bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ferroptosis is involved in deoxynivalenol-induced intestinal damage in pigs
Authors: Liu Meng , Zhang Lei , Mo Yixin , Li Jiahuan , Yang Jiacheng , Wang Juan , Karrow Niel Alexander , Wu Hao , Sun Lvhui 
Published: March 2023

Abstract
Background
Deoxynivalenol (DON) is a widespread issue for feed and food safety, leading to animal and human health risks. The objective of this study was to determine whether ferroptosis is involved in DON-induced intestinal injury in piglets. Three groups of 21-day-old male weanling piglets (n = 7/group) were fed a control diet, or diet adding 1.0 or 3.0 mg DON/kg. At week 4, serum and small intestines were collected to assay for biochemistry, histology, redox status and ferroptosis-related genes expression. In addition, the involvement of ferroptosis and the role of FTL gene in DON-induced cell death were further verified in the IPEC-J2 cells.

Results
Compared to the control, dietary supplementation of DON at 1.0 and 3.0 mg/kg induced different degrees of damage in the duodenum, jejunum and ileum, and increased (P < 0.05) serum lipopolysaccharide concentration by 46.2%–51.4%. Dietary DON supplementation at 1.0 and (or) 3.0 mg/kg increased (P < 0.05) concentrations of malondialdehyde (17.4%–86.5%) and protein carbonyl by 33.1%–92.3% in the duodenum, jejunum and ileum. In addition, dietary supplemented with DON upregulated (P < 0.05) ferroptotic gene (DMT1) and anti-ferroptotic genes (FTL and FTH1), while downregulated (P < 0.05) anti-ferroptotic genes (FPN, FSP1 and CISD1) in the duodenum of the porcine. Furthermore, the in vitro study has demonstrated that deferiprone, a potent ferroptotic inhibitor, mitigated (P < 0.05) DON-induced cytotoxicity in porcine small intestinal IPEC-J2 cells. Additionally, deferiprone prevented or alleviated (P < 0.05) the dysregulation of ferroptosis-related genes (ACSL4 and FTL) by DON in IPEC-J2 cells. Moreover, specific siRNA knockdown FTL gene expression compromised the DON-induced cell death in IPEC-J2 cells.

Conclusions
In conclusion, this study revealed that ferroptosis is involved in DON-induced intestinal damage in porcine, and sheds a new light on the toxicity of DON to piglets.
Supranutrition of microalgal docosahexaenoic acid and calcidiol improved growth performance, tissue lipid profiles, and tibia characteristics of broiler chickens
Authors: Kalia Sahil , Magnuson Andrew D. , Sun Tao , Liu Guanchen , Kim Woo Kyun , Johnson Zackary , Lei Xin Gen 
Published: March 2023

Abstract
Background
Docosahexaenoic acid (DHA) and calcidiol could be enriched in chicken for improving public nutrition and health. It remains unclear if supranutritional levels of DHA and calcidiol impair growth performance or metabolism of broiler chickens. This study was to determine singular and combined effects of high levels of supplemental DHA-rich microalgal biomass or oil and calcidiol on growth performance, concentrations of triglycerides, cholesterol, and nonesterfied fatty acids in plasma, liver, breast, and thigh, and biophysical properties of tibia.

Methods
In Exp. 1, 144 day-old Cornish chicks were divided into 4 groups (6 cages/treatment, 6 birds/cage), and were fed a corn-soybean meal basal diet (BD), BD + 10,000 IU calcidiol/kg (BD + Cal), BD + 1% DHA-rich Aurantiochytrium (1.2 g DHA/kg; BD + DHA), and BD + Cal + DHA for 6 weeks. In Exp. 2, 180 day-old chicks were divided into 5 groups, and were fed: BD, BD + DHA (0.33% to 0.66% oil, 1.5 to 3.0 g DHA/kg), BD + DHA + EPA (1.9% to 3.8% eicosapentaenoic acid-rich Nannochloropsis sp. CO18, 0.3 to 0.6 g EPA/kg), BD + DHA + calcidiol (6000 to 12,000 IU/kg diet), and BD + DHA + EPA + Cal for 6 weeks.

Results
Birds fed BD + Cal diet in Exp. 1 and BD + DHA + EPA diet in Exp. 2 had higher (P < 0.05) body weight gain (10%–11%) and gain:feed ratio (7%), and lower (P < 0.05) total cholesterol and triglyceride concentrations in plasma (18%–54%), liver (8%–26%), breast (19%–26%), and thigh (10%–19%), respectively, over the controls. The two diets also improved (P < 0.05) tibial breaking strength (8%–24%), total bone volume (2%–13%), and (or) bone mineral density (3%–19%) of chickens.

Conclusion
Supranutrition of dietary calcidiol and DHA alone or together did not produce adverse effects, but led to moderate improvements of growth performance, lipid profiles of plasma and muscle, and bone properties of broiler chickens.
Key mechanism of enzymatic dehairing technology for leather-making: permeation behaviors of protease into animal hide and the mechanism of charge regulation
Authors: Gao Mengchu , Song Jinzhi , Zhang Xu , Zhang Chunxiao , Peng Biyu , Chattha Sadaqat Ali 
Published: March 2023

AbstractEnzymes have been widely used as alternatives to conventional chemicals in cleaner leather processes due to their advantages of meeting increasing environmental demands. Especially, enzymatic unhairing based on protease has been applied to leather-making for a long time, however, it still has the key problem of slow permeation in the animal hide, resulting in slow unhairing rate, poor hair removal effect, excessive proteolysis of hide collagen, and decreased leather quality. Aiming at the key problem of bio-unhairing technology, fluorescent labeling technique and confocal laser scanning microscopy were used to investigate the protease permeation behaviors into the animal hide based on well-prepared labeled proteases, as well as the quantitative analysis of the protease amount in different hide layers. The results show that the protease mainly permeates the bovine hide through transfollicular routes from the hair side, and although the intercellular-interfibrillar pathway also exists, it does not play an important role. Additionally, the protease permeation behaviors into the hide are greatly impacted by the charge states of the hide and protease proteins, depending on the isoelectric points (pI) of the proteins and solution pH values. When the solution pH is not between the pI values of the two proteins, the similarly charged protease can quickly and deeply penetrate the hide because of the electrostatic repulsion. The established mechanism provides a theoretical basis for developing an efficient enzymatic unhairing technology for leather-making, and this can also be applied to other processes involving the enzyme permeation into the hide or leather.
Graphical Abstract
Trans (In)Visibility in Art
Authors: Thompto Chelsea 
Published: March 2023

Abstract
Through an examination of how the art world engages with transness, the piece begins with an exploration of why we need an understanding of trans subjectivity that is not beholden to or subsumed by the art world's overriding attention and interest in queer subjectivities and concerns. The author then describes how trans methodologies are applied within their artistic and curatorial practice and how those methodologies are situated within the broader context of the art world. Particular focus is given to codes as both the subject (social, governmental, and technical codes) and medium (visual and computer codes) of the author's work.
103 Cerebrospinal Fluid Drainage in Acute Spinal Cord Injury: A Multi-Center, Randomized, Controlled Trial
Authors: Theodore Nicholas , Martirosyan Nikolay L. , Hersh Andrew , Ehresman Jeff , Ahmed Ali Karim , Danielson Jill , Sullivan Cindy , Shank Christopher D. , Almefty Kaith K. , Lemole G. Michael , Kakarla Udaya K. , Hadley Mark N. 
Published: March 2023

INTRODUCTION:
The devastating sequelae of spinal cord injury (SCI) are worsened by ischemia and inflammation that occur following the primary mechanical damage to the cord. Optimizing spinal cord perfusion pressure (SCPP), calculated as the difference between mean arterial pressure (MAP) and intrathecal pressure (ITP), may improve long-term neurological outcomes. MAP augmentation is frequently used to improve perfusion; however, the efficacy of ITP reduction is less clear.

METHODS:
Patients with acute cervical SCI presenting within 24 hours were screened for eligibility. All patients received lumbar drain placement and appropriate decompressive surgery. Patients in the control group received MAP elevation only, while patients in the interventional group received MAP elevation and CSFD for a target ITP of below 10 mm Hg for 5 days. ITP and MAP were recorded hourly. Patients underwent functional assessments at enrollment, 72 hours, 90 days, and 180 days after injury.

RESULTS:
A total of 11 patients were enrolled, and four were randomized to receive CSFD. Patients in the CSFD cohort had a mean ITP of 5.3 ± 2.5 mm Hg compared to 15 ± 3.0 mm Hg in the control group. SCPP improved significantly from 77 ± 4.5 mm Hg in the control group to 101 ± 6.3 mm Hg in the experimental group (p < 0.01). Total motor scores improved by 15 ± 8.4 points and 57 ± 24 points in the control and CSFD groups, respectively, over 180 days. No adverse events were attributable to CSFD.

CONCLUSIONS:
CSFD is feasible and an effective mechanism for reducing ITP and improving SCPP in the acute period after SCI. The complication profile was similar between both groups, and long-term improvements in motor and sensory function were seen with CSFD.
108 A Novel Robotic-Assisted Platform for Spinal Decompression Procedures
Authors: Simaan Ranin , Eastlack Robert , Khoo Larry T. , Smith William Douglas , Ellegala Dilantha B. , Ashkenazi Ely , Harel Ran , Millgram Michael 
Published: March 2023

INTRODUCTION:
Removal of pathologic tissue during degenerative spinal surgery cases near a bone-nerve interface presents a challenge during spinal decompression, especially in minimally invasive procedures. Robotic systems for spinal surgeries can potentially offer greater accuracy than manual operations. However, today’s robotic systems are designed only for placement of fusion hardware and lack the ability to work in-situ and in proximity to neural structures.

METHODS:
In the proposed approach, the surgeon utilizes a 6-degrees-of-freedom joystick to control an industrial grade robotic arm connected to curved-at-the-tip high-speed, shielded drilling end-effectors to perform various bone removal tasks. Live visual feedback is displayed from top-view and endoscopic camera views. Force readouts, correlated to the force exerted on the end-effector through tissue contact, provide real time visual feedback. Additional safety restrictions are designed into the system to prevent excessive force. System orientation training was conducted on vertebral models. Initially, three spine surgeons used the system to perform ipsilateral decompression and foraminotomy in four surgeries in a live pig model. Next, six surgeons used the system to perform ipsilateral decompression on two human cadavers. All surgeons completed questionnaires assessing procedure efficacy and system usability.

RESULTS:
Animal studies: Required decompression was achieved in all cases, with no complications and minimum-to-moderate bleeding. Intuitive usability and acceptable kinematic range of motion of the robotic system was confirmed. Cadaver study: Questionnaire results demonstrated high scores of confidence in the technique (4.7/5), overall satisfaction (4.4/5) and achievement of adequate decompression (3.9/5). All neural structures remained intact.

CONCLUSIONS:
This preliminary data indicates that the proposed robotic system can facilitate safe and precise decompression through removal of sufficient tissue removal at the bone/nerve interface. Further studies with a medical grade robotic arm are planned.
113 The Use of Machine Learning of Carotid Web Angioarchitecture for Predicting Stroke Risk
Authors: von Oiste Grace , Narayan Vinayak , Moin Mustafa Nasir , Raz Eytan , Shapiro Maksim , Rutledge Caleb , Nelson Peter Kim , Riina Howard A. , Oermann Eric , Nossek Erez 
Published: March 2023

INTRODUCTION:
Carotid webs (CWs) are a known mechanism for stroke in young adults without other vascular risk factors. Altered hemodynamics distal to the web may cause flow stagnation with the potential for distal embolization of clots. Although there are some computational flow models studies of CW, currently there are no well-described CT angiographic features to predict stroke risk.

METHODS:
Anatomical data of the internal carotid artery (ICA), common carotid artery (CCA), the CW and its “distal pouch” angioarchitecture was gathered as part of a retrospective cohort study from symptomatic (stroke) and asymptomatic (non-stroke) patients. Principal component analysis was applied to anatomical and angioarchitectural features, and the two components were plotted to investigate whether the stroke and non-stroke patients were easily separable. We built a predictive model of stroke risk using these features with Firth regression to reduce bias related to small datasets.

RESULTS:
The first two principal components of the anatomical and angioarchitectural features clearly distinguish between stroke patients and non-stroke patients. The firth regression and 5-fold cross validation revealed that CCA web “pouch” angle (p=.014), ICA web “pouch” tip angle (p=.023), CCA web “pouch” tip angle (p = .017), and ICA web “pouch” angle (p = .016) are the most important features to model and assess stroke risk. Conversely, CCA and ICA anatomy (diameter and angle) on their own were not found to be risk factors for stroke. Overall, pouch angles in respect to flow trajectory in the CCA and in the ICA are significant risk factors as compared to vessel sizes and flow relationships between them.

CONCLUSIONS:
This study demonstrates that carotid web angioarchitecture and carotid anatomy data from diagnostic angiography may be used to assess stroke risk, allowing physicians to tailor care for each patient according to risk stratification.
131 Hedgehog Signaling Mediates Astrocytic Response and Blood-Brain Barrier Repair Following Traumatic Central Nervous System Injury
Authors: Rallo Michael Stephen , Wang Hui , Xu Zhiyan , Matise Michael , Schoeffler Eve 
Published: March 2023

INTRODUCTION:
Injury to the central nervous system (CNS) provokes a multicellular response to facilitate restoration of tissue homeostasis. Astrocytes consolidate at the lesion site to form a “glial scar” which restricts leukocyte infiltration and repairs the blood-brain barrier (BBB). However, this “scar” has been considered an impediment to regeneration and functional recovery. Therefore, uncovering molecular regulators that may be therapeutically targeted to promote pro-regenerative astrocyte phenotypes is of great interest.

METHODS:
Genetic reporter and conditional mutant mice were used to monitor, constitutively activate, or ablate Hh signaling following stereotactically-induced penetrating cortical or spinal cord injury. Outcomes including reactive astrocyte proliferation and polarization, leukocyte restriction, and blood-brain barrier repair were assessed via immunohistochemistry.

RESULTS:
Astrocytic expression of the Hh target gene Gli1 was downregulated acutely following injury but restored in the subacute phase. Constitutive activation of Hh signaling reduced astrocytic proliferation (%BrdU/EdU+ = 9.6% vs. 51.0%, p<0.01) and polarization (L/W Ratio = 2.8 vs. 1.5, p < 0.01). Additionally, in the spinal cord, constitutive activation impaired migration and integration of reactive astrocytes into the white matter lesion site. In animals with intact Hh signaling, the BBB recovered by 28 days after injury as evidenced by low levels of plasma protein and leukocyte infiltration. In contrast, conditional ablation of Hh signaling from 14-16 days after injury resulted in persistent BBB defects at 28 days.

CONCLUSIONS:
Our results suggest that acute downregulation of Hh signaling is required to specify reactive astrocyte properties including polarization and cell cycle re-entry. However, restoration of Hh signaling, which occurs subacutely from 10-28 days after injury and coincides with glial scar maturation, is required for leukocyte restriction and BBB repair. Understanding the temporospatial dynamics of postinjury Hh signaling is essential to modeling future therapeutic targets.
134 Retrograde Adeno-Associated Viruses-mediated Gene Transfer to Primary Nociceptors via Paw Injection Modulates Pain-Related Phenotypes
Authors: Unda Santiago R. , Antoniazzi Aldana M. , Norman Sofya , Urien Louise , Marongiu Roberta , Kaplitt Michael Gordon 
Published: March 2023

INTRODUCTION:
Primary nociceptors are the first neurons involved in processing normal and pathological pain. Novel biological approaches such as gene therapies targeting these neurons have great potential, but delivery can be challenging when open or percutaneous infusion into the dorsal root ganglion (DRG) is needed.

METHODS:
Primary nociceptors were first targeted unilaterally via right hind paw injection of a retrograde adeno-associated virus serotype 2 (AAVRetro) or a mosaic AAVRetro/rh10 vector encoding a constitutive hM3Dq chemogenetic transgene. A second cohort of mice received the same vectors via unilateral intraneural injection in the right sciatic nerve. Changes in pain-related behaviors were assessed 45-60 min following intraperitoneal administration of the ligand clozapine-n-oxide (CNO) using the Von Frey and Hargreaves tests every other week for 6 weeks post-AAVRetro injection.

RESULTS:
Immunofluorescence and RNA in-situ hybridization of paw injected mice revealed transduction of primary nociceptors in the DRG from L4 to L6 segments, including TrkA, Trpv1, CGRP, and NaV1.8 positive neurons. Chemogenetic activation elicited robust mechanical allodynia responses at 4-week post-RetroAAV delivery in paw injected mice, whilst in sciatic injected mice we observed an earlier pain phenotype starting at 2-week post-RetroAAV administration. No thermal hyperalgesia responses were observed.

CONCLUSIONS:
We demonstrate for the first time that AAVRetro effectively transduces DRG nociceptors via paw injection. Furthermore, chemogenetic activation caused a strong pain phenotype similar to mice injected in the sciatic nerve. These results support further exploration of non-invasive delivery of retrograde viral vectors to modulate pain neurons for potential therapeutic applications.
163 Integrative Genomics Analysis Implicates Decreased FGD6 Expression Underlying Risk of Intracranial Aneurysm Rupture
Authors: Hale Andrew T. , He Jing , Jones Jesse 
Published: March 2023

INTRODUCTION:
The genetic determinants of intracranial aneurysm rupture (rIA) are largely unknown. To identify and characterize genetic risk factors for rIA, we perform a genome-wide association study (GWAS) containing 84,353 individuals (7,843 rIA cases and 76,510 controls). We then use functional genomics approaches to delineate the mechanistic consequences of rIA risk loci.

METHODS:
We perform a meta-analysis across 24 published GWAS of rIA. Logistic regression was used to identify rIA-associated single nucleotide polymorphisms (SNPs). Gene-burden, expression quantitative trait loci (eQTL) mapping, and analysis of publicly-available single-cell RNA sequencing (scRNA-seq) data from normal human brain endothelial and perivascular cells was used to delineate cell-lineage expression of rIA-associated genes.

RESULTS:
We identify 5 independent genetic loci reaching genome-wide significance (p < 5.0 x 10-8) for rIA: rs73392700 (CDKN2B, OR = 1.12), rs6841581 (EDNRA, OR = 0.77), rs11661542 (RBBP8, OR=0.84), rs62516550 (RP1, OR = 1.20), and rs12310399 (FGD6, OR = 1.16). FGD6, to our knowledge, has not been implicated in prior GWAS of (r)IA. We then quantified gene-level mutation-burden across ∼20,000 genes, and only FGD6 (containing 21 rIA-associated SNPs) reached transcriptome-wide significance. Functional eQTL mapping indicates that rs12310399 causes decreased FGD6 gene expression in arterial tissue. scRNA-seq identified high expression of FGD6 in 1 of 3 arterial lineages, but absent in perivascular cells, identifying the likely cell-lineage underlying FGD6-mediated rIA risk.

CONCLUSIONS:
We perform the largest genetic study of rIA to date. We identify and characterize a previously unknown risk loci for rIA containing FGD6. Elucidation of high-risk genetic loci may instruct population-genetic screening and clinical-genetic testing strategies to identify patients predisposed to rIA enabling early treatment and improved patient outcomes.
166 The Protective Role of GPR39 in Subarachnoid Hemorrhage
Authors: Mazur-Hart David , Bah Thierno , Siler Dominic Aaron , Pike Martin , Cetas Justin Schultz , Alkayed Nabil 
Published: March 2023

INTRODUCTION:
Aneurysmal subarachnoid hemorrhage (SAH) is a devastating stroke with high morbidity and mortality. It causes an early brain injury (EBI), the severity of which can predict delayed cerebral ischemia (DCI). Neuroinflammation is a key component of EBI. The G protein-coupled receptor 39 (GPR39) is expressed in brain, and it has been shown to modulate neuroinflammation.

METHODS:
Endovascular perforation technique induced SAH in GPR39 knockout (KO) and wild-type (WT) littermate mice. Laser-Doppler was used to monitor cortical perfusion before, during, and right after SAH. Body mass and neurological deficit (neuroscore) were assessed daily after SAH. T2-weighted MRI was used to measure ventricular volumes, and T2*-weighted gradient recalled echo (GRE) MRI was used to assess cortical vein engorgement at 24 hours after SAH. Behavioral deficit was assessed using the accelerating rotarod at baseline and on days 2, 3 and 4 after SAH and balance beam on days 2, 3 and 4 after SAH.

RESULTS:
SAH caused an acute, communicating hydrocephalus with engorged cortical veins. WT and KO mice exhibited significant weight loss and deficits in neuroscore after SAH compared to sham mice. GPR39 KO mice had a significantly worse neuroscore than WT mice 3 days after SAH (mean 20.7 vs. 22.3; n = 12 vs. 15, respectively; p = 0.01). Additionally, GPR39 KO mice exhibited worse scores on rotarod 2 days after SAH (mean latency to fall 138.9 vs. 108.8; n=12 vs 15, respectively, p = 0.07) and balance beam 1 day after SAH (mean time to traverse 24.8 vs. 31.8; n = 8 vs. 11, respectively, p = 0.1).

CONCLUSIONS:
Our findings indicate that mice with GPR39 deletion exhibit worse outcomes in neuroscore and sensorimotor domains. These results suggest that GPR39 plays a protective role and may serve as a therapeutic target in SAH.