bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dust exposure: a novel environmental risk factor for conjunctivochalasis?
Authors: Katipoğlu Zeynep , Zengin Nazmi 
Published: June 2021

Objective: This study aimed to determine the relationship between clinical symptoms and findings of patients diagnosed with conjunctivochalasis in our clinic and the risk factors reported in the literature, to determine new possible etiological factors, and to compare routine tear assessment methods with novel strip meniscometry in these patients. Materials and Methods: The study included patients who presented to our clinic between March 2019 and June 2019 and were diagnosed with conjunctivochalasis. The Ocular Surface Disease Index was used to assess ocular surface symptoms. Anterior segment examination included tear break-up time, corneal staining, localization of conjunctivochalasis, and the presence of pinguecula or pterygium. For each patient, tears were measured using both Schirmer and strip meniscometry. Patients with conjunctivochalasis were evaluated as lid-parallel conjunctival folds grade 1, 2, or 3. Results: There was a total of 57 participants, including 31 women (54.4%) and 26 men (45.6%). Lid-parallel conjunctival folds grade was found to be statistically significantly associated with dust exposure ( p = 0.034). Multiple regression analysis revealed that dust exposure was an independent predictor of being diagnosed with lid-parallel conjunctival folds grade 2 versus lid-parallel conjunctival folds grade 1 (odds ratio = 3.515, p = 0.029). Moreover, Schirmer’s test and strip meniscometry results were positively correlated in patients with conjunctivochalasis ( r = 0.302 and p = 0.022). Conclusion: We conclude that external factors are prominent in patients with conjunctivochalasis, especially dust exposure. In addition, strip meniscometry may be preferred as a more practical and noninvasive alternative to investigate dry eye symptoms in patients with conjunctivochalasis.
Renal cell carcinoma with renocolic fistula presenting as an emphysematous pyelonephritis in a non-functioning kidney: case report
Authors: Rajput Manharsinh , Deka Phanindra Mohan , Singhania Sharwan Kumar 
Published: June 2021

Abstract
Background
The uniqueness of this case is in its rarity and divergent presentation.

Case presentation
Here, we report a case of 56-year-old male patient with pain in the left flank for 1 year. On evaluation, patient was diagnosed with multiple left renal calculi and emphysematous pyelonephritis with non-functioning kidney. Intraoperatively, dense perinephric adhesions, necrotic kidney and renocolic fistula were encountered. The patient underwent left nephrectomy with resection anastomosis of descending colon segment with loop ileostomy. Histopathological examination showed a poorly differentiated high-grade clear cell carcinoma with squamous metaplasia.

Conclusion
Renal cell carcinoma can present in unusual ways. Sometimes, it can mimic emphysematous pyelonephritis because of fistulous communication with gut. It is rare but challenging for urologists to diagnose and manage such cases.
How much do the conventional parameters contribute to the biological toxicity of surface water in different types of villages?
Authors: Shao Ying , Fan Yueting , Yang Yinjie , Zhou Min , Li Tingting , Fang Fang , Wang Chenchen , Jiang Yanxue , Chen Zhongli , Guo Jinsong 
Published: June 2021

Abstract
Background
In rural areas, the surface water quality is seriously threatened by pollution from agriculture, breeding, industrial and tourism activities. Even though many strategies and programs were launched for rural environment management, it is challenging to tackle the serious surface water pollution in villages. Since pollution status varies with the type of villages, there is no single parameter that defines environment quality completely. Until recently, most of rural surface water quality monitoring programs focus only on the conventional parameters, while can these conventional parameters reflect comprehensive status of water quality? To study how much the conventional parameters contribute to biological toxicity of surface water in villages, the in situ parameters of pH, DO, EC, ORP, laboratorial parameters of COD, TN, NO3−-N, NO2−-N, NH4+-N, TP, and PO43−-P and acute toxicity were analyzed for the surface water samples those were collected from six types of villages, named breeding, agricultural, handicraft, industrial, agricultural and breeding, and tourism. The correlation analysis was applied to establish the linkages and contributions of each parameter.

Results
The results showed that all detected surface waters were alkaline, and the concentration of TN and most of COD concentrations in all six types of villages were higher than the Class V limits specified in environmental quality standards for surface water (GB3838-2002). Pearson’s correlation analysis showed that significantly positive correlations were found for the acute toxicity effects and laboratorial parameters of NO2−-N, NH4+-N and PO43−-P in agricultural villages, and negative correlations were found for the acute toxicity effects and laboratorial parameters of TN and NO3−-N. No significant correlation was observed in breeding villages and industrial villages.

Conclusion
The problems of nitrogen pollution and aerobic pollution are still serious in villages, and more attention should be paid in further rural environment management. NH4+-N could contribute to the acute toxicity of surface water in the most of investigated villages, while no significant correlation was observed between acute toxicity and conventional parameters in industrial villages and tourism villages. Environmental monitoring programs focusing just on the classical conventional parameters are far from sufficient, since the main toxic contributors are quite different in diverse villages. The outcomes of the present study contribute to demonstrate the performance and usefulness of bioanalytical techniques for water quality assessment.
Effects of different vasopressors on the contraction of the superior mesenteric artery and uterine artery in rats during late pregnancy
Authors: Wang Tingting , Liao Limei , Tang Xiaohui , Li Bin , Huang Shaoqiang 
Published: June 2021

Abstract
Background
Hypotension after neuraxial anaesthesia is one of the most common complications during caesarean section. Vasopressors are the most effective method to improve hypotension, but which of these drugs is best for caesarean section is not clear. We assessed the effects of vasopressors on the contractile response of uterine arteries and superior mesenteric arteries in pregnant rats to identify a drug that increases the blood pressure of the systemic circulation while minimally affecting the uterine and placental circulation.

Methods
Isolated ring segments from the uterine and superior mesenteric arteries of pregnant rats were mounted in organ baths, and the contractile responses to several vasopressor agents were studied. Concentration-response curves for norepinephrine, phenylephrine, metaraminol and vasopressin were constructed.

Results
The contractile response of the mesenteric artery to norepinephrine, as measured by the pEC50 of the drug, was stronger than the uterine artery (5.617 ± 0.11 vs. 4.493 ± 1.35, p = 0.009), and the contractile response of the uterine artery to metaraminol was stronger than the mesenteric artery (pEC50: 5.084 ± 0.17 vs. 4.92 ± 0.10, p = 0.007). There was no statistically significant difference in the pEC50 of phenylephrine or vasopressin between the two blood vessels.

Conclusions
In vitro experiments showed that norepinephrine contracts peripheral blood vessels more strongly and had the least effect on uterine artery contraction. These findings support the use of norepinephrine in mothers between the time of neuraxial anaesthesia and the delivery of the foetus.
A national survey on COVID-19 second-wave lockdowns on older adults’ mental wellbeing, health-seeking behaviours and social outcomes across Australia
Authors: Siette Joyce , Seaman Karla , Dodds Laura , Ludlow Kristiana , Johnco Carly , Wuthrich Viviana , Earl Joanne K. , Dawes Piers , Strutt Paul , Westbrook Johanna I. 
Published: June 2021

Abstract
Background
The impact of severe second lockdown measures on older adults’ wellbeing is unknown. We aimed to (i) identify the impact of the second lockdown that resulted from the second wave of COVID-19 cases on older Australians’ quality of life; (ii) compare the impact of second wave lockdowns in Victoria, Australia’s second most populous State, to those in other States and Territories not in lockdown.

Methods
A national cross-sectional study of community-dwelling older adults completed online questionnaires for quality of life, social networks, healthcare access, and perceived impact of COVID-19 between July to September 2020. Tobit regression was used to measure the relationships of healthcare service access and social networks with quality of life of older adults in Victoria compared to those in the rest of Australia.

Results
A total of 2,990 respondents (mean [SD] age, 67.3 [7.0]; 66.8 % female) participated. At time of data collection, Victoria’s second COVID-19 lockdown had been in force for an average 51.7 days. Median quality of life scores were significantly higher in Victoria compared to the rest of Australia (t2,827=2.25 p = 0.025). Being female (95 % CI, -0.051–0.020), having lower educational attainment (95 % CI, -0.089–-0.018), receiving government benefits (95 % CI, -0.054–-0.024), having small social networks (95 % CI, 0.006–0.009) and self-reported physical chronic health conditions were all independent predictors of lower quality of life.

Conclusions
Longer-term studies are required to provide more robust evidence of the impact as restrictions lift and normal social conventions return.
Increased cerebrospinal fluid adenosine 5'-triphosphate in patients with amyotrophic lateral sclerosis
Authors: Nukui Takamasa , Matsui Atsushi , Niimi Hideki , Sugimoto Tomoyuki , Hayashi Tomohiro , Dougu Nobuhiro , Konishi Hirofumi , Yamamoto Mamoru , Anada Ryoko , Matsuda Noriyuki , Kitajima Isao , Nakatsuji Yuji 
Published: June 2021

Abstract
Background
Extracellular adenosine 5'-triphosphate (ATP) has been suggested to cause neuroinflammation and motor neuron degeneration by activating microglia and astrocytes in amyotrophic lateral sclerosis (ALS). Since we have developed a highly sensitive ATP assay system, we examined cerebrospinal fluid (CSF) ATP levels in patients with ALS whether it can be a useful biomarker in ALS.

Methods
Forty-eight CSF samples from 44 patients with ALS were assayed for ATP with a newly established, highly sensitive assay system using luciferase luminous reaction. CSF samples from patients with idiopathic normal pressure hydrocephalus (iNPH) were assayed as a control. Patients were divided into two groups depending on their disease severity, as evaluated using the Medical Research Council (MRC) sum score. Correlations between the CSF ATP levels and other factors, including clinical data and serum creatinine levels, were evaluated.

Results
CSF ATP levels were significantly higher in patients with ALS than in the iNPH (716 ± 411 vs. 3635 ± 5465 pmol/L, p < 0.01). CSF ATP levels were significantly higher in the more severe group than in the iNPH group (6860 ± 8312 vs. 716 ± 411 pmol/L, p < 0.05) and mild group (6860 ± 8312 vs. 2676 ± 3959 pmol/L, p < 0.05) respectively. ALS functional rating scale-revised (ALSFRS-R) (37.9 ± 5.7 vs. 42.4 ± 2.8, p < 0.01) and serum creatinine levels (0.51 ± 0.13 vs. 0.68 ± 0.23 mg/dL, p < 0.05) were significantly lower in the severe group than in the mild group respectively. A negative correlation of CSF ATP levels with MRC sum score was demonstrated in the correlation analysis adjusted for age and sex (r = -0.3, p = 0.08).

Conclusions
Extracellular ATP is particularly increased in the CSF of patients with advanced ALS. CSF ATP levels may be a useful biomarker for evaluating disease severity in patients with ALS.
Timing of initiation of breastfeeding and its determinants at a tertiary hospital in Ghana: a cross-sectional study
Authors: Boakye-Yiadom Adwoa Pokua , Nguah Samuel Blay , Ameyaw Emmanuel , Enimil Anthony , Wobil Priscilla Naa Lomle , Plange-Rhule Gyikua 
Published: June 2021

Abstract
Background
Early initiation of breastfeeding (EIBF), breastfeeding within first hour after birth, is known to have major benefits for both the mother and newborn. EIBF rates, however, tends to vary between and within countries. This study set out to determine the prevalence of EIBF at the Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana, and to evaluate the determinants of EIBF and time to initiation of breastfeeding.

Methods
A cross-sectional study was conducted at the KATH postnatal wards between August and October 2014. Three hundred and eighty-two mothers delivering at KATH were recruited and data on time to initiation of breastfeeding, antenatal, delivery and immediate postnatal periods were collected. Data analyses using both binary and ordinal logistic regressions with stepwise elimination were used to determine the relationship between EIBF and time to initiation of breastfeeding on one side, and the maternal, pregnancy, delivery and neonatal associated factors.

Results
EIBF was done in 39.4% (95%CI: 34.3–44.5) of the newborns with breastfeeding initiated between 1 to 6 h for 19.7%, 6 to 11 h in 4.8%, 11 to 16 h in 4.8% and after 16 h in 28.5% of the deliveries. A higher number of antenatal care visits (AOR = 1.14, 95%CI: 1.04–1.25, p = 0.006), delivery by caesarean section (AOR = 0.07, 95%CI: 0.01–0.79, p = 0.031) and infant rooming-in with mother (AOR: 31.67, 95%CI: 5.59–179.43, p <  0.001) were significantly and independently associated with EIBF. Factors independently associated with longer time to initiation of breastfeeding were older maternal age (AOR = 1.04, 95%CI: 1.00–1.09, p = 0.039), Akan ethnicity (AOR = 1.92, 95%CI: 1.14–3.22, p = 0.014), first-born child (AOR = 2.06, 95%CI: 1.18–3.58, p = 0.011), mother rooming-in with newborn (AOR = 0.01. 95%CI: 0.00–0.02, p <  0.001), increasing fifth minute APGAR score (AOR = 0.73, 95%CI: 0.58–0.93, p = 0.010) and using prelacteals (AOR = 2.42, 95%CI: 1.34–4.40, p = 0.004).

Conclusions
The low EIBF rate and prolonged time to initiation of breastfeeding at a major tertiary health facility is a major concern. Key interventions will need to be implemented at KATH and possibly other tertiary healthcare facilities in Ghana and beyond to improve EIBF rate and time to breastfeeding.
BCL-xL is correlated with disease severity in neonatal infants with early sepsis
Authors: Wenshen Wu , Qi Peng , Tianli Huang , Jinfeng Liao , Ning Li 
Published: June 2021

Abstract
Background
Sepsis is the most common cause of morbidity and mortality in neonatal infants. It is essential to find an accurate and sensitive biomarker to confirm and treat neonatal sepsis in order to decrease the rate of mortality. The aim of this study was to investigate the association between disease severity in patients with sepsis and TNF-α, B cell lymphoma-extra-large (BCL-xL), and serum Mitochondrial membrane potential (MMP).

Methods
We investigated the correlation between SNAP-II score and levels of TNF-α, BCL-xL, and MMP-index, respectively. The receiver-operating characteristics (ROC) was to assess the diagnostic value of the the Bcl-xL in the diagnosis of the of septic shock.

Results
A total of 37 infants were diagnosed with sepsis. SNAP-II was positively correlated with the level of BCL-xL (r = 0.450, P = 0.006). The area under the BCL-xL curve was 83.0 %, and the 95 % CI was 67.1–93.3 %. The septic shock threshold was > 3.022 ng/mL, and the sensitivity and specificity were 75.0 and 95.2 %, respectively. The positive predictive value was 92.3 %, and the negative predictive value was 83.3 %. Furthermore, the level of SNAP-II was > 10, and BCL-xL was > 3.022 ng/mL as the threshold, and the sensitivity, specificity, positive predictive value, and negative predictive value of septic shock were 93.8 %, 95.2 %, 93.8 %, and 95.2 %, respectively.

Conclusions
BCL-xL is associated with the progression of sepsis. The combination of BCL-xL and SNAP-II could be early predicte the severity of the disease.
A systems pharmacology approach based on oncogenic signalling pathways to determine the mechanisms of action of natural products in breast cancer from transcriptome data
Authors: Odongo Regan , Demiroglu-Zergeroglu Asuman , Çakır Tunahan 
Published: June 2021

Abstract
Background
Narrow spectrum of action through limited molecular targets and unforeseen drug-related toxicities have been the main reasons for drug failures at the phase I clinical trials in complex diseases. Most plant-derived compounds with medicinal values possess poly-pharmacologic properties with overall good tolerability, and, thus, are appropriate in the management of complex diseases, especially cancers. However, methodological limitations impede attempts to catalogue targeted processes and infer systemic mechanisms of action. While most of the current understanding of these compounds is based on reductive methods, it is increasingly becoming clear that holistic techniques, leveraging current improvements in omic data collection and bioinformatics methods, are better suited for elucidating their systemic effects. Thus, we developed and implemented an integrative systems biology pipeline to study these compounds and reveal their mechanism of actions on breast cancer cell lines.

Methods
Transcriptome data from compound-treated breast cancer cell lines, representing triple negative (TN), luminal A (ER+) and HER2+ tumour types, were mapped on human protein interactome to construct targeted subnetworks. The subnetworks were analysed for enriched oncogenic signalling pathways. Pathway redundancy was reduced by constructing pathway-pathway interaction networks, and the sets of overlapping genes were subsequently used to infer pathway crosstalk. The resulting filtered pathways were mapped on oncogenesis processes to evaluate their anti-carcinogenic effectiveness, and thus putative mechanisms of action.

Results
The signalling pathways regulated by Actein, Withaferin A, Indole-3-Carbinol and Compound Kushen, which are extensively researched compounds, were shown to be projected on a set of oncogenesis processes at the transcriptomic level in different breast cancer subtypes. The enrichment of well-known tumour driving genes indicate that these compounds indirectly dysregulate cancer driving pathways in the subnetworks.

Conclusion
The proposed framework infers the mechanisms of action of potential drug candidates from their enriched protein interaction subnetworks and oncogenic signalling pathways. It also provides a systematic approach for evaluating such compounds in polygenic complex diseases. In addition, the plant-based compounds used here show poly-pharmacologic mechanism of action by targeting subnetworks enriched with cancer driving genes. This network perspective supports the need for a systemic drug-target evaluation for lead compounds prior to efficacy experiments.
Genetic aetiology of primary adrenal insufficiency in Chinese children
Authors: Chang Zhuo , Lu Wei , Zhao Zhuhui , Xi Li , Li Xiaojing , Ye Rong , Ni Jinwen , Pei Zhou , Zhang Miaoying , Cheng Ruoqian , Zheng Zhangqian , Sun Chengjun , Wu Jing , Luo Feihong 
Published: June 2021

Abstract
Background
Primary adrenal insufficiency (PAI) is life-threatening, and a definitive aetiological diagnosis is essential for management and prognostication. We conducted this study to investigate the genetic aetiologies of PAI in South China and explore their clinical features.

Methods
Seventy children were enrolled in this cross-sectional study. Clinical information was collected, and combined genetic tests were performed according to the children’s manifestations. Statistical analysis was performed among the different groups. In silico or in vitro experiments were applied to determine the pathogenicity of novel variants.

Results
Among the 70 children, 84.3% (59/70) were diagnosed with congenital adrenal hyperplasia (CAH), and 21-hydroxylase deficiency (21-OHD) was genetically confirmed in 91.5% of these cases. Salt wasting (SW), simple virilization (SV), and non-classic (NC) CAH accounted for 66.1% (39/59), 30.5% (18/59), and 3.4% (2/59) of the cases, respectively. The 17-hydroxyprogesterone (17-OHP) and testosterone (TES) levels were significantly higher in children with SW than with SV. The 17-OHP and cortisol levels in female SW patients were significantly higher than those in males. The 17-OHP, cortisol, dehydroepiandrosterone (DHEAS) and TES levels in female SW patients were significantly higher than those in female SV patients. Additionally, 72.7% (8/11) of uncharacterized PAI patients had positive genetic findings. Among all the patients, two novel variants in the CYP21A2 gene (c.833dupT and c.651 + 2T > G) were found. A microdeletion (Xp21.2–21.3) and five novel variants, including 2 in the NR0B1 gene (c.323–324CG > GA and c.1231_1234delCTCA), 2 in the AAAS gene (c.399 + 1G > A and c.250delT) and 1 in the NNT gene (c.2274delT), were detected. The novel variant c.399 + 1G > A in the AAAS gene was further confirmed to lead to exon 4 skipping during mRNA transcription and produce a truncated ALADIN protein.

Conclusions
We found ethnicity-based differences in the CYP21A2 gene variant spectrum among different study populations. Female 21-OHD patients tended to have higher 17-OHP and TES levels, which warrants caution in relation to the effects of virilization. Novel gene variants detected in the CYP21A2, NR0B1, AAAS and NNT genes expanded the genetic spectrum of PAI, however, further improvement of genetic testing tools beyond our protocol are still needed to uncover the complete aetiology of PAI in children.
Relationship between polymorphism of receptor SCARB2 gene and clinical severity of enterovirus-71 associated hand-foot-mouth disease
Authors: Wang Xia , Liu Hong , Li Ying , Su Rui , Liu Yamin , Qiao Kunyan 
Published: June 2021

Abstract
Background
To investigate the relationship between polymorphism of scavenger receptor class B member 2 (SCARB2) gene and clinical severity of enterovirus (EV)-71 associated hand-foot-mouth disease (HFMD).

Methods
Among the 100 recruited cases, 56 were in the severe HFMD group (case group) and 44 were in the general HFMD group (control group). By screening functional single nucleotide polymorphisms (SNPs) and hot SNPs, and performing SNP site optimization, some SNP sites of SCARB2 gene were selected for analysis. Genotyping was performed using a MassArray platform. PLINK software was used for statistical processing and analysis of the correlation differences between the mutant genotypes in the severe and general HFMD groups. The relationship between the SNPs and clinical severity of enterovirus (EV)-71 associated HFMD was assessed.

Results
28 SNPs in SCARB2 were selected by site optimization. Then three loci were not in agreement with the minor allele frequency (MAF) in the 1000 Han Chinese in Beijing (CHB) dataset. Another three loci could not be detected. Nine loci were not suitable for further analysis (MAF < 0.01 and Hardy–Weinberg [HWE] P < 0.001). A total of 13 sites were subsequently analyzed. Through Fisher analysis, the frequency of the rs6812193 T allele was 0.134 and 0.034 in the severe and general HFMD groups, respectively (P 0.023 < 0.05, odds ratio [OR] 4.381 > 1). Logistic regression analysis of rs6812193 T alleles between the severe and general HFMD groups, respectively (P 0.023 < 0.05, OR 4.412 > 1, L95 1.210 > 1). Genotype logistic regression analysis of the rs6812193 alleles CT + TT versus CC gave an OR of 4.56 (95% confidence interval [95% CI] 1.22–17.04, P = 0.012).

Conclusion
The rs6812193 T allele was a susceptibility SNP for SHFMD, and the rs6812193 polymorphism might be significantly associated with the susceptibility to EV-71 infection.