bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical hypertension in trauma patients following prehospital emergency anaesthesia: a multi-centre retrospective observational study
Authors: Sagi Liam , Price James , Lachowycz Kate , Starr Zachary , Major Rob , Keeliher Chris , Finbow Benjamin , McLachlan Sarah , Moncur Lyle , Steel Alistair , Sherren Peter B. , Barnard Ed B G
Published: December 2023

Background

Critical hypertension in major trauma patients is associated with increased mortality. Prehospital emergency anaesthesia (PHEA) is performed for 10% of the most seriously injured patients. Optimising oxygenation, ventilation, and cerebral perfusion, whilst avoiding extreme haemodynamic fluctuations are the cornerstones of reducing secondary brain injury. The aim of this study was to report the differential determinants of post-PHEA critical hypertension in a large regional dataset of trauma patients across three Helicopter Emergency Medical Service (HEMS) organisations.

Methods

A multi-centre retrospective observational study of consecutive adult trauma patients undergoing PHEA across three HEMS in the United Kingdom; 2015–2022. Critical hypertension was defined as a new systolic blood pressure (SBP) > 180mmHg within 10 min of induction of anaesthesia, or > 10% increase if the baseline SBP was > 180mmHg prior to induction. Purposeful logistical regression was used to explore variables associated with post-PHEA critical hypertension in a multivariable model. Data are reported as number (percentage), and odds ratio (OR) with 95% confidence interval (95%CI).

Results

30,744 patients were attended by HEMS during the study period; 2161 received PHEA and 1355 patients were included in the final analysis. 161 (11.9%) patients had one or more new episode(s) of critical hypertension ≤ 10 min post-PHEA. Increasing age (compared with 16–34 years): 35–54 years (OR 1.76, 95%CI 1.03–3.06); 55–74 years (OR 2.00, 95%CI 1.19–3.44); ≥75 years (OR 2.38, 95%CI 1.31–4.35), pre-PHEA Glasgow Coma Scale (GCS) motor score four (OR 2.17, 95%CI 1.19–4.01) and five (OR 2.82, 95%CI 1.60–7.09), patients with a pre-PHEA SBP > 140mmHg (OR 6.72, 95%CI 4.38–10.54), and more than one intubation attempt (OR 1.75, 95%CI 1.01–2.96) were associated with post-PHEA critical hypertension.

Conclusion

Delivery of PHEA to seriously injured trauma patients risks haemodynamic fluctuation. In adult trauma patients undergoing PHEA, 11.9% of patients experienced post-PHEA critical hypertension. Increasing age, pre-PHEA GCS motor score four and five, patients with a pre-PHEA SBP > 140mmHg, and more than intubation attempt were independently associated with post-PHEA critical hypertension.
Fasting hepatic insulin clearance reflects postprandial hepatic insulin clearance: a brief report
Authors: Okura Tsuyoshi , Nakamura Risa , Kitao Sonoko , Ito Yuichi , Anno Mari , Matsumoto Kazuhisa , Shoji Kyoko , Matsuzawa Kazuhiko , Izawa Shoichiro , Okura Hiroko , Ueta Etsuko , Kato Masahiko , Imamura Takeshi , Taniguchi Shin-ichi , Yamamoto Kazuhiro
Published: December 2023

Background

Hepatic insulin clearance (HIC) is an important pathophysiology of type 2 diabetes mellitus (T2DM). HIC was reported to decrease in patients with type 2 diabetes and metabolic syndrome. HIC is originally calculated by post-load insulin and C-peptide from the oral glucose tolerance test (OGTT). However, OGTT or meal tolerance tests are a burden for patients, and OGTT is not suitable for overt diabetes due to the risk of hyperglycemia. If we can calculate the HIC from the fasting state, it is preferable. We hypothesized that fasting HIC correlates with postprandial HIC in both participants with T2DM and without diabetes. We investigated whether fasting HIC correlates with postprandial HIC in overt T2DM and nondiabetes subjects (non-DM) evaluated by using glucose clamp and meal load.

Methods

We performed a meal tolerance test and hyperinsulinemic–euglycemic clamp in 70 subjects, 31 patients with T2DM and 39 non-DM subjects. We calculated the postprandial C-peptide AUC-to-insulin AUC ratio as the postprandial HIC and the fasting C-peptide-to-insulin ratio as the fasting HIC. We also calculated whole-body insulin clearance from the glucose clamp test.

Results

The fasting HIC significantly correlated with postprandial HIC in T2DM (r_S = 0.82, P < 0.001). Nondiabetes subjects also showed a significant correlation between fasting and postprandial HIC (r_S = 0.71, P < 0.001). Fasting HIC in T2DM was correlated with BMI, HbA1c, gamma-glutamyl transpeptidase, HOMA-IR, HOMA-beta, M/I, and whole-body insulin clearance. Fasting HIC in nondiabetes subjects was correlated with HOMA-IR and HOMA-beta.

Conclusions

These results suggest that fasting HIC is strongly correlated with postprandial HIC in both overt T2DM and non-DM patients, as evaluated by the meal test and glucose clamp method. Fasting HIC could be a convenient marker of HIC.
A European Society of Oncologic Imaging (ESOI) survey on the radiological assessment of response to oncologic treatments in clinical practice
Authors: Cappello Giovanni , Romano Vittorio , Neri Emanuele , Fournier Laure , D’Anastasi Melvin , Laghi Andrea , Zamboni Giulia A. , Beets-Tan Regina G. H. , Schlemmer Heinz-Peter , Regge Daniele
Published: December 2023

Objectives

To present the results of a survey on the assessment of treatment response with imaging in oncologic patient, in routine clinical practice. The survey was promoted by the European Society of Oncologic Imaging to gather information for the development of reporting models and recommendations.

Methods

The survey was launched on the European Society of Oncologic Imaging website and was available for 3 weeks. It consisted of 5 sections, including 24 questions related to the following topics: demographic and professional information, methods for lesion measurement, how to deal with diminutive lesions, how to report baseline and follow-up examinations, which previous studies should be used for comparison, and role of RECIST 1.1 criteria in the daily clinical practice.

Results

A total of 286 responses were received. Most responders followed the RECIST 1.1 recommendations for the measurement of target lesions and lymph nodes and for the assessment of tumor response. To assess response, 48.6% used previous and/or best response study in addition to baseline, 25.2% included the evaluation of all main time points, and 35% used as the reference only the previous study. A considerable number of responders used RECIST 1.1 criteria in daily clinical practice (41.6%) or thought that they should be always applied (60.8%).

Conclusion

Since standardized criteria are mainly a prerogative of clinical trials, in daily routine, reporting strategies are left to radiologists and oncologists, which may issue local and diversified recommendations. The survey emphasizes the need for more generally applicable rules for response assessment in clinical practice.

Critical relevance statement

Compared to clinical trials which use specific criteria to evaluate response to oncological treatments, the free narrative report usually adopted in daily clinical practice may lack clarity and useful information, and therefore, more structured approaches are needed.

Key points

· Most radiologists consider standardized reporting strategies essential for an objective assessment of tumor response in clinical practice.

· Radiologists increasingly rely on RECIST 1.1 in their daily clinical practice.

· Treatment response evaluation should require a complete analysis of all imaging time points and not only of the last.

Graphical Abstract
The heterogeneity of mesenchymal stem cells: an important issue to be addressed in cell therapy
Authors: Li Jingxuan , Wu Zewen , Zhao Li , Liu Yang , Su Yazhen , Gong Xueyan , Liu Fancheng , Zhang Liyun
Published: December 2023

With the continuous improvement of human technology, the medical field has gradually moved from molecular therapy to cellular therapy. As a safe and effective therapeutic tool, cell therapy has successfully created a research boom in the modern medical field. Mesenchymal stem cells (MSCs) are derived from early mesoderm and have high self-renewal and multidirectional differentiation ability, and have become one of the important cores of cell therapy research by virtue of their immunomodulatory and tissue repair capabilities. In recent years, the application of MSCs in various diseases has received widespread attention, but there are still various problems in the treatment of MSCs, among which the heterogeneity of MSCs may be one of the causes of the problem. In this paper, we review the correlation of MSCs heterogeneity to provide a basis for further reduction of MSCs heterogeneity and standardization of MSCs and hope to provide a reference for cell therapy.
Electrical stimulation affects the differentiation of transplanted regionally specific human spinal neural progenitor cells (sNPCs) after chronic spinal cord injury
Authors: Patil Nandadevi , Korenfeld Olivia , Scalf Rachel N. , Lavoie Nicolas , Huntemer-Silveira Anne , Han Guebum , Swenson Riley , Parr Ann M.
Published: December 2023

Background

There are currently no effective clinical therapies to ameliorate the loss of function that occurs after spinal cord injury. Electrical stimulation of the rat spinal cord through the rat tail has previously been described by our laboratory. We propose combinatorial treatment with human induced pluripotent stem cell-derived spinal neural progenitor cells (sNPCs) along with tail nerve electrical stimulation (TANES). The purpose of this study was to examine the influence of TANES on the differentiation of sNPCs with the hypothesis that the addition of TANES would affect incorporation of sNPCs into the injured spinal cord, which is our ultimate goal.

Methods

Chronically injured athymic nude rats were allocated to one of three treatment groups: injury only, sNPC only, or sNPC + TANES. Rats were sacrificed at 16 weeks post-transplantation, and tissue was processed and analyzed utilizing standard histological and tissue clearing techniques. Functional testing was performed. All quantitative data were presented as mean ± standard error of the mean. Statistics were conducted using GraphPad Prism.

Results

We found that sNPCs were multi-potent and retained the ability to differentiate into mainly neurons or oligodendrocytes after this transplantation paradigm. The addition of TANES resulted in more transplanted cells differentiating into oligodendrocytes compared with no TANES treatment, and more myelin was found. TANES not only promoted significantly higher numbers of sNPCs migrating away from the site of injection but also influenced long-distance axonal/dendritic projections especially in the rostral direction. Further, we observed localization of synaptophysin on SC121-positive cells, suggesting integration with host or surrounding neurons, and this finding was enhanced when TANES was applied. Also, rats that were transplanted with sNPCs in combination with TANES resulted in an increase in serotonergic fibers in the lumbar region. This suggests that TANES contributes to integration of sNPCs, as well as activity-dependent oligodendrocyte and myelin remodeling of the chronically injured spinal cord.

Conclusions

Together, the data suggest that the added electrical stimulation promoted cellular integration and influenced the fate of human induced pluripotent stem cell-derived sNPCs transplanted into the injured spinal cord.
Seasonal changes of soil microbiota and its association with environmental factors in coal mining subsidence area
Authors: Wang Meng , Sun Mengyao , Zhao Yue , Shi Yuying , Sun Shuo , Wang Shen , Zhou Yiping , Chen Lei
Published: December 2023

As a special type of wetland, the new wetland in the coal mining subsidence area is highly sensitive to environmental changes. In recent years, more and more attention has been paid to the studies of soil microbial diversity in newly born wetlands in coal mining subsidence areas. However, there are few reports on the seasonal variation of soil microbial diversity and its relationship with soil physical and chemical properties. In this study, 16S rRNA gene sequencing technology was used to analyze the seasonal changes of soil microbial composition and functional diversity in newly formed wetlands in coal mining subsidence areas, and to determine the seasonal changes of soil nutrient elements and physical and chemical properties in coal mining subsidence areas, so as to analyze the correlation between soil microbial diversity and soil nutrient elements and physical and chemical properties in newly formed wetlands in coal mining subsidence areas. A total of 16,050 OTUs were obtained after sample gene noise reduction. Proteobacteria, Acidobacteriota and Bacteroidota were the highest abundance in the coal mining subsidence area of Jining. The two seasons gathered separately, and temperature (Temp), total phosphorus (TP), available phosphorus (AP), total organic carbon (TOC) and dry matter content (DMC) were the key factors for the seasonal change of soil microbial community in the wetland of the coal mining subsidence area of Jining. The contents of Temp, AP and TP were significantly correlated with the abundance of soil microorganisms in summer subsidence area, while the contents of DMC and TOC were significantly correlated with the abundance of soil microorganisms in winter subsidence area. Soil microbial diversity in coal mining subsidence area was correlated with the seasons. Temp, TP, AP, TOC and DMC were the key factors for the seasonal change of soil microbial community in the wetland of the coal mining subsidence area of Jining.
Diagnostic performance of CL Detect rapid-immunochromatographic test for cutaneous leishmaniasis: a systematic review and meta-analysis
Authors: Gebremeskele Behailu Taye , Adane Gashaw , Adem Mohammed , Tajebe Fitsumbrhan
Published: December 2023

Background

Sensitive, robust, and fast point-of-care tests are needed for cutaneous leishmaniasis (CL) diagnosis. The recently developed CL Detect rapid test (InBios) for detecting Leishmania peroxidoxin antigen has been evaluated in several studies. However, diagnostic performances were controversial. Therefore, this systematic review and meta-analysis aimed to determine the pooled sensitivity and specificity of CL Detect for CL diagnosis.

Methods

PubMed, Scopus, EMBASE, ScienceDirect, and Google Scholar were sources of articles. We included studies reporting the diagnostic accuracy of CL Detect and CL-suspected patients in the English language. The methodological qualities of the included studies were appraised using the quality assessment of diagnostic accuracy studies-2 (QUADAS‐2). Meta-analysis was conducted using Stata 14.2 and R software.

Results

A total of 9 articles were included. The study sample size ranged from 11 to 274. The sensitivities of the individual studies ranged from 23 to 100%, and the specificities ranged from 78 to 100%. Pooled sensitivity and specificity were 68% (95% CI, 41–86%) and 94% (95% CI, 87–97%), respectively. AUC displayed 0.899. Pooled sensitivity was lower (47%, 95% CI, 34–61%) when PCR was used as a reference than microscopy (83%, 95% CI, 39–97%). Pooled sensitivity was lower (48%, 95% CI, 30–67%) for all lesion durations compared to ≤ 4 months (89%, 95% CI, 43–99%).

Conclusions

CL Detect has poor sensitivity and does not meet the minimal sensitivity of 95% of target product profiles designed for CL point-of-care tests. Currently, the CL Detect test looks unsuitable for CL diagnosis, despite its high specificity. Findings are limited by the low number of studies available. Further large-scale studies are recommended.

Systematic review registration

PROSPERO CRD42022323497.
Functional traits: the pathways to riverine plant resistance in times of hydropeaking
Authors: Baladrón Alejandro , Bejarano María Dolores , Boavida Isabel
Published: December 2023

Hydropeaking, which refers to rising or falling discharges caused by the turning on or off of hydro-turbines to generate electricity, is a topic of growing interest due to its impact on fluvial ecosystems. To date, most hydropeaking studies have focused on the impact of peak fluctuations on invertebrate and fish communities, but little attention has been paid to its impact on riverine plants and how functional traits may make them resistant to hydropeaking. We performed a review to assess how a set of 32 plant functional traits can be expressed in riverine plant species, and found evidence of how such expression affects their capacity to cope with common sources of hydropeaking disturbance (i.e., inundation, fast water drawdown, and rapid water fluctuations linked to up-ramping and down-ramping hydropeaking operations). The information here presented can simplify the evaluation of impacts on riverine plant communities worldwide, as well as to detect suitable species to successfully restore rivers affected by hydropower production.
Gut microbiota affects the estrus return of sows by regulating the metabolism of sex steroid hormones
Authors: Liu Min , Zhang Jia , Zhou Yunyan , Xiong Shuqi , Zhou Mengqing , Wu Lin , Liu Qin , Chen Zhe , Jiang Hui , Yang Jiawen , Liu Yuxin , Wang Yaxiang , Chen Congying , Huang Lusheng
Published: December 2023

Background

Sex hormones play important roles in the estrus return of post-weaning sows. Previous studies have demonstrated a complex and bi-directional regulation between sex hormones and gut microbiota. However, the extent to which the gut microbiota affects estrus return of post-weaning sows is largely unknown.

Results

In this study, we first screened 207 fecal samples from well-phenotyped sows by 16S rRNA gene sequencing and identified significant associations between microbes and estrus return of post-weaning sows. Using metagenomic sequencing data from 85 fecal samples, we identified 37 bacterial species that were significantly associated with estrus return. Normally returning sows were characterized by increased abundances of L. reuteri and P. copri and decreased abundances of B. fragilis, S. suis, and B. pseudolongum. The changes in gut microbial composition significantly altered the functional capacity of steroid hormone biosynthesis in the gut microbiome. The results were confirmed in a validation cohort. Significant changes in sex steroid hormones and related compounds were found between normal and non-return sows via metabolome analysis. An integrated analysis of differential bacterial species, metagenome, and fecal metabolome provided evidence that normal return-associated bacterial species L. reuteri and Prevotella spp. participated in the degradation of pregnenolone, progesterone, and testosterone, thereby promoting estrogen biosynthesis. Furthermore, the microbial metabolites related to sow energy and nutrient supply or metabolic disorders also showed relationships with sow estrus return.

Conclusions

An integrated analysis of differentially abundant bacterial species, metagenome, and fecal metabolome revealed the involvement of L. reuteri and Prevotella spp. in sow estrus return. These findings provide deep insight into the role of gut microbiota in the estrus return of post-weaning sows and the complex cross-talk between gut microbiota and sex hormones, suggesting that the manipulation of the gut microbiota could be an effective strategy to improve sow estrus return after weaning.
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

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

Traumatic 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

Capillary 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

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

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

Vehicle 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

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

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

Acute 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

Efferent 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

Global 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.
Impact of diastolic pulmonary gradient and pulmonary vascular remodeling on survival after left ventricular assist device implantation and heart transplantation
Authors: Laimoud Mohamed , Hakami Emad , Maghirang Mary Jane , Mohamed Tahir
Published: December 2023

Background

The left ventricular assist devices (LVADs) are increasingly used for advanced heart failure as a bridge to heart transplantation or as a destination therapy. The aim of this study was to investigate the changes of diastolic pulmonary gradient (DPG), pulmonary vascular resistance (PVR) and transpulmonary gradient (TPG) after LVAD implantation and their impact on survival after LVAD and heart transplantation.

Results

A total of 73 patients who underwent LVAD (HeartMate III) implantation between 2016 and 2022 were retrospectively studied. According to pre-LVAD catheterization, 49 (67.1%) patients had DPG < 7 mmHg and 24 (32.9%) patients had DPG ≥ 7 mmHg. The patients with a pre-VAD DPG ≥ 7 mmHg had higher frequencies of right ventricular (RV) failure (p < 0.001), RVAD insertion (p < 0.001), need for renal replacement therapy (p = 0.002), total mortality (p = 0.036) and on-VAD mortality (p = 0.04) with a longer ICU stay (p = 0.001) compared to the patients with DPG < 7 mmHg. During the follow-up period of 38 (12–60) months, 24 (32.9%) patients died. Pre-LVAD DPG ≥ 7 mmHg (adjusted HR 1.83, 95% CI 1.21–6.341, p = 0.039) and post-LVAD DPG ≥ 7 mmHg (adjusted HR 3.824, 95% CI 1.482–14.648, p = 0.002) were associated with increased risks of mortality. Neither pre-LVAD TPG ≥ 12 (p = 0.505) nor post-LVAD TPG ≥ 12 mmHg (p = 0.122) was associated with an increased risk of death. Pre-LVAD PVR ≥ 3 WU had a statistically insignificant risk of mortality (HR 2.35, 95% CI 0.803–6.848, p = 0.119) while post-LVAD PVR ≥ 3 WU had an increased risk of death (adjusted HR 2.37, 95% CI 1.241–7.254, p = 0.038). For post-transplantation mortality, post-LVAD DPG ≥ 7 mmHg (p = 0.55), post-LVAD TPG ≥ 12 mmHg (p = 0.85) and PVR ≥ 3 WU (p = 0.54) did not have statistically increased risks. The logistic multivariable regression showed that post-LVAD PVR ≥ 3 WU (p = 0.013), post-LVAD DPG ≥ 7 mmHg (p = 0.026) and RVF (p = 0.018) were the predictors of mortality after LVAD implantation. Pre-LVAD DPG ≥ 7 mmHg (p < 0.001) and pre-LVAD PVR ≥ 3 WU (p = 0.036) were the predictors of RVF after LVAD implantation.

Conclusions

Persistently high DPG was associated with right ventricular failure and mortality after LVAD implantation rather than after heart transplantation. DPG is a better predictor of pulmonary vascular remodeling compared to TPG and PVR. Further larger prospective studies are required in this field due to the growing numbers of patients with advanced heart failure, as possible candidates for LVAD implantation, and limitations of heart transplantation.
Mental health status of patients with bipolar disorder during COVID-19 lockdown: a cross-sectional study at El Khanka Psychiatric Hospital
Authors: Gabrielle Fiby F. , El-Shahawi Heba H. , Ghamry Reem H. El , Basha Marwa Y.
Published: December 2023

Background

The COVID-19 pandemic necessitated a number of measures including lockdowns and social distancing. These measures affected mental health in healthy individuals and mentally affected patients. Studies examining the effectiveness of such strategies are still limited, and those with bipolar disorder (BD) are an especially vulnerable population. The current research aimed to evaluate the mental health status of BD patients throughout the pandemic, particularly as regards increasing the rate of relapse and appearance of other psychiatric comorbidities, and to evaluate and contrast the acute stress and psychological association experienced by persons with BD and those without mental diseases through the pandemic.

Results

A total of 103 participants were involved in the study, 50 in the diseased group and 53 in the healthy group. Concerning demographic data, there was significant variation among the two groups concerning gender, marital status, education, employment, and socio-economic status. A study of COVID-19’s association with psychometric data revealed a significantly higher score of IES-R in healthy participants compared to diseased. A comparison of COVID-19-affected patients and COVID-19-not affected patients revealed a statistically significant association between the IES-R median score result and COVID-19 effects.

Conclusion

There was no significant distinction between healthy and diseased groups concerning scales of depression, anxiety, or insomnia. However, COVID-19 pandemic significantly affected routine life stress and acute stress measured by IES-R.
Translation and validation of the Arabic version of the Digital Stress Scale (DSS-A) with three Arabic-speaking samples
Authors: Krägeloh Christian U. , Medvedev Oleg N. , Alyami Hussain , Alammar Hetaf A. , Hamdan-Mansour Ayman , Alyami Emad , Alsoudi Sharif , Henning Marcus A. , Alyami Mohsen M.
Published: December 2023

Objective

Given the ubiquitous nature of digital technologies such as smartphones, research has increasingly focused on the health outcomes of prolonged use of such technologies. The Digital Stress Scale (DSS) has been developed recently, but it is currently only available in English and Chinese, and validations in other languages are warranted.

Methods

The 24-item DSS was translated into Arabic using the method of translation and back-translation. Using a general population sample (n = 1069) from Saudi Arabia, Oman, and Jordan, the psychometric properties of the Arabic DSS (DSS-A) were investigated using higher-order confirmatory factor analysis.

Results

The original five-factor structure was replicated for the DSS-A without the need for any modifications such as item deletion or reassignment of items to another factor. Reliability was excellent for the total scale score (α = 0.92) as well as for the five subscales (α ranged between 0.81 and 0.91). Convergent validity was supported by significant correlations between the DSS-A and psychological distress.

Conclusion

The strong psychometric properties of the DSS-A imply that this scale can now be used with high validity and reliability to explore the role of digital stress and its sub-characteristics in Arabic-speaking populations.