bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of comutation in signaling pathways to predict the clinical outcomes of immunotherapy
Authors: Qiu Jiayue , Li Xiangmei , He Yalan , Wang Qian , Li Ji , Wu Jiashuo , Jiang Ying , Han Junwei 
Published: December 2022

AbstractBackgroundImmune checkpoint blockades (ICBs) have emerged as a promising treatment for cancer. Recently, tumour mutational burden (TMB) and neoantigen load (NAL) have been proposed to be potential biomarkers to predict the efficacy of ICB; however, they were limited by difficulties in defining the cut-off values and inconsistent detection platforms. Therefore, it is critical to identify more effective predictive biomarkers for screening patients who will potentially benefit from immunotherapy. In this study, we aimed to identify comutated signaling pathways to predict the clinical outcomes of immunotherapy.MethodsHere, we comprehensively analysed the signaling pathway mutation status of 9763 samples across 33 different cancer types from The Cancer Genome Atlas (TCGA) by mapping the somatic mutations to the pathways. We then explored the comutated pathways that were associated with increased TMB and NAL by using receiver operating characteristic (ROC) curve analysis and multiple linear regressions.ResultsOur results revealed that comutation of the Spliceosome (Sp) pathway and Hedgehog (He) signaling pathway (defined as SpHe-comut+) could be used as a predictor of increased TMB and NAL and was associated with increased levels of immune-related signatures. In seven independent immunotherapy cohorts, we validated that SpHe-comut+patients exhibited a longer overall survival (OS) or progression-free survival (PFS) and a higher objective response rate (ORR) than SpHe-comut−patients. Moreover, a combination of SpHe-comut status with PD-L1 expression further improved the predictive value for ICB therapy.ConclusionOverall, SpHe-comut+was demonstrated to be an effective predictor of immunotherapeutic benefit in seven independent immunotherapy cohorts and may serve as a potential and convenient biomarker for the clinical application of ICB therapy.
Associations between life’s essential 8 and non-alcoholic fatty liver disease among US adults
Authors: Wang Lili , Yi Jiayi , Guo Xinli , Ren Xiangpeng 
Published: December 2022

Abstract
Background
Nonalcoholic fatty liver disease (NAFLD) is closely associated with Cardiovascular disease (CVD). We aim to examine the association of Life’s Essential 8 (LE8), the recently updated measurement of cardiovascular health (CVH), with the presence of NAFLD among US adults.

Methods
This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey in 2017–2018 and included adults 20 years or older. LE8 score (range 0–100) was measured according to American Heart Association definitions and was categorized into low (0–49), moderate (50–79), and high (80–100) CVH. NAFLD was determined by transient elastography measured hepatic steatosis in the absence of other liver diseases and excess alcohol use. Multivariable logistic and restricted cubic spline models were used to assess the associations.

Results
Among 3588 participants included (weighted mean age, 48.0 years; 95% confidence interval [CI] 46.4–49.7 years), 1839 were female (weighted percentage, 51.6%; 95% CI 49.0–54.2%) and 1483 were determined to have NAFLD (weighted percentage, 36.5%; 95% CI 33.3–39.7%). The weighted mean LE8 score of the study population was 67.9 (95% CI 66.6–69.2). After the adjustment of potential confounders, higher LE8 scores were associated with reduced odds of NAFLD (odds ratio [OR] for per 10 score increase, 0.67; 95% CI 0.59–0.76) and a nonlinear dose–response relationship was observed. Similar patterns were also identified in the association of health behavior and health factor scores with NAFLD. The inversed association of LE8 score and NAFLD was significantly stronger among younger, Asian, and participants with higher education and income level.

Conclusions
LE8 and its subscales scores were negatively associated with the presence of NAFLD in non-linear fashions. Promoting adherence to optimal CVH levels may be beneficial to reduce the burden of NAFLD as well as CVD.
Donor support for Health Policy and Systems Research: barriers to financing and opportunities for overcoming them
Authors: Kentikelenis Alexander , Ghaffar Abdul , McKee Martin , Dal Zennaro Livia , Stuckler David 
Published: December 2022

Abstract
Background
The vast investments that have been made in recent decades in new medicines, vaccines, and technologies will only lead to improvements in health if there are appropriate and well-functioning health systems to make use of them. However, despite the growing acceptance by major global donors of the importance of health systems, there is an enthusiasm gap when it comes to disbursing funds needed to understand the intricacies of how, why and when these systems deliver effective interventions. To understand the reasons behind this, we open up the black box of donor decision-making vis-à-vis Health Policy and Systems Research (HPSR) financing: what are the organizational processes behind the support for HPSR, and what are the barriers to increasing engagement?

Methods
We conducted 27 semi-structured interviews with staff of major global health funders, asking them about four key issues: motivations for HPSR financing; priorities in HPSR financing; barriers for increasing HPSR allocations; and challenges or opportunities for the future. We transcribed the interviews and manually coded responses.

Results
Our findings point to the growing appreciation that funders have of HPSR, even though it is often still seen as an ‘afterthought’ to larger programmatic interventions. In identifying barriers to funding HPSR, our informants emphasised the perceived lack of mandate and capacities of their organizations. For most funding organisations, a major barrier was that their leadership often voiced scepticism about HPSR’s long time horizons and limited ability to quantify results.

Conclusion
Meeting contemporary health challenges requires strong and effective health systems. By allocating more resources to HPSR, global donors can improve the quality of their interventions, and also contribute to building up a stock of knowledge that domestic policymakers and other funders can draw on to develop better targeted programmes and policies.
Sinonasal mucosal melanoma with smooth muscle differentiation: a potential pathological diagnostic pitfall
Authors: Tang Hao , He Yutao , Chen Ying , Xu Wenfeng , Xu Yujuan , Li Xianyun , Guo Deyu 
Published: December 2022

AbstractBackgroundSinonasal mucosal melanoma (SNMM) is a rare malignant melanoma originating from melanocytes derived from multipotent neural crest cells. Its incidence accounts for less than 1 % of all malignant melanomas, with five-year survival rate about 25 %. Occasionally, it is incredibly formidable to make a compelling diagnosis when malignant melanoma with other diverse differentiation.Case presentationHerein, we presented a 54-year-old male case of SNMM with smooth muscle differentiation, defined by histopathology and positive immunostaining for the smooth muscle specific markers of a-SMA, H-caldesmon, calponin and Desmin, as well as specific melanocyte markers of HMB-45, Melan-A, SOX10, and PNL2.ConclusionsMucosal melanoma with smooth muscle differentiation is remarkably infrequent, and reported only 4 cases to date. It would be a potential pathological diagnostic pitfall. It is important to understand this variation of malignant melanoma for avoiding misdiagnosis.
Achilles tendon thickness reduces immediately after a marathon
Authors: Scott Isabelle , Malliaras Peter , Tardioli Alex , Hales Sarah , Morrissey Dylan , Migliorini Filippo , Maffulli Nicola 
Published: December 2022

Abstract
Background
The purpose of the present investigation was to evaluate the immediate effect of running a marathon on Achilles tendon anteroposterior thickness.

Methods
In 25 runners who took part in the London marathon, ultrasonography was used to measure the Achilles tendon thickness pre- and immediately post-marathon and to identify any structural abnormalities indicating tendinopathy. Pain was recorded using a numerical rating scale at baseline and post-marathon. Twenty-one participants were included in the final analysis.

Results
Running a marathon resulted in a significant decrease (− 13%, p < 0.01) in anteroposterior diameter of the Achilles tendon immediately following the marathon. There was no change in the proportion of Achilles tendons with structural abnormalities (34%) or pain (12%) following the marathon (p > 0.05).

Conclusion
Running a marathon resulted in an immediate reduction in anteroposterior diameter of the Achilles tendon. This finding may have implications for injury prevention and recovery following a marathon.
Histopathological and radiographical evaluation of caprine demineralized bone matrix in a critical ulnar defect in a rabbit model
Authors: Alimi Olawale Alimi , Abubakar Adamu Abdul , Yakubu Abubakar Sadiq , Shehu Sani Abdullahi , Abdulkadir Salman Zubairu 
Published: December 2022

Abstract
Background
Caprine species satisfy the conditions of an ideal donor animal when compared to bovine species that has been extensively studied and commercialized for bone xenograft. Histopathological and radiological evaluations of caprine demineralized bone matrix (CDBM) were therefore carried out for fracture healing properties for its possible use in bone grafting procedures.

Materials and methods
Twenty-four rabbits were used for this study and were divided randomly into three groups of eight (n = 8) rabbits each. Critical bone defect was created on the ulnar diaphysis under xylazine-ketamine anaesthesia for autogenous bone graft (ABG) group, CDBM group and the last group was left unfilled as negative control (NC). Immediate post-grafting radiograph was taken and repeated on days 14, 28, 42 and 56 to monitor the evidence of radiographic healing. The animals were euthanized on day 56 and defect sites were harvested for histopathology.

Results
There was a progressive evidence of radiographic healing and bone formation in all the groups with significance difference (P = 0.0064). When compared with ABG, NC differ significantly (P < 0.0001) whereas the CDBM did not differ significantly (P = 0.6765). The histopathology sections of ABG and CDBM showed normal bone tissue while the NC section was predominated by fibrous connective tissue. There was therefore an overall significant difference (P = 0.0001) in which CDBM did not differ from ABG (P = 0.2946) while NC did (P = 0.0005).

Conclusion
The ABG and CDBM groups showed a similar healing effect in the critical bone defect. Therefore, CDBM could be used as an effective alternative to ABG in orthopaedics to circumvent the limitations and complications associated with it.

Level of evidence
Not applicable.
TREM2 dependent and independent functions of microglia in Alzheimer’s disease
Authors: Hou Jinchao , Chen Yun , Grajales-Reyes Gary , Colonna Marco 
Published: December 2022

AbstractMicroglia are central players in brain innate immunity and have been the subject of extensive research in Alzheimer’s disease (AD). In this review, we aim to summarize the genetic and functional discoveries that have advanced our understanding of microglia reactivity to AD pathology. Given the heightened AD risk posed by rare variants of the microglial triggering receptor expressed on myeloid cells 2 (TREM2), we will focus on the studies addressing the impact of this receptor on microglia responses to amyloid plaques, tauopathy and demyelination pathologies in mouse and human. Finally, we will discuss the implications of recent discoveries on microglia and TREM2 biology on potential therapeutic strategies for AD.
Effect of high-flow oxygen versus T-piece ventilation strategies during spontaneous breathing trials on weaning failure among patients receiving mechanical ventilation: a randomized controlled trial
Authors: Lee Hong Yeul , Lee Jinwoo , Lee Sang-Min 
Published: December 2022

Abstract
Background
A spontaneous breathing trial (SBT) is used to determine whether patients are ready for extubation, but the best method for choosing the SBT strategy remains controversial. We investigated the effect of high-flow oxygen versus T-piece ventilation strategies during SBT on rates of weaning failure among patients receiving mechanical ventilation.

Methods
This randomized clinical trial was conducted from June 2019 through January 2022 among patients receiving mechanical ventilation for ≥ 12 h who fulfilled the weaning readiness criteria at a single-center medical intensive care unit. Patients were randomized to undergo either T-piece SBT or high-flow oxygen SBT. The primary outcome was weaning failure on day 2, and the secondary outcomes were weaning failure on day 7, ICU and hospital length of stay, and ICU and in-hospital morality.

Results
Of 108 patients (mean age, 67.0 ± 11.1 years; 64.8% men), 54 received T-piece SBT and 54 received high-flow oxygen SBT. Weaning failure on day 2 occurred in 5 patients (9.3%) in the T-piece group and 3 patients (5.6%) in the high-flow group (difference, 3.7% [95% CI, − 6.1–13.6]; p = 0.713). Weaning failure on day 7 occurred in 13 patients (24.1%) in the T-piece group and 7 patients (13.0%) in the high-flow group (difference, 11.1% [95% CI, − 3.4–25.6]; p = 0.215). A post hoc subgroup analysis showed that high-flow oxygen SBT was significantly associated with a lower rate of weaning failure on day 7 (OR, 0.17 [95% CI, 0.04–0.78]) among those patients intubated because of respiratory failure (p for interaction = 0.020). The ICU and hospital length of stay and mortality rates did not differ significantly between the two groups. During the study, no serious adverse events were recorded.

Conclusions
Among patients receiving mechanical ventilation, high-flow oxygen SBT did not significantly reduce the risk of weaning failure compared with T-piece SBT. However, the study may have been underpowered to detect a clinically important treatment effect for the comparison of high-flow oxygen SBT versus T-piece SBT, and a higher percentage of patients with simple weaning and a lower weaning failure rate than expected should be considered when interpreting the findings.
Clinical trial registration This trial was registered with ClinicalTrials.gov (number NCT03929328) on April 26, 2019.
Dietary and lifestyle associations with microbiome diversity
Authors: Watson Katherine M. , Siemens Kyla N. , Anand Sudarshan , Gardner Ivy H. , Sharpton Thomas J. , Dewey Elizabeth N. , Martindale Robert , Gaulke Christopher A. , Tsikitis Vassiliki Liana 
Published: December 2022

Abstract
Background
Microbial dysbiosis has been closely linked with colorectal cancer development. However, data is limited regarding the relationship of the mucosal microbiome, adenomatous polyps and dietary habits. Understanding these associations may elucidate pathways for risk stratification according to diet.

Results
Patients undergoing screening colonoscopy were included in our prospective, single center study and divided into adenoma or no adenoma cohorts. Oral, fecal, and mucosal samples were obtained. Microbial DNA was extracted, and amplicon libraries generated using primers for the 16S rRNA gene V4 region. Patient and dietary information was collected. Of 104 participants, 44% presented with polyps, which were predominantly tubular adenomas (87%). Adenoma formation and multiple patient dietary and lifestyle characteristics were associated with mucosal microbiome diversity. Lifestyle factors included age, body mass index, adenoma number, and dietary consumption of red meats, processed meats, vegetables, fruit, grain, fermented foods and alcohol.

Conclusion
In this study we showed associations between dietary habits, adenoma formation and the mucosal microbiome. These early findings suggest that ongoing research into diet modification may help reduce adenoma formation and subsequently the development of CRC.
Job scheduling problem in fog-cloud-based environment using reinforced social spider optimization
Authors: Kuppusamy P. , Kumari N. Marline Joys , Alghamdi Wael Y. , Alyami Hashem , Ramalingam Rajakumar , Javed Abdul Rehman , Rashid Mamoon 
Published: December 2022

AbstractFog computing is an emerging research domain to provide computational services such as data transmission, application processing and storage mechanism. Fog computing consists of a set of fog server machines used to communicate with the mobile user in the edge network. Fog is introduced in cloud computing to meet data and communication needs for Internet of Things (IoT) devices. However, the vital challenges in this system are job scheduling, which is solved by examining the makespan, minimizing energy depletion and proper resource allocation. In this paper, we introduced a reinforced strategy Dynamic Opposition Learning based Social Spider Optimization (DOLSSO) Algorithm to enhance individual superiority and schedule workflow in Fog computing. The extensive experiments were conducted using the FogSim simulator to generate the dataset and an energy-efficient open-source tool utilized to model and simulate resource management in fog computing. The performance of the formulated model is ratified using two test cases. The proposed algorithm attained the optimized schedule with minimized cost function concerning the CPU processing period and assigned memory. Our simulation outcomes show the efficacy of the introduced technique in handling job scheduling issues, and the results are contrasted with five existing metaheuristic techniques. The results show that the proposed method achieves 10% - 15% better CPU utilization and 5%-10% less energy consumption than the other techniques.
Sodium butyrate alleviates deoxynivalenol-induced hepatic cholesterol metabolic dysfunction via RORγ-mediated histone acetylation modification in weaning piglets
Authors: Zong Qiufang , Qu Huan , Zhao Yahui , Liu Haoyu , Wu Shenglong , Wang Shuai , Bao Wenbin , Cai Demin 
Published: December 2022

Abstract
Background
Cholesterol is an essential component of lipid rafts in cell plasma membrane, which exerts a hepatoprotective role against mycotoxin exposure in pigs, and cholesterol metabolism is vulnerable to epigenetic histone acetylation. Therefore, our present study aimed to investigate whether a histone deacetylase inhibitor (sodium butyrate [NaBu]) could protect the porcine liver from deoxynivalenol (DON) exposure by modulating cholesterol metabolism. Herein, we randomly divided 28 pigs into four groups, which were fed an uncontaminated basal diet, contaminated diet (4 mg DON/kg), uncontaminated diet supplemented with 0.2% NaBu or 4 mg/kg DON contaminated diet (4 mg DON/kg) supplemented with 0.2% NaBu for 28 d.

Results
We found that the serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were all increased in pigs exposed to DON, indicative of significant liver injury. Furthermore, the cholesterol content in the serum of DON-exposed pigs was significantly reduced, compared to the healthy Vehicle group. Transcriptome analysis of porcine liver tissues revealed that the cholesterol homeostasis pathway was highly enriched due to DON exposure. In which we validated by qRT-PCR and western blotting that the cholesterol program was markedly activated. Importantly, NaBu effectively restored parameters associated with liver injury, along with the cholesterol content and the expression of key genes involved in the cholesterol biosynthesis pathway. Mechanistically, we performed a ChIP-seq analysis of H3K27ac and showed that NaBu strongly diminished DON-increased H3K27ac genome-wide enrichment. We further validated that the elevated H3K27ac and H3K9ac occupancies on cholesterol biosynthesis genes were both decreased by NaBu, as determined by ChIP-qPCR analysis. Notably, nuclear receptor RORγ, a novel regulator of cholesterol biosynthesis, was found in the hyperacetylated regions. Again, a remarkable increase of RORγ at both mRNA and protein levels in DON-exposed porcine livers was drastically reduced by NaBu. Consistent with RORγ expression, NaBu also hindered RORγ transcriptional binding enrichments on these activated cholesterol biosynthesis genes like HMGCR, SQLE, and DHCR24. Furthermore, we conducted an in vitro luciferase reporter assay to verify that porcine RORγ directly bonds to the promoters of the above target genes.

Conclusions
Collectively, our results demonstrate the utility of the natural product NaBu as a potential anti-mycotoxin nutritional strategy for regulating cholesterol metabolism via RORγ-mediated histone acetylation modification.
Data analytics for crop management: a big data view
Authors: Chergui Nabila , Kechadi Mohand Tahar 
Published: December 2022

AbstractRecent advances in Information and Communication Technologies have a significant impact on all sectors of the economy worldwide. Digital Agriculture appeared as a consequence of the democratisation of digital devices and advances in artificial intelligence and data science. Digital agriculture created new processes for making farming more productive and efficient while respecting the environment. Recent and sophisticated digital devices and data science allowed the collection and analysis of vast amounts of agricultural datasets to help farmers, agronomists, and professionals understand better farming tasks and make better decisions. In this paper, we present a systematic review of the application of data mining techniques to digital agriculture. We introduce the crop yield management process and its components while limiting this study to crop yield and monitoring. After identifying the main categories of data mining techniques for crop yield monitoring, we discuss a panoply of existing works on the use of data analytics. This is followed by a general analysis and discussion on the impact of big data on agriculture.
Development of miniaturized pick-up amplification circuit for plasma particle detectors on board satellites
Authors: Kikukawa Motoyuki , Asamura Kazushi , Zushi Takahiro , Kurita Satoshi , Kojima Hirotsugu 
Published: December 2022

AbstractPlasma particles and waves are important observation targets in space plasmas for understanding the mechanisms of energy and momentum transfer between waves and particles because space plasmas are essentially collisionless. Multi-point observations are crucial for understanding the spatial–temporal variations of space plasmas. To realize such observations by a large number of satellites, onboard instruments should be miniaturized to reduce their required resources. This paper proposes a small amplifier for plasma particle detectors onboard satellites. This charge-sensitive amplifier converts an electron cloud emitted from the detector, for example a microchannel plate, to a current pulse that can be handled by a time-of-flight measurement circuit to determine the particle velocity and thus mass. The amplifier is realized using application-specific integrated circuit technology to minimize size. Its dimensions are estimated to be $$2120\,\mathrm{ \mu m }\times 1680\,\mathrm{ \mu m}$$

2120

μ
m

×
1680

μ
m

, which are much smaller than those of a conventional amplifier. The response time of the proposed amplifier has a variation of less than $$1.2\,\mathrm{ ns}$$

1.2

ns

over the range of expected input levels. The amplifier can handle up to $$2\times {10}^{7}$$

2
×

10

7

signals per second and has a sensitivity of $$1.5\,\mathrm{ V}/\mathrm{pC}$$

1.5

V
/
pC

at $$20\,\mathrm{^\circ{\rm C} }$$

20

∘

C

.
Graphical Abstract