bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Resistant Starch Consumption in Adult Patients With Chronic Kidney Disease: A Systematic Review
Authors: Kingra Kulwant , Curtis Sarah , Mollard Rebecca C. , Shamloo Maryam , Askin Nicole , Tangri Navdeep , MacKay Dylan 
Published: July 2022

Background: Resistant starches (RSs) are not digested by human digestive enzymes and pass through the upper digestive tract to become substrates for colonic bacteria. Resistant starch supplementation has shown promising results in altering the microbiota of animal models of chronic kidney disease (CKD). Resistant starch consumption may influence the production of uremic toxins in CKD. Objective: To conduct a systematic review to determine whether the consumption of RS reduces the progression of kidney disease in adult patients with CKD. Design: We included randomized controlled trials comparing RS supplementation to placebo, no treatment, or standard care. Cochrane Central, Embase, MEDLINE, Web of Science, and CINAHL databases were searched. There was no limitation on publication date, but only English manuscripts were included. The search was conducted in July 2020. Patients: Adult outpatient populations with CKD, using any recognized diagnostic criteria. Measurements: The primary outcome was change in glomerular filtration rate (GFR) from baseline through the end of the trial in patients not on dialysis; secondary outcomes included change in uremic toxin concentrations (p-cresol/p-cresyl sulfate [p-CS], indoxyl sulfate [IS]) and inflammatory markers (tumor necrosis factor alpha [TNF-α], C-reactive protein [CRP], interleukin 6 [IL-6]) from baseline through the end of the trial, and changes in self-reported symptom scores. Methods: The Cochrane Collaboration Risk of Bias tool was used to assess risk of bias in included studies. The systematic review results are reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Results: We identified 4 unique studies, reported in 9 publications that met our inclusion criteria, including a total of 215 enrolled participants. Results were calculated using data from the longest reported follow-up time. The primary outcome of changes in kidney function markers was only studied in 1 trial; this trial reported an increase in creatinine and a decrease in blood urea nitrogen; no changes in GFR were reported. A review of the secondary outcomes showed an overall decline in IS, TNF-α, and IL-6, in RS groups, but with mixed results in p-CS and CRP/high-sensitivity CRP. Safety data showed that RS was well tolerated with no reports of excessive side effects. Limitations: We determined a meta-analysis was not feasible due to clinical heterogeneity between study populations and differences in reported outcomes in the included studies. Conclusion: There is limited and inconsistent evidence on the impact of RS in adult patients with CKD. Further research is needed to determine the safety and efficacy of RS supplementation in this population.
Frankincense essential oil nanoemulsion specifically induces lung cancer apoptosis and inhibits survival pathways
Authors: Abd-Rabou Ahmed A. , Edris Amr E. 
Published: July 2022

Abstract
Background
The volatile fraction of frankincense (Boswellia sacra) oleogum was extracted, formulated in nanoemulsion and tested against lung cancer A549 cell line. First, the gum was hydro-distilled to isolate the volatile fraction (essential oil), which was analyzed via gas chromatography to identify its major volatile constituents. Then, the oil was formulated in two water-based nanoemulsions which differ from one another in the presence of propylene glycol (PG), which is used in the formulation step as a co-surfactant. The pure essential oil as well as its major volatile compound (α-pinene), its two nanoemulsions and a reference drug (Doxorubicin) were evaluated against lung cancer A549 cell lines and WI-38 normal lung cells. The evaluation included cytotoxicity (MTT and IC50), apoptosis (flow cytometric analysis) in addition to genetic assessments for some intrinsic and extrinsic genes relevant to apoptosis and survival pathways.

Results
Chromatographic analysis of frankincense essential oil revealed that α-pinene is the major volatile compound which constituent about 60% of that oil. Emulsification of the oil using the low energy technique gave nanoemulsions having major intense particles population (85–90%) with z-average diameter below 20.0 nm. Frankincense oil nanoemulsion fabricated with (PG) showed the best cytotoxic activity toward lung cancer A549 cell compared to PG-free nanoemulsion, α-pinene and the reference drug doxorubicin, along different incubation periods. Flow cytometric analysis also indicated that PG-containing nanoemulsion can induce cancer cells toward apoptosis better than the other formula and the pure oils. The same nanoemulsion was found to upregulate the pro-apoptotic genes [DR5, FAAD, Caspase 8 (Cas8), p53, and Bax] and downregulate the anti-apoptotic and reoccurrence genes (Bcl-2, NF-kB, and STAT-3). Most importantly, the PG-containing nanoemulsion had the least cytotoxic effect on the normal WI-38 lung cells.

Conclusions
These results point out to the potentials of frankincense essential oil (rich in α-pinene) and its PG-nanoemulsion as a promising adjuvant from plant-source to potentiate the activity of the systematic anti-lung cancer drugs.
Performance of the No-U-Turn sampler in multi-trait variance component estimation using genomic data
Authors: Nishio Motohide , Arakawa Aisaku 
Published: July 2022

AbstractBackgroundMulti-trait genetic parameter estimation is an important topic for target traits with few records and with a low heritability and when the genetic correlation between target and secondary traits is strong. However, estimating correlations between multiple traits is difficult for both Bayesian and non-Bayesian inferences. We extended a Hamiltonian Monte Carlo approach using the No-U-Turn Sampler (NUTS) to a multi-trait animal model and investigated the performance of estimating (co)variance components and breeding values, compared to those for restricted maximum likelihood and Gibbs sampling with a population size of 2314 and 578 in a simulated and real pig dataset, respectively. For real data, we used publicly available data for three traits from the Pig Improvement Company (PIC). For simulation data, we generated two quantitative traits by using the genotypes of the PIC data. For NUTS, two prior distributions were adopted: Lewandowski-Kurowicka-Joe (LKJ) and inverse-Wishart distributions.ResultsFor the two simulated traits with heritabilities of 0.1 and 0.5, most estimates of the genetic and residual variances for NUTS with the LKJ prior were closer to the true values and had smaller root mean square errors and smaller mean absolute errors, compared to NUTS with inverse-Wishart priors, Gibbs sampling and restricted maximum likelihood. The accuracies of estimated breeding values for lowly heritable traits for NUTS with LKJ and inverse-Wishart priors were 14.8% and 11.1% higher than those for Gibbs sampling and restricted maximum likelihood, respectively, with a population size of 578. For the trivariate animal model with real pig data, the estimates of the genetic correlations for Gibbs sampling and restricted maximum likelihood were strongly affected by population size, compared to NUTS. For both the simulated and pig data, the genetic variances and heritabilities for NUTS with an inverse-Wishart prior were overestimated for low-heritability traits when the population size was 578.ConclusionsThe accuracies of variance components and breeding values estimates for a multi-trait animal model using NUTS with the LKJ prior were equal to or higher than those obtained with restricted maximum likelihood or Gibbs sampling. Therefore, when the population size is small, NUTS with an LKJ prior could be an alternative sampling method for multi-trait analysis in animal breeding.
Epidemiology and clinical characteristics of infection/colonization due to carbapenemase-producing Enterobacterales in neonatal patients
Authors: Wang Jiansheng , Lv Yuanpeng , Yang Weiwei , Zhao Peng , Yin Changfu 
Published: July 2022

Abstract
Background
The aim of this study was to elucidate the epidemiological features of carbapenemase-producing Enterobacterales (CPE) in the pediatric and neonatal patients, to describe clinical characteristics of neonatal patients with CPE infections, and to assess risk factors for neonatal rectal colonization with CPE.

Results
A total of 439 carbapenem-resistant Enterobacterales (CRE) isolates recovered from 367 infant patients were characterised, including 397 isolates of Klebsiella pneumoniae (KP) and 42 isolates of Escherichia coli (EC). Carbapenemase gene blaNDM-1 was the most commonly detected, accounting for 86.56% (n = 380), followed by blaKPC-2 (9.11%, 40) and blaIMP-4 (4.33%, 19). MLST analysis showed 17 different STs detected within CPKP isolates, with ST20, ST2068, ST36 and ST17 being the most frequently isolated types. Eleven STs were identified within CPEC isolates, with ST325 being the dominant types. Eight isolates of NDM-1 producing KP, belonging to ST23, were identified as having hypervirulent traits. The main infections caused by CPE were pneumonia (n = 90) and sepsis (n = 16). All infected patients received monotherapy, with meropenem and ciprofloxacin being the most commonly used antibiotics. All pneumonia patients were cured or improved after treatment. Of the 16 patients with sepsis, 9 were cured or improved, 3 died, and 4 abandoned treatment without any clinical improvement. The rectal prevalences of CPE in the 0–3 days old (DO), the 4–28 DO, and the 29 DO-1 year old groups were decreased from 15.31%, 27.37% and 14.29% in the first stool screening period to 11.78%, 19.59% and 4.07% in the second stool screening period, respectively. Multivariate analysis showed that cesarean section, acidosis, respiration failure, gastric lavage and enema were independent risk factors for rectal colonization in the 0–3 DO group, whereas cesarean section, cephalosporins, gastric lavage and residence in rural area were independently associated with rectal colonization in the 4–28 DO group. The implementation of a series of evidence-based control measures eventually contained the CPE transmission.

Conclusions
Continued vigilance, epidemiological studies, and multimodal infection prevention strategies are urgently needed due to frequent importations.
Transcription-associated metabolomic profiling reveals the critical role of frost tolerance in wheat
Authors: Lv Liangjie , Dong Ce , Liu Yuping , Zhao Aiju , Zhang Yelun , Li Hui , Chen Xiyong 
Published: July 2022

Abstract
Background
Low temperature is a crucial stress factor of wheat (Triticum aestivum L.) and adversely impacts on plant growth and grain yield. Multi-million tons of grain production are lost annually because crops lack the resistance to survive in winter. Particularlly, winter wheat yields was severely damaged under extreme cold conditions. However, studies about the transcriptional and metabolic mechanisms underlying cold stresses in wheat are limited so far.

Results
In this study, 14,466 differentially expressed genes (DEGs) were obtained between wild-type and cold-sensitive mutants, of which 5278 DEGs were acquired after cold treatment. 88 differential accumulated metabolites (DAMs) were detected, including P-coumaroyl putrescine of alkaloids, D-proline betaine of mino acids and derivativ, Chlorogenic acid of the Phenolic acids. The comprehensive analysis of metabolomics and transcriptome showed that the cold resistance of wheat was closely related to 13 metabolites and 14 key enzymes in the flavonol biosynthesis pathway. The 7 enhanced energy metabolites and 8 up-regulation key enzymes were also compactly involved in the sucrose and amino acid biosynthesis pathway. Moreover, quantitative real-time PCR (qRT-PCR) revealed that twelve key genes were differentially expressed under cold, indicating that candidate genes POD, Tacr7, UGTs, and GSTU6 which were related to cold resistance of wheat.

Conclusions
In this study, we obtained the differentially expressed genes and differential accumulated metabolites in wheat under cold stress. Using the DEGs and DAMs, we plotted regulatory pathway maps of the flavonol biosynthesis pathway, sucrose and amino acid biosynthesis pathway related to cold resistance of wheat. It was found that candidate genes POD, Tacr7, UGTs and GSTU6 are related to cold resistance of wheat. This study provided valuable molecular information and new genetic engineering clues for the further study on plant resistance to cold stress.
Role of publicly funded health insurance in financial protection of the elderly from hospitalisation expenditure in India-findings from the longitudinal aging study
Authors: Garg Samir , Bebarta Kirtti Kumar , Tripathi Narayan 
Published: July 2022

Abstract
Background
The elderly face a greater burden of illnesses than other age groups and have a more frequent need of healthcare, including in-patient hospitalisations. Catastrophic expenditure on hospitalisation of the elderly poses a significant challenge to India’s aim of achieving Universal Health Coverage (UHC). India has implemented a policy of Publicly Funded Health Insurance (PFHI) to provide free inpatient care by empanelling private and public hospitals. The existing studies have examined the performance of PFHI in financial protection of the elderly.

Methods
This study utilised the Longitudinal Ageing Study in India (LASI) Wave 1, conducted in 2017–18. LASI is a large-scale nationally representative survey collecting data on elderly health including illness burden, healthcare use and out of pocket expenditure (OOPE). It covered a sample 72,250 individuals aged 45 or above. Financial Protection was measured in terms of Catastrophic Health Expenditure (CHE). Multivariate analysis was conducted to find effect of PFHI on OOPE—quantile and logistic models were applied for OOPE and CHE respectively. For robustness, Propensity Score Matching (PSM) model was applied.

Results
Of the hospitalisations, 35% had taken place in public hospitals. The mean OOPE for a hospitalisation in public sector was Indian Rupees (INR) 8276, whereas it was INR 49,700 in private facilities. Incidence of CHE was several times greater for using private hospitals as compared to public hospitals. Multi-variate analyses showed that enrolment under PFHI was not associated with lower OOPE or CHE. PSM model also confirmed that PFHI-enrolment had no effect on OOPE or CHE. Use of private facilities was a key determinant of OOPE, irrespective of enrolment under PFHI.

Conclusions
This was the first study in India to examine the performance of PFHI in the context of catastrophic hospitalisation expenditure faced by the elderly. It found that PFHI was not effective in financial protection of the elderly. The ongoing reliance on a poorly regulated private sector seems to be a key limitation of PFHI policy. Governments need to find more effective ways of protecting the elderly from catastrophic health expenditure if the goal of UHC has to be realized.
Clinical characteristics and antibodies against Echinococcus granulosus recombinant antigen P29 in patients with cystic echinococcosis in China
Authors: Tao Jia , Du Xiancai , Liu Kejun , Wang Chan , Lv Yongxue , Wang Minglei , Yang Zhiqi , Yang Jihui , Li Shasha , Wu Changyou , Li Minghao , Zhao Wei 
Published: July 2022

AbstractObjectivesCystic echinococcosis (CE) is a neglected parasitic zoonotic disease caused by the larval stage of the tapewormEchinococcusgranulosus(E. granulosus). This study aimed to understand the clinical characteristics of human CE in Ningxia Hui Autonomous Region (NHAR) located in northwest China and to investigate the antibody profiles against the recombinantE. granulosusantigen P29 (rEg.P29) in plasma of CE patients.MethodsA total of 37 human CE patients, along with 37 healthy donors enrolled in this study and demographic and clinical data were analyzed, including age, gender, laboratory data, symptoms, and cysts description. Plasma levels of cytokines, total IgG, and total IgE were determined by sandwich ELISA kits. Specific antibodies against rEg.P29 and hydatid cyst fluid (HCF) were assessed by indirect ELISA.ResultsThe results revealed that females have a higher percentage of CE patients than males. The incidence of CE reached a peak in the 41–50 years-old group. The liver was the most frequent location, accounting for 91.9%. Based on the CT images, cysts of 34 patients who had liver involvement, were classified as 1 (2.9%) CE1, 12 (35.3%) CE2, 5 (14.7%) CE3a, 1 (2.9%) CE3b, and 15 (44.2%) CE5. Twenty-nine (78.4%) patients had a single cyst and 8 (21.6%) had at least two cysts. The most frequently reported symptom was upper abdominal pain. The plasma level of IL-6 and total IgE were significantly increased in CE patients compared with healthy donors. Additionally, IgG response to rEg.P29 in CE patients was significantly higher than in healthy donors, and the dominant IgG subclass was IgG4. Further analysis of different patient groups revealed that rEg.P29-specific IgG and IgG4 were only elevated in CE patients with CE2 type cysts.ConclusionsThis study systematically investigated the clinical characteristics of patients with CE and may provide a reference basis for the diagnosis and treatment of CE in NHAR. Furthermore, tests of specific IgG and IgG4 against rEg.P29 can be used as an assisted method for imaging techniques to identify cystic activity and determine the best therapeutic approach for CE.
The value of eosinophil count in the diagnosis of preeclampsia among pregnant women attending the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia, 2021
Authors: Gelaw Yemataw , Asrie Fikir , Walle Muluken , Getaneh Zegeye 
Published: July 2022

AbstractBackgroundCurrently, studies showed that eosinophil count had clinical significance in the diagnosis and prognosis of diseases. But, the clinical significance of eosinophil count in pregnancy specifically in preeclampsia (PE) is not well studied. The main objective of the present study was to assess the diagnosis value of eosinophils counts among pregnant women with PE.MethodsA comparative cross-sectional study was conducted on a total of 126 pregnant women at the University of Gondar Comprehensive Specialized Hospital, using a convenient sampling technique. Socio-demographic and clinical data were collected by questionnaire and datasheet from patient’s charts, respectively. A total of six ml of blood was collected from each study participant; three ml for complete cell count analysis using Sysmex XS-500i hematology analyzer and three ml for liver function tests using Humastar 200 chemistry analyzer. The data were entered into Epi-data and exported to SPSS 20 for analysis. The independent t-test was used for normally distributed data and, the Mann–Whitney U test was used for non-normally distributed data. Binary logistic regression and receiver operative curve analyses were also done to assess the diagnosis value of eosinophils count.P-value < 0.05 was considered statistically significant.ResultsThe eosinophils count of PE pregnant women were significantly lower than the normotensive (NT) pregnant women (median (IQR): 50 (10—200) vs. 120 (60 – 270); (p = 0.002). The eosinophil count ≤ 55 cells/µL had an AUC of 0.66 (95% CI; 0.56—0.75) for diagnosis of PE with a sensitivity of 50.8%, specificity of 77.8%, and positive and negative predictive value of 69.6% and 61.3%, respectively. The abnormal AST and ALT results were significantly higher among PE pregnant women compared to NT pregnant women (AOR: 14.86; 95% CI: 4.97—44.4 and Fischer exact testp-value = 0.001, respectively).ConclusionThe eosinophil count ≤ 55cells/µl had a reasonable/acceptable AUC which may use in the diagnosis of PE. AST and ALT were also significantly higher in PE pregnant women compared to NT pregnant women. Multicenter longitudinal studies with a large sample size are recommended to verify the role of eosinophil count in the diagnosis of PE.
Discovery of a novel ALK/ROS1/FAK inhibitor, APG-2449, in preclinical non-small cell lung cancer and ovarian cancer models
Authors: Fang Douglas D. , Tao Ran , Wang Guangfeng , Li Yuanbao , Zhang Kaixiang , Xu Chunhua , Zhai Guoqin , Wang Qixin , Wang Jingwen , Tang Chunyang , Min Ping , Xiong Dengkun , Chen Jianyong , Wang Shaomeng , Yang Dajun , Zhai Yifan 
Published: July 2022

Abstract
Background
Tyrosine kinase inhibitors (TKIs) are mainstays of cancer treatment. However, their clinical benefits are often constrained by acquired resistance. To overcome such outcomes, we have rationally engineered APG-2449 as a novel multikinase inhibitor that is highly potent against oncogenic alterations of anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 receptor tyrosine kinase (ROS1), and focal adhesion kinase (FAK). Here we present the preclinical evaluation of APG-2449, which exhibits antiproliferative activity in cells carrying ALK fusion or secondary mutations.

Methods
KINOMEscan® and LANCE TR-FRET were used to characterize targets and selectivity of APG-2449. Water-soluble tetrazolium salt (WST-8) viability assay and xenograft tumorigenicity were employed to evaluate therapeutic efficacy of monotherapy or drug combination in preclinical models of solid tumors. Western blot, pharmacokinetic, and flow cytometry analyses, as well as RNA sequencing were used to explore pharmacokinetic–pharmacodynamic correlations and the mechanism of actions driving drug combination synergy.

Results
In mice bearing wild-type or ALK/ROS1-mutant non-small-cell lung cancer (NSCLC), APG-2449 demonstrates potent antitumor activity, with correlations between pharmacokinetics and pharmacodynamics in vivo. Through FAK inhibition, APG-2449 sensitizes ovarian xenograft tumors to paclitaxel by reducing CD44+ and aldehyde dehydrogenase 1-positive (ALDH1+) cancer stem cell populations, including ovarian tumors insensitive to carboplatin. In epidermal growth factor receptor (EGFR)-mutated NSCLC xenograft models, APG-2449 enhances EGFR TKI-induced tumor growth inhibition, while the ternary combination of APG-2449 with EGFR (osimertinib) and mitogen-activated extracellular signal-regulated kinase (MEK; trametinib) inhibitors overcomes osimertinib resistance. Mechanistically, phosphorylation of ALK, ROS1, and FAK, as well as their downstream components, is effectively inhibited by APG-2449.

Conclusions
Taken together, our studies demonstrate that APG-2449 exerts potent and durable antitumor activity in human NSCLC and ovarian tumor models when administered alone or in combination with other therapies. A phase 1 clinical trial has been initiated to evaluate the safety and preliminary efficacy of APG-2449 in patients with advanced solid tumors, including ALK+ NSCLC refractory to earlier-generation ALK inhibitors.

Trial registration
Clinicaltrial.gov registration: NCT03917043 (date of first registration, 16/04/2019) and Chinese clinical trial registration: CTR20190468 (date of first registration, 09/04/2019).