bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presepsin as a predictor of septic shock in patients with urinary tract infection
Authors: Sekine Yoshitaka , Kotani Kazuhiko , Oka Daisuke , Nakayama Hiroshi , Miyazawa Yoshiyuki , Syuto Takahiro , Arai Seiji , Nomura Masashi , Koike Hidekazu , Matsui Hiroshi , Shibata Yasuhiro , Murakami Masami , Suzuki Kazuhiro 
Published: October 2021

Abstract
Background
Recently, presepsin has been reported to be a useful biomarker for early diagnosis of sepsis and evaluation of prognosis in septic patients. However, few reports have evaluated its usefulness in patients with urinary tract infections (UTI). This study aimed to evaluate whether presepsin could be a valuable marker for detecting severe sepsis, and whether it could predict the therapeutic course in patients with UTI compared with markers already used: procalcitonin (PCT) and C-reactive protein (CRP).

Methods
From April 2014 to December 2016, a total of 50 patients with urinary tract infections admitted to Gunma university hospital were enrolled in this study. Vital signs, presepsin, PCT, CRP, white blood cell (WBC) count, causative agents of urinary-tract infections, and other data were evaluated on the enrollment, third, and fifth days. The patients were divided into two groups: with (n = 11) or without (n = 39) septic shock on the enrollment day, and with (n = 7) or without (n = 43) sepsis on the fifth day, respectively. Presepsin was evaluated as a biomarker for systemic inflammatory response syndrome (SIRS) or septic shock.

Results
Regarding the enrollment day, there was no significant difference of presepsin between the SIRS and non-SIRS groups (p = 0.276). The median value of presepsin (pg/mL) was significantly higher in the septic shock group (p < 0.001). Multivariate logistic regression analysis showed that presepsin (≥ 500 pg/ml) was an independent risk factor for septic shock (p = 0.007). ROC curve for diagnosing septic shock indicated an area under the curve (AUC) of 0.881 for presepsin (vs. 0.690, 0.583, and 0.527 for PCT, CRP and WBC, respectively). Regarding the 5th day after admission, the median presepsin value on the enrollment day was significantly higher in the SIRS groups than in the non-SIRS groups (p = 0.006). On the other hand, PCT (≥ 2 ng/ml) on the enrollment day was an independent risk factor for SIRS. ROC curve for diagnosing sepsis on the fifth day indicated an AUC of 0.837 for PCT (vs. 0.817, 0.811, and 0.802 for presepsin, CRP, and WBC, respectively).

Conclusions
This study showed that presepsin may be a good marker for diagnosing septic shock based on admission data in patients with UTI.
Effects of early geometric confinement on the transcriptomic profile of human cerebral organoids
Authors: Sen Dilara , Voulgaropoulos Alexis , Keung Albert J. 
Published: October 2021

Abstract
Background
Human cerebral organoids (hCO) are attractive systems due to their ability to model important brain regions and transcriptomics of early in vivo brain development. To date, they have been used to understand the effects of genetics and soluble factors on neurodevelopment. Interestingly, one of the main advantages of hCOs are that they provide three dimensionality that better mimics the in vivo environment; yet, despite this central feature it remains unclear how spatial and mechanical properties regulate hCO and neurodevelopment. While biophysical factors such as shape and mechanical forces are known to play crucial roles in stem cell differentiation, embryogenesis and neurodevelopment, much of this work investigated two dimensional systems or relied on correlative observations of native developing tissues in three dimensions. Using hCOs to establish links between spatial factors and neurodevelopment will require the use of new approaches and could reveal fundamental principles of brain organogenesis as well as improve hCOs as an experimental model.

Results
Here, we investigated the effects of early geometric confinements on transcriptomic changes during hCO differentiation. Using a custom and tunable agarose microwell platform we generated embryoid bodies (EB) of diverse shapes mimicking several structures from embryogenesis and neurodevelopment and then further differentiated those EBs to whole brain hCOs. Our results showed that the microwells did not have negative gross impacts on the ability of the hCOs to differentiate towards neural fates, and there were clear shape dependent effects on neural lineage specification. In particular we observed that non-spherical shapes showed signs of altered neurodevelopmental kinetics and favored the development of medial ganglionic eminence-associated brain regions and cell types over cortical regions. Transcriptomic analysis suggests these mechanotransducive effects may be mediated by integrin and Wnt signaling.

Conclusions
The findings presented here suggest a role for spatial factors in brain region specification during hCO development. Understanding these spatial patterning factors will not only improve understanding of in vivo development and differentiation, but also provide important handles with which to advance and improve control over human model systems for in vitro applications.
Early childhood caries, primary caregiver oral health knowledge and behaviours and associated sociological factors in Australia: a systematic scoping review
Authors: Andrew Lesley , Wallace Ruth , Wickens Nicole , Patel Jilen 
Published: October 2021

Abstract
Background
Early childhood caries disproportionately affects vulnerable groups and remains a leading cause of preventable hospital admissions for Western Australian children. The Western Australia State Oral Health Plan seeks to improve child oral health through universal and targeted health promotion initiatives with primary caregivers. These initiatives require evidence of primary caregiver oral health knowledge and behaviours and baseline data on early childhood caries. The objective of this systematic scoping review was to understand current oral health knowledge and practices of primary caregivers of children aged 0–4 years, identify influential socioecological determinants, and identify data on early childhood caries in the Western Australian context.

Methods
A systematic scoping review framework identified articles published between 2010 and 2021, using Scopus, PubMed, Medline, CINAHL, PsycINFO, selected article reference lists, and oral health websites. The lack of Western Australian specific literature prompted the inclusion of Australia-wide articles. Articles were screened via author consensus, with eight selected.

Results
Western Australia and nation-wide data on early childhood caries are limited and mostly dated. WA data from children aged 2–3 years, collected in 2006, suggests the prevalence is 2.9% in this state, with national data of children from 0 to 3 years, collected from 2006 and 2008, suggesting an early childhood caries prevalence of 3.4–8% of children aged 18 months, rising sharply by 36 months of age. Nationally, fewer than half the primary caregivers reported following evidence-based oral health recommendations for their young children. Perceptions of the role of dental services for young children tends to be focussed on treatment, rather than surveillance and prevention. Knowledge of dietary and oral hygiene practices is inconsistent and awareness of the Child Dental Benefit Schedule low. Young children’s oral health status is clearly associated with socioecological factors, including socioeconomic status.

Conclusions
Recent early childhood caries data and evidence of primary care-givers’ oral health knowledge and behaviours are unavailable in Western Australia, a similar situation exists nationwide. To realise the Western Australian and National Oral Health Plans, research is required to address this knowledge gap.
Challenges of peer assisted learning in online clinical skills training of ophthalmology module
Authors: Nisar Sumera , Mahboob Usman , Khan Rehan Ahmed , Rehman Durraiz 
Published: October 2021

Abstract
Background
Online communication has taken over in the last 2 years due to the frequent lockdowns because of the COVID-19 pandemic. Overburdened physicians in this pandemic are struggling to get enough time to teach clinical skills online to the students. Also, due to student’s safety issues, the students cannot fully attend the clinics. Therefore, in this scenario, online PAL (Peer Assisted Learning) sessions for clinical skill teaching and learning can be an effective alternative for undergraduate medical students. The academic limitations caused by the COVID-19 related lockdown however can have a pleasurable outcome if certain challenges, related to online PAL, are overcome. Therefore, the present study aims to identify the challenges of Peer Assisted Learning (PAL) sessions during online clinical skills training in the Ophthalmology module of undergraduate medical students.

Methods
This qualitative exploratory study, utilizing online focus group discussions to explore the challenges of online PAL in training and learning of clinical skills were carried at the Ophthalmology department of Batterjee Medical College, Jeddah; Saudi Arabia. A purposive convenient sampling technique was used to collect data. Data were transcribed and analyzed using thematic analysis.

Results
The study identified six themes that were further divided into smaller subthemes. The subthemes derived from the collected data were organized under the following major themes; infrastructure, learning environment, psychological problems, interaction deficit, learning desires, and desire for feedback on performance. The major challenge reported by the medical student during online PAL sessions was infrastructure in terms of network connection, scheduling, and timing of the session. The unprofessional learning environment, psychological problems in terms of behavioral issues and personality changes, interaction deficit with peers, tutor, and patient, learning desires, and desire for feedback on performance were the other important challenges faced by the students.

Conclusion
The challenges explored by our study can be used by the medical educators to incorporate online PAL as an effective, efficient, and alternative teaching and learning modality in the curriculum especially in compromised circumstances like the current COVID-19 pandemic.
Impact of universal home visits on child health in Bauchi State, Nigeria: a stepped wedge cluster randomised controlled trial
Authors: Omer Khalid , Joga Altine , Dutse Umar , Hasan Khalid , Aziz Amar , Ansari Umaira , Gidado Yagana , Baba Muhd Chadi , Gamawa Adamu Ibrahim , Mohammad Rilwanu , Andersson Neil , Cockcroft Anne 
Published: October 2021

Abstract
Background
Nigeria is the second biggest contributor to global child mortality. Infectious diseases continue to be major killers. In Bauchi State, Nigeria, a stepped wedge cluster randomised controlled trial tested the health impacts of universal home visits to pregnant women and their spouses. We present here the findings related to early child health.

Methods
The home visits took place in eight wards in Toro Local Government Authority, randomly allocated into four waves with a delay of 1 year between waves. Female and male home visitors visited all pregnant women and their spouses every 2 months during pregnancy, with a follow up visit 12–18 months after the birth. They presented and discussed evidence about household prevention and management of diarrhoea and immunisation. We compared outcomes among children 12–18 months old born to mothers visited during the first year of intervention in each wave (intervention group) with those among children 12–18 months old pre-intervention in subsequent waves (control group). Primary outcomes included prevalence and management of childhood diarrhoea and immunisation status, with intermediate outcomes of household knowledge and actions. Generalised Estimating Equations (GEE), with an exchangeable correlation matrix and ward as cluster, tested the significance of differences in outcomes.

Results
The analysis included 1796 intervention and 5109 control children. In GEE models including other characteristics of the children, intervention children were less likely to have suffered diarrhoea in the last 15 days (Odds Ratio (OR) 0.40, 95% confidence interval (CI) 0.30–0.53) and more likely to have received increased fluids and continued feeding in their last episode of diarrhoea (OR 6.06, 95% CI 2.58–14.20). Mothers of intervention children were more likely to identify lack of hygiene as a cause of diarrhoea (OR 2.24, 95% CI 1.27–3.95) and their households had better observed hygiene (OR 3.29, 95% CI 1.45–7.45). Intervention children were only slightly more likely to be fully immunised (OR 1.67, 95% CI 0.78–3.57).

Conclusions
Evidence-based home visits to both parents stimulated household actions that improved prevention and management of childhood diarrhoea. Such visits could help to improve child health even in settings with poor access to quality health services.

Trial registration
ISRCTN82954580. Date: 11/08/2017. Retrospectively registered.
Association of MTHFR C677T variant genotype with serum folate and Vit B12 in Iranian patients with colorectal cancer or adenomatous polyps
Authors: Ghorbani Mahla , Azghandi Marjan , Khayami Reza , Baharara Javad , Kerachian Mohammad Amin 
Published: October 2021

Abstract
Background
The incidence of colorectal cancer (CRC) has increased during recent years in Iran and other developing countries. Clinical studies suggest that essential folate dietary intake and moderate deficiency of methylenetetrahydrofolate reductase (MTHFR) may protect and reduce the risk of CRC. The present study aimed to investigate the clinical significance of C677T polymorphism within the MTHFR gene and its correlation with the serum folate and Vit B12 in the Iranian population suffering from CRC.

Methods
Blood samples were taken from 1017 Iranian individuals (517 cases and 500 controls) who were referred for colonoscopy. TaqMan probe assay was performed for C677T MTHFR polymorphism. Sera were fractionated from the blood samples of 43 patients and controls and folate and Vit B12 concentrations were measured by a monobind kit. The correlation of MTHFR polymorphisms and folate/vitamin-B12 with CRC risk was analyzed.

Results
In the current study, we found the frequency of three different genotypes of MTHFR polymorphism in the Iranian population i.e., CC, CT, and TT, to be 51.31, 26.73, 21.96 and 61, 32.2, 6.8 in case and control groups, respectively. The homozygote genotype of MTHFR rs1801133 polymorphism is associated with an increased risk of CRC by 3.68, 1.42, and 3.74-fold in codominant, dominant, and recessive models respectively (p value < 0.01). Our study revealed that there was no significant difference between the amount of folate and Vit B12 in the case and control groups (p value > 0.05).

Conclusions
This study revealed that there was no significant difference between the amount of folate and Vit B12 in the case and control groups. Furthermore, our results demonstrated a higher risk association for 677TT and 677TT + C677T genotypes of MTHFR compared with 677CC carriers among CRC patients.
Analyzing the whole-transcriptome profiles of ncRNAs and predicting the competing endogenous RNA networks in cervical cancer cell lines with cisplatin resistance
Authors: Lv Huimin , Jin Shanshan , Zou Binbin , Liang Yuxiang , Xie Jun , Wu Suhui 
Published: October 2021

Abstract
Background
Cervical cancer (CC) is one of the most common malignant tumors in women. In order to identify the functional roles and the interaction between mRNA and non-coding RNA (ncRNA, including lncRNA, circRNA and miRNA) in CC cisplatin (DDP) resistance, the transcription profile analysis was performed and a RNA regulatory model of CC DDP resistance was proposed.

Methods
In this study, whole-transcriptome sequencing analysis was conducted to study the ncRNA and mRNA profiles of parental SiHa cells and DDP resistant SiHa/DDP cells. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed for pathway analysis based on the selected genes with significant differences in expression. Subsequently, ceRNA network analyses were conducted using the drug resistance-related genes and signal-transduction pathways by Cytoscape software. Furthermore, a ceRNA regulatory pathway, namely lncRNA-AC010198.2/hsa-miR-34b-3p/STC2, was selected by RT-qPCR validation and literature searching. Further validation was done by both dual-luciferase reporter gene assays and RNA pull-down assays. Besides that, the changes in gene expression and biological function were further studied by performing si-AC010198.2 transfection and DDP resistance analyses in the SiHa and SiHa/DDP cells, respectively.

Results
Using bioinformatics and dual-luciferase reporter gene analyses, we found that AC010198.2/miR-34b-3p/STC2 may be a key pathway for DDP resistance in CC cells. Significant differences in both downstream gene expression and the biological function assays including colony formation, migration efficiency and cell apoptosis were identified in AC010198.2 knockdown cells.

Conclusions
Our study will not only provide new markers and potential mechanism models for CC DDP resistance, but also discover novel targets for attenuating it.
EF24 exerts cytotoxicity against NSCLC via inducing ROS accumulation
Authors: Chang Minghui , Shang Ming , Yuan Fang , Guo Wei , Wang Cuijuan 
Published: October 2021

Abstract
Background
The role of Diphenyldifluoroketone (EF24), a synthetic analogue of curcumin with noteworthy antitumor potential, remains unclear in non-small cell lung cancer (NSCLC). Herein, the inhibitory effect of EF24 on NSCLC and its mechanism were studied.

Methods
Cytotoxicity was measured by MTT assay, colony formation assay and xenograft model. Cell apoptosis and reactive oxygen species (ROS) level were quantified by flow cytometer. Protein level was detected by western blot assay. Mitochondria and autophagosomes were observed using transmission electron microscope and confocal microscopy.

Results
In-vitro, EF24 significantly induced proliferation inhibition, apoptosis, mitochondrial fission and autophagy of NSCLC cell lines. These cytotoxic effects were significantly attenuated by two reactive oxygen species (ROS) scavengers, indicating its anti-cancer effects largely depend on ROS accumulation. In-vivo, EF24 inhibited tumor growth in a dose-dependent manner. Moreover, no pathological changes of heart, lung, spleen, kidney and liver of mice were observed. Collectively, EF24 induced ROS accumulation, in turn activates cell apoptosis, and then exerts its cytotoxicity on NSCLC cells.

Conclusions
The results showed that EF24 exerted cytotoxicity against NSCLC via ROS accumulation. Thus, EF24 might serve as a potential anti-cancer agent for the treatment of NSCLC.
FAM49B promotes breast cancer proliferation, metastasis, and chemoresistance by stabilizing ELAVL1 protein and regulating downstream Rab10/TLR4 pathway
Authors: Li Yanhui , Xiong Yue , Wang Zhen , Han Jianjun , Shi Sufang , He Jinglan , Shen Na , Wu Wenjuan , Wang Rui , Lv Weiwei , Deng Yajun , Liu Weiguang 
Published: October 2021

Abstract
Background
Breast cancer (BC) is one of the most common cancers and the leading cause of death in women. Previous studies have demonstrated that FAM49B is implicated in several tumor progression, however, the role and mechanism of FAM49B in BC remain to be explored. Therefore, in this study, we aimed to systematically study the role of FAM49B in the proliferation, metastasis, apoptosis, and chemoresistance of BC, as well as the corresponding molecular mechanisms and downstream target.

Methods
The ONCOMINE databases and Kaplan–Meier plotter databases were analyzed to find FAM49B and its prognostic values in BC. FAM49B expression in BC and adjacent non-tumor tissues was detected by western blot and IHC. Kaplan–Meier analysis was used to identify the prognosis of BC patients. After FAM49B knockdown in MCF-7 and MDA-MB-231 cells, a combination of co-immunoprecipitation, MTT, migration, and apoptosis assays, nude mouse xenograft tumor model, in addition to microarray detection and data analysis was used for further mechanistic studies.

Results
In BC, the results showed that the expression level of FAM49B was significantly higher than that in normal breast tissue, and highly expression of FAM49B was significantly positively correlated with tumor volume, histological grade, lymph node metastasis rate, and poor prognosis. Knockdown of FAM49B inhibited the proliferation and migration of BC cells in vitro and in vivo. Microarray analysis revealed that the Toll-like receptor signaling pathway was inhibited upon FAM49B knockdown. In addition, the gene interaction network and downstream protein validation of FAM49B revealed that FAM49B positively regulates BC cell proliferation and migration by promoting the Rab10/TLR4 pathway. Furthermore, endogenous FAM49B interacted with ELAVL1 and positively regulated Rab10 and TLR4 expression by stabilizing ELAVL1. Moreover, mechanistic studies indicated that the lack of FAM49B expression in BC cells conferred more sensitivity to anthracycline and increased cell apoptosis by downregulating the ELAVL1/Rab10/TLR4/NF-κB signaling pathway.

Conclusion
These results demonstrate that FAM49B functions as an oncogene in BC progression, and may provide a promising target for clinical diagnosis and therapy of BC.
Time to scale up molecular surveillance for anti-malarial drug resistance in sub-saharan Africa
Authors: Nsanzabana Christian 
Published: October 2021

AbstractArtemisinin resistance has emerged and spread in the Greater Mekong Sub-region (GMS), followed by artemisinin-based combination therapy failure, due to both artemisinin and partner drug resistance. More worrying, artemisinin resistance has been recently reported and confirmed in Rwanda. Therefore, there is an urgent need to strengthen surveillance systems beyond the GMS to track the emergence or spread of artemisinin and partner drug resistance in other endemic settings. Currently, anti-malarial drug efficacy is monitored primarily through therapeutic efficacy studies (TES). Even though essential for anti-malarial drug policy change, these studies are difficult to conduct, expensive, and may not detect the early emergence of resistance. Additionally, results from TES may take years to be available to the stakeholders, jeopardizing their usefulness. Molecular markers are additional and useful tools to monitor anti-malarial drug resistance, as samples collected on dried blood spots are sufficient to monitor known and validated molecular markers of resistance, and could help detecting and monitoring the early emergence of resistance. However, molecular markers are not monitored systematically by national malaria control programmes, and are often assessed in research studies, but not in routine surveillance. The implementation of molecular markers as a routine tool for anti-malarial drug resistance surveillance could greatly improve surveillance of anti-malarial drug efficacy, making it possible to detect resistance before it translates to treatment failures. When possible, ex vivo assays should be included as their data could be useful complementary, especially when no molecular markers are validated.