bluuebunny/crossref_metadata_2025_split huggingface dataset:
A consortia of clinical E. coli strains with distinct in vitro adherent/invasive properties establish their own co-colonization niche and shape the intestinal microbiota in inflammation-susceptible mice
Authors: Bleich Rachel M. , Li Chuang , Sun Shan , Ahn Ju-Hyun , Dogan Belgin , Barlogio Cassandra J. , Broberg Christopher A. , Franks Adrienne R. , Bulik-Sullivan Emily , Carroll Ian M. , Simpson Kenneth W. , Fodor Anthony A. , Arthur Janelle C. 
Published: December 2023

Abstract
Background
Inflammatory bowel disease (IBD) patients experience recurrent episodes of intestinal inflammation and often follow an unpredictable disease course. Mucosal colonization with adherent-invasive Escherichia coli (AIEC) are believed to perpetuate intestinal inflammation. However, it remains unclear if the 24-year-old AIEC in vitro definition fully predicts mucosal colonization in vivo. To fill this gap, we have developed a novel molecular barcoding approach to distinguish strain variants in the gut and have integrated this approach to explore mucosal colonization of distinct patient-derived E. coli isolates in gnotobiotic mouse models of colitis.

Results
Germ-free inflammation-susceptible interleukin-10-deficient (Il10−/−) and inflammation-resistant WT mice were colonized with a consortium of AIEC and non-AIEC strains, then given a murine fecal transplant to provide niche competition. E. coli strains isolated from human intestinal tissue were each marked with a unique molecular barcode that permits identification and quantification by barcode-targeted sequencing. 16S rRNA sequencing was used to evaluate the microbiome response to E. coli colonization. Our data reveal that specific AIEC and non-AIEC strains reproducibly colonize the intestinal mucosa of WT and Il10−/− mice. These E. coli expand in Il10−/− mice during inflammation and induce compositional dysbiosis to the microbiome in an inflammation-dependent manner. In turn, specific microbes co-evolve in inflamed mice, potentially diversifying E. coli colonization patterns. We observed no selectivity in E. coli colonization patterns in the fecal contents, indicating minimal selective pressure in this niche from host-microbe and interbacterial interactions. Because select AIEC and non-AIEC strains colonize the mucosa, this suggests the in vitro AIEC definition may not fully predict in vivo colonization potential. Further comparison of seven E. coli genomes pinpointed unique genomic features contained only in highly colonizing strains (two AIEC and two non-AIEC). Those colonization-associated features may convey metabolic advantages (e.g., iron acquisition and carbohydrate consumption) to promote efficient mucosal colonization.

Conclusions
Our findings establish the in vivo mucosal colonizer, not necessarily AIEC, as a principal dysbiosis driver through crosstalk with host and associated microbes. Furthermore, we highlight the utility of high-throughput screens to decode the in vivo colonization dynamics of patient-derived bacteria in murine models.
Genetic ablation of Sarm1 attenuates expression and mislocalization of phosphorylated TDP-43 after mouse repetitive traumatic brain injury
Authors: Dogan Elif O. , Bouley James , Zhong Jianjun , Harkins Ashley L. , Keeler Allison M. , Bosco Daryl A. , Brown Robert H. , Henninger Nils 
Published: December 2023

AbstractTraumatic brain injury (TBI), particularly when moderate-to-severe and repetitive, is a strong environmental risk factor for several progressive neurodegenerative disorders. Mislocalization and deposition of transactive response DNA binding protein 43 (TDP-43) has been reported in both TBI and TBI-associated neurodegenerative diseases. It has been hypothesized that axonal pathology, an early event after TBI, may promote TDP-43 dysregulation and serve as a trigger for neurodegenerative processes. We sought to determine whether blocking the prodegenerative Sarm1 (sterile alpha and TIR motif containing 1) axon death pathway attenuates TDP-43 pathology after TBI. We subjected 111 male Sarm1 wild type, hemizygous, and knockout mice to moderate-to-severe repetitive TBI (rTBI) using a previously established injury paradigm. We conducted serial neurological assessments followed by histological analyses (NeuN, MBP, Iba-1, GFAP, pTDP-43, and AT8) at 1 month after rTBI. Genetic ablation of the Sarm1 gene attenuated the expression and mislocalization of phosphorylated TDP-43 (pTDP-43) and accumulation of pTau. In addition, Sarm1 knockout mice had significantly improved cortical neuronal and axonal integrity, functional deficits, and improved overall survival after rTBI. In contrast, removal of one Sarm1 allele delayed, but did not prevent, neurological deficits and neuroaxonal loss. Nevertheless, Sarm1 haploinsufficient mice showed significantly less microgliosis, pTDP-43 pathology, and pTau accumulation when compared to wild type mice. These data indicate that the Sarm1-mediated prodegenerative pathway contributes to pathogenesis in rTBI including the pathological accumulation of pTDP-43. This suggests that anti-Sarm1 therapeutics are a viable approach for preserving neurological function after moderate-to-severe rTBI.
Capillary leak and endothelial permeability in critically ill patients: a current overview
Authors: Saravi Babak , Goebel Ulrich , Hassenzahl Lars O. , Jung Christian , David Sascha , Feldheiser Aarne , Stopfkuchen-Evans Matthias , Wollborn Jakob 
Published: December 2023

AbstractCapillary leak syndrome (CLS) represents a phenotype of increased fluid extravasation, resulting in intravascular hypovolemia, extravascular edema formation and ultimately hypoperfusion. While endothelial permeability is an evolutionary preserved physiological process needed to sustain life, excessive fluid leak—often caused by systemic inflammation—can have detrimental effects on patients’ outcomes. This article delves into the current understanding of CLS pathophysiology, diagnosis and potential treatments. Systemic inflammation leading to a compromise of endothelial cell interactions through various signaling cues (e.g., the angiopoietin–Tie2 pathway), and shedding of the glycocalyx collectively contribute to the manifestation of CLS. Capillary permeability subsequently leads to the seepage of protein-rich fluid into the interstitial space. Recent insights into the importance of the sub-glycocalyx space and preserving lymphatic flow are highlighted for an in-depth understanding. While no established diagnostic criteria exist and CLS is frequently diagnosed by clinical characteristics only, we highlight more objective serological and (non)-invasive measurements that hint towards a CLS phenotype. While currently available treatment options are limited, we further review understanding of fluid resuscitation and experimental approaches to target endothelial permeability. Despite the improved understanding of CLS pathophysiology, efforts are needed to develop uniform diagnostic criteria, associate clinical consequences to these criteria, and delineate treatment options.
Graphical Abstract
Elevated FBXL6 activates both wild-type KRAS and mutant KRASG12D and drives HCC tumorigenesis via the ERK/mTOR/PRELID2/ROS axis in mice
Authors: Xiong Hao-Jun , Yu Hong-Qiang , Zhang Jie , Fang Lei , Wu Di , Lin Xiao-Tong , Xie Chuan-Ming 
Published: December 2023

Abstract
Background
Kirsten rat sarcoma (KRAS) and mutant KRASG12D have been implicated in human cancers, but it remains unclear whether their activation requires ubiquitination. This study aimed to investigate whether and how F-box and leucine-rich repeat 6 (FBXL6) regulates KRAS and KRASG12D activity in hepatocellular carcinoma (HCC).

Methods
We constructed transgenic mouse strains LC (LSL-Fbxl6KI/+;Alb-Cre, n = 13), KC (LSL-KrasG12D/+;Alb-Cre, n = 10) and KLC (LSL-KrasG12D/+;LSL-Fbxl6KI/+;Alb-Cre, n = 12) mice, and then monitored HCC for 320 d. Multiomics approaches and pharmacological inhibitors were used to determine oncogenic signaling in the context of elevated FBXL6 and KRAS activation. Co‑immunoprecipitation (Co-IP), Western blotting, ubiquitination assay and RAS activity detection assay were employed to investigate the underlying molecular mechanism by which FBXL6 activates KRAS. The pathological relevance of the FBXL6/KRAS/extracellular signal-regulated kinase (ERK)/mammalian target of rapamycin (mTOR)/proteins of relevant evolutionary and lymphoid interest domain 2 (PRELID2) axis was evaluated in 129 paired samples from HCC patients.

Results
FBXL6 is highly expressed in HCC as well as other human cancers (P < 0.001). Interestingly, FBXL6 drives HCC in transgenic mice. Mechanistically, elevated FBXL6 promotes the polyubiquitination of both wild-type KRAS and KRASG12D at lysine 128, leading to the activation of both KRAS and KRASG12D and promoting their binding to the serine/threonine-protein kinase RAF, which is followed by the activation of mitogen-activated protein kinase kinase (MEK)/ERK/mTOR signaling. The oncogenic activity of the MEK/ERK/mTOR axis relies on PRELID2, which induces reactive oxygen species (ROS) generation. Furthermore, hepatic FBXL6 upregulation facilitates KRASG12D to induce more severe hepatocarcinogenesis and lung metastasis via the MEK/ERK/mTOR/PRELID2/ROS axis. Dual inhibition of MEK and mTOR effectively suppresses tumor growth and metastasis in this subtype of cancer in vivo. In clinical samples, FBXL6 expression positively correlates with p-ERK (χ2 = 85.067, P < 0.001), p-mTOR (χ2 = 66.919, P < 0.001) and PRELID2 (χ2 = 20.891, P < 0.001). The Kaplan–Meier survival analyses suggested that HCC patients with high FBXL6/p-ERK levels predicted worse overall survival (log‑rank P < 0.001).

Conclusions
FBXL6 activates KRAS or KRASG12D via ubiquitination at the site K128, leading to activation of the ERK/mTOR/PRELID2/ROS axis and tumorigenesis. Dual inhibition of MEK and mTOR effectively protects against FBXL6- and KRASG12D-induced tumorigenesis, providing a potential therapeutic strategy to treat this aggressive subtype of liver cancer.
Geographic location and ethnicity comprehensively influenced vitamin D status in college students: a cross-section study from China
Authors: Luo Yingyi , Qu Chunbo , Zhang Rui , Zhang Jingyi , Han Dan , Na Lixin 
Published: December 2023

Abstract
Background
Vitamin D plays an important role in the health of adolescents, whereas vitamin D status of Chinese college students was seldom studied in China. To explore the vitamin D status and its relationship with ethnicity and geographic location in Chinese college students.

Methods
The freshmen were taken a physical examination by trained medical personnel after they reported to university. Demographic information including age, gender, ethnicity, region of original residence was collected using a questionnaire survey. Serum 25(OH)D3 concentrations were measured using a liquid chromatograph mass spectrometer. Multiple regression analyses were used to explore the factors that influence serum 25(OH)D3 levels.

Results
Totally 3220 freshmen who came from 26 provinces, autonomous districts or municipalities were recruited, with a mean age of 18.75 ± 1.18 years and 70.2% of them were female. The mean serum 25(OH)D3 levels were 18.51 ± 6.54 ng/mL, and the proportion of vitamin D deficiency (< 20 ng/mL) and insufficiency (20 ~  < 30 ng/mL) was 64.4% and 30.2%, respectively. The combined proportion of vitamin D deficiency and insufficiency was increased with the latitude increased. Miao had the highest serum 25(OH)D3 levels, whereas Kazak ethnic had the lowest (22.51 ng/mL vs. 13.94 ng/mL) among different ethnic groups. Female students, students from city, Uighur and Kazak ethnic, residing in high latitude was significantly associated with lower serum 25(OH)D3 levels (P < 0.05).

Conclusions
Vitamin D deficiency is an important health problem in Chinese college students. Sunlight activities, dietary and life-style intervention for college students according to geographic location and ethnicities should be considered.
Driver behavior while using Level 2 vehicle automation: a hybrid naturalistic study
Authors: Cooper Joel M. , Crabtree Kaedyn W. , McDonnell Amy S. , May Dominik , Strayer Sean C. , Tsogtbaatar Tushig , Cook Danielle R. , Alexander Parker A. , Sanbonmatsu David M. , Strayer David L. 
Published: December 2023

AbstractVehicle automation is becoming more prevalent. Understanding how drivers use this technology and its safety implications is crucial. In a 6–8 week naturalistic study, we leveraged a hybrid naturalistic driving research design to evaluate driver behavior with Level 2 vehicle automation, incorporating unique naturalistic and experimental control conditions. Our investigation covered four main areas: automation usage, system warnings, driving demand, and driver arousal, as well as secondary task engagement. While on the interstate, drivers were advised to engage Level 2 automation whenever they deemed it safe, and they complied by using it over 70% of the time. Interestingly, the frequency of system warnings increased with prolonged use, suggesting an evolving relationship between drivers and the automation features. Our data also revealed that drivers were discerning in their use of automation, opting for manual control under high driving demand conditions. Contrary to common safety concerns, our data indicated no significant rise in driver fatigue or fidgeting when using automation, compared to a control condition. Additionally, observed patterns of engagement in secondary tasks like radio listening and text messaging challenge existing assumptions about automation leading to dangerous driver distraction. Overall, our findings provide new insights into the conditions under which drivers opt to use automation and reveal a nuanced behavioral profile that emerges when automation is in use.
Endophytic Bacillus spp. from native chilli cultivars and their effect against fruit rot pathogen of Bhut Jolokia (Capsicum chinense Jacq.)
Authors: Sarmah Partha Pratim , Nath Hiranya Kumar Deva , Nath Tankeswar 
Published: December 2023

Abstract
Background
Fruit rot disease is one of the most important factors limiting the production potential of Bhut Jolokia (Capsicum chinense Jacq.), which is known as one of the hottest chillies in the world. The management strategies are highly dependent on synthetic chemicals which are causing a detrimental impact on the environment. Considering the factors, this study focuses on exploring potential endophytic microflora from native chilli cultivars which can suppress the fruit rot pathogen.

Results
Endophytic microflora occurs ubiquitously in plants that possess various plant-benefiting abilities. A total of 34 endophytic isolates were obtained from different chilli cultivars. These endophytic isolates were subjected to screening in vitro for their potential to suppress the incitant pathogen Colletotrichumgloeosporioides (the causal agent of chilli fruit rot), which was confirmed based on cultural, morphological, pathogenicity and molecular studies. The preliminary screening yielded four bacterial endophytic isolates capable of suppressing the pathogen which was found non-pathogenic to Bhut Jolokia plant. On the basis of morphological, biochemical and molecular identification, the four most promising isolates were identified as Bacillus velezensis, B. mycoides, B. altitudinis and B. cereus, respectively, and used for further in vitro tests. B. velezensis showed the highest inhibition (68.67%) on mycelial growth of C. gloeosporioides, followed by B. mycoides (65.33%), B. altitudinis (52.89%) and B. cereus (45.33%). Among the compatible combination, the highest efficacy (56.00%) was found in the combination of B. velezensis and B. altitudinis.

Conclusion
From the present study, it can be concluded that B. velezensis and B. mycoides alone and in combination can be used as potential biocontrol agent in managing the fruit rot of Bhut Jolokia considering their performance in field conditions.
COVID-19 and optic neuritis: a series of three cases and a critical review
Authors: Chakraborty Uddalak , Chaudhuri Jasodhara , Datta Amlan Kusum , Mukherjee Adreesh , Pandit Alak , Ray Biman Kanti , Gangopadhyay Goutam 
Published: December 2023

Abstract
Background
The novel coronavirus disease (COVID-19) has claimed innumerable lives globally since its onset and several extrapulmonary manifestations of the disease have been reported in association with COVID-19. Although optic neuropathy has been previously linked to a variety of infections, neuro-ophthalmological associations of SARS-CoV-2 have been sparsely reported till date. Our aim was to report the clinical profile and outcome of patients diagnosed with parainfectious/postinfectious optic neuritis (ON) associated with COVID-19.

Case presentation
In this case series, we have discussed the clinical presentation, laboratory parameters and outcome in a series of three patients of ON associated with COVID-19 and also compared those findings against existing literature. Among the three patients, two patients (Case 1, 3) were incidentally diagnosed with COVID-19 during the course of hospital admission and contributed to a parainfectious association with ON, while one patient (Case 2) had an antecedent history of COVID-19 as evidenced by her antibody titers thus contributing to a postinfectious association. Notably, all these patients were asymptomatic or had mild manifestations of COVID-19 and all of them tested negative for myelin oligodendrocyte glycoprotein (MOG) antibodies. They were treated accordingly and their visual outcomes were noted in follow-up.

Conclusion
ON with or without MOG seropositivity, probably attributed to molecular mimicry has surfaced up considerably in association with COVID-19. This article provides a comprehensive overview of clinical presentation and outcome of ON associated with parainfectious/postinfectious COVID-19 in three cases and a critical analysis of existing literature.
Acute subdural hematoma in a footballer following a head-ball of the ball: a rare neurosurgical complication
Authors: Eyenga Victor-Claude , Esene Ignatius N. , Bikono Ernestine A. 
Published: December 2023

AbstractAcute subdural hematoma is a frequent complication of high-energy head injuries. Herein, we report an unusual case of this condition that occurred in a young footballer after he head-balled a football. A 37-year-old footballer, during a match, jumped and gave a head shot on the ball. Upon landing, he felt severe headaches forcing him out of the stadium. About 4 h later, he lost consciousness and went into a coma. After resuscitation, he remained clouded, with cephalalgia and had left hemiparesis. The performed brain scan revealed an acute right fronto-parietal subdural hematoma and the patient benefited from craniotomy surgery in our department with simple postoperative suites. The authors, after a brief discussion of the biomechanics of this serious condition, ask all the actors of this very popular sport, to consider the possibility of occurrence of this condition in players.
The brain-liver cholinergic anti-inflammatory pathway and viral infections
Authors: Martínez-Meza Samuel , Singh Bhavya , Nixon Douglas F. , Dopkins Nicholas , Gangcuangco Louie Mar A. 
Published: December 2023

AbstractEfferent cholinergic signaling is a critical and targetable source of immunoregulation. The vagus nerve (VN) is the primary source of cholinergic signaling in the body, and partially innervates hepatic functionality through the liver-brain axis. Virus-induced disruption of cholinergic signaling may promote pathogenesis in hepatotropic and neurotropic viruses. Therefore, restoring VN functionality could be a novel therapeutic strategy to alleviate pathogenic inflammation in hepatotropic and neurotropic viral infections alike. In this minireview, we discuss the physiological importance of cholinergic signaling in maintaining liver-brain axis homeostasis. Next, we explore mechanisms by which the VN is perturbed by viral infections, and how non-invasive restoration of cholinergic signaling pathways with bioelectronic medicine (BEM) might ameliorate hepatic inflammation and neuroinflammation in certain viral infections.
Transforming standards into classrooms for knowledge-in-use: an effective and coherent project-based learning system
Authors: He Peng , Krajcik Joseph , Schneider Barbara 
Published: December 2023

AbstractGlobal science education reform calls for developing student knowledge-in-use that applies the integrated knowledge of core ideas and scientific practices to make sense of phenomena or solve problems. Knowledge-in-use development requires a long-term, standards-aligned, coherent learning system, including curriculum and instruction, assessment, and professional learning. This paper addresses the challenge of transforming standards into classrooms for knowledge-in-use and presents an iterative design process for developing a coherent and standards-aligned learning system. Using a project-based learning approach, we present a theory-driven, empirically validated learning system aligned with the U.S. science standards, consisting of four consecutive curriculum and instruction materials, assessments, and professional learning to support students’ knowledge-in-use in high school chemistry. We also present the iterative development and testing process with empirical evidence to support the effectiveness of our learning system in a five-year NSF-funded research project. This paper discusses the theoretical perspectives of developing an NGSS-aligned, coherent, and effective learning system and recaps the development and testing process by unpacking all essential components in our learning system. We conclude that our theory-driven and empirically validated learning system would inform high school teachers and researchers across countries in transforming their local science standards into curriculum materials to support students’ knowledge-in-use development.