: January 2024

AbstractTriple-negative breast cancer (TNBC) cells are in a more hypoxic and starved state than non-TNBC cells, which makes TNBC cells always maintain high autophagy levels. Emerging evidence has demonstrated that circular RNAs (circRNAs) are involved in the progress of tumorigenesis. However, the regulation and functions of autophagy-induced circRNAs in TNBC remain unclear. In our study, autophagy-responsive circRNA candidates in TNBC cells under amino acid starved were identified by RNA sequencing. The results showed that circEGFR expression was significantly upregulated in autophagic cells. Knockdown of circEGFR inhibited autophagy in TNBC cells, and circEGFR derived from exosomes induced autophagy in recipient cells in the tumor microenvironment. In vitro and in vivo functional assays identified circEGFR as an oncogenic circRNA in TNBC. Clinically, circEGFR was significantly upregulated in TNBC and was positively associated with lymph node metastasis. CircEGFR in plasma-derived exosomes was upregulated in breast cancer patients compared with healthy people. Mechanistically, circEGFR facilitated the translocation of Annexin A2 (ANXA2) toward the plasma membrane in TNBC cells, which led to the release of Transcription Factor EB (a transcription factor of autophagy-related proteins, TFEB) from ANXA2-TFEB complex, causing nuclear translocation of TFEB, thereby promoting autophagy in TNBC cells. Meanwhile, circEGFR acted as ceRNA by directly binding to miR-224-5p and inhibited the expression of miR-224-5p, which weakened the suppressive role of miR-224-5p/ATG13/ULK1 axis on autophagy. Overall, our study demonstrates the key role of circEGFR in autophagy, malignant progression, and metastasis of TNBC. These indicate circEGFR is a potential diagnosis biomarker and therapeutic target for TNBC.
Cerebrovascular responses to a 90° tilt in healthy neonates
Authors: Tran Nhu N. , Chwa Jason S. , Brady Kenneth M. , Borzage Matthew , Brecht Mary-Lynn , Woon Jessica X. , Miner Anna , Merkel Carlin A. , Friedlich Philippe , Peterson Bradley S. , Wood John C. 
Published: January 2024

Abstract
Background
Tilts can induce alterations in cerebral hemodynamics in healthy neonates, but prior studies have only examined systemic parameters or used small tilt angles (<90°). The healthy neonatal population, however, are commonly subjected to large tilt angles (≥90°). We sought to characterize the cerebrovascular response to a 90° tilt in healthy term neonates.

Methods
We performed a secondary descriptive analysis on 44 healthy term neonates. We measured cerebral oxygen saturation (rcSO2), oxygen saturation (SpO2), heart rate (HR), breathing rate (BR), and cerebral fractional tissue oxygen extraction (cFTOE) over three consecutive 90° tilts. These parameters were measured for 2-min while neonates were in a supine (0°) position and 2-min while tilted to a sitting (90°) position. We measured oscillometric mean blood pressure (MBP) at the start of each tilt.

Results
rcSO2 and BR decreased significantly in the sitting position, whereas cFTOE, SpO2, and MBP increased significantly in the sitting position. We detected a significant position-by-time interaction for all physiological parameters.

Conclusion
A 90° tilt induces a decline in rcSO2 and an increase in cFTOE in healthy term neonates. Understanding the normal cerebrovascular response to a 90° tilt in healthy neonates will help clinicians to recognize abnormal responses in high-risk infant populations.

Impact

Healthy term neonates (≤14 days old) had decreased cerebral oxygen saturation (~1.1%) and increased cerebral oxygen extraction (~0.01) following a 90° tilt.

We detected a significant position-by-time interaction with all physiological parameters measured, suggesting the effect of position varied across consecutive tilts.

No prior study has characterized the cerebral oxygen saturation response to a 90° tilt in healthy term neonates.
Multiomic analysis implicates nuclear hormone receptor signalling in clustering epilepsy
Authors: de Nys Rebekah , van Eyk Clare L. , Ritchie Tarin , Møller Rikke S. , Scheffer Ingrid E. , Marini Carla , Bhattacharjee Rudrarup , Kumar Raman , Gecz Jozef 
Published: January 2024

AbstractClustering Epilepsy (CE) is an epileptic disorder with neurological comorbidities caused by heterozygous variants of the X chromosome gene Protocadherin 19 (PCDH19). Recent studies have implicated dysregulation of the Nuclear Hormone Receptor (NHR) pathway in CE pathogenesis. To obtain a comprehensive overview of the impact and mechanisms of loss of PCDH19 function in CE pathogenesis, we have performed epigenomic, transcriptomic and proteomic analysis of CE relevant models. Our studies identified differential regulation and expression of Androgen Receptor (AR) and its targets in CE patient skin fibroblasts. Furthermore, our cell culture assays revealed the repression of PCDH19 expression mediated through ERα and the co-regulator FOXA1. We also identified a protein-protein interaction between PCDH19 and AR, expanding upon the intrinsic link between PCDH19 and the NHR pathway. Together, these results point to a novel mechanism of NHR signaling in the pathogenesis of CE that can be explored for potential therapeutic options.
Identification of novel molecular subtypes to improve the classification framework of nasopharyngeal carcinoma
Authors: Lin Wanzun , Chen Xiaochuan , Huang Zongwei , Ding Qin , Yang Hanxuan , Li Ying , Lin Duo , Lin Jun , Zhang Haojiong , Yang Xuelian , Li Chao , Chen Chuanben , Qiu Sufang 
Published: January 2024

AbstractBackgroundNasopharyngeal carcinoma (NPC) treatment is largely based on a ‘one-drug-fits-all’ strategy in patients with similar pathological characteristics. However, given its biological heterogeneity, patients at the same clinical stage or similar therapies exhibit significant clinical differences. Thus, novel molecular subgroups based on these characteristics may better therapeutic outcomes.MethodsHerein, 192 treatment-naïve NPC samples with corresponding clinicopathological information were obtained from Fujian Cancer Hospital between January 2015 and January 2018. The gene expression profiles of the samples were obtained by RNA sequencing. Molecular subtypes were identified by consensus clustering. External NPC cohorts were used as the validation sets.ResultsPatients with NPC were classified into immune, metabolic, and proliferative molecular subtypes with distinct clinical features. Additionally, this classification was repeatable and predictable as validated by the external NPC cohorts. Metabolomics has shown that arachidonic acid metabolites were associated with NPC malignancy. We also identified several key genes in each subtype using a weighted correlation network analysis. Furthermore, a prognostic risk model based on these key genes was developed and was significantly associated with disease-free survival (hazard ratio, 1.11; 95% CI, 1.07–1.16;P < 0.0001), which was further validated by an external NPC cohort (hazard ratio, 7.71; 95% CI, 1.39–42.73;P < 0.0001). Moreover, the 1-, 3-, and 5-year areas under the curve were 0.84 (95% CI, 0.74–0.94), 0.81 (95% CI, 0.73–0.89), and 0.82 (95% CI, 0.73–0.90), respectively, demonstrating a high predictive value.ConclusionsOverall, we defined a novel classification of nasopharyngeal carcinoma (immune, metabolism, and proliferation subtypes). Among these subtypes, metabolism and proliferation subtypes were associated with advanced stage and poor prognosis of NPC patients, whereas the immune subtype was linked to early stage and favorable prognosis.
TRPM8 inhibits substance P release from primary sensory neurons via PKA/GSK-3beta to protect colonic epithelium in colitis
Authors: Zhang Zehua , Yan Xiaohan , Kang Le , Leng Zhuyun , Ji Yingjie , Yang Shuangzhu , Du Xiaojing , Fang Kang , Wang Zeyu , Li Zhaoxing , Sun Mingchuang , Zhao Ziying , Feng Anqi , Chen Zhukai , Zhang Shihan , Wan Dong , Chen Tao , Xu Meidong 
Published: January 2024

AbstractTransient receptor potential melastatin 8 (TRPM8) is a cold sensory receptor in primary sensory neurons that regulates various neuronal functions. Substance P (SP) is a pro-inflammatory neuropeptide secreted by the neurons, and it aggravates colitis. However, the regulatory role of TRPM8 in SP release is still unclear. Our study aimed to investigate TRPM8’s role in SP release from primary sensory neurons during colitis and clarify the effect of SP on colonic epithelium. We analyzed inflammatory bowel disease patients’ data from the Gene Expression Omnibus dataset. Dextran sulfate sodium (DSS, 2.5%)-induced colitis in mice, mouse dorsal root ganglion (DRG) neurons, ND7/23 cell line, and mouse or human colonic organoids were used for this experiment. Our study found that TRPM8, TAC1 and WNT3A expression were significantly correlated with the severity of ulcerative colitis in patients and DSS-induced colitis in mice. The TRPM8 agonist (menthol) and the SP receptor antagonist (Aprepitant) can attenuate colitis in mice, but the effects were not additive. Menthol promoted calcium ion influx in mouse DRG neurons and inhibited the combination and phosphorylation of PKAca from the cAMP signaling pathway and GSK-3β from the Wnt/β-catenin signaling pathway, thereby inhibiting the effect of Wnt3a-driven β-catenin on promoting SP release in ND7/23 cells. Long-term stimulation with SP inhibited proliferation and enhanced apoptosis in both mouse and human colonic organoids. Conclusively, TRPM8 inhibits SP release from primary sensory neurons by inhibiting the interaction between PKAca and GSK-3β, thereby inhibiting the role of SP in promoting colonic epithelial apoptosis and relieving colitis.
Caloric restriction leads to druggable LSD1-dependent cancer stem cells expansion
Authors: Pallavi Rani , Gatti Elena , Durfort Tiphanie , Stendardo Massimo , Ravasio Roberto , Leonardi Tommaso , Falvo Paolo , Duso Bruno Achutti , Punzi Simona , Xieraili Aobuli , Polazzi Andrea , Verrelli Doriana , Trastulli Deborah , Ronzoni Simona , Frascolla Simone , Perticari Giulia , Elgendy Mohamed , Varasi Mario , Colombo Emanuela , Giorgio Marco , Lanfrancone Luisa , Minucci Saverio , Mazzarella Luca , Pelicci Pier Giuseppe 
Published: January 2024

AbstractCaloric Restriction (CR) has established anti-cancer effects, but its clinical relevance and molecular mechanism remain largely undefined. Here, we investigate CR’s impact on several mouse models of Acute Myeloid Leukemias, including Acute Promyelocytic Leukemia, a subtype strongly affected by obesity. After an initial marked anti-tumor effect, lethal disease invariably re-emerges. Initially, CR leads to cell-cycle restriction, apoptosis, and inhibition of TOR and insulin/IGF1 signaling. The relapse, instead, is associated with the non-genetic selection of Leukemia Initiating Cells and the downregulation of double-stranded RNA (dsRNA) sensing and Interferon (IFN) signaling genes. The CR-induced adaptive phenotype is highly sensitive to pharmacological or genetic ablation of LSD1, a lysine demethylase regulating both stem cells and dsRNA/ IFN signaling. CR + LSD1 inhibition leads to the re-activation of dsRNA/IFN signaling, massive RNASEL-dependent apoptosis, and complete leukemia eradication in ~90% of mice. Importantly, CR-LSD1 interaction can be modeled in vivo and in vitro by combining LSD1 ablation with pharmacological inhibitors of insulin/IGF1 or dual PI3K/MEK blockade. Mechanistically, insulin/IGF1 inhibition sensitizes blasts to LSD1-induced death by inhibiting the anti-apoptotic factor CFLAR. CR and LSD1 inhibition also synergize in patient-derived AML and triple-negative breast cancer xenografts. Our data provide a rationale for epi-metabolic pharmacologic combinations across multiple tumors.
iPSC-derived models of PACS1 syndrome reveal transcriptional and functional deficits in neuron activity
Authors: Rylaarsdam Lauren , Rakotomamonjy Jennifer , Pope Eleanor , Guemez-Gamboa Alicia 
Published: January 2024

AbstractPACS1 syndrome is a neurodevelopmental disorder characterized by intellectual disability and distinct craniofacial abnormalities resulting from a de novo p.R203W variant in phosphofurin acidic cluster sorting protein 1 (PACS1). PACS1 is known to have functions in the endosomal pathway and nucleus, but how the p.R203W variant affects developing neurons is not fully understood. Here we differentiated stem cells towards neuronal models including cortical organoids to investigate the impact of the PACS1 syndrome-causing variant on neurodevelopment. While few deleterious effects were detected in PACS1(+/R203W)neural precursors, mature PACS1(+/R203W)glutamatergic neurons exhibited impaired expression of genes involved in synaptic signaling processes. Subsequent characterization of neural activity using calcium imaging and multielectrode arrays revealed the p.R203W PACS1 variant leads to a prolonged neuronal network burst duration mediated by an increased interspike interval. These findings demonstrate the impact of the PACS1 p.R203W variant on developing human neural tissue and uncover putative electrophysiological underpinnings of disease.
Generating dual structurally and functionally skin-mimicking hydrogels by crosslinking cell-membrane compartments
Authors: Wu Feng , Ren Yusheng , Lv Wenyan , Liu Xiaobing , Wang Xinyue , Wang Chuhan , Cao Zhenping , Liu Jinyao , Wei Jie , Pang Yan 
Published: January 2024

AbstractThe skin is intrinsically a cell-membrane-compartmentalized hydrogel with high mechanical strength, potent antimicrobial ability, and robust immunological competence, which provide multiple protective effects to the body. Methods capable of preparing hydrogels that can simultaneously mimic the structure and function of the skin are highly desirable but have been proven to be a challenge. Here, dual structurally and functionally skin-mimicking hydrogels are generated by crosslinking cell-membrane compartments. The crosslinked network is formed via free radical polymerization using olefinic double bond-functionalized extracellular vesicles as a crosslinker. Due to the dissipation of stretching energy mediated by vesicular deformation, the obtained compartment-crosslinked network shows enhanced mechanical strength compared to hydrogels crosslinked by regular divinyl monomers. Biomimetic hydrogels also exhibit specific antibacterial activity and adequate ability to promote the maturation and activation of dendritic cells given the existence of numerous extracellular vesicle-associated bioactive substances. In addition, the versatility of this approach to tune both the structure and function of the resulting hydrogels is demonstrated through introducing a second network by catalyst-free click reaction-mediated crosslinking between alkyne-double-ended polymers and azido-decorated extracellular vesicles. This study provides a platform to develop dual structure- and function-controllable skin-inspired biomaterials.