bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significant differences in FcγRIIa, FcγRIIIa and FcγRIIIb genes polymorphism and anti-malarial IgG subclass pattern are associated with severe Plasmodium falciparum malaria in Saudi children
Authors: Nasr Amre , Aljada Ahmad , Hamid Osama , Elsheikh Hatim A. , Masuadi Emad , Al-Bawab Ahmad , Alenazi Themer H. , Abushouk Amir , Salah Ayman M. 
Published: September 2021

Abstract
Background
The FcγRs genotypes have been reported to play a key role in the defence against malaria parasites through both cellular and humoral immunity. This study aimed to investigate the possible correlation between FcγR (IIa, IIIa, and IIIb) genes polymorphism and the clinical outcome for anti‐malarial antibody response of Plasmodium falciparum infection among Saudi children.

Methods
A total of 600 volunteers were enrolled in this study, including 200 malaria-free control (MFC) subjects, 218 patients with uncomplicated malaria (UM) and 182 patients with severe malaria (SM). The FcγR genotypes were analysed using PCR amplification methods, and measurements of immunoglobulin were determined using enzyme-linked immunosorbent assay (ELISA) technique.

Results
The data revealed that the FcγRIIa-R/R131 showed a statistically significant association with SM patients when compared to UM patients. Furthermore, higher levels of IgG1, IgG2, and IgG4 were associated with the FcγRIIa-H/H131 genotype among UM patients. Although the FcγRIIa-F/V176 genotype was not associated with UM, it showed a significant association with severe malaria. Interestingly, the FcγRIIIa-V/V176 genotype offered protection against SM. Moreover, SM patients carrying the FcγRIIIa-F/F genotype showed higher levels of AMA-1-specific IgG2 and IgG4 antibodies. The FcγRIIIb-NA1/NA1 and FcγRIIIb-NA2/NA2 genotypes did not show significant differences between the UM and the MFC groups. However, the genotype FcγRIIIb-NA2/NA2 was statistically significantly associated with SM patients.

Conclusions
The data presented in this study suggest that the influence of the FcγRIIa-R/R131, FcγRIIIa-F/F176 and FcγRIIIb-NA2/NA2 genotypes are statistically significantly associated with SM patients. However, the FcγRIIa-H/H13 and FcγRIIIa-V/V176 genotypes have demonstrated a protective effect against SM when compared to UM patients. The impact of the FcyR (IIa, IIIa and IIIb) gene variants and anti-malaria IgG subclasses play an important role in susceptibility to malaria infection and disease outcome in Saudi children.
HA-coated collagen nanofibers for urethral regeneration via in situ polarization of M2 macrophages
Authors: Niu Yuqing , Stadler Florian J. , Yang Xu , Deng Fuming , Liu Guochang , Xia Huimin 
Published: September 2021

Abstract
In situ tissue engineering utilizes the regenerative potential of the human body to control cell function for tissue regeneration and has shown considerable prospect in urology. However, many problems are still to be understood, especially the interactions between scaffolds and host macrophages at the wound site and how these interactions direct tissue integration and regeneration. This study was designed to evaluate the efficacy of hyaluronic acid (HA) functionalized collagen nanofibers in modulating the pro-healing phenotype expression of macrophages for urethral regeneration. Tubular HA-collagen nanofibers with HA-coating were prepared by coaxial electrospinning. The formation of a thin HA-coating atop each collagen nanofiber endowed its nanofibrous mats with higher anisotropic wettability and mechanical softness. The macrophages growing on the surface of HA-collagen nanofibers showed an elongated shape, while collagen nanofibers’ surface exhibited a pancake shape. Immunofluorescence and ELISA analysis showed that elongation could promote the expression of M2 phenotype marker and reduce the secretion of inflammatory cytokines. In vivo experiments showed that tubular HA-collagen nanofibers significantly facilitate male puppy urethral regeneration after injury. In the regenerated urethra bridged by tubular HA-collagen nanofibers, anti-inflammatory M2 macrophages are recruited to the surface of the scaffold, which can promote angiogenesis and endogenous urothelial progenitor cell proliferation.
Can integrated care improve the efficiency of hospitals? Research based on 200 Hospitals in China
Authors: Peng Zixuan , Zhu Li , Wan Guangsheng , Coyte Peter C. 
Published: September 2021

Abstract
Background
The shift towards integrated care (IC) represents a global trend towards more comprehensive and coordinated systems of care, particularly for vulnerable populations, such as the elderly. When health systems face fiscal constraints, integrated care has been advanced as a potential solution by simultaneously improving health service effectiveness and efficiency. This paper addresses the latter. There are three study objectives: first, to compare efficiency differences between IC and non-IC hospitals in China; second, to examine variations in efficiency among different types of IC hospitals; and finally, to explore whether the implementation of IC impacts hospital efficiency.

Methods
This study uses Data Envelopment Analysis (DEA) to calculate efficiency scores among a sample of 200 hospitals in H Province, China. Tobit regression analysis was performed to explore the influence of IC implementation on hospital efficiency scores after adjustment for potential confounding. Moreover, the association between various input and output variables and the implementation of IC was investigated using regression techniques.

Results
The study has four principal findings: first, IC hospitals, on average, are shown to be more efficient than non-IC hospitals after adjustment for covariates. Holding output constant, IC hospitals are shown to reduce their current input mix by 12% and 4% to achieve optimal efficiency under constant and variable returns-to-scale, respectively, while non-IC hospitals have to reduce their input mix by 26 and 20% to achieve the same level of efficiency; second, with respect to the efficiency of each type of IC, we show that higher efficiency scores are achieved by administrative and virtual IC models over a contractual IC model; third, we demonstrate that IC influences hospitals efficiency by impacting various input and output variables, such as length of stay, inpatient admissions, and staffing; fourth, while bed density per nurse was positively associated with hospital efficiency, the opposite was shown for bed density per physician.

Conclusions
IC has the potential to promote hospital efficiency by influencing an array of input and output variables. Policies designed to facilitate the implementation of IC in hospitals need to be cognizant of the complex way IC impacts hospital efficiency.
Effect of birthweight measurement quality improvement on low birthweight prevalence in rural Ethiopia
Authors: Baye Estifanos , Abate Firehiwot Workneh , Eglovitch Michelle , Shiferie Fisseha , Olson Ingrid E. , Shifraw Tigest , Kidane Workagegnehu Tarekegn , Yibeltal Kalkidan , Tsegaye Sitota , Derebe Mulatu Melese , Isanaka Sheila , Wylie Blair J. , Molina Rose L. , Chan Grace J. , Worku Amare , Mullany Luke C. , Worku Alemayehu , Berhane Yemane , Lee Anne C. C. 
Published: September 2021

Abstract
Background
Low birthweight (LBW) (< 2500 g) is a significant determinant of infant morbidity and mortality worldwide. In low-income settings, the quality of birthweight data suffers from measurement and recording errors, inconsistent data reporting systems, and missing data from non-facility births. This paper describes birthweight data quality and the prevalence of LBW before and after implementation of a birthweight quality improvement (QI) initiative in Amhara region, Ethiopia.

Methods
A comparative pre-post study was performed in selected rural health facilities located in West Gojjam and South Gondar zones. At baseline, a retrospective review of delivery records from February to May 2018 was performed in 14 health centers to collect birthweight data. A birthweight QI initiative was introduced in August 2019, which included provision of high-quality digital infant weight scales (precision 5 g), routine calibration, training in birth weighing and data recording, and routine field supervision. After the QI implementation, birthweight data were prospectively collected from late August to early September 2019, and December 2019 to June 2020. Data quality, as measured by heaping (weights at exact multiples of 500 g) and rounding to the nearest 100 g, and the prevalence of LBW were calculated before and after QI implementation.

Results
We retrospectively reviewed 1383 delivery records before the QI implementation and prospectively measured 1371 newborn weights after QI implementation. Heaping was most frequently observed at 3000 g and declined from 26% pre-initiative to 6.7% post-initiative. Heaping at 2500 g decreased from 5.4% pre-QI to 2.2% post-QI. The percentage of rounding to the nearest 100 g was reduced from 100% pre-initiative to 36.5% post-initiative. Before the QI initiative, the prevalence of recognized LBW was 2.2% (95% confidence interval [CI]: 1.5–3.1) and after the QI initiative increased to 11.7% (95% CI: 10.1–13.5).

Conclusions
A QI intervention can improve the quality of birthweight measurements, and data measurement quality may substantially affect estimates of LBW prevalence.
FGFR2 alteration as a potential therapeutic target in poorly cohesive gastric carcinoma
Authors: Wang Yue , Shi Tao , Wang Xuan , Hu Jinwei , Yu Lixia , Liu Qin , Wu Nandie , Liu Baorui , Wei Jia 
Published: September 2021

Abstract
Background
Poorly cohesive (PC) is a unique histologic subtype of gastric cancer (GC), with an increasing incidence in recent years. However, the molecular characteristics and therapeutic targets of PC GC are not yet well studied and there are no effective therapies for these patients.

Methods
Formalin fixed paraffin embedded (FFPE) samples of 556 GC patients, including 64 PC GC, were collected for next-generation sequencing (NGS). Clinical characteristics and genomic profiling were analyzed. FGFR2 expression was detected by quantitative real time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). FGFR2 inhibitors response was studied in vitro.

Results
Among 556 GC patients, PC GC patients were younger (P = 0.004), had lower tumor mutation burden (TMB-L) (P = 0.001) than non-PC GC. The top 10 most frequently mutated genes in PC GC were TP53 (48%), CDH1 (31%), ARID1A (14%), FGFR2 (14%), ERBB2 (9%), CDKN2A (9%), FGF3 (8%), LRP1B (9%), FGF19 (8%) and FGF4 (8%). Noticeably, FGFR2 is more frequently mutated than non-PC GC (14% vs. 6%, P = 0.037), including copy number variants (CNVs, 12.5%) and gene rearrangements (3.1%, FGFR2/VTI1A and FGFR2/TACC2). Former studies have confirmed that gain of copy number could increase FGFR2 expression and sensitivity to FGFR2 inhibitors in GC. However, no research has verified the function of FGFR2 rearrangements in GC. Our results showed that cell lines of GC transfected with TACC2-FGFR2 fusion had increased mRNA and protein expression of FGFR2, and were more sensitive to FGFR2 inhibitors. FGFR2 inhibitors might be a new therapeutic target for PC GC. In addition, we found patients of PC GC harboring gene rearrangements (n = 9) had poorer overall survival (OS) in comparison with patients without any gene rearrangement (n = 19) (16.0 months vs 21.0 months, P = 0.043). Gene rearrangement might be an adverse prognostic factor for PC GC patients.

Conclusions
FGFR2 alterations were recurrent in PC GC and FGFR2 inhibitors might be a new therapeutic target for PC GC.
Aging triggers an upregulation of a multitude of cytokines in the male and especially the female rodent hippocampus but more discrete changes in other brain regions
Authors: Porcher Latarsha , Bruckmeier Sophie , Burbano Steven D. , Finnell Julie E. , Gorny Nicole , Klett Jennifer , Wood Susan K. , Kelly Michy P. 
Published: September 2021

Abstract
Background
Despite widespread acceptance that neuroinflammation contributes to age-related cognitive decline, studies comparing protein expression of cytokines in the young versus old brains are surprisingly limited in terms of the number of cytokines and brain regions studied. Complicating matters, discrepancies abound—particularly for interleukin 6 (IL-6)—possibly due to differences in sex, species/strain, and/or the brain regions studied.

Methods
As such, we clarified how cytokine expression changes with age by using a Bioplex and Western blot to measure multiple cytokines across several brain regions of both sexes, using 2 mouse strains bred in-house as well as rats obtained from NIA. Parametric and nonparametric statistical tests were used as appropriate.

Results
In the ventral hippocampus of C57BL/6J mice, we found age-related increases in IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, IL-9, IL-10, IL-12p40, IL-12p70, IL-13, IL-17, eotaxin, G-CSF, interfeuron δ, KC, MIP-1a, MIP-1b, rantes, and TNFα that are generally more pronounced in females, but no age-related change in IL-5, MCP-1, or GM-CSF. We also find aging is uniquely associated with the emergence of a module (a.k.a. network) of 11 strongly intercorrelated cytokines, as well as an age-related shift from glycosylated to unglycosylated isoforms of IL-10 and IL-1β in the ventral hippocampus. Interestingly, age-related increases in extra-hippocampal cytokine expression are more discreet, with the prefrontal cortex, striatum, and cerebellum of male and female C57BL/6J mice demonstrating robust age-related increase in IL-6 expression but not IL-1β. Importantly, we found this widespread age-related increase in IL-6 also occurs in BALB/cJ mice and Brown Norway rats, demonstrating conservation across species and rearing environments.

Conclusions
Thus, age-related increases in cytokines are more pronounced in the hippocampus compared to other brain regions and can be more pronounced in females versus males depending on the brain region, genetic background, and cytokine examined.
Pain trajectories and possible predictors of a favourable course of low back pain in patients consulting musculoskeletal physicians in The Netherlands
Authors: Schuller Wouter , Ostelo Raymond W. , Rohrich Daphne C. , Heymans Martijn W. , de Vet Henrica C. W. 
Published: September 2021

Abstract
Background
In The Netherlands, low back pain patients can consult physicians specialized in musculoskeletal (MSK) medicine. Previous studies have reported on the characteristics of patients consulting MSK physicians, and the treatment options used. There are no studies yet reporting on the course of Low Back Pain (LBP) after treatment by musculoskeletal (MSK) physicians in The Netherlands.

Methods
In an observational cohort study MSK physicians recorded data about all low back pain patients presenting for a first consultation. At baseline they recorded age, gender, type and duration of the main complaint, and concomitant complaints. At the end of treatment they recorded the type of treatment and the number of treatment sessions. Patients were recruited to answer questionnaires at baseline, and at 6-weekly intervals during a follow-up period of six months. Patient questionnaires included information about previous medical consumption, together with PROMs measuring the level of pain and functional status. Latent Class Growth Analysis (LCGA) was used to classify patients into different groups according to their pain trajectories. Baseline variables were evaluated as predictors of a favourable trajectory using logistic regression analyses, and treatment variables were evaluated as possible confounders.

Results
A total of 1377 patients were recruited, of whom 1117 patients (81%) answered at least one follow-up measurement. LCGA identified three groups of patients with distinct pain trajectories. A first group (N = 226) with high pain levels showed no improvement, a second group (N = 578) with high pain levels showed strong improvement, and a third group (N = 313) with mild pain levels showed moderate improvement. The two groups of patients presenting with high baseline pain scores were compared, and a multivariable model was constructed with possible predictors of a favourable course. Male gender, previous specialist visit, previous pain clinic visit, having work, a shorter duration of the current episode, and a longer time since the complaints first started were predictors of a favourable course. The multivariable model showed a moderate area under the curve (0.68) and a low explained variance (0.09).

Conclusions
In low back pain patients treated by musculoskeletal physicians in The Netherlands three different pain trajectories were identified. Baseline variables were of limited value in predicting a favourable course.
The influence of the gut microbiome on BCG-induced trained immunity
Authors: Stražar Martin , Mourits Vera P. , Koeken Valerie A. C. M. , de Bree L. Charlotte J. , Moorlag Simone J. C. F. M. , Joosten Leo A. B. , van Crevel Reinout , Vlamakis Hera , Netea Mihai G. , Xavier Ramnik J. 
Published: September 2021

AbstractBackgroundThe bacillus Calmette-Guérin (BCG) vaccine protects against tuberculosis and heterologous infections but elicits high inter-individual variation in specific and nonspecific, or trained, immune responses. While the gut microbiome is increasingly recognized as an important modulator of vaccine responses and immunity in general, its potential role in BCG-induced protection is largely unknown.ResultsStool and blood were collected from 321 healthy adults before BCG vaccination, followed by blood sampling after 2 weeks and 3 months. Metagenomics based on de novo genome assembly reveals 43 immunomodulatory taxa. The nonspecific, trained immune response is detected by altered production of cytokines IL-6, IL-1β, and TNF-α upon ex vivo blood restimulation withStaphylococcus aureusand negatively correlates with abundance ofRoseburia. The specific response, measured by IFN-γ production uponMycobacterium tuberculosisstimulation, is associated positively withRuminococcusandEggerthella lenta. The identified immunomodulatory taxa also have the strongest effects on circulating metabolites, withRoseburiaaffecting phenylalanine metabolism. This is corroborated by abundances of relevant enzymes, suggesting alternate phenylalanine metabolism modules are activated in aRoseburiaspecies-dependent manner.ConclusionsVariability in cytokine production after BCG vaccination is associated with the abundance of microbial genomes, which in turn affect or produce metabolites in circulation.Roseburiais found to alter both trained immune responses and phenylalanine metabolism, revealing microbes and microbial products that may alter BCG-induced immunity. Together, our findings contribute to the understanding of specific and trained immune responses after BCG vaccination.
On the existence and stability of two positive solutions of a hybrid differential system of arbitrary fractional order via Avery–Anderson–Henderson criterion on cones
Authors: Matar Mohammed M. , abu Jarad Manar , Ahmad Manzoor , Zada Akbar , Etemad Sina , Rezapour Shahram 
Published: September 2021

AbstractThe main objective of this paper is to investigate the existence, uniqueness, and Ulam–Hyers stability of positive solutions for fractional integro-differential boundary values problem. Uniqueness result is obtained by using the Banach principle. For obtaining two positive solutions, we apply another fixed point criterion due to Avery–Anderson–Henderson on cones by establishing some inequalities. An illustrative example is presented to indicate the validity of the obtained results. The results are new and provide a generalization to some known results in the literature.
Optical measurement of tissue perfusion changes as an alternative to electrocardiography for heart rate monitoring in Atlantic salmon (Salmo salar)
Authors: Svendsen Eirik , Økland Finn , Føre Martin , Randeberg Lise L. , Finstad Bengt , Olsen Rolf E. , Alfredsen Jo A. 
Published: September 2021

AbstractBackgroundWelfare challenges in salmon farming highlights the need to improve understanding of the fish’s response to its environment and rearing operations. This can be achieved by monitoring physiological responses such as heart rate (HR) for individual fish. Existing solutions for heart rate monitoring are typically based on Electrocardiography (ECG) which is sensitive to placement and electrode orientation. These factors are difficult to control and affects the reliability of the principle, prompting the desire to find an alternative to ECG for heart rate monitoring in fish. This study was aimed at adapting an optical photoplethysmography (PPG) sensor for this purpose. An embedded sensor unit measuring both PPG and ECG was developed and tested using anesthetized Atlantic salmon in a series of in-vivo experiments. HR was derived from PPG and compared to the ECG baseline to evaluate its efficacy in estimating heart rate.ResultsThe results show that PPG HR was estimated with an accuracy of 0.7 ± 1.0% for 660 nm and 1.1 ± 1.2% for 880 nm wavelengths, respectively, relative to the ECG HR baseline. The results also indicate that PPG should be measured in the anterior part of the peritoneal cavity in the direction of the heart.ConclusionA PPG/ECG module was successfully adapted to measure both ECG and PPG in-vivo for anesthetized Atlantic salmon. Using ECG as baseline, PPG analysis results show that that HR can be accurately estimated from PPG. Thus, PPG has the potential to become an alternative to ECG HR measurements in fish.
Effects of household chaos and parental responsiveness on child executive functions: a novel, multi-method approach
Authors: Andrews Krysta , Dunn James R. , Prime Heather , Duku Eric , Atkinson Leslie , Tiwari Ashwini , Gonzalez Andrea 
Published: September 2021

Abstract
Background
Executive functions can be adversely affected by contextual risks in the home environment including chaos and parenting challenges. Furthermore, household chaos negatively influences parenting practices. Few studies, however, have examined the role of parenting in the association between household chaos and child executive functions.

Methods
Using a sample of 128 school-aged children (mean = 61.9 months, SD = 2.0, range 58–68 months) and their mothers, the present study examined direct and indirect effects (via parental responsiveness) of household chaos on child executive functioning. Multi-measures were used including performance-based assessments, behavioural observations, questionnaires, and video-home tours.

Results
Household chaos had both a direct effect on child executive functions (β = − .31, 95% CI [− .58, − .04]) and an indirect effect (β = − .05, 95% [− .13, − .01]) via parental responsiveness. Further, the indirect effect was only significant for household instability.

Conclusion
These findings indicate that parental responsiveness may be compromised by household chaos, with implications for the executive functions of school-aged children. Preventative strategies are needed to improve the stability in the home and strengthen parenting practices.