bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between expression of PD-L1 and HIF-1α in glioma cells under hypoxia
Authors: Ding Xing-chen , Wang Liang-liang , Zhang Xue-dong , Xu Jun-long , Li Pei-feng , Liang Hua , Zhang Xian-bin , Xie Li , Zhou Zi-han , Yang Jia , Weichselbaum Ralph R. , Yu Jin-ming , Hu Man 
Published: June 2021

AbstractHypoxia inducible factor-1α (HIF-1α) up-regulates the expression of programmed death ligand-1 (PD-L1) in some extracranial malignancies. However, whether it could increase PD-L1 expression in intracranial tumor is still unknown. Here, we explored the relationship between HIF-1α and PD-L1 expression in glioma, and investigated their clinical significance. In glioma patients, HIF-1α and PD-L1 were overexpressed in high grade glioma tissues and were significantly associated with poor survival. In glioma cells, PD-L1 expression was induced under hypoxia condition, and the enhanced PD-L1 expression was abrogated by either HIF-1α knock-down or HIF-1α inhibitor treatment. Furthermore, ChIP-qPCR analysis showed the direct binding of HIF-1α to PD-L1 proximal promoter region, providing evidence that HIF-1α up-regulates PD-L1 in glioma. In glioma murine model, the combination treatment with HIF-1α inhibitor and anti-PD-L1 antibody caused a more pronounced suppressive effect on tumor growth compared to either monotherapy. Immunologically, the combination treatment improved both dendritic cell (DC) and CD8+ T cell activation. Overall, our results demonstrated that positive correlation between PD-L1 and HIF-1α in glioma, and provide an alternative strategy, inhibiting HIF-1α, as combination therapies with immunotherapies to advance glioma treatment.
Symptomatic eating epilepsy: two novel pediatric patients and review of literature
Authors: Vercellino Fabiana , Siri Laura , Brisca Giacomo , Scala Marcello , Riva Antonella , Severino Mariasavina , Striano Pasquale 
Published: June 2021

AbstractEating epilepsy (EE) is a form of reflex epilepsy in which seizures are triggered by eating. It is a rare condition but a high prevalence has been reported in Sri Lanka. In EE, the ictal semiology includes focal seizures with or without secondary generalization or generalized seizures. Some cases are idiopathic while focal structural changes on imaging, if present, are often confined to the temporal lobe or perisylvian region. On the other hand, some cases support the hypothesis of a genetic aetiology. The prognosis of EE is extremely variable due to the different nature of the underlying disorder. We describe two patients with symptomatic eating epilepsy, a 13-year-old boy with a bilateral perisylvian polymicrogyria and a 2-year-old boy with a genetic cause. The presence of structural lesions or the dysfunction of specific cortical regions in the context of a germline genetic alteration might lead to a hyperexcitation fostering the epileptogenesis. We review the available literature to clarify the aetiopathogenesis and the mechanisms underlying EE to improve the diagnosis and the management of these rare conditions.
Organosolv pretreatment assisted by carbocation scavenger to mitigate surface barrier effect of lignin for improving biomass saccharification and utilization
Authors: Chu Qiulu , Tong Wenyao , Chen Jianqiang , Wu Shufang , Jin Yongcan , Hu Jinguang , Song Kai 
Published: June 2021

Abstract
Background
Ethanol organosolv (EOS) pretreatment is one of the most efficient methods for boosting biomass saccharification as it can achieve an efficient fractionation of three major constituents in lignocellulose. However, lignin repolymerization often occurs in acid EOS pretreatment, which impairs subsequent enzymatic hydrolysis. This study investigated acid EOS pretreatment assisted by carbocation scavenger (2-naphthol, 2-naphthol-7-sulfonate, mannitol and syringic acid) to improve biomass fractionation, coproduction of fermentable sugars and lignin adsorbents. In addition, surface barrier effect of lignin on cellulose hydrolysis was isolated from unproductive binding effect of lignin, and the analyses of surface chemistry, surface morphology and surface area were carried out to reveal the lignin inhibition mitigating effect of various additives.

Results
Four different additives all helped mitigate lignin inhibition on cellulose hydrolysis in particular diminishing surface barrier effect, among which 2-naphthol-7-sulfonate showed the best performance in improving pretreatment efficacy, while mannitol and syringic acid could serve as novel green additives. Through the addition of 2-naphthol-7-sulfonate, selective lignin removal was increased up to 76%, while cellulose hydrolysis yield was improved by 85%. As a result, 35.78 kg cellulose and 16.63 kg hemicellulose from 100 kg poplar could be released and recovered as fermentable sugars, corresponding to a sugar yield of 78%. Moreover, 22.56 kg ethanol organosolv lignin and 17.53 kg enzymatic hydrolysis residue could be recovered as lignin adsorbents for textile dye removal, with the adsorption capacities of 45.87 and 103.09 mg g−1, respectively.

Conclusions
Results in this work indicated proper additives could give rise to the form of less repolymerized surface lignin, which would decrease the unproductive binding of cellulase enzymes to surface lignin. Besides, the supplementation of additives (NS, MT and SA) resulted in a simultaneously increased surface area and decreased lignin coverage. All these factors contributed to the diminished surface barrier effect of lignin, thereby improving the ease of enzymatic hydrolysis of cellulose. The biorefinery process based on acidic EOS pretreatment assisted by carbocation scavenger was proved to enable the coproduction of fermentable sugars and lignin adsorbents, allowing the holistic utilization of lignocellulosic biomass for a sustainable biorefinery.

Graphic abstract
Comparison of four outdoor mosquito trapping methods as potential replacements for human landing catches in western Kenya
Authors: Abong’o Bernard , Gimnig John E. , Longman Bradley , Odongo Tobias , Wekesa Celestine , Webwile Amos , Oloo Benjamin , Nduta Mercy , Muchoki Margaret , Omoke Diana , Wacira Daniel , Opondo Kevin , Ochomo Eric , Munga Stephen , Donnelly Martin J. , Oxborough Richard M. 
Published: June 2021

AbstractIntroductionLongitudinal monitoring of outdoor-biting malaria vector populations is becoming increasingly important in understanding the dynamics of residual malaria transmission. However, the human landing catch (HLC), the gold standard for measuring human biting rates indoors and outdoors, is costly and raises ethical concerns related to increased risk of infectious bites among collectors. Consequently, routine data on outdoor-feeding mosquito populations are usually limited because of the lack of a scalable tool with similar sensitivity to outdoor HLC.MethodologyTheAnophelestrapping sensitivity of four baited proxy outdoor trapping methods—Furvela tent trap (FTT), host decoy trap (HDT), mosquito electrocuting traps (MET) and outdoor CDC light traps (OLT)—was assessed relative to HLC in a 5 × 5 replicated Latin square conducted over 25 nights in two villages of western Kenya. Indoor CDC light trap (ILT) was run in one house in each of the compounds with outdoor traps, while additional non-Latin square indoor and outdoor HLC collections were performed in one of the study villages.ResultsThe MET, FTT, HDT and OLT sampled approximately 4.67, 7.58, 5.69 and 1.98 times moreAn. arabiensiscompared to HLC, respectively, in Kakola Ombaka. Only FTT was more sensitive relative to HLC in samplingAn. funestusin Kakola Ombaka (RR = 5.59, 95% CI 2.49–12.55,P < 0.001) and Masogo (RR = 4.38, 95% CI 1.62–11.80,P = 0.004) and in samplingAn. arabiensisin Masogo (RR = 5.37, 95% CI 2.17–13.24,P < 0.001). OLT sampled significantly higher numbers ofAn. coustaniin Kakola Ombaka (RR = 3.03, 95% CI 1.65–5.56,P < 0.001) and Masogo (RR = 2.88, 95% CI 1.15–7.22,P = 0.02) compared to HLC. OLT, HLC and MET sampled mostlyAn. coustani, FTT had similar proportions ofAn. funestusandAn. arabiensis, while HDT sampled predominantlyAn. arabiensisin both villages. FTT showed close correlation with ILT in vector abundance for all three species at both collection sites.ConclusionFTT and OLT are simple, easily scalable traps and are potential replacements for HLC in outdoor sampling ofAnophelesmosquitoes. However, the FTT closely mirrored indoor CDC light trap in mosquito indices and therefore may be more of an indoor mimic than a true outdoor collection tool. HDT and MET show potential for sampling outdoor host-seeking mosquitoes. However, the traps as currently designed may not be feasible for large-scale, longitudinal entomological monitoring. Therefore, the baited outdoor CDC light trap may be the most appropriate tool currently available for assessment of outdoor-biting and malaria transmission risk.Graphic abstract
Pens versus syringes to deliver insulin among elderly patients with type 2 diabetes: a randomized controlled clinical trial
Authors: Machry Rafael Vaz , Cipriani Gustavo Fonseca , Pedroso Henrique Umpierre , Nunes Rafaela Ramos , Pires Thayme Luisa Souza , Ferreira Raquel , Vescovi Betina , de Moura Gabriela Pereira , Rodrigues Ticiana Costa 
Published: June 2021

Abstract
Background
Diabetes mellitus (DM) is a prevalent disease among elderly population. As the disease progresses, insulin may become necessary. The use of pens application seems to be more practical. However, the influence of this method on glycemic control needs to be defined in elderly people.

Methods
Randomized clinical trial comparing pens and syringes for insulin application among patients with type 2 DM over 60 years old and Glycated Hemoglobin > 8.5% at baseline. The follow-up was 24 weeks, with monthly medical visits to adjust the treatment. All patients received insulin NPH and, if necessary, insulin Regular. We assessed glycemic control, adherence to treatment, hypoglycemia occurrence, need for adjustment in treatment and impact on quality of life,

Results
We included 121 patients with mean age of 65.75 years. Sixty-one were randomized for pen group (PG) and 60 patients for syringe group (SG). At baseline, mean HbA1c was 10.34 ± 1.66% and 9.90 ± 1.25% (p = 0.103) in PG and SG respectively. Mean HbA1c was 8.39 ± 1.28% in PG and 8.85 ± 1.74% in SG (p = 0.101) at 24 weeks. However, there was a more significant reduction in PG (− 1.94 ± 1.93% in PG and − 1.04 ± 1.46% in SG, p < 0.05) during follow-up. We found no difference in treatment adherence rates, hypoglycemia, greater need for insulin doses or oral medication, and progression to basal-bolus insulin scheme. We also found no difference in the impact of the disease on quality of life between groups.

Conclusion
Although we did not find any difference in the impact on quality of life, frequency of hypoglycemia or adherence, the PG showed a reduction in HbA1c higher in 24 weeks of follow-up.
Clinical trial registration: NCT02517242
A re-testing range is recommended for 13C- and 14C-urea breath tests for Helicobacter pylori infection in China
Authors: Wang Xiangyu , Zhang Shuzhen , Chua Eng Guan , He Yongsheng , Li Xiaofeng , Liu Aijun , Chen Haiting , Wise Michael J. , Marshall Barry J. , Sun Dayong , Li Xuehong , Tay Chin Yen 
Published: June 2021

Abstract
Background
The urea breath test (UBT) is widely used for diagnosing Helicobacter pylori infection. In the Shenzhen Kuichong People’s Hospital, some UBT findings were contradictory to the histology outcomes, therefore this study aimed to assess and compare the diagnostic performance of both 13C- and 14C-UBT assays.

Methods
We recruited 484 H. pylori-treatment naïve patients, among which 217 and 267 were tested by the 13C-UBT or 14C-UBT, respectively. The cutoff value for H. pylori positivity based on manufacturer’s instruction was 4% delta over baseline (DOB) for the 13C-UBT, and 100 disintegrations per minute (DPM) for the 14C-UBT. Gastric biopsies of the antrum and corpus were obtained during endoscopy for histopathology.

Results
In patients who were tested using the 13C-UBT kit, histopathology was positive in 136 out of 164 UBT-positive patients (82.9% concordance), and negative in 46 out of 53 UBT-negative cases (86.8% concordance). For the 14C-UBT-tested patients, histopathology was positive for H. pylori in 186 out of 220 UBT-positive patients (84.5% concordance), and negative in 41 out of 47 UBT-negative cases (87.2% concordance). While the 13C-UBT and 14C-UBT each had a high sensitivity level of 95.1% and 96.9%, respectively, their specificity was low, at 62.2% and 54.7%, respectively. By using new optimal cutoff values and including an indeterminate range (3–10.3% DOB for 13C-UBT and 87–237 DPM for 14C-UBT), the specificity values can be improved to 76.7% and 76.9% for the 13C- and 14C-UBT, respectively.

Conclusions
The establishment of an indeterminate range is recommended to allow for repeated testing to confirm H. pylori infection, and thereby avoiding unnecessary antibiotic treatment.
Trial registration: Chinese Clinical Trial Registry, ChiCTR2000041570. Registered 29 December 2020- Retrospectively registered, http://www.chictr.org.cn/edit.aspx?pid=66416&htm=4
Primary prescription adherence for obstructive lung disease in a primary care population
Authors: Singer Alexander G. , Katz Alan , LaBine Lisa , Lix Lisa M. , Yogendran Marina , Sinha Ian , Abrams Elissa M. 
Published: June 2021

Abstract
Background
The objective of this study was to determine primary prescription adherence for obstructive lung diseases (e.g., asthma, COPD) in an adult primary care patient population over a 3-year period.

Methods
A retrospective analysis of electronic medical record and administrative data was performed to determine primary adherence, defined as dispensation of a new prescription within 90 days of the date the prescription was written. Multivariable logistic regression models were used to test predictors of prescription primary adherence.

Results
Of 13,220 prescriptions for obstructive airway disease, 75.9% (N = 10,038) were filled. In multivariate analysis, depression, certain age groups (18–44 years), higher income quartile were associated with reduced prescription adherence. However, 1–2 ER visits in the previous year (compared to no ER visits), number of ambulatory visits in the previous year, and number of hospitalizations in the previous year, did not increase the likelihood of prescription adherence.

Interpretation
This study provides important insights about factors associated with prescription nonadherence and is the first study examining primary medication adherence with medications for obstructive lung disease in adults, providing indications of prescription nonadherence patterns among a broad population.
Performance of nanoScan PET/CT and PET/MR for quantitative imaging of 18F and 89Zr as compared with ex vivo biodistribution in tumor-bearing mice
Authors: Chomet Marion , Schreurs Maxime , Vos Ricardo , Verlaan Mariska , Kooijman Esther J. , Poot Alex J. , Boellaard Ronald , Windhorst Albert D. , van Dongen Guus AMS , Vugts Danielle J. , Huisman Marc C. , Beaino Wissam 
Published: June 2021

Abstract
Introduction
The assessment of ex vivo biodistribution is the preferred method for quantification of radiotracers biodistribution in preclinical models, but is not in line with current ethics on animal research. PET imaging allows for noninvasive longitudinal evaluation of tracer distribution in the same animals, but systemic comparison with ex vivo biodistribution is lacking. Our aim was to evaluate the potential of preclinical PET imaging for accurate tracer quantification, especially in tumor models.

Methods
NEMA NU 4-2008 phantoms were filled with 11C, 68Ga, 18F, or 89Zr solutions and scanned in Mediso nanoPET/CT and PET/MR scanners until decay. N87 tumor-bearing mice were i.v. injected with either [18F]FDG (~ 14 MBq), kept 50 min under anesthesia followed by imaging for 20 min, or with [89Zr]Zr-DFO-NCS-trastuzumab (~ 5 MBq) and imaged 3 days post-injection for 45 min. After PET acquisition, animals were killed and organs of interest were collected and measured in a γ-counter to determine tracer uptake levels. PET data were reconstructed using TeraTomo reconstruction algorithm with attenuation and scatter correction and regions of interest were drawn using Vivoquant software. PET imaging and ex vivo biodistribution were compared using Bland–Altman plots.

Results
In phantoms, the highest recovery coefficient, thus the smallest partial volume effect, was obtained with 18F for both PET/CT and PET/MR. Recovery was slightly lower for 11C and 89Zr, while the lowest recovery was obtained with 68Ga in both scanners. In vivo, tumor uptake of the 18F- or 89Zr-labeled tracer proved to be similar irrespective whether quantified by either PET/CT and PET/MR or ex vivo biodistribution with average PET/ex vivo ratios of 0.8–0.9 and a deviation of 10% or less. Both methods appeared less congruent in the quantification of tracer uptake in healthy organs such as brain, kidney, and liver, and depended on the organ evaluated and the radionuclide used.

Conclusions
Our study suggests that PET quantification of 18F- and 89Zr-labeled tracers is reliable for the evaluation of tumor uptake in preclinical models and a valuable alternative technique for ex vivo biodistribution. However, PET and ex vivo quantification require fully described experimental and analytical procedures for reliability and reproducibility.
The association of DAT gene methylation with striatal DAT availability in healthy subjects
Authors: Pak Kyoungjune , Seok Ju Won , Nam Hyun-Yeol , Seo Seongho , Lee Myung Jun , Kim Keunyoung , Kim In Joo 
Published: June 2021

Abstract
Background
DNA methylation inhibits gene expression by preventing transcription factors from binding to DNA. Functioning of nigrostriatal dopaminergic neurons is influenced by the expression of the dopamine transporter (DAT), and genetic variations in the gene encoding DAT contribute to differences in reward processing. We aimed to investigate the action of DAT methylation on DAT protein expression measured by positron emission tomography (PET).

Methods
The emission data were acquired over 90 min with 50 frames after injection of 18F-FP-CIT using PET. Binding potentials (BPNDs) of ventral striatum, caudate nucleus, putamen were measured with the simplified reference tissue method. Genomic DNA was extracted from subjects’ blood sampling. Methylation of 4 regions in SLC6A3 gene was assessed using bisulfite pyrosequencing. The mean percentage of methylation (%) for each cluster was calculated by taking the average of all CpG site methylation levels measured within the cluster. Subjects were assessed with the Generalized Reward and Punishment Expectancy Scales (GRAPES) that consists of 30 items related with the reward and punishment that individuals expect for their behaviors.

Results
Thirty-five healthy males, with an age range between 20 and 30 years, and a mean age of 24.4 ± 2.7 years, were included in this study. The mean percentage of methylation (%) from cluster C showed a trend of positive correlation with DAT availability of ventral striatum (rho = 0.3712, p = 0.0281), not significant after correction for multiple comparisons, and a significant correlation with GRAPES A: reward expectancy scale (rho = 0.7178, p < 0.0001).

Conclusion
DAT methylation from peripheral blood showed a trend of positive correlation with DAT availability of ventral striatum in healthy subjects; however, it was not significant after correction for multiple comparison. The degrees of methylation from cluster C of DAT in peripheral blood were significantly correlated with reward scales of GRAPES A: reward expectancy scale. The association between DAT methylation and DAT expression needs to be investigated further.
Manipulating the soil microbiomes during a community recovery process with plant beneficial species for the suppression of Fusarium wilt of watermelon
Authors: Zhang Xu , Xue Chao , Fang Dan , He Xiaohui , Wei Mengyu , Zhuo Chenjin , Jin Junyao , Shen Biao , Li Rong , Ling Ning , Shen Qirong 
Published: June 2021

AbstractFusarium wilt is a devastating disease which impacts watermelon production. Soil fumigation using dazomet followed by biological organic fertilizer was applied to suppress the Fusarium wilt disease. We propose that fumigation suppresses the soil indigenous community, especially the soil-borne pathogens, while the utilization of bio-organic fertilizer facilitates the recovery of the soil microbiome to a beneficial, suppressive state through the introduction of plant growth-promoting microorganisms. Greenhouse experiment showed that applied biological organic fertilizer after dazomet fumigation effective restrain the disease incidence with a 93.6% disease control. Fumigation strongly decreased soil microbial diversity and altered relative taxa abundances, suggesting the possibility of niche release by the resident soil microbial community. Fumigation followed by bio-fertilizer transformed the soil microbial community composition and resulted in higher relative abundances of beneficial microbial groups such as Bacillus (8.5%) and Trichoderma (13.5%), coupled with lower Fusarium abundance compared to other treatments. Network analysis illustrated that soil fumigation decreased interactions within the soil microbial community with less nodes and links while bio-fertilizer addition promoted node interactions. In addition, bio-fertilizer addition after fumigation resulted in the beneficial species becoming the key network connectors. Collectively, fumigation appears to release the resident soil niche resulting in lower diversity while the beneficial microbes introduced by bio-fertilizer addition colonize these niches, leading to a more complex community with fewer pathogens that suppresses Fusarium wilt disease incidence.
Fecal microbial composition and functional diversity of Wuzhishan pigs at different growth stages
Authors: Shao Mingying , Wang Zhixin , He Yingzhi , Tan Zhen , Zhang Jibin 
Published: June 2021

AbstractThe mammalian gut microbiome participates in almost all life processes in the host. In addition to diet, the breed is the main factor affecting changes in the swine gut microbiota. The composition of the gut microbiota changes significantly during different growth stages. Research on developmental changes in the gut microbiota of indigenous Chinese pig breeds is limited. In this study, the fecal microbiota of Wuzhishan pigs (a Chinese indigenous miniature pig) at different growth stages was investigated using high-throughput 16S rRNA sequencing. Firmicutes and Bacteroidetes were the two dominant phyla, accounting for more than 80% of all sequences. With increasing age, the fecal microbial diversity increased, and the proportion of Firmicutes increased, whereas the proportion of Bacteroidetes decreased. A total of 49 biomarkers with statistical differences were detected in the four growth stages. The different microbiota among groups enhanced the ability to degrade fiber, carbohydrates, and other substances during the growth stages. The endocrine system was different in multiple growth stage paired comparisons, which was attributed to the different body statuses in the growth stages. This study revealed developmental changes in the structure and function of gut microbes in local pigs.
Certain approximation properties of Brenke polynomials using Jakimovski–Leviatan operators
Authors: Wani Shahid Ahmad , Mursaleen M. , Nisar Kottakkaran Sooppy 
Published: June 2021

AbstractIn this article, we establish the approximation by Durrmeyer type Jakimovski–Leviatan operators involving the Brenke type polynomials. The positive linear operators are constructed for the Brenke polynomials, and thus approximation properties for these polynomials are obtained. The order of convergence and the weighted approximation are also considered. Finally, the Voronovskaya type theorem is demonstrated for some particular case of these polynomials.