bluuebunny/crossref_metadata_2025_split huggingface dataset:
Position-dependent roles of somatic cells in phototaxis of Volvox
Authors: Harada Keigo , Komasaka Yukariko , Yamada Keisuke , Iizuka Takumi , Otani Minato , Murayama Yoshihiro 
Published: October 2024

Abstract
A spherical green alga, Volvox, achieves phototaxis via a simple on/off switch of flagellar beating in response to changes in light intensity, without the need for complex signal transduction between cells. Moreover, the alga can change its susceptibility to light in order to adapt to its environment. To identify the mechanisms of susceptibility regulation, experiments were conducted at three different levels: population, individual, and cellular. The light intensity dependence of the average velocity at the population level and that of the change in flow speed obtained at the individual level were consistent, indicating that susceptibility regulation occurred in each Volvox colony. Furthermore, by measuring the probability of stopping flagellar beating when the light intensity was changed, susceptibility regulation was found to result from the properties of somatic cells as differential and adaptive photosensors. These photosensing properties deteriorated from the anterior to the posterior regions of the colony. Considering the mechanical motion of a Volvox colony, the position-dependent ability of somatic cells indicates that the anterior cells play the role of a rudder, whereas the posterior cells play the role of a rower. The position-dependent properties of somatic cells imply an early stage of cell differentiation that allows for an efficient response to changes in the circumstances.
Reprogramming with Atoh1, Gfi1, and Pou4f3 promotes hair cell regeneration in the adult organ of Corti
Authors: McGovern Melissa M , Ghosh Sumana , Dupuis Colleen , Walters Bradley J , Groves Andrew K 
Published: October 2024

Abstract
Cochlear hair cells can be killed by loud noises, ototoxic drugs, and natural aging. Once lost, mammalian hair cells do not naturally regenerate, leading to permanent hearing loss. Since the mammalian cochlea lacks any intrinsic ability to regenerate, genetic reprogramming of cochlear supporting cells that lie adjacent to hair cells is a potential option for hearing restoration therapies. We targeted cochlear supporting cells with three hair cell transcription factors: Atoh1, or Atoh1 + Gfi1, or Atoh1 + Gfi1 + Pou4f3 and found that 1- and 2-factor reprogramming is not sufficient to reprogram adult supporting cells into hair cells. However, activation of all three hair cell transcription factors reprogrammed some adult supporting cells into hair cell-like cells. We found that killing endogenous hair cells significantly improved the ability of supporting cells to be reprogrammed and regenerated numerous hair cell-like cells throughout the length of the cochlea. These regenerated hair cell-like cells expressed myosin VIIa and parvalbumin, as well as the mature outer hair cell protein prestin, were innervated, expressed proteins associated with ribbon synapses, and formed rudimentary stereociliary bundles. Finally, we demonstrate that supporting cells remained responsive to transcription factor reprogramming for at least 6 weeks after hair cell damage, suggesting that hair cell reprogramming may be effective in the chronically deafened cochlea.
Mapping uterine calcium dynamics during the ovulatory cycle in live mice
Authors: Combs David J , Moult Eric M , England Sarah K , Cohen Adam E 
Published: October 2024

Abstract
Uterine contraction patterns vary during the ovulatory cycle and throughout pregnancy, but prior measurements have produced limited and conflicting information on these patterns. We combined a virally delivered genetically encoded calcium reporter (GCaMP8m) and ultra-widefield imaging in live nonpregnant mice to characterize uterine calcium dynamics at organ scale throughout the estrous cycle. Prior to ovulation (proestrus and estrus), uterine excitations primarily initiated in a region near the oviduct, but after ovulation (metestrus and diestrus), excitations initiated at loci homogeneously distributed throughout the organ. The frequency of excitation events was lowest in proestrus and estrus, higher in metestrus, and highest in diestrus. These results establish a platform for mapping uterine activity and demonstrate that an anatomically localized trigger for uterine excitations depends on the estrous cycle phase.
Do stress hormones influence choice? A systematic review of pharmacological interventions on the HPA axis and/or SAM system
Authors: Sarmiento Luis Felipe , Ríos-Flórez Jorge Alexander , Rincón Uribe Fabio Alexis , Rodrigues Lima Rafael , Kalenscher Tobias , Gouveia Amauri , Nitsch Felix Jan 
Published: October 2024

Abstract
The hypothalamus–pituitary–adrenal axis (HPA axis) and the sympathetic–adrenal–medullary system (SAM system), two neuroendocrine systems associated with the stress response, have often been implicated to modulate decision-making in various domains. This systematic review summarizes the scientific evidence on the effects of pharmacological HPA axis and SAM system modulation on decision-making. We found 6375 references, of which 17 studies fulfilled our inclusion criteria. We quantified the risk of bias in our results with respect to missing outcome data, measurements, and selection of the reported results. The included studies administered hydrocortisone, fludrocortisone (HPA axis stimulants), yohimbine, reboxetine (SAM system stimulants), and/or propranolol (SAM system inhibitor). Integrating the evidence, we found that SAM system stimulation had no impact on risk aversion, loss aversion or intertemporal choice, while SAM system inhibition showed a tentative reduction in sensitivity to losses. HPA axis stimulation had no effect on loss aversion or reward anticipation but likely a time-dependent effect on decision under risk. Lastly, combined stimulation of both systems exhibited inconsistent results that could be explained by dose differences (loss aversion) and sex differences (risk aversion). Future research should address time-, dose-, and sex-dependencies of pharmacological effects on decision-making.
Role of bone marrow mesenchymal stem cell-derived exosomes in reducing neurotoxicity and depression-like behaviors induced by doxorubicin in rats
Authors: Abdel-Gawad Doaa R I , Khalil Fatma , Shehata Olfat , Ibrahim Marwa A , El-Samannoudy SalmaI , Mahdi Emad A , Shaban Nema S 
Published: October 2024

AbstractBackgroundDoxorubicin (DOX) is a broad-spectrum antitumor drug while its use is limited nowadays due to its neurobiological side effects associated with depression. Bone marrow mesenchymal stem cells (BM-MSCs) derived exosomes are a promising regenerative therapy. In this study, we investigated the therapeutic potentiality of BM-MSCs derived exosomes against the neurotoxicity induced by DOX.MethodsTwenty-four male albino rats were divided equally in to three groups as follow: group 1 (control), group 2 (rats injected intraperitoneally (i.p|) with DOX at a dose 2.5mg/Kg), and group 3 (rats injected with DOX and BM-MSCs derived exosomes i.p at a dose 1.5ml/Kg). During the experiment the behavior tests were noted, after three weeks rats were sacrificed, serum and brain samples were collected for biochemical, molecular and histopathological examinations.ResultsThe results revealed that DOX causing impairment of the locomotor and increasing the anxiety like behavior of rats, marked neuropathological changes, significant elevation of MDA content and TNF-α concentration, reduction of phospholipase (PLD) and acetylcholinesterase (AChE) protein concentration in addition, there were up regulation of JNK, NF-κB and p38 genes and down regulation of Erk1.ConclusionExosomal therapy improved the substantial neurotoxicity of DOX through modulating the markers involved in the neurotoxic signalling pathway of DOX that resulting in improving the pathological lesions and the animal behaviours.
“Exploring therapeutic potential and toxicological profiles of Cuscuta species: insights from pharmacological studies and an anti-cholinergic toxicity report.”
Authors: Bhandare Saurabh Dilip 
Published: October 2024

Abstract
This study examines the therapeutic potential and toxicological profiles of Cuscuta species based on recent pharmacological investigations: “a therapeutic potential vs. toxicological risks of Cuscuta species: a pharmacological-toxicology dilemma.” The study encompasses diverse research areas, including the mitigation of Bisphenol A (BPA)-induced ovarian damage using Cuscuta chinensis flavonoids (CCFs), acute and sub-acute toxicity assessments of Cuscuta chinensis Lam. water extract (CLW), and observations on Cuscuta campestris toxicity in horses. In addition, this scientific study discusses the interplant communication dynamics between soybean and the parasitic dodder (Cuscuta australis) under nutrient deficiency conditions. Key significant findings highlight the efficacy of CCFs in alleviating BPA-induced ovarian damage, the safety profile of CLW within specified doses, and clinical manifestations of C. campestris toxicity in horses. Moreover, insights into interplant communication mechanisms emphasise the significance of protein-mediated interactions in nutrient-deficient environments. The report illustrates the potential toxicity of Dodder in humans, and further research findings into its chemical composition and toxicological profiles reveal great data on its phytotoxicity. Greater awareness and understanding of the risks associated with consuming Dodder and other similar plant species are crucial for preventing plant intoxication and have been a significant major focus of the present toxicology study of Cuscuta species. Hence, by addressing these objectives, the scientific study aims to balance the therapeutic benefits of Cuscuta species with their potential toxicological risks, contributing to a more nuanced understanding of their role in pharmacology and toxicology. This dual focus is crucial for guiding future research and informing safe usage practices.
Di(2-ethylhexyl) phthalate exposure aggravates hypoxia/reoxygenation injury in cerebral endothelial cells by downregulating epithelial cadherin expression
Authors: Kim Jin Hee , Lee Jae Hoon , Nan Zhengyu , Choi Ja Woo , Song Jong Wook 
Published: October 2024

Abstract
Di-(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer that has adverse health effects. Most phthalates exhibit reproductive toxicity and are associated with diseases such as cardiovascular disorders. However, the effect of DEHP exposure on acute hypoxia/reperfusion injury remains unknown. Therefore, we assessed whether hypoxia/reperfusion injury is aggravated by exposure to DEHP and investigated plausible underlying mechanisms, including oxidative stress and expression of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) and endothelial junctional proteins. bEnd.3 cells were exposed to DEHP and subsequently subjected to oxygen–glucose deprivation (OGD). Cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) proliferation assay. The effect of DEHP/OGD/reoxygenation (R) was evaluated by assessing the levels of NO, reactive oxygen species (ROS), and PGE2. The expression of COX-2, cleaved caspase-3, cleaved PARP, inducible nitric oxide synthase (iNOS), and the endothelial tight junction proteins claudin-5 and ZO-1 was evaluated using quantitative polymerase chain reaction and western blotting. OGD/R decreased cell viability, and DEHP exposure before OGD/R further aggravated cell viability. DEHP/OGD/R significantly increased NO, PGE2, and ROS production following OGD/R. In the DEHP/OGD/R group, iNOS, COX-2, cleaved caspase-3, and cleaved PARP expression increased, and claudin-5 and ZO-1 levels decreased compared with those in the OGD/R group. E-Cadherin expression decreased significantly after DEHP/OGD/R exposure compared with that after OGD/R; this decrease in expression was recovered by treatment with the COX-2 inhibitor indomethacin and antioxidant N-acetylcysteine. Exposure to DEHP exacerbated hypoxia-reoxygenation injury. The enhanced damage upon DEHP exposure was associated with increased oxidative stress and COX-2 expression, leading to E-cadherin downregulation and increased apoptosis.
A High-Quality Genome Resource for the Oak Wilt Pathogen Bretziella fagacearum
Authors: Chahal Karandeep , Mahey Mohit , Medina-Mora Carmen , Ahrendt Steven , Riley Robert , Lipzen Anna , Yan Juying , Savage Emily , Koriabine Maxim , Ng Vivian , Grigoriev Igor V. , Harrington Thomas C. , Patterson Eric L. , Miles Timothy D. , Sakalidis Monique L. 
Published: October 2024

Bretziella fagacearum is a destructive vascular wilt fungal pathogen affecting oaks in the United States and Canada. The epidemiology of oak wilt varies across different geographical locations, indicating the need to investigate the population dynamics of B. fagacearum to discern potential differences in its genotypes using genomic tools. A good-quality genome of B. fagacearum is crucial as a reference for population genetics studies. Here, we report a high-quality genome of B. fagacearum isolate C519. The genome assembly consists of nine scaffolds, corresponding to the nine chromosomes, totaling 27,072,536 bp with a GC content of 47.29%. It is predicted to encode 7,554 proteins, which are annotated using RNA sequencing data from the same isolate. The circular mitochondrial genome consists of a chromosome of 174,403 bp with a GC content of 28.59% and contains 54 open reading frames, including 14 core genes, 28 tRNAs, 4 rRNAs, and 8 hypothetical proteins. The reference genome can enhance the understanding of molecular epidemiology and biology of B. fagacearum, aiding in identifying genetic variations and pathogen–host interactions and developing diagnostic tools and disease management strategies. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2025.
Emc1 is essential for vision and zebrafish photoreceptor outer segment morphogenesis
Authors: McCann Tess , Sundaramurthi Husvinee , Walsh Ciara , Virdi Sanamjeet , Alvarez Yolanda , Sapetto‐Rebow Beata , Collery Ross F. , Carter Stephen P. , Moran Ailis , Mulholland Ruth , O'Connor John J. , Taylor Michael R. , Rauch Nora , Starostik Margaret R. , English Milton A. , Swaroop Anand , Geisler Robert , Reynolds Alison L. , Kennedy Breandán N. 
Published: October 2024

AbstractInherited retinal diseases (IRDs) are a rare group of eye disorders characterized by progressive dysfunction and degeneration of retinal cells. In this study, we characterized the raifteirí (raf) zebrafish, a novel model of inherited blindness, identified through an unbiased ENU mutagenesis screen. A mutation in the largest subunit of the endoplasmic reticulum membrane protein complex, emc1 was subsequently identified as the causative raf mutation. We sought to elucidate the cellular and molecular phenotypes in the emc1−/− knockout model and explore the association of emc1 with retinal degeneration. Visual behavior and retinal electrophysiology assays demonstrated that emc1−/− mutants had severe visual impairments. Retinal histology and morphometric analysis revealed extensive abnormalities, including thinning of the photoreceptor layer, in addition to large gaps surrounding the lens. Notably, photoreceptor outer segments were drastically smaller, outer segment protein expression was altered and hyaloid vasculature development was disrupted. Transcriptomic profiling identified cone and rod‐specific phototransduction genes significantly downregulated by loss of emc1. These data shed light on why emc1 is a causative gene in inherited retinal disease and how outer segment morphogenesis is regulated.
Immunotherapy and new treatments
Authors: Jakymec Yaroslav Andrew , Greiwe Justin , Bernstein Jonathan A. 
Published: October 2024

Purpose of review
This review comes at a time where new techniques in immunotherapy administration are being developed, new innovations are being incorporated to standard techniques, and new regulations are being adopted regarding the creation and storage of allergen extracts. Prior to the release of updated practice parameters regarding allergic rhinitis and immunotherapies, this review article provides a synopsis of current recommendations, a comparison of the practices in the United States and those of Europe, and an examination of experimental methods that are being studied.

Recent findings
This article seeks to review and discuss the various methods of administration, build up schedules, efficacy, effect on other atopic symptoms, and safety associated with allergen immunotherapy.

Summary
Innovations in standard techniques, such as new allergoids for SCIT, appear to be effective in improving symptoms and increasing IgG levels for grass allergens. Data for newer techniques is less clear. There appears to be increased treatment-related adverse events for ILIT, worse symptom scores compared with placebo for IDIT, and insufficient studies regarding the effectiveness of EPIT for aeroallergens. New regulations seek to standardize the documentation, storage, and creation of allergen extracts.
Risk of Venous Thromboembolism in Adolescents Undergoing Pelvic Osteotomy: Insights From a Propensity-matched Retrospective Cohort Study
Authors: Mittal Mehul M. , Lee Tiffany M. , Acevedo Katalina V. , Hosseinzadeh Pooya 
Published: October 2024

Background:
Pelvic osteotomies are surgical procedures that are commonly performed in adolescents and young adults to improve stability or correct various deformities. Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), are dreaded complications of any major procedure including pelvic osteotomies. Unlike adults, the incidence of DVT and need for prophylactic measures are not well understood in the adolescents. The purpose of this study is to understand the need for VTE prophylaxis in adolescents and determine if their risk profile aligns with adults, who have more established VTE prophylactic guidelines in place for these surgeries.

Methods:
This retrospective cohort study utilized data from the TriNetX Research Network, which includes records from over 80 healthcare organizations and more than 120 million patients. De-identified patient data from January 1, 2003, to March 1, 2024, were extracted using relevant ICD-9 and ICD-10 procedural codes. The study included 2 cohorts: patients aged 13 to 17 years (adolescents) and patients 18 years and older (adults) who underwent pelvic osteotomies. To control for confounding variables, propensity score matching was employed based on sex and relevant comorbidities, including diabetes mellitus, tobacco use, and overweight/obesity. Statistical significance was set at P<0.01.

Results:
A total of 2374 patients successfully matched in each cohort. Within 90 days following surgical intervention, adult patients had overall risks of 4.5%, 1.9%, and 5.9%, whereas adolescent patients had overall risks of 1.3%, 0.5%, and 1.4% for DVT (RR: 3.419), PE (RR: 4.182), and either DVT or PE (RR: 4.118), respectively.

Conclusions:
This study examines the rate of VTE in a large cohort of adolescents undergoing pelvic osteotomies. Although we found the rates to be lower in adolescents compared with adults, the high absolute risk in adolescents—above 1%, the threshold established in the literature for considering prophylaxis—underscores the need for tailored risk stratification strategies and targeted thromboprophylaxis protocols for this population.

Levels of Evidence:
Level III: case-control study or retrospective cohort study.
Therapeutic Potential of Mesenchymal Stem Cell–Derived Extracellular Vesicles Carrying MicroRNAs for Modulating Autophagy and Cellular Degeneration in Intervertebral Disc Degeneration
Authors: Wang LinFeng , Wang Yang , Jiao Jianhang , Jiang Weibo , Yu Tong , Wang Zhonghan , Li Mufeng , Wu Minfei , Pan Su 
Published: October 2024

Study Design.
This research utilized bioinformatics and in vitro modeling to assess the effects of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) containing specific microRNAs (miRNAs) on the autophagy and degeneration of nucleus pulposus cells in intervertebral disc degeneration (IDD).

Objective.
To determine the therapeutic potential of MSC-EVs loaded with miRNAs in modulating pathologic changes in IDD.

Background.
IDD is characterized by changes in gene expression that contribute to cell degeneration and reduced disc integrity. MSC-EVs are known for their role in cellular communication and potentially reversing these degenerative processes.

Materials and Methods.
Key differentially expressed miRNAs and mRNAs in MSC-EVs were identified using bioinformatics analysis. Three miRNAs (miR-486-5p, miR-3648, and miR-1827) typically downregulated in IDD were selected for further study. The bone marrow-derived MSC-EVs used in this study were cultured in a two-dimensional environment. These MSC-EVs were isolated with the purpose of delivering the selected miRNAs to IDD nucleus pulposus cells in vitro, targeting specifically the upregulated genes (SMAD2, ESR1, MAVS, and MMP14) associated with autophagy and degeneration.

Results.
MSC-EV treatment led to significant downregulation of target genes, enhanced cellular proliferation, and decreased apoptosis and autophagy. Overexpression of these target genes produced the opposite effects, confirming the miRNAs’ regulatory roles.

Conclusions.
MSC-EVs carrying specific miRNAs can effectively modulate gene expression, reduce degenerative processes, and promote cellular proliferation in IDD, indicating a promising therapeutic strategy for treating IDD and potentially other degenerative diseases. Further investigations are warranted to explore MSC-EV applications in regenerative medicine.