bluuebunny/crossref_metadata_2025 huggingface dataset:
Analisis Bauran Pemasaran untuk Mempengaruhi Permintaan Pasar dalam Memilih TK
Authors: Dwimala Bunga , Maimunah Maimunah
Published: January 2021

Penelitian ini bertujuan untuk mengetahui bagaimana menganalisis strategi bauran pemasaran untuk mempengaruhi permintaan pasar dan mendeskripsikan dampak setelah diterapkannya strategi bauran pemasaran (marketing mix) terhadap permintaan pasar. Metode penelitian yang digunakan adalah penelitian kualitatif dan penelitian lapangan (field research), yaitu peneliti melakukan penelitian langsung ke lokasi penelitian untuk mendapatkan dan mengumpulkan data. Teknik pengumpulan data yang digunakan adalah wawancara, observasi dan dokumentasi. Hasil dari penelitian adalah strategi bauran yang digunakan dalam menciptakan produk sangat memperhatikan kualitas baik dari sumber daya manusia, sarana dan prasarana tempat bermain, pembelajaran agama seperti Sholat Dhuha, belajar berwudhu’, hafalan surat-surat pendek, dan terutama ketika mengajarkan sholat dan puasa senin dan kamis, dan  memfasilitasi entrepeneurship itu melalui ajang ‘Entrepeneurship day’, kemudian harga yang diberikan standard menengah ke atas walaupun demikian memberi kebijaksanaan yaitu membayar uang masuk sekolah dengan dicicil. Memberi beasiswa bagi siswa yang tidak mampu dan siswa yang berprestasi. Selain itu juga, memberikan layanan yang baik bagi anak- anak dan orang tua. Tempat yang strategis menjadi pilihan orang tua dikarenakan sekolahnya terletak di pinggir jalan dan berdekatan dengan perumahan yang berada di sekitar jakabaring. Hal ini menjadi permintaan pasar yang banyak, dan siswa semakin meningkat dari tahun ke tahun.
Computational Methods for Chromosome-Scale Haplotype Reconstruction
Authors: Garg Shilpa
Published: January 2021

High-quality chromosome-scale haplotype sequences— of diploid genomes, polyploid genomes and metagenomes — provide important insights into genetic variation associated with disease and biodiversity. However, whole-genome short read sequencing does not yield haplotype information that spans whole chromosomes directly. Computational assembly of shorter haplotype fragments is required for haplotype reconstruction, which can be challenging owing to limited fragment lengths and high haplotype and repeat variability across genomes. Recent advancements in long-read and chromosome-scale sequencing technologies, alongside computational innovations, are improving the reconstruction of haplotypes at the level of whole chromosomes. Here, we review recent methodological progress in these areas and discuss perspectives that could enable routine high-quality haplotype reconstruction in clinical and evolutionary studies.
Expediente
Authors: Editorial Comissão
Published: January 2021

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Estimating Heritability of Glycaemic Response to Metformin using Nationwide Electronic Health Records and
Population-Sized Pedigree
Authors: Kalka Iris , Gavrieli Amir , Shilo Smadar , Rossman Hagai , Artzi Nitzan Shalom , Segal Eran
Published: January 2021

Variability of response to medication is a well known phenomenon, determined by both
environmental and genetic factors. Understanding the heritable component of the response
to medication is of great interest but challenging due to several reasons, including small
study cohorts and computational limitations. Here, we studied the heritability of variation in
the glycaemic response to metformin, first-line therapeutic agent for type 2 diabetes (T2D),
by leveraging 17 years of electronic health records (EHR) data from Israel’s largest
healthcare service provider, consisting of over five million patients of diverse ethnicities and
socio-economic background. Our cohort consisted of 74,871 T2D patients treated with
metformin, with an accumulated number of 1,358,776 HbA1C measurements and 323,260
metformin prescriptions. We estimated the explained variance of glycated hemoglobin
(HbA1c%) reduction due to heritability by constructing a six-generation population-size
pedigree from national registries and linking it to medical health records. Using Linear Mixed
Model-based framework, a common-practice method for heritability estimation, we
calculated a heritability measure of h2 = 15.9% (95% CI, 1.2% − 30.5%) for absolute
reduction of HbA1c% after metformin treatment in males and h2 = 20.9% (95% CI,
7.5% − 34.3%) in females. Results remained unchanged after adjusting for pre-treatment
HbA1c% in females, and for both genders in proportional reduction of HbA1c%. To the best
of our knowledge, our work is the first to estimate heritability of drug response using EHR
data. We demonstrated that while response to metformin treatment has a heritable
component, most of the variation is likely due to other factors, further motivating non-genetic
analyses aimed at unraveling metformin’s mechanism of action.
Operando Analyses of Highly Enhanced Water Splitting by Electronically Modulated Non-noble Metal Carbides
Authors: Roy Soumyabrata , Bagchi Debabrata , Dheer Lakshay , Sarma Saurav , Rajaji Vincent , Narayana Chandrabhas , Waghmare Umesh , Peter Sebastian
Published: January 2021

Designing non-noble metal based electrocatalysts for efficient overall water splitting (OWS) solves a critical bottleneck of sustainable water electrolyzer technology. Here, we elucidate real-time mechanistic insights into the promotional effect of Ni substitution on the bifunctional OWS activity of N-doped graphite carbon (NGC) supported molybdenum and tungsten carbides (Ni-MoC/WC@NGC). Ni substitution yields multi-fold improvement in water splitting activity over the pristine systems that are comparable to commercial Pt/C for HER and better than IrO2 in case of OER. Ni-MoC@NGC champions in HER activity exhibiting an onset overpotential of 65 mV and current density of 140 mA/cm2 at -370 mV (v RHE) in acidic media. Their excellent OWS activity in alkaline media prompted us to construct a H2O electrolyzer where the bifunctional Ni-MoC@NGC system shows a comparable cell voltage to the PtǁIrO2 pair and could split water aided by a 1.5V AAA commercial battery. First principle calculations and in-situ probing of the local Ni and W sites through quick-XAS during electrochemical processes provide valuable insights into how the adsorption energies of intermediates and reaction kinetics are modulated at different catalytic sites with the promotional electronic effect of Ni substitution.
COVID-19 severity and complications associated with low diversity, dysbiosis and predictive metagenome features of the oropharyngeal microbiome.
Authors: Castilhos Juliana de , Zamir Eli , Hippchen Theresa , Rohrbach Roman , Schmidt Sabine , Hengler Silvana , Schumacher Hanna , Neubauer Melanie , Kunz Sabrina , Müller-Esch Tonia , Hiergeist Andreas , Gessner Andre , Khalid Dina , Gaiser Rogier , Cullin Nyssa , Beuthien-Baumann Bettina , Krämer Alwin , Bartenschlager Ralf , Jäger Dirk , Müller Michael , Herth Felix , Duerschmied Daniel , Schneider Jochen , Schmid Roland , Eberhardt Johann , Khodamoradi Yascha , Vehreschild Maria , Teufel Andreas , Ebert Matthias , Hau Peter , Salzberger Bernd , Poeck Hendrik , Elinav Eran , Merle Uta , Stein-Thoeringer Christoph
Published: January 2021

Coronavirus 2 (SARS-CoV-2) infection and the resulting COVID-19 illness vary from asymptomatic disease, mild upper respiratory tract infection, pneumonia1, to a life-threatening multi-organ failure with case fatality rates ranging from 0.27–13.4%2,3. Despite increasing knowledge of the clinical and immunological features underlying COVID-191,4−6, biological variables explaining the course of infection and its severity remain elusive. At the entry site of SARS-CoV2, the oropharyngeal microbiome represents a hub integrating viral and immune signals at the start of the infection7–10. To evaluate the role of the oropharyngeal microbiome in COVID-19, we performed a multi-center, cross-sectional clinical study analyzing the oropharyngeal microbial metagenomes in healthy adults, patients with non-SARS-CoV-2 infections, or with mild, moderate and severe COVID-19 encompassing a total of 345 participants. Significantly reduced microbiome diversity and high dysbiosis were observed in hospitalized patients with severe COVID-19, which was further associated with a loss of microbial genes and metabolic pathways. In this cohort, diversity measures were also associated with need for intensive care treatments as major clinical parameters in COVID-19. We further applied random forest machine learning to unravel microbial features for segregating clinical outcomes in hospitalized cases, and observed oropharyngeal microbiome abundances of Haemophilus or Streptococcus species as most important features. These findings provide insights into the role of the oropharyngeal microbiome in SARS-CoV-2 infection, and may suggest new biomarkers for COVID-19 severity.
Comparison of Quantitative Parameters in Diabetics Without Clinical Signs of Diabetic Retinopathy and Healthy Individuals Using Swept-source Optical Coherence Tomography Angiography
Authors: Beka Sophie , Podkowinski Dominika , Wendelstein Jascha , Mursch-Edlmayr Anna-Sophie , Mariacher Siegfried , Bolz Matthias
Published: January 2021

Automated image analysis is the future for retinal imaging in order to early diagnose retinal diseases like diabetic retinopathy. Swept source coherence tomography angiography offers new insights in retinal vascularization. Data sets for each stage of diabetic retinopathy are crucial to compare findings to the healthy population and to develop further algorithms. We recruited 39 eyes of Type-2 diabetics without diabetic retinopathy comparing them to 43 eyes of age and gender matched individuals using swept source coherence tomography angiography. Vessel and perfusion density in the superficial and deep retinal plexus, as well foveal-avascular zone expansion, using Macular Density V 0.7 algorithm were evaluated. We found no significant change in vessel and perfusion density in both plexus, as well no difference in the foveal-avascular zone between healthy and diabetic eyes without clinical diabetic retinopathy. Current parameters of vascular analysis used in swept- source optical coherence tomography angiography are not valid to detect possible early, subclinical changes in patients with diabetes. However, the presented data set is of high value for future studies, as is represents a complete and clean data set. As automated image analysis is the future in diabetic retinopathy the presented data will be used in future studies.
Effects of drinking hydrogen-rich water in men at risk of peripheral arterial disease: a randomized placebo-controlled trial
Authors: Gu Qianqian , Liu Boyan , Xue Junli , Zhao Min , Zhang Xiaoyi , Wang Mingyue , Zhang Mengyu , Xue Yazhuo , Qin Shucun
Published: January 2021

Aims Smoking, hypertension, hyperlipidemia, and diabetes are considered to increase the incidence of peripheral arterial disease (PAD). They can activate endogenous free radicals, cause inflammation and oxidative stress, and lead to endothelial cell dysfunction. Hydrogen (H2) has been proven to decrease oxidative stress, improve cell function, and reduce chronic inflammation. The purpose of this research was to validate the role of H2 in individuals who are at risk of PAD.Methods Sixty subjects were randomly assigned to placebo (PBO) group or H2-rich water (HRW) group and drank either bottled pure water or H2-rich water (245 mL/time, 3 times/d) for ten weeks.Results The pulse wave velocity was ameliorated in the HRW group with no significant change in the ankle-brachial index. The serum total cholesterol of the HRW group was significantly reduced compared to the placebo group. In addition, compared to baseline, the levels of lipoprotein(a) was decreased, the malondialdehyde content was reduced, the superoxide dismutase activity was increased, and the expression of intercellular cell adhesion molecule-1 was decreased significantly in the HRW group. The oxidized phospholipid of 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphatidylcholine level in the HRW group were significantly reduced compared to the placebo group. Finally, H2 significantly improved the antioxidant, antiinflammatory, and antiapoptotic abilities of high-density lipoprotein (HDL).Conclusions Drinking HRW can improve vascular sclerosis indicators, improve dyslipidemia, reduce vascular oxidative stress and inflammation, and improve HDL function. H2 may be used to prevent and relieve PAD caused by major risk factors such as smoking, hypertension, hyperlipidemia, and diabetes.
Postoperative Bone Marrow Lesions (BMLs) are Associated with Pain Severity in Patients Undergoing Open Wedge High Tibial Osteotomy (OWHTO)
Authors: Zhu Bo , Wang Tong-Fu , Zhu Jia-Wang , Wang Zeng-Liang , Cao Jian-Gang , Zhao Jun-Wei , Chen De-Sheng
Published: January 2021

Background: The purpose of the study was to investigate the relationship between postoperative bone marrow lesions (BMLs) and pain severity in patients undergoing open wedge high tibial osteotomy (OWHTO). Methods: We retrospectively reviewed the patients undergoing OWHTO between April 2018 and April 2020. The demographic and clinical data of patients were collected. Clinically, VAS and Knee injury and Osteoarthritis Outcome Score (KOOS) were used to assess pain level and functional outcomes of patients. Histologically, The MRI Osteoarthritis Knee Score (MOAKS) was used to assess semi-quantitatively the total BMLs size in medial tibiofemoral (MTF), lateral tibiofemoral (LTF), and patellofemoral (PF) joints. Results: 98 patients were enrolled in the study, including 57 male and 41 female patients. The VAS scores improved significantly from 6.1 ± 0.8 to 1.5 ± 0.9 (p < 0.001), and all subscales of KOOS improved significantly after surgery (p < 0.001). There were no significant difference between the pre-and postoperative total BMLs size in PF and LTF joints (p > 0.05). We observed significant improvements in the total BMLs size of MTF joint (p < 0.001). All patients had preoperative MTF joint BMLs, in contrast, 13 patients had no postoperative MTF joint BMLs. The independent sample t-test showed that the VAS scores and KOOS pain scores improved better in patients without postoperative MTF joint BMLs (p < 0.001). Pearson correlations showed that postoperative MTF joint BMLs were correlated with postoperative VAS (p < 0.001) and KOOS pain (p < 0.001). Conclusion: Our study demonstrates that MTF joint BMLs improved significantly after OWTHO. We confirmed that the presence of postoperative MTF joint BMLs are strongly associated with pain severity, the greater the improvement in postoperative MTF joint BMLs, the less pain. Our findings provide valuable understandings of OWHTO in the treatment of Knee osteoarthritis (KOA), and potential future directions for KOA treatment approaches.
Reduction of Lateral Shoots by RNA Interference and by Chemical Mutation of Genes Involved in Axillary Meristem Regulation and Field Trials of Mutant Lines in Nicotiana Tabacum L.
Authors: Hamano Kaori , Sato Seiki , Arai Masao , Negishi Yuta , Nakamura Takashi , Komatsu Tomoyuki , Naragino Tsuyoshi , Suzuki Shoichi
Published: January 2021

BackgroundLateral branches vigorously proliferate in tobacco after topping of inflorescence portions of stems for maturation of leaves to be harvested. Therefore, tobacco varieties with reduced lateral shoots are highly desired by farmers.ResultsGenetic reduction of lateral shoots was attempted in tobacco. Two groups of genes were examined by RNA interference: homologues of the genes reported as involved in the formation of lateral shoots in other plants, and genes highly expressed in primordial stages of axillary buds. Although "primary" lateral shoots that grew after the plants were topped off when flower buds emerged were not much affected, "secondary" lateral shoots, which appeared from the abaxial sides of the bases of the primary lateral shoots, were suppressed significantly by knock-down of five genes, NtLs, NtBl1, NtREV, VE7, and VE12. Chemical mutation of three of them, NtLs, NtBl1, and NtREV, similarly reduced secondary and "tertiary" lateral shoots but not primary ones. The mutation of NtLs and NtBl1 was backcrossed into an elite variety. The backcross lines were examined for agronomic characteristics in field trials conducted in commercial tobacco production areas. The lines were satisfactory for leaf tobacco production overall and showed good potential as new tobacco varieties.ConclusionSuppression of the five genes reduced only secondary and tertiary lateral shoots in tobacco although similar approaches reduced all branches in other plant species. Nevertheless, the mutant lines might greatly relieve farmers because secondary and tertiary lateral shoots are especially cumbersome because they emerge when farmers are burdened by the labor-intensive leaf harvest.
Impact of microRNAs in Interaction with Environmental Factors on Autism Spectrum Disorder: An Exploratory Pilot Study
Authors: Cui LiHua , Du WenRan , Xu Ning , Dong JingYi , Xia BingJie , Ma JingYi , Yan RuoTong , Wang LanYing , Feng FuMin
Published: January 2021

Background: The aim of this study was to explore the main effects of miRNAs as well as their interaction effects with well-replicated autism spectrum disorder (ASD) environmental risk factors on the risk of ASD.Methods: 159 ASD children (ASD group) and 159 healthy children (control group), aged 2-6 years, were included in this study. ASD diagnoses were based on DSM-5 criteria. The extensive medical and demographic characterization of the two groups were recorded. And microRNAs (miRNAs) in serum were detected by qRT-PCR. Results: Comparing to control group, ASD group had significant higher rates of maternal stress during pregnancy (p<0.001), maternal drinking during pregnancy (p=0.006), threatened abortion (p=0.011), pregnancy-induced hypertension (p=0.032), gestational diabetes (p=0.039), maternal anemia during pregnancy (p<0.001), umbilical cord knot (p<0.001), neonatal jaundice (p<0.001), family psychiatric history (p=0.001), and much lower birth weight (p=0.012). Furthermore, ASD group had much lower expression levels of has-miR-181b-5p (p<0.001) and has-miR-320a (p<0.001), and significant higher levels of has-miR-19b-3p (p<0.001). The multivariate logistic regression analysis revealed that the interactions of has-miR-320a and maternal stress during pregnancy (OR=39.42, p<0.001), has-miR-19b-3p and neonatal jaundice (OR=2.44, p<0.001), has-miR-181b-5p and family psychiatric history (OR=8.65, p=0.001) could increase ASD risk. Conclusions:The dysregulation of has-miR-181b-5p,has-miR-320a and has-miR-19b-3p could interact with environmental factors, such as maternal stress during pregnancy, neonatal jaundice and family psychiatric history, to impact the risk of ASD.
Evaluation of Response Time in Monitoring System on the Accuracy of Recording Individual Feeding Behavior and Feed Intake in Dairy Cows
Authors: Wang Rong , Gao Cheng , Wang Min , Zhang Xiumin , Ma Zhiyuan , Wu Duanqin , Wei Zhongshan , Li Zhicai , Gao Shuai , Tan Zhiliang
Published: January 2021

Background: The advent of monitoring system can automatically collect the quantitative data of the feeding behavior and feed intake of individual cattle, and the immediate response system always records many non-eating visits. Increasing response time of trigger helps to decrease recording non-eating visits, but may also miss some small periods of recording feed intake. This study was to evaluate the effect of response time in monitoring system on the accuracy of recording individual feeding behavior and feed intake in dairy cows. The first experiment was to investigate the distribution of 10-h feeding behaviors of 8 Holstein dairy cows after morning feeding by using infra-red camera. The second experiment was to investigate accuracy of feed intake recorded by the monitoring system with different response times (0.3, 3, 6, 12 and 24 s) in comparison with direct weighting. The third experiment was to investigate effect of excluding the data of time interval after response time on feed intake and visiting behaviors recorded by the monitoring system, when responding time was set as 0.3 s. Results: The results showed that the most of eating and non-eating visits had duration larger than 24 s (99.0%) and less than 24 s (65.3%), respectively. Comparing with actual feed intake obtained by direct weighting, increasing response time greatly increased the recorded feed intake, with the greatest difference occurring at 6 s of response time (P = 0.001). Although increasing time interval after response time linearly increased mean, median feed intake per visit and 10-h feed intake (P < 0.01), it had little influence on 10-h feed intake (< 0.1%) and eating visit (< 5%). Conclusions: Setting immediate response (0.3 s) in monitoring system helps to get actual feed intake, but can obtain a lot of non-eating visits. Increasing response time helps to decrease the recording of non-eating visits, but can overestimate feed intake.
A Comprehensive Analysis of a Novel Real-time Adaptive Assist-as-needed Controller for Robot-assisted Rehabilitation for Stroke Patients
Authors: Arantes Ana Paula , Bressan Nadja , McGibbon Chris
Published: January 2021

Background: Rehabilitation therapy plays an essential role in assisting stroke patients in regaining function. For this reason, many studies have been conducted to optimize rehabilitation interventions to improve effectiveness and efficiency. In this context, robotic devices for rehabilitation and assistance can be effective. Several studies have demonstrated that using a robot as a therapy tool can significantly reduce motor impairment. However, the slacking behavior, in which the patient lets the robot guide their movements even when they are capable of doing so by themselves, has been identified as a major barrier to reaching the full potential of robot-assist rehabilitation. This paper developed a novel electromyographical-based adaptive assist-as-needed (aAAN) controller aiming to avoid this slacking behavior. Methods: Five stroke patients were recruited to test the controller. Motor impairment status was documented with the Fugl-Meyer (FMA) assessment. In this experiment, horizontal arms tasks were conducted with the robot off and on to assess the subject’s performance in both scenarios. Velocity, time, and position were quantified as performance parameters during the training. Arm and shoulder EMG and electroencephalography (EEG) were used to assess the performance of the controller. Results: The cross-sectional results showed strong second-order relationships between Fugl-Meyer score and outcome measures, where performance metrics (path length and accuracy) were sensitive to change in participants with lower functional status. In comparison, speed and electrophysiological metrics (EMG and EEG) were more sensitive to change in participants with higher functional status. EEG signal amplitude increased when the robot suggested that the robot was inducing a challenge during the training tasks. Conclusion: The preliminary results were very promising; slacking was avoided for all participants during training with the aAAN controller.
Prevalence and Risk Factors for Latent Tuberculosis in Polish Healthcare Workers: The Comparison of Tuberculin Skin Test and Interferon-gamma Release Assay (IGRA) Performance.
Authors: Szturmowicz Monika , Broniarek-Samson Beata , Demkow Urszula
Published: January 2021

Background: Tuberculosis is still one of the most common infectious diseases worldwide. Health care workers (HCW) are at particular risk of the disease due to their constant exposure to TB patients or their specimens, nevertheless no specific surveillance is widely recommended in this group of professionals. Both, tuberculin skin test (TST) and interferon-gamma-release-assays (IGRAs) are widely applied to detect latent tuberculosis infection (LTBI). The aim of the present study was to evaluate the prevalence and risks of LTBI in the population of Polish HCW, to identify factors associated with LTBI, as well as to determine the rate of the discordance between the results of the two applied tests in relation to various factors in a TB endemic setting.Material and methods: LTBI status was prospectively evaluated in 222 HCW, 204 females, 18 males, aged 40.8±9 years, with tuberculin skin test (TST) and interferon gamma release assay (QuantiFERON-TB-Gold in Tube – QFT GIT). Results: TST≥10 mm was found in 58% of HCW, QFT GIT≥0.35 IU/ml in 23%. These results are comparable with previously published data concerning general Polish population, investigated in the same period of time. Nevertheless the relative number of positive QFT GIT in HCW above 45 years of age exceeded those obtained in general population. The risk of obtaining positive QFT GIT was significantly increased in the participants older than 44 years, in those employed >10 years, and in those who reported the direct contact with tuberculous patients or infected biological materials. The concordance between TST and IGRA was poor (kappa 0.23), especially in younger participants, possibly due to BCG vaccination in childhood. Conclusion: The increased risk of LTBI in Polish HCW was related to age, duration of employment and contact with infectious patients or their biological specimens. TB infection control measures in health care facilities in Poland are still insufficient. It is crucial to increase awareness about the importance of detecting and treating LTBI of HCW.
STAT3 Inhibits Cell Proliferation at Least in Part Via Directly Negatively Regulating FST Gene Expression
Authors: Xu Haidong , Ma Guangwei , Mu Fang , Ning Bolin , Li Hui , Wang Ning
Published: January 2021

Background: Follistatin (FST) is a secretory glycoprotein and belongs to the TGF-β superfamily. Previously, we found that two single nucleotide polymorphisms (SNPs) of sheep FST gene were significantly associated with wool quality traits in Chinese Merino sheep (Junken type), indicating that FST is involved in the regulation of hair follicle development and hair trait formation. The transcription regulation of human and mouse FST genes has been widely investigated, and many transcription factors have been identified to regulate FST gene, such as erythroid 2-related factor 2 (Nrf2), Estrogen-related receptor-β (ERRβ), β-catenin/transcription factor 4 (TCF4) and transcription factor Sp1. However, to date, the transcriptional regulation of sheep FST is largely unknown. The objective of this study was to investigate the transcriptional regulation of sheep FST gene in hair follicles. Results: Genome walking analysis revealed that the gap region upstream of sheep genomic FST gene was 775 bp long. Transcription factor binding site analysis showed sheep FST promoter region contained a conserved putative binding site for signal transducer and activator of transcription 3 (STAT3), located at nucleotides -423 to -416 relative to the first nucleotide (A, +1) of the initiation codon (ATG). The dual-luciferase reporter assays showed that STAT3 inhibited the activity of the FST promoter reporter, and the mutation of the putative STAT3 binding site attenuated the inhibitory effect of STAT3 on the FST promoter activity. Furthermore, chromatin immunoprecipitation assay (ChIP) indicated that STAT3 directly binds to the FST promoter. The further functional study displayed that FST and STAT3 played opposite roles in cell proliferation. Overexpression of FST significantly promoted the proliferation of sheep fetal fibroblasts (SFFs) and human keratinocyte (HaCaT) cells, and overexpression of STAT3 significantly inhibited the proliferation of SFFs and HaCaT cells, which was accompanied by a significantly reduced expression of FST gene (P < 0.05). Conclusions: STAT3 directly negatively regulates sheep FST gene and inhibits cell proliferation. The findings will contribute to understanding molecular mechanisms that underlie hair follicle development and wool trait formation.
Grounds for surrogate decision-making in Japanese clinical practice: A qualitative survey
Authors: Tanaka Masashi , Ohnishi Kayoko , Enzo Aya , Okita Taketoshi , Asai Atsushi
Published: January 2021

Background In the coming years, surrogate decision-making is expected to become highly prevalent in Japanese clinical practice. Further, there has been a recent increase in activities promoting advance care planning, which potentially affects the manner in which judgements are made by surrogate decision-makers. This study aims to clarify the grounds on which surrogate decision-makers in Japan base their judgements.Methods In this qualitative study, semi-structured interviews were conducted to examine the judgement grounds in surrogate decision-making for critical life-sustaining treatment choices in acute care hospitals.Results A total of 228 participants satisfied the inclusion criteria, and 15 were selected for interviews. We qualitatively analysed the content of 14 interview transcripts, excluding one that did not meet the inclusion criteria. Based on this analysis, we extracted 4 core categories, 17 categories, 35 subcategories, and 55 codes regarding judgement grounds in surrogate decision-making. The four core categories were as follows: patient preference–oriented factor (Type 1), patient interest–oriented factor (Type 2), family preference–oriented factor (Type 3), and balanced patient/family preference–oriented factor (Type 4). The Type 4 core category represented attempts to balance the preferences of the patient with those of the surrogate decision-maker.Conclusions Surrogate decision-makers based their decisions on important aspects related to a patient’s life, and they considered not only the patient’s preferences and best interests but also their own preferences. As the need for surrogate decisions will increase in the future, decision-makers will need to consider judgement grounds from a more diverse perspective.
Analysis of multiple cytokines in aqueous humor of patients with idiopathic macular hole
Authors: Wang Heping , Li Yuqi , Han Song , Niu Tongtong
Published: January 2021

Background: Idiopathic macular holes are common ophthalmic manifestations with unknown pathogenesis. Thus far, there has been minimal research regarding the causes of idiopathic macular holes, especially with respect to the underlying immune mechanism. To provide clarity regarding the treatment and prognosis of idiopathic macular holes, specifically regarding the levels of cytokines in affected patients, this study examined and analyzed multiple cytokine levels in aqueous humor from patients with idiopathic macular holes.Methods: This comparative cross-sectional study included 38 patients in two groups: a cataract control group (n=17) and an idiopathic macular hole group (n=21). The levels of 48 cytokines in aqueous humor were detected by multiplex analysis with antibody-coupled magnetic beads. The Kolmogorov–Smirnov test was used to check whether the data were normally distributed; Student’s t-test and the Mann–Whitney U test were used to assess differences in cytokine levels between the two groups. Spearman correlation analysis was used to assess relationships among cytokine levels in the experimental group. Signaling pathways containing cytokines with significantly different expression in the experimental group were identified.Results: There were significant differences in aqueous humor cytokine levels between patients with idiopathic macular holes and patients in the cataract control group. Notably, hepatocyte growth factor (p=0.0001), GM-CSF (p=0.0111), and IFN-γ (p=0.0120) were significantly upregulated in the experimental group, while TNF-α (p=0.0032), GRO-α (p<0.0001), and MIF (p<0.0001) were significantly downregulated in the experimental group. Furthermore, the GM-CSF level showed significant positive correlations with levels of IL-1 (r=0.67904, p<0.001), IL-4 (r=0.76017, p<0.001), and IFN-γ (r=0.59922, p=0.004097) in the experimental group. Moreover, the levels of nerve growth factor and hepatocyte growth factor showed a significant positive correlation (r=0.64951, p=0.001441) in the experimental group.Conclusions: Patients with idiopathic macular holes showed significant variation in aqueous humor immune response after the onset of hole formation, including the recruitment of immune cells and regulation of cytokine expression. Our findings also suggest that it is not appropriate to use patients with macular holes as the control group in studies of aqueous humor cytokine levels in ophthalmic diseases.
Prognostic significance of preoperative neutrophil-to-lymphocyte ratio in papillary renal cell carcinoma patients after receiving curative surgery based on a retrospective cohort
Authors: Zhang Zhilei , Yu Yongbo , Zheng Jilu , Zhang Mingxin , Niu Haitao
Published: January 2021

Background: Inflammatory response biomarkers have been studied as promising prognostic factors in renal cell carcinoma (RCC), but few studies have focused on papillary renal cell carcinoma (PRCC). This study was performed to evaluate the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR) in PRCC patients. Methods: In total, 122 postoperative PRCC patients selected from 366 non-clear cell renal cell carcinoma (nccRCC) patients were enrolled from our institution between 2012 and 2020. The optimal cutoff value of the NLR was assessed by receiver operating characteristic (ROC) curve analysis, and the Kaplan–Meier method and Cox's proportional hazards regression models were performed to analyze the association of the NLR with overall survival (OS). In addition, the potential of tumor-node-metastasis (TNM) stage, the NLR and an NLR-TNM system to predict survival were compared with ROC curves, and clinical usefulness of the predicting models were assessed by decision curve analysis. Results: A threshold value of 2.39 for the NLR for OS analysis was determined by ROC curve analysis. An NLR≥2.39 was associated with a more advanced TNM stage (P<0.01) and larger tumors (P<0.05) than a low NLR, as well as pathological subtype Ⅱ (P<0.05), and the patients with a high NLR also exhibited significantly worse overall survival outcomes (P<0.05). The NLR was determined to be a significant independent prognostic indicator by univariable and multivariable analyses (HR = 5.56, P<0.05). Furthermore, TNM stage and the NLR were integrated, and the area under the curve (AUC) of for the NLR-TNM system was larger than that of for the TNM system when predicting overall survival (0.84 VS 0.73, P=0.04). Decision curve analysis also demonstrated a better clinical value for the NLR-TNM model to predict the prognosis. Conclusion: A high preoperative NLR was associated with poor clinical and pathologic parameters in patients with PRCC; moreover, the NLR was also an independent prognostic factor for the OS of patients with PRCC. The NLR-TNM system, which was a model that integrated the NLR with TNM staging, could improve the ability to predict overall survival.
What mechanisms drive uptake of family planning when integrated with childhood immunisation in Ethiopia? A realist evaluation
Authors: Krishnaratne Shari , Hamon Jessie K. , Hoyt Jenna , Chantler Tracey , Landegger Justine , Spilotros Nathaly , Demissie Shiferaw Dechasa , Mohammed Siraj , Webster Jayne
Published: January 2021

Background: Maternal and child health are key priorities among the Sustainable Development Goals, which include a particular focus on reducing morbidity and mortality among women of reproductive age, newborns, and children under the age of five. Two components of maternal and child health are family planning (FP) and immunisation. Providing these services through an integrated delivery system could increase the uptake of vaccines and modern contraceptive methods (MCMs) particularly during the post-partum period. Methods: A realist evaluation was conducted in two woredas in Ethiopia to determine the key mechanisms and their triggers that drive successful implementation and service uptake of an intervention of integrated delivery of immunisations and FP. The methodological approach included the development of an initial programme theory and the selection of relevant, published implementation related theoretical frameworks to aid organisation and cumulation of findings. Data from 23 semi-structured interviews were then analysed to determine key empirical mechanisms and drivers and to test the initial programme theory. These mechanisms were mapped against published theoretical frameworks and a revised programme theory comprised of context-mechanism-outcome configurations was developed. A critique of theoretical frameworks for abstracting empirical mechanisms was also conducted. Results: Key contextual factors identified were: the use of trained Health Extension Workers (HEWs) to deliver FP services; a strong belief in values that challenged FP among religious leaders and community members; and a lack of support for FP from male partners based on religious values. Within these contexts, empirical mechanisms of acceptability, access, and adoption of innovations that drove decision making and intervention outcomes among health workers, religious leaders, and community members were identified to describe intervention implementation. Conclusions: Linking context and intervention components to the mechanisms they triggered helped explain the intervention outcomes, and more broadly how and for whom the intervention worked. Linking empirical mechanisms to constructs of implementation related theoretical frameworks provided a level of abstraction through which findings could be cumulated across time, space, and conditions by theorising middle-range mechanisms.
Knowledge, attitude, practice and associated factors among patients with type 2 diabetes in Cotonou, Southern Benin
Authors: Alaofe Halimatou , Hounkpatin Waliou Amoussa , Djrolo Francois , Ehiri John , Rosales Cecilia
Published: January 2021

Background: Type 2 diabetes (T2D) is becoming an epidemic with significant disability and premature death in Sub-Saharan Africa, including Benin. However, little is known about the level of knowledge, attitude, and practice (KAP) necessary for diabetic patients to enhance therapeutic outcomes and prevent diabetes complications. The study aimed to assess patients’ KAP levels and identify the factors associated in Cotonou, southern Benin. Methods: A cross-sectional study was conducted from July to August 2019 among 300 diabetic patients from four health centers. Data was collected using validated questionnaires. KAP levels were determined by calculating the scores, and multivariate logistic regression was used to explore factors influencing KAP scores. Results: About 53%, 52%, and 47% of all patients had good knowledge, attitude, and practice towards diabetes. In logistic regression, factors such as being female, married, educated, government/non-government employee, and longer duration of diabetes were significantly associated with good knowledge. Being married, having a longer duration of diabetes, and good knowledge were significantly associated with a good attitude while being educated, having a longer duration of diabetes, and good knowledge with good practice. Conclusions: Lack of knowledge, poor attitude, and inadequate practice were found in this surveyed community, suggesting a need for structured educational programs to assist diabetic patients. However, education should be considered a priority for male, newly diagnosed, and uneducated patients.
An Intersectional Analysis of the Composite Index of Anthropometric Failures in India
Authors: Ulahannan Sabu K , Basappa Yogish Channa , Joice Sangeetha V , Srini Prashanth N
Published: January 2021

Background: Nutritional inequality in India has been estimated typically using stunting, wasting and underweight separately which hide the overall magnitude and severity of undernutrition. We used the Composite Index of Anthropometric Failure (CIAF) that combines all three forms of anthropometric failures to assess the severity of undernutrition and identify the most vulnerable social groups and geographical hotspots.Method: CIAF was constructed using child anthropometric data from the fourth round of the National Family Health Survey (NFHS-4, 2015-16). We considered 24 intersecting sub-groups based on intersections across four main axes of inequality i.e., caste [Scheduled Tribe (ST), Scheduled Caste (SC) and Other], economic position (poor and non-poor), place of residence (rural and urban) and gender (male and female) (eg. ST-Poor-Rural-Female). Cross-tabulation and logistic regression were done to assess the odds of CIAF among intersecting groups and to identify the most vulnerable sub-groups. Concentration curve was plotted to visualise economic position inequality in child undernutrition across caste categories. Choropleth maps were constructed and descriptive analysis of the district-level prevalence of CIAF was performed to identify the geographic clustering of undernutrition.Results: Overall 55.32% of children were undernourished by CIAF and 6.62% of children have simultaneous three anthropometric failure. In sub-group analysis, children from ST and SC caste have a higher risk of undernutrition irrespective of other axis of inequality. Compared with CIAF, economic position inequality was amplified for simultaneous-three-failures among all caste categories. Economic position inequalities within caste are more for other caste and SC categories than with ST. Economic position, caste and gender based inequality in all three failures is more consistent in rural areas than with urban areas. Based on the analysis of the high prevalence in the co-occurrence of two or three failures, 111 districts from 12 of 29 states in India were identified across four geographic clusters.Conclusions: The study shows social and eco-geographical clustering of multi-dimensional anthropometric failures and indicates the need for focused nutritional interventions among SC and ST community in general and ST children from the poor households. Furthermore, governance interventions that target entire regions across districts and states combined with decentralised planning are needed.
Facilitating participation in cardiovascular preventive initiatives among people with diabetes: a qualitative study
Authors: Dahl Marie , Søndergaard Susanne Friis , Diederichsen Axel , Pouwer Frans , Pedersen Susanne S. , Søndergaard Jens , Lindholt Jes
Published: January 2021

Background: Type 2 diabetes (T2D) is associated with a significantly increased risk of cardiovascular disease (CVD). The DIAabetic CArdioVAscular Screening and intervention trial (DIACAVAS) was designed to clarify whether advanced imaging for subclinical atherosclerosis combined with medical treatment is an effective strategy to develop individualised treatment algorithms for Danish men and women with T2D aged 40–60. But in the DIACAVAS pilot study, the uptake was only 41%. Consequently, we explored how people experienced living with T2D to understand how to improve the uptake in initiatives targeting the prevention of CVD. Methods: We used semi-structured interviews to obtain information on how the respondents experienced having T2D. For supplementary information, we used structured interviews on e.g. socioeconomic factors. From April to October 2019, 17 participants aged 40–60 years were recruited from general practices and diabetes outpatient clinics in Denmark. Several levels of analysis were involved consistent with inductive content analysis. Results: The participants’ experiences of living with T2D fell along two continuums, from an emotional to a cognitive expression and from reactive to proactive disease management. This led to identification of four archetypal characteristics: (I) powerlessness, (II) empowerment, (III) health literacy, and (IV) self-efficacy. These characteristics indicated the importance of using different approaches to facilitate participation in cardiovascular preventive initiatives. Additionally, findings inspired us to develop a model for facilitating participation in future preventive initiatives. Conclusion: Encouraging people with T2D to participate in cardiovascular preventive initiatives may necessitate a tailored invitation strategy. We propose a model for an invitational process that takes into consideration invitees’ characteristics, including powerlessness, empowerment, health literacy and self-efficacy. This model may enhance participation in such initiatives. However, participation is a general concern, not only in relation to cardiovascular prevention. Our proposed model may be applicable in preventive services for people with T2D in general.
Exploring wealth-related inequalities in maternal and child health coverage in Latin America and the Caribbean
Authors: Colomé-Hidalgo Manuel , Campos Juan Donado , De Miguel Ángel Gil
Published: January 2021

Background. Maternal and child health have shown important advances in the world in recent years. However, national averages indicators hide large inequalities in access and quality of care in population subgroups. We explore wealth-related inequalities affecting health coverage and interventions in reproductive, maternal, newborn, and child health in Latin America and the Caribbean.Methods. We analyzed representative national surveys from 15 countries conducted between 2001 and 2016. We estimated maternal-child health coverage gaps using the Composite Coverage Index – a weighted average of interventions that include family planning, maternal and newborn care, immunizations, and treatment of sick children. We measured absolute and relative inequality to assess gaps by wealth quintile. Pearson’s correlation coefficient was used to test the association between the coverage gap and population attributable risk.Results. The Composite Coverage Index showed patterns of inequality favoring the wealthiest subgroups. In eight countries the national coverage was higher than the global median (78.4%; 95% CI: 73.1-83.6) and increased significantly as inequality decreased (Pearson r = 0.9; p <0.01).Conclusions. There are substantial inequalities between socioeconomic groups. Reducing inequalities will improve coverage indicators for women and children. Additional health policies, programs, and practices are required to promote equity.