bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of miR-500a-3p/CDK6 axis suppresses aerobic glycolysis and colorectal cancer progression
Authors: Liu Yu , Tang Wentao , Ren Li , Liu Tianyu , Yang Meng , Wei Ye , Chen Yijiao , Ji Meiling , Chen Guosong , Chang Wenju , Xu Jianmin 
Published: March 2022

Abstract
Background
Colorectal cancer (CRC) is one of the lethal cancers with a high mortality rate worldwide and understanding the mechanisms behind its progression is critical for improving patients’ prognosis and developing therapeutics. MiR-500a-3p has been demonstrated to be involved in the progression of several human cancers but its role in CRC remains unclear. The aim of this study is to uncover the expression pattern and mechanisms of action of miR-500a-3p during the CRC progression.

Methods
The expression of miR-500a-3p and Cyclin-dependent kinases 6 (CDK6) in 134 CRC tissues were tested by quantitative PCR (qPCR) and immunohistochemistry staining (IHC), respectively. The effect of miR-500a-3p on cell proliferation was explored in vitro and in vivo. The glycolysis of CRC cells was determined by Mass Spectrometry and Seahorse XF 96 Extracellular Flux Analyzer. A dual-luciferase reporter assay was performed to validate the relationship between miR-500a-3p and CDK6.

Results
miR-500a-3p was abnormally downregulated in CRC tissues and cell lines and was negatively associated with a worse prognosis. miR-500a-3p mimics impeded CRC cell proliferation in vitro and in vivo. miR-500a-3p inhibited glucose consumption, lactate and ATP production, and down-regulated the expression of hexokinase2 (HK2). In silico prediction combined with western blot and luciferase assay confirmed that CDK6 is a direct target of miR-500a-3p. Overexpression of CDK6 phenotypically rescued the inhibitory effect of miR-500a-3p on the proliferation and glycolysis of CRC cells.

Conclusions
Our study revealed a potential tumor-suppressive role of miR-500a-3p in CRC, specifically targeting CDK6 and inhibiting cancer cell proliferation and aerobic glycolysis, which may provide new insights into novel prognostic biomarkers and therapeutic targets for CRC.
MiR-25 overexpression inhibits titanium particle-induced osteoclast differentiation via down-regulation of mitochondrial calcium uniporter in vitro
Authors: Hu Weifan , Yu Yongbo , Sun Yang , Yuan Feng , Zhao Fengchao 
Published: March 2022

Abstract
Background
Mitochondrial calcium uniporter (MCU) is an important ion channel regulating calcium transport across the mitochondrial membrane. Calcium signaling, particularly via the Ca2+/NFATc1 pathway, has been identified as an important mediator of the osteoclast differentiation that leads to osteolysis around implants. The present study aimed to investigate whether down-regulation of MCU using microRNA-25 (miR-25) mimics could reduce osteoclast differentiation induced upon exposure to titanium (Ti) particles.

Methods
Ti particles were prepared. Osteoclast differentiation of RAW264.7 cells was induced by adding Ti particles and determined by TRAP staining. Calcium oscillation was determined using a dual-wavelength technique. After exposure of the cells in each group to Ti particles or control medium for 5 days, relative MCU and NFATc1 mRNA expression levels were determined by RT-qPCR. MCU and NFATc1 protein expression was determined by western blotting. NFATc1 activation was determined by immunofluorescence staining. Comparisons among multiple groups were conducted using one-way analysis of variance followed by Tukey test, and differences were considered significant if p < 0.05.

Results
MCU expression was reduced in response to miR-25 overexpression during the process of RAW 264.7 cell differentiation induced by Ti particles. Furthermore, osteoclast formation was inhibited, as evidenced by the low amplitude of calcium ion oscillation, reduced NFATc1 activation, and decreased mRNA and protein expression levels of nuclear factor-κB p65 and calmodulin kinases II/IV.

Conclusions
Regulation of MCU expression can impact osteoclast differentiation, and the underlying mechanism likely involves the Ca2+/NFATc1 signal pathway. Therefore, MCU may be a promising target in the development of new strategies to prevent and treat periprosthetic osteolysis.
Single-cell and spatially resolved analysis uncovers cell heterogeneity of breast cancer
Authors: Liu Si-Qing , Gao Zhi-Jie , Wu Juan , Zheng Hong-Mei , Li Bei , Sun Si , Meng Xiang-Yu , Wu Qi 
Published: March 2022

AbstractThe heterogeneity and the complex cellular architecture have a crucial effect on breast cancer progression and response to treatment. However, deciphering the neoplastic subtypes and their spatial organization is still challenging. Here, we combine single-nucleus RNA sequencing (snRNA-seq) with a microarray-based spatial transcriptomics (ST) to identify cell populations and their spatial distribution in breast cancer tissues. Malignant cells are clustered into distinct subpopulations. These cell clusters not only have diverse features, origins and functions, but also emerge to the crosstalk within subtypes. Furthermore, we find that these subclusters are mapped in distinct tissue regions, where discrepant enrichment of stromal cell types are observed. We also inferred the abundance of these tumorous subpopulations by deconvolution of large breast cancer RNA-seq cohorts, revealing differential association with patient survival and therapeutic response. Our study provides a novel insight for the cellular architecture of breast cancer and potential therapeutic strategies.
A serpiginous lesion of scrotum
Authors: Romano Sara , Dall’Amico Roberto , Declich Valentina , Barbi Egidio 
Published: March 2022

Abstract
Background
Median raphe cyst is usually benign and asymptomatic male genitalia lesions. Although uncommon, infection may be a complication.

Case presentation
We report the case of a 4-year-old child presented to the emergency department for a serpiginous and redness lesion extended from the basis of the penis until the perineum. An infected median raphe cyst was suspected, and the patient underwent surgical treatment and antibiotic therapy with complete resolution of symptoms. Liquid culture resulted positive for Serratia Marcescens.

Conclusion
Infection is a rare complication, especially in childhood. To prevent relapses and clinical symptoms, the majority of authors recommend surgical excision followed by primary closure. In case of infections caused by Serratia Marcescens, chronic granulomatous disease should always be rule out.
Randomized controlled trial: neostigmine for intra-abdominal hypertension in acute pancreatitis
Authors: He Wenhua , Chen Peng , Lei Yupeng , Xia Liang , Liu Pi , Zhu Yong , Zeng Hao , Wu Yao , Ke Huajing , Huang Xin , Cai Wenhao , Sun Xin , Huang Wei , Sutton Robert , Zhu Yin , Lu Nonghua 
Published: March 2022

AbstractBackgroundIntra-abdominal hypertension (IAH) in acute pancreatitis (AP) is associated with deterioration in organ function. This trial aimed to assess the efficacy of neostigmine for IAH in patients with AP.MethodsIn this single-center, randomized trial, consenting patients with IAH within 2 weeks of AP onset received conventional treatment for 24 h. Patients with sustained intra-abdominal pressure (IAP) ≥ 12 mmHg were randomized to receive intramuscular neostigmine (1 mg every 12 h increased to every 8 h or every 6 h, depending on response) or continue conventional treatment for 7 days. The primary outcome was the percent change of IAP at 24 h after randomization.ResultsA total of 80 patients were recruited to neostigmine (n = 40) or conventional treatment (n = 40). There was no significant difference in baseline parameters. The rate of decrease in IAP was significantly faster in the neostigmine group compared to the conventional group by 24 h (median with 25th–75th percentile: −18.7% [− 28.4 to − 4.7%] vs. − 5.4% [− 18.0% to 0],P = 0.017). This effect was more pronounced in patients with baseline IAP ≥ 15 mmHg (P = 0.018). Per-protocol analysis confirmed these results (P = 0.03). Stool volume was consistently higher in the neostigmine group during the 7-day observational period (allP < 0.05). Other secondary outcomes were not significantly different between neostigmine and conventional treatment groups.ConclusionNeostigmine reduced IAP and promoted defecation in patients with AP and IAH. These results warrant a larger, placebo-controlled, double-blind phase III trial.Trial registrationClinical Trial No:NCT02543658(registered August /27, 2015).
Distribution of delirium motor subtypes in the intensive care unit: a systematic scoping review
Authors: la Cour Kirstine N. , Andersen-Ranberg Nina C. , Weihe Sarah , Poulsen Lone M. , Mortensen Camilla B. , Kjer Cilia K. W. , Collet Marie O. , Estrup Stine , Mathiesen Ole 
Published: March 2022

AbstractBackgroundDelirium is the most common cerebral dysfunction in the intensive care unit (ICU) and can be subdivided into a hypoactive, hyperactive, or mixed motor subtype based on the clinical manifestation. The aim of this review was to describe the distribution, pharmacological interventions, and outcomes of delirium motor subtypes in ICU patients.MethodsThis systematic scoping review was performed according to the PRISMA-ScR and Cochrane guidelines. We performed a systematic search in six major databases to identify relevant studies. A meta-regression analysis was performed where pooled estimates with 95% confidence intervals were computed by a random effect model.ResultsWe included 131 studies comprising 13,902 delirious patients. There was a large between-study heterogeneity among studies, including differences in study design, setting, population, and outcome reporting. Hypoactive delirium was the most prevalent delirium motor subtype (50.3% [95% CI 46.0–54.7]), followed by mixed delirium (27.7% [95% CI 24.1–31.3]) and hyperactive delirium (22.7% [95% CI 19.0–26.5]). When comparing the delirium motor subtypes, patients with mixed delirium experienced the longest delirium duration, ICU and hospital length of stay, the highest ICU and hospital mortality, and more frequently received administration of specific agents (antipsychotics, α2-agonists, benzodiazepines, and propofol) during ICU stay. In studies with high average age for delirious patients (> 65 years), patients were more likely to experience hypoactive delirium.ConclusionsHypoactive delirium was the most prevalent motor subtype in critically ill patients. Mixed delirium had the worst outcomes in terms of delirium duration, length of stay, and mortality, and received more pharmacological interventions compared to other delirium motor subtypes. Few studies contributed to secondary outcomes; hence, these results should be interpreted with care. The large between-study heterogeneity suggests that a more standardized methodology in delirium research is warranted.
Endemicity and genetic diversity of Hepatitis delta virus among Pygmies in Cameroon, Central Africa
Authors: Foupouapouognigni Yacouba , Mfonkou Jacques Delors Toumansie , Boyomo Onana , Gessain Antoine , Njouom Richard 
Published: March 2022

Abstract
Objective
A single study conducted about three decades ago on hepatitis D virus (HDV) infection among Baka pygmies in Cameroon reported a very high anti-HDV antibodies prevalence of 46%, but HDV genetic diversity has not been studied in this population. The genetic diversity of strains from endemic ancient populations may help to understand the origin and evolutionary history of viruses. This study aimed to investigate the HDV seroprevalence and the genetic diversity in three remote Cameroonian Pygmies with chronic HBV infection.

Results
An unusually high 69% (36/52) level of HDV infection was found among HBsAg-positive pygmies in Cameroon. HDV RNA was detected and sequenced in 38.8% (14/36). The phylogenetic analysis revealed that 9/14 strains (64.3%) were identified and classified as genotype 1 (HDV-1) and 5/14 (35.6%) as genotype 7 (HDV-7), respectively with a bootstrap value of 100%. The further analysis showed the co-circulation of highly diverse HDV genotypes HDV-1 and HDV-7 in this population. These results highlight the endemicity of HDV infection in Central Africa. The highly diverse HDV-1 and HDV-7 in pygmies suggest an African origin of HDV. However, further studies are needed with larger sample size.
Catastrophic health expenditure due to hospitalisation for COVID-19 treatment in India: findings from a primary survey
Authors: Garg Samir , Bebarta Kirtti Kumar , Tripathi Narayan , Krishnendhu C. 
Published: March 2022

Abstract
Objective
The COVID-19 pandemic has caused widespread illness and a significant proportion of the infected required hospitalisation for treatment. People in developing countries like India were vulnerable to high hospitalisation costs. Despite its crucial importance, few primary studies are available on this aspect of the pandemic. This study was aimed at finding out the out of pocket expenditure (OOPE) and incidence of catastrophic expenditure on hospitalisation of persons infected with COVID-19. A primary survey of 492 randomly selected hospitalisations of individuals tested positive for COVID-19 in high-burden districts during August to November 2020 was carried out telephonically in Chhattisgarh state of India.

Results
Public hospitals accounted for 69% of the hospitalisations for COVID-19 treatment. Mean OOPE per hospitalisation was Indian Rupees (INR) 4871 in public hospitals and INR 169,504 in private hospitals. Around 3% of hospitalisations in public hospitals and 59% in private hospitals resulted in catastrophic expenditure, at a threshold of 40% of non-food annual household expenditure. Enrolment under publicly or privately funded health insurance was not effective in curtailing OOPE. Multivariate analysis showed that utilisation of private hospitals was a key determinant of incurring catastrophic expenditure.
Early infant feeding and allergic respiratory diseases in Ibb city, Yemen
Authors: Obaid Jamil M. A. S. , Ali Waheed A. M. , Al-badani Antar F. A. M. , Damag Zakaria M. , Aziz Tariq A. , Al-Ansi Yosef M. , Sadek Khawla A. 
Published: March 2022

Abstract
Background
Allergic respiratory diseases (ARD) are a highly prevalent health problem affecting infants and children in Yemen. Early infant feeding predisposition to the development of ARD has been a controversial question. The aim of this study is to investigate the association between early feeding before 6 months of age and the development of ARD among children attending Childhood and Maternity Public Hospital (CMPH), Ibb, Yemen Republic.

Subjects and methods
The study population included 151 child patients attending the pediatric clinic at CMPH. Upon clinical and laboratory examinations, 72 out of 151 patients had ARD, while the other 79 had diseases other than ARD; all of them were used in risk assessment. Fifteen blood samples from healthy volunteers were used in laboratory investigations as a control. Complete blood count and IgE level were investigated for all participants. Children's parents were requested to give an informed consent and fill questionnaire about demography and history details.

Results
Early infant feeding was a significant risk factor for the development of ARD with an odds ratio (OR) of 6.8 and 95% confidence interval (CI) 3.0 to 15.3. Artificial milk particularly was risk factor with an OR of 6.1 and 95% confidence interval 2.7 to 13.5. Artificial milk exhibited more wheezing and asthma attack than others (OR 4.3, 95% CI 1.9 to 9.4 and OR 7.6, 95% CI 3.5 to 16.3, respectively). The risk of wheezing and asthma attack also increase with early feeding generally (OR 3.0, 95% CI 1.3 to 7.2 and OR 4.8, 95% CI 2.2 to 8.1, respectively). The patients had a higher sensitization markers than the control, such as eosinophil count and total serum IgE. The highest levels of IgE ever reported existed among early fed patients with artificial milk.

Conclusions
Early infant feeding, particularly with artificial milk, is a risk factor predisposing infants to the development of allergic respiratory disease presented with more clinical features of wheezing and asthma attack.
Study on identification, assay and organoleptic quality of veterinary medicines in Ethiopia
Authors: Tefera Belachew , Bacha Belachew , Belew Sileshi , Ravinetto Raffaella , Andualem Tenaw , Abegaz Zerihun , Zelelew Ayalew , Uma Gudeta , Setegn Tadese , Hunduma Abdisa , Jemal Dinsefa , Daba Diriba , Belete Bizuayehu 
Published: March 2022

Abstract
Background
Medicines of poor quality are currently prevailing problems undermining the quality of health care services in veterinary and human medicine. In this study, physico-chemical quality of veterinary medicines was evaluated.

Methods
A total of 959 veterinary medicines samples were collected during routine regulatory activities, i.e. pre-registration, re-registration, consignment checking and post-marketing surveillance, in Ethiopia. The samples were transported to Animal Products, Veterinary Drug and Feed Quality Assessment Centre (APVD-FQAC), which is the quality control laboratory of the Veterinary Drug and Feed Administration and Control Authority (VDFACA) and stored until analysis. The samples were subjected to visual inspection and chemical analysis following the United States, European or British Pharmacopoeias, or manufacturer’s methods.

Results
The findings revealed that 12 (1.3%) of tested products showed defects in physical characteristics, packaging, or labelling information, while a total of 66 (6.9%) samples of the investigated products failed to comply with the Pharmacopoeias and supplier’s specification limit set for assay. Of these, 60 samples did not comply with the minimum assay specification limit.

Conclusion
Overall, 8.2% of the investigated veterinary medicine samples did not comply with the specification set for the investigated quality attributes and thus were categorized as of poor quality. This indicates the need for continued strengthening of regulatory functions.
Visualization formats of patient-reported outcome measures in clinical practice: a systematic review about preferences and interpretation accuracy
Authors: Albers Elaine A. C. , Fraterman Itske , Walraven Iris , Wilthagen Erica , Schagen Sanne B. , van der Ploeg Iris M. , Wouters Michel W. J. M. , van de Poll-Franse Lonneke V. , de Ligt Kelly M. 
Published: March 2022

Abstract
Purpose
The use of Patient-Reported Outcome Measures (PROMs) for individual patient management within clinical practice is becoming increasingly important. New evidence about graphic visualization formats for PROMs scores has become available. This systematic literature review evaluated evidence for graphic visualization formats of PROMs data in clinical practice for patients and clinicians, for both individual and group level PROMs data.

Methods
Studies published between 2000 and 2020 were extracted from CINAHL, PubMed, PsychInfo, and Medline. Studies included patients ≥ 18 years old in daily clinical practice. Papers not available in English, without full-text access, or that did not specifically describe visualization of PROMs data were excluded. Outcomes were: visualization preferences; interpretation accuracy; guidance for clinical interpretation.

Results
Twenty-five out of 789 papers were included for final analysis. Most frequently studied formats were: bar charts, line graphs, and pie charts. Patients preferred bar charts and line graphs as these were easy and quick for retrieving information about their PROMs scores over time. Clinicians’ interpretation accuracy and preferences were similar among graphic visualization formats. Scores were most often compared with patients’ own previous scores; to further guide clinical interpretation, scores were compared to norm population scores. Different ‘add-ons’ improved interpretability for patients and clinicians, e.g. using colors, descriptions of measurement scale directionality, descriptive labels, and brief definitions.

Conclusion
There was no predominant graphical visualization format approach in terms of preferences or interpretation accuracy for both patients and clinicians. Detailed clarification of graph content is essential.
Efficacy and tolerability of ketogenic diet therapy in 55 Chinese children with drug-resistant epilepsy in Northwest China
Authors: Dou Xiangjun , Wang Zhijing , Li Xia , Wang Yan , Jia Shanshan , Song Xixiao , Wang Dong 
Published: March 2022

Abstract
Background
Due to the tradition of carbohydrate-rich diet, challenges exist for ketogenic diet (KD) implementation in Northwest China. This study was aimed to investigate the efficacy and tolerability of KD therapy administered with gradual initiation protocols in Chinese children with pharmacoresistant epilepsy in Northwest China.

Methods
In this single-center study, 55 children with drug-resistant epilepsy were enrolled from June 2013 to June 2019. The efficacy of KD, reasons for discontinuation, duration of retention and rate of adverse events were evaluated.

Results
Fifty-five children aged from 2.2 months to 169.7 months were included, with a median age at KD initiation of 14.1 months, and 32 cases (58.2%) responded to the diet therapy at the last contact. The responder rates were 16.4% (9/55), 36.4% (20/55), 30.9% (17/55), 27.3% (15/55) at 1, 3, 6 and 12 months, respectively. Univariate analysis indicated that the duration of epilepsy and the duration of KD therapy were predictors for KD effectiveness. Poor compliance and lack of response were main reasons for discontinuation of KD. There are a few side effects of KD, most of which were minor.

Conclusions
The KD therapy with a gradual-initiation protocol is effective and tolerable for children with drug-resistant epilepsy in Northwest China. Early start of KD and KD duration of more than 6 months may be predictive factors for KD efficacy.
Atomistic-scale investigation of self-healing mechanism in Nano-silica modified asphalt through molecular dynamics simulation
Authors: Long Zhengwu , Tang Xianqiong , Guo Nanning , Ding Yanhuai , Ma Wenbo , You Lingyun , Xu Fu 
Published: March 2022

AbstractAs one of the most widely used nanomaterials in asphalt modification, the nano-silica (nano-SiO2) can significantly improve the self-healing behavior of asphalt eco-friendly. However, understanding of the self-healing mechanism of nano-SiO2in asphalt is still limited. The objective of the study is to reveal the self-healing mechanism of nano-SiO2in asphalt by using molecular dynamics (MD) simulations from the nanoscale. A 10 Å (Å) vacuum pad was added between the two same stable asphalt models to represent the micro-cracks inside the asphalt. The self-healing process of virgin asphalt, oxidation aging asphalt, and nano-SiO2modified asphalt was studied using density evolution, relative concentration, diffusion coefficient, activation energy, and pre-exponential factor. The simulation results conclude that nano-SiO2improves the self-healing ability of asphalt by increasing the diffusion rate of molecules with aromatic structures without alkyl side chains and molecules with structures with longer alkyl chains. The self-healing capability of asphalt may be principally determined by the diffusion of light components such as saturate, while nano-SiO2only plays an inducing role. The research findings could provide insights to understand the self-healing mechanism of nano-SiO2in asphalt for promoting the sustainability of bitumen pavements while increasing their durability.Graphical abstract