bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial creatine kinase 1 in non-small cell lung cancer progression and hypoxia adaptation
Authors: Li Ming , Liu Huan , Li Juan , Guo Shuai , Lv Yan 
Published: July 2021

Abstract
Background
Hypoxia is a prominent feature of solid cancer. This research aims to expose the role of mitochondrial creatine kinase 1 (CKMT1) in non-small cell lung cancer (NSCLC) progression and hypoxia adaptation.

Methods
The mRNA and protein expression of CKMT1 in NSCLC tissues were detected by using GEPIA web, immunohistochemistry and qRT-PCR. For hypoxia, cells were exposed to the 1% O2 atmosphere. The protein levels of HIF-1α and CKMT1 in H1650 and H1299 cells exposed to hypoxia were determined by western blot. The roles of CKMT1 on the proliferation, invasion and hypoxia adaptation of NSCLC cells were measured by CCK8, colony formation and transwell assays. Luciferase activity assay and HIF1 specific inhibitor (LW6) assay indicated the related function of hypoxia and CKMT1.

Results
CKMT1 was highly expressed in NSCLC tissues, and the high level of CKMT1 was significantly correlated with the high pathological grade of NSCLC. Knockdown of CKMT1 inhibited the cell proliferation and invasion of H1650 and H1299 cells, which could be rescued by hypoxia. Hypoxia induced the accumulation of HIF-1α and the expression of CKMT1 in H1650 and H1299 cells. Furthermore, HIF-1 as a transcription factor of CKMT1, could up-regulated the expression of CKMT1 under hypoxia.

Conclusions
In summary, CKMT1 has the potential as a target for NSCLC hypoxic targeted therapy.
LncRNA MONC suppresses the malignant phenotype of Endometrial Cancer Stem Cells and Endometrial Carcinoma Cells by regulating the MiR-636/GLCE axis
Authors: Li Yibing , Huo Jianing , He Junjian , Ma Xiaoxin 
Published: June 2021

Abstract
Background
Emerging evidence shows that abnormal expression of long non-coding RNA is involved in the occurrence and development of various tumors. LncRNA MONC is abnormally expressed in head and neck squamous cell carcinoma, lung cancer, colorectal cancer, and acute megakaryocytic leukemia, but the biological function and potential regulatory mechanism of MONC in endometrial cancer stem cells (ECSCs) and endometrial cancer cells (ECCs) have not been studied. In this study, we aimed to explore the tumor suppressive effect and mechanism of MONC in regulating ECSCs and ECCs.

Methods
We used qRT-PCR to detect the expression of MONC, miR-636 and GLCE in normal human endometrial tissues and endometrial carcinoma (EC) tissues. Luciferase assay was used to verify the binding sites between MONC and miR-636 and between miR-636 and GLCE. Double fluorescence in situ hybridization was used to locate MONC and miR-636 in cells. ECSCs were obtained by flow cytometry sorting assay. Sphere formation assay, CCK-8 assay, transwell invasion assay, cell cycle analysis and apoptosis assay were used to detect the effects of MONC/miR-636/GLCE axis on the malignant biological behavior of ECSCs and ECCs. The effect of MONC on the epithelial-to-mesenchymal transition (EMT) process was detected using western blot. Finally, we conducted in vivo verification through Tumor xenografts in BALB/C nude mice.

Results
In this study, we found MONC is low expression in endometrial carcinoma (EC) and patients in the MONC high-expression group had a better prognosis. MONC and miR-636 are relatively co-localized in the cytoplasm. MONC directly inhibits the malignant biological behavior of ECSCs and ECCs by directly inhibiting miR-636. Simultaneously, miR-636 may indirectly reduce the expression of MONC. Down-regulation of miR-636 may promote GLCE expression by targeting the 3′-untranslated region (UTR) of the downstream gene GLCE, thereby inhibiting the progression of ECSCs. MONC combined with miR-636 inhibited tumor epithelial-to-mesenchymal transition (EMT) process. In addition, we verified the tumor suppressive effect of MONC in nude mice, miR-636 can rescue the tumor suppressive effect of overexpressing MONC.

Conclusions
In conclusion, this study showed that MONC inhibits the malignant phenotypes of ECSCs and ECCs by regulating the miR-636/GLCE axis. Thus the MONC/miR-636/GLCE axis may provide novel treatment avenues for human EC.
Upregulated CD58 is associated with clinicopathological characteristics and poor prognosis of patients with pancreatic ductal adenocarcinoma
Authors: Zhang Yalu , Liu Qiaofei , Liu Jingkai , Liao Quan 
Published: June 2021

Abstract
Background
CD58 has been demonstrated to be abnormally expressed in multiple hematopoietic malignancies and solid tumors and plays an essential role in tumorigenesis and progression; however, its clinical significance and prognostic value in pancreatic ductal adenocarcinoma (PDAC) remain unknown.

Methods
Based on diverse online public databases and 81 PDAC samples of tissue microarray-based immunohistochemistry (IHC), we evaluated CD58 expression in PDAC patients and analyzed its association with clinicopathological characteristics, clinical outcomes, and infiltration of immune cells in PDAC. Furthermore, the correlation between CD58 and the cancer stem cell (CSC)-related, epithelial–mesenchymal transition (EMT)-related, and immune-related markers were detected. Besides, the functional enrichment analysis and related pathways were analyzed and visualized.

Results
CD58 expression was elevated in pancreatitis and PDAC tissues than normal pancreas or adjacent nontumor tissues. The positive cases of CD58 (e.g. more than 50% positive cells) in PDAC account for 95.06% (77/81). Upregulated CD58 in cancer tissues was associated with worse histological grade, larger tumor size, and poorer overall survival and disease-free survival in PDAC patients. Furthermore, Cox multivariate regression analysis revealed that CD58 was an independent prognostic factor in PDAC. CD58 expression was correlated with infiltrations of neutrophils, CD8+ T cells, and dendritic cells (DCs). In addition, correlation gene analysis indicated that CD58 expression was strongly correlated with immune-related, EMT-related, and CSC-related markers. Functional enrichment analysis and KEGG pathway manifested that CD58 might be involved in PDAC initiation and progression.

Conclusions
CD58 expression is upregulated in PDAC tissues and its high expression is notably related to poor survival of PDAC. Therefore, CD58 may serve as a novel and effective marker for predicting the prognosis of PDAC patients.
Balanced impacts of fitness and drug pressure on the evolution of PfMDR1 polymorphisms in Plasmodium falciparum
Authors: Duvalsaint Marvin , Conrad Melissa D. , Tukwasibwe Stephen , Tumwebaze Patrick K. , Legac Jennifer , Cooper Roland A. , Rosenthal Philip J. 
Published: June 2021

Abstract
Background
Anti-malarial drug resistance may be limited by decreased fitness in resistant parasites. Important contributors to resistance are mutations in the Plasmodium falciparum putative drug transporter PfMDR1.

Methods
Impacts on in vitro fitness of two common PfMDR1 polymorphisms, N86Y, which is associated with sensitivity to multiple drugs, and Y184F, which has no clear impact on drug sensitivity, were evaluated to study associations between resistance mediators and parasite fitness, measured as relative growth in competitive culture experiments. NF10 P. falciparum lines engineered to represent all PfMDR1 N86Y and Y184F haplotypes were co-cultured for 40 days, and the genetic make-up of the cultures was characterized every 4 days by pyrosequencing. The impacts of culture with anti-malarials on the growth of different haplotypes were also assessed. Lastly, the engineering of P. falciparum containing another common polymorphism, PfMDR1 D1246Y, was attempted.

Results
Co-culture results were as follows. With wild type (WT) Y184 fixed (N86/Y184 vs. 86Y/Y184), parasites WT and mutant at 86 were at equilibrium. With mutant 184 F fixed (N86/184F vs. 86Y/184F), mutants at 86 overgrew WT. With WT N86 fixed (N86/Y184 vs. N86/184F), WT at 184 overgrew mutants. With mutant 86Y fixed (86Y/Y184 vs. 86Y/184F), WT and mutant at 86 were at equilibrium. Parasites with the double WT were in equilibrium with the double mutant, but 86Y/Y184 overgrew N86/184F. Overall, WT N86/mutant 184F parasites were less fit than parasites with all other haplotypes. Parasites engineered for another mutation, PfMDR1 1246Y, were unstable in culture, with reversion to WT over time. Thus, the N86 WT is stable when accompanied by the Y184 WT, but incurs a fitness cost when accompanied by mutant 184F. Culturing in the presence of chloroquine favored 86Y mutant parasites and in the presence of lumefantrine favored N86 WT parasites; piperaquine had minimal impact.

Conclusions
These results are consistent with those for Ugandan field isolates, suggest reasons for varied haplotypes, and highlight the interplay between drug pressure and fitness that is guiding the evolution of resistance-mediating haplotypes in P. falciparum.
Timing and causes of death in severe COVID-19 patients
Authors: de Roquetaillade Charles , Bredin Swann , Lascarrou Jean-Baptiste , Soumagne Thibaud , Cojocaru Mariana , Chousterman Benjamin Glenn , Leclerc Maxime , Gouhier Albin , Piton Gaël , Pène Frédéric , Stoclin Annabelle , Llitjos Jean-François 
Published: June 2021

Abstract
Background
Previous studies reporting the causes of death in patients with severe COVID-19 have provided conflicting results. The objective of this study was to describe the causes and timing of death in patients with severe COVID-19 admitted to the intensive care unit (ICU).

Methods
We performed a retrospective study in eight ICUs across seven French hospitals. All consecutive adult patients (aged ≥ 18 years) admitted to the ICU with PCR-confirmed SARS-CoV-2 infection and acute respiratory failure were included in the analysis. The causes and timing of ICU deaths were reported based on medical records.

Results
From March 1, 2020, to April 28, 287 patients were admitted to the ICU for SARS-CoV-2 related acute respiratory failure. Among them, 93 patients died in the ICU (32%). COVID-19-related multiple organ dysfunction syndrome (MODS) was the leading cause of death (37%). Secondary infection-related MODS accounted for 26% of ICU deaths, with a majority of ventilator-associated pneumonia. Refractory hypoxemia/pulmonary fibrosis was responsible for death in 19% of the cases. Fatal ischemic events (venous or arterial) occurred in 13% of the cases. The median time from ICU admission to death was 15 days (25th–75th IQR, 7–27 days). COVID-19-related MODS had a median time from ICU admission to death of 14 days (25th–75th IQR: 7–19 days), while only one death had occurred during the first 3 days since ICU admission.

Conclusions
In our multicenter observational study, COVID-19-related MODS and secondary infections were the two leading causes of death, among severe COVID-19 patients admitted to the ICU.
Early individualized positive end-expiratory pressure guided by electrical impedance tomography in acute respiratory distress syndrome: a randomized controlled clinical trial
Authors: He Huaiwu , Chi Yi , Yang Yingying , Yuan Siyi , Long Yun , Zhao Pengyu , Frerichs Inéz , Fu Feng , Möller Knut , Zhao Zhanqi 
Published: June 2021

Abstract
Background
Individualized positive end-expiratory pressure (PEEP) by electrical impedance tomography (EIT) has potential interest in the optimization of ventilation distribution in acute respiratory distress syndrome (ARDS). The aim of the study was to determine whether early individualized titration of PEEP with EIT improved outcomes in patients with ARDS.

Methods
A total of 117 ARDS patients receiving mechanical ventilation were randomly assigned to EIT group (n = 61, PEEP adjusted based on ventilation distribution) or control group (n = 56, low PEEP/FiO2 table). The primary outcome was 28-day mortality. Secondary and exploratory outcomes were ventilator-free days, length of ICU stay, incidence of pneumothorax and barotrauma, and difference in Sequential Organ Failure Assessment (SOFA) score at day 1 (ΔD1-SOFA) and day 2 (ΔD2-SOFA) compared with baseline.

Measurements and main results
There was no statistical difference in the value of PEEP between the EIT group and control group, but the combination of PEEP and FiO2 was different between groups. In the control group, a significantly positive correlation was found between the PEEP value and the corresponding FiO2 (r = 0.47, p < 0.00001) since a given matched table was used for PEEP settings. Diverse combinations of PEEP and FiO2 were found in the EIT group (r = 0.05, p = 0.68). There was no significant difference in mortality rate (21% vs. 27%, EIT vs. control, p = 0.63), ICU length of stay (13.0 (7.0, 25.0) vs 10.0 (7.0, 14.8), median (25th–75th percentile); p = 0.17), and ventilator-free days at day 28 (14.0 (2.0, 23.0) vs 19.0 (0.0, 24.0), p = 0.55) between the two groups. The incidence of new barotrauma was zero. Compared with control group, significantly lower ΔD1-SOFA and ΔD2-SOFA were found in the EIT group (p < 0.001) in a post hoc comparison. Moreover, the EIT group exhibited a significant decrease of SOFA at day 2 compared with baseline (paired t-test, difference by − 1 (− 3.5, 0), p = 0.001). However, the control group did show a similar decrease (difference by 1 (− 2, 2), p = 0.131).

Conclusion
Our study showed a 6% absolute decrease in mortality in the EIT group: a statistically non-significant, but clinically non-negligible result. This result along with the showed improvement in organ function might justify further reserach to validate the beneficial effect of individualized EIT-guided PEEP setting on clinical outcomes of patients with ARDS.
Trial registration: ClinicalTrials, NCT02361398. Registered 11 February 2015—prospectively registered, https://clinicaltrials.gov/show/NCT02361398.
SMOOTH-seq: single-cell genome sequencing of human cells on a third-generation sequencing platform
Authors: Fan Xiaoying , Yang Cheng , Li Wen , Bai Xiuzhen , Zhou Xin , Xie Haoling , Wen Lu , Tang Fuchou 
Published: June 2021

AbstractThere is no effective way to detect structure variations (SVs) and extra-chromosomal circular DNAs (ecDNAs) at single-cell whole-genome level. Here, we develop a novel third-generation sequencing platform-based single-cell whole-genome sequencing (scWGS) method named SMOOTH-seq (single-molecule real-time sequencing of long fragments amplified through transposon insertion). We evaluate the method for detecting CNVs, SVs, and SNVs in human cancer cell lines and a colorectal cancer sample and show that SMOOTH-seq reliably and effectively detects SVs and ecDNAs in individual cells, but shows relatively limited accuracy in detection of CNVs and SNVs. SMOOTH-seq opens a new chapter in scWGS as it generates high fidelity reads of kilobases long.
Presepsin values and prognostic nutritional index predict mortality in intensive care unit patients with sepsis: a pilot study
Authors: Shimoyama Yuichiro , Umegaki Osamu , Kadono Noriko , Minami Toshiaki 
Published: June 2021

Abstract
Objective
Sepsis is a major cause of mortality for critically ill patients. This study aimed to determine whether presepsin values can predict mortality in patients with sepsis.

Results
Receiver operating characteristic (ROC) curve analysis, Log-rank test, and multivariate analysis identified presepsin values and Prognostic Nutritional Index as predictors of mortality in sepsis patients. Presepsin value on Day 1 was a predictor of early mortality, i.e., death within 7 days of ICU admission; ROC curve analysis revealed an AUC of 0.84, sensitivity of 89%, and specificity of 77%; and multivariate analysis showed an OR of 1.0007, with a 95%CI of 1.0001–1.0013 (p = 0.0320).
Onco-fertility and personalized testing for potential for loss of ovarian reserve in patients undergoing chemotherapy: proposed next steps for development of genetic testing to predict changes in ovarian reserve
Authors: Sun Bei , Yeh John 
Published: June 2021

AbstractWomen of reproductive age undergoing chemotherapy face the risk of irreversible ovarian insufficiency. Current methods of ovarian reserve testing do not accurately predict future reproductive potential for patients undergoing chemotherapy. Genetic markers that more accurately predict the reproductive potential of each patient undergoing chemotherapy would be critical tools that would be useful for evidence-based fertility preservation counselling. To assess the possible approaches to take to develop personalized genetic testing for these patients, we review current literature regarding mechanisms of ovarian damage due to chemotherapy and genetic variants associated with both the damage mechanisms and primary ovarian insufficiency. The medical literature point to a number of genetic variants associated with mechanisms of ovarian damage and primary ovarian insufficiency. Those variants that appear at a higher frequency, with known pathways, may be considered as potential genetic markers for predictive ovarian reserve testing. We propose developing personalized testing of the potential for loss of ovarian function for patients with cancer, prior to chemotherapy treatment. There are advantages of using genetic markers complementary to the current ovarian reserve markers of AMH, antral follicle count and day 3 FSH as predictors of preservation of fertility after chemotherapy. Genetic markers will help identify upstream pathways leading to high risk of ovarian failure not detected by present clinical markers. Their predictive value is mechanism-based and will encourage research towards understanding the multiple pathways contributing to ovarian failure after chemotherapy.
Diagnostic value of brain MR imaging and its correlation with clinical presentation and cognitive functions in idiopathic intracranial hypertension patients
Authors: Elmaaty Ali Ahmed Abou , Zarad Carmen Ali , Belal Tamer Ibrahim , Elserafy Tamer Sabry 
Published: June 2021

Abstract
Background
Idiopathic intracranial hypertension (IIH) is a neurological disorder of unknown etiology and ambiguous pathophysiology due to cerebrospinal fluid dysregulation. This study is designed to evaluate the role of brain magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) in diagnosis of IIH, to clarify the nature and extent of cognitive deficits, and to detect if there is a correlation between radiology, clinical findings, and cognitive dysfunctions in those patients.

Results
The study included 34 patients and 34 age-, sex-, body mass index (BMI)-, and education-matched healthy control subjects. MR brain imaging and Montreal cognitive assessment (MoCA) test were used for both groups. MRI and MRV sensitivity for IIH diagnosis were 85.2% and 85.3% with 100% and 94.1% specificity respectively. 44.1% had cognitive impairment, memory was the most affected domain, followed by attention, abstraction, and orientation with statistically significantly lower total MoCA score (p < 0.005). Domain comparisons reveal a statistically significantly lower memory/delayed recall (p < 0.001) and abstract scores (p < 0.007) in IIH cases versus control subjects. In comparing patients with cognitive impairment (CI) versus those without CI, there were statistically significantly higher CI in low education level, presence of diplopia, hormonal contraceptive use, abnormal MRI brain, papilledema grades, BMI, and opening pressure.

Conclusions
Presence of more than or equal 3 MR imaging findings, bilateral transverse sinus stenosis, and less than or equal 4 combined conduit score increase the specificity and sensitivity of MRI and MRV for IIH diagnosis. IIH had detrimental effect on different cognitive domains especially when patient have low education level, diplopia, papilledema ≥ grade III, high OP ≥ 61.5 cm H2O, and BMI ≥ 34 Kg/m2 with abnormal MRI and MRV findings.
Metal contamination and coexistence of metal and antibiotic resistance in Vibrio species recovered from aquaculture ponds with and without history of antibiotic usage in Southwest Nigeria
Authors: Adekanmbi Abimbola Olumide , Olawuni Ololade Grace , Olaposi Adedolapo Victoria 
Published: June 2021

Abstract
Background
The use of metal-containing and antimicrobial compounds is a common practice in aquaculture operations in Nigeria. Only a few studies have focused on the impact of these chemicals on metal and antibiotic resistance development in the bacterial flora of aquaculture. This study therefore sets out to fill this gap.

Results
Five metals, namely copper (Cu), zinc (Zn), lead (Pb), nickel (Ni) and chromium (Cr), were detected at different concentrations in the pond water samples, with most values obtained exceeding the maximum recommended national standard for fisheries and recreation water quality criteria set by the National Environmental Standards and Regulations Enforcement Agency (NESREA) in Nigeria. A total of 121 Vibrio spp. were recovered from the aquaculture pond water with Vibrio cholerae having the highest frequency (37) followed by Vibrio parahaemolyticus (36), Vibrio vulnificus (36) and Vibrio alginolyticus (12). Seventy-five isolates were recovered from ponds with history of antibiotic use, while the ponds with no recognized history of antibiotic use had forty-six isolates. The percentage resistance to antibiotics in the isolates was: ampicillin (88.5%), amoxicillin–clavulanate (44.3%), tetracycline (41%), trimethoprim-sulfamethoxazole (22.1%), chloramphenicol (15.6%), ciprofloxacin (11.5%), imipenem (5.7%), ceftazidime (4.1%) and gentamicin (0%). All the isolates tolerated all the metals to 400 µg/mL concentration while only the trio of Pb, Ni and Cr were tolerated beyond the concentration. Zn and Cu appeared to be the most toxic metals on Vibrio spp., with no isolate surviving beyond the 400 µg/mL concentration mark, while 57 of the 121 isolates survived Cr at the highest concentration (3200 µg/mL), making it the most tolerated of the metals.

Conclusion
This study reports a high level of metal contamination in the aquaculture ponds studied. The concentration of the metals exceeded the maximum permissible limits in Nigeria. Also, there was coexistence of metal and antibiotic resistance in the bacteria recovered from the aquaculture ponds. There is a need to regulate the use of chemicals, especially antibiotics and some biocidal compounds, to clamp down on the introduction of metals and antibiotics into the aquaculture systems, as these chemicals could facilitate the development of resistance traits in aquaculture bacteria by creating a selective pressure in the aquaculture environment.
Premarital screening for genetic blood disorders — an integrated review on the knowledge and attitudes of Middle Eastern university students
Authors: Natarajan Jansirani , Joseph Mickael Antoine 
Published: June 2021

Abstract
Background
Genetic blood disorders are prevalent in the Middle Eastern countries causing physical, mental, and economic handicap. Premarital screening (PMS) is actively implemented to reduce the burgeoning load of these disorders. Literature shows a low response rate for PMS in this region. This integrated review aims to identify the knowledge and attitude of university students on PMS, as they are at the verge of entering into marriage relationships.

Main body of the abstract
We systematically reviewed the electronic databases like MEDLINE, PubMed, CINAHL, and Scopus. Studies reporting about the knowledge and attitudes of Middle Eastern university students between 2010 and 2020 are included in the review. Twelve cross-sectional descriptive studies conducted in six countries met the inclusion criteria. Majority of the studies reported good level of knowledge on PMS among the university students, whereas not all of them agreed to undergo PMS due to various religious and cultural beliefs.

Short conclusion
We recommend massive health education programs at the higher secondary and university levels to create better awareness on PMS. To improve the attitude towards PMS, life cycle approach and support of the religious leaders could be sought.