bluuebunny/crossref_metadata_2025 huggingface dataset:
AKTIVITAS ANTI DIABETES MELLITUS TANAMAN DURIAN (Durio zibethinus Murr.) TERHADAP KADAR GLUKOSA DARAH PUASA MENCIT YANG DIINDUKSI ALOKSAN
Authors: Amir Muh. Nur , Sulitiani Yuyun , Indriani Indriani , Pratiwi Inda , Wahyudin Elly , Manggau Marianti A , Sumarheni Sumarheni , Ismail Ismail
Published: December 2020

Durian (Durio zibethinus Murr.) telah lama digunakan sebagai salah satu pengobatan tradisional untuk mengobati berbagai macam penyakit, termasuk untuk penderita diabetes mellitus. Penelitian ini bertujuan untuk menentukan aktivitas ekstrak etanol durian dalam menurunkan kadar glukosa darah pada mencit yang diinduksi aloksan dosis 125 mg / kgBB dan diberi beban glukosa 20%. Sebanyak 36 ekor mencit dibagi menjadi 6 kelompok perlakuan. Kelompok I sebagai kontrol sehat, kelompok II diinduksi dengan aloksan dan diberikan NaCMC 1% (kontrol negatif), kelompok III diinduksi dengan aloksan dan diberikan Acarbose® (kontrol positif), kelompok IV diinduksi dengan aloksan dan diberikan ekstrak etanol akar durian (EDR), ekstrak klika (ESB) dan ekstrak daun (EDL) dosis 125 mg / kgBB, kelompok V diinduksi dengan aloksan dan diberikan ekstrak etanol akar durian (EDR), ekstrak klika (ESB) dan ekstrak daun (EDL) dosis 250 mg / kgBB, kelompok VI diinduksi dengan aloksan dan diberikan ekstrak etanol akar durian (EDR), ekstrak klika (ESB) dan ekstrak daun (EDL) dosis 500 mg / kgBB. Pengukuran kadar glukosa darah dilakukan sebelum induksi alloxan (t-0), 3x24 jam setelah induksi (t-3), dan setiap 30 menit setelah pemberian perlakuan ekstrak dan larutan glukosa hingga menit ke-180 (t30, t60, t90, t120, t150 dan t180), yang dilakukan pengukuran menggunakan alat glukometer (Nesco®). Persen penurunan kadar glukosa darah yang paling tinggi ditunjukkan setelah menit ke-180 pada kelompok EDR dengan dosis 125 mg / kgBB, ESB dosis  250 mg / kgBB dan EDL dosis 500 mg / kgBB yaitu  sebesar 50,60%, 105,62%, dan 62,97%.
ANALISIS RESIDU PESTISIDA KLORPIRIFOS PADA BERAS (Oryza sativa) YANG BERASAL KECAMATAN BAEBUNTA KABUPATEN LUWU UTARA
Authors: Nurjannah Nurjannah , Yulianty Risfah , Marzuki Asnah , Kasim Syaharuddin , Djide Nana Juniarti Natsir
Published: December 2020

Penggunaan pestisida di Indonesia sudah merupakan bagian yang tidak terpisahkan dalam sistem pertanian. Klorpirifos merupakan salah satu kelompok pestisida golongan organofosfat yang banyak digunakan untuk membunuh berbagai serangga. Adanya residu klorpirifos dapat menyebabkan gangguan kesehatan sehingga deteksi residu klorpirifos dalam produk pangan merupakan hal yang penting. Penelitian ini dilakukan untuk mengetahui kadar residu klorpirifos pada beras yang berasal dari Kecamatan Baebunta, Kabupaten Luwu Utara dan keamanannya untuk dikonsumsi. Sampel beras diambil langsung dari beberapa petani di Kecamatan Baebunta, Kabupaten Luwu Utara. Sampel diekstraksi dan di clean-up menggunakan metode QuEChERS dan dianalisis menggunakan GC/MS. Kadar residu klorpirifos dibandingkan dengan standar Batas Maksimum Residu (BMR)pada SNI. Hasil penelitian menunjukkan bahwa residu klorpirifos pada sampel A, B dan C masing-masing sebesar 0,133; 0,092; dan 0,308 mg/kg. Dengan demikian, beras yang berasal dari Kecamatan Baebunta Kabupaten Luwu Utara memiliki kadar residu di bawah nilai BMR (0,5 mg/kg) sehingga aman untuk dikonsumsi
Identifikasi Mekanisme Fungsional Senyawa Bioaktif Peptida dari Organisme Laut sebagai Inhibitor Alami Angiotensin-I Converting Enzyme (ACE) secara In silico
Authors: Fakih Taufik Muhammad , Dewi Mentari Luthfika
Published: December 2020

Inhibitor alami Angiotensin-I Converting Enzyme (ACE) berbasis peptida bioaktif saat ini menjadi fokus penelitian karena sifatnya yang unik dan memilki berbagai peran biologis penting diantaranya adalah sebagai kandidat pengobatan hipertensi. Terdapat beberapa peptida bioaktif yang dihasilkan oleh organisme laut dan telah terbukti mampu menghambat enzim ACE, antara lain peptida bioaktif yang berasal dari udang (SV, IF, dan WP) serta peptida bioaktif yang berasal dari ikan hiu (CF, EY, MF, dan FE). Pada penelitian ini dilakukan identifikasi, evaluasi, dan eksplorasi terhadap interaksi yang terjadi antara molekul peptida bioaktif dengan makromolekul ACE secara in silico menggunakan motode penambatan molekuler berbasis protein-peptida. Sekuensing peptida bioaktif dimodelkan menjadi konformasi 3D terlebih dahulu menggunakan software PEP-FOLD. Konformasi terbaik dipilih untuk kemudian dilakukan studi interaksi molekuler terhadap makromolekul ACE menggunakan software PatchDock. Interaksi molekuler yang terjadi diamati lebih lanjut menggunakan software BIOVIA Discovery Studio 2020.  Berdasarkan hasil dari penambatan molekuler berbasis protein-peptida, peptida bioaktif CF dan IF yang berasal dari udang dan peptida bioaktif MF yang berasal dari ikan hiu memiliki afinitas yang baik, yaitu dengan ACE score masing-masing adalah −380,62 kJ/mol, −436,43 kJ/mol, dan −349,91 kJ/mol. Dengan demikian, peptida bioaktif laut tersebut diprediksi dapat dipilih sebagai kandidat inhibitor alami enzim ACE berbasis peptida sebagai alternatif antihipertensi.
Analisis Kemometrik Senyawa Inhibitor Tirosinase Menggunakan Spektrofotometer IR (FTIR)
Authors: Risal Yus
Published: December 2020

Tujuan dari percobaan adalah untuk mengetahui dan menganalisis kesamaan serta karakteristik yang khas dari senyawa inhibitor tirosinase seperti arbutin, asam kojik dari beberapa ekstrak seperti ekstrak (Curcuma xanthorrhiza) temu lawak, ekstrak (Curcuma zedoaria) kunyit putih, ekstrak (Lavandula afficianalis) lavender, ekstrak (Ocimum basilicum) selasih, ekstrak (Piper cubeba) kemukus, ekstrak (Piper retrofractum) cabai jawa dan ekstrak (Zingiber zerumbet) lempuyang yang dianalisis menggunakan spektrofotometer infra merah (FTIR) dan selanjutnya dilanjutkan analisis dengan menggunakan metode kemometrik yang terdiri dari PCA (Principal Component Analysis) dan CA (Cluster Analysis). Dari hasil penelitian, analisis PCA yang dicapai komponen utama dengan eigenvalue sekitar 99,8 % dari total varian, hasil analisis kemometrik PCA didapatkan senyawa inhibitor tirosinase berupa senyawa asam kojik, ekstrak (Zingiber zerumbet) lempuyang, ekstrak (Ocimum basilicum) selasih dan ekstrak (Lavandula afficianalis) lavender berada dalam satu kuadran. Untuk analisis CA menunjukkan asam kojik ada kemiripan karakteristik dengan (Zingiber zerumbet) lempuyang tingkat kesamaan adalah 75,85; jarak Euclidean 0,202.
Optimization of the Statin Therapy Algorithm in Outpatient Practice: Adherence and Economic Benefits
Authors: Davitashvili S. A. , Nebieridze D. V. , Akhmedzhanov N. M. , Lishuta A. S. , Safaryan A. S.
Published: December 2020

Aim. To study adherence to recommended treatment, additional clinical and economic benefits of a titration-free statin therapy regimen.

Material and methods. Ambulatory patients (n=300) with a high or very high risk of hypercholesterolemia who have indications for statin treatment for primary or secondary prevention of cardiovascular diseases is included in a non-randomized trial. Patients are divided into 2 groups. Group 1 had a titration regimen of statins in accordance with current recommendations (group 1A [n=50] – primary cardiovascular prevention; group 1B [n=100] – secondary cardiovascular prevention). Group 2 received a titration-free statin regimen in fixed doses (group 2A [n=50] – primary cardiovascular prevention; group 2B [n=100] – secondary cardiovascular prevention). Patients were prescribed atorvastatin (10-80 mg/day) or rosuvastatin (10- 40 mg/day). Group 1 patients had visits to the doctor after 1, 3, 6 and 12 months from the start of statin use, group 2 patients after 3 and 12 months. Treatment adherence, effects on surrogate and hard endpoints, and cost-effectiveness of the two statin regimens were evaluated.

Results. The target level of low-density lipoprotein cholesterol (LDL-C) after 12 months in group 2 was achieved in 56.4% of patients versus 53.4% in group 1. The average level of LDL-C decreased by 1.84±0.44 mmol / l in group 2 versus a decrease of 1.61±0.47 mmol / L in group 1. The costeffectiveness ratio was 9658.72 rubles in group 2 versus 8341.73 rubles in group 1 for a 1 mmol / l LDL-C level decrease in 1 patient within a year. An increase in annual costs per patient in group 2 compared with group 1 by 75.76 rubles reduced the relative risk of developing a combined endpoint by 1% per year.

Conclusion. The use of a titration-free statin treatment regimen allowed us not only to more effectively control of LDL-c levels in patients with high and very high cardiovascular risk compared to the traditional statin therapy regimen, but also to obtain economic advantages in patients with high and very high cardiovascular risk.
Contaminants of Emerging Concern
Authors: Kuskopf Laura , Sheehan Madoc , Whelan Anna
Published: December 2020

There are potentially many thousands of municipally derived contaminants of emerging concern (CECs) present in discharged wastewaters that may cause adverse effects in receiving aquatic environments. Wastewater authorities, therefore, may face the momentous task of investigating these compounds with little or no prior CEC data for their sewage treatment plants (STPs). Such is the case for the Cleveland Bay Sewage Treatment Plant (CBSTP). To evaluate the potential environmental risk posed by municipal CECs, it is first necessary to understand which CECs are present in discharging wastewater, how they will be sampled and quantified, and which CECs are the most concerning regarding ecological risk. A Sampling Analysis and Quality Plan (SAQP) is a valuable tool that can be used to critically review and detail the strategy that will be adopted to achieve these outcomes. As such, this paper describes the development of a SAQP for screening wastewaters released from the CBSTP into Cleveland Bay as part of a preliminary CEC assessment. This paper describes the qualitative decision-making process employed to shortlist CECs into those perceived to pose the greatest ecological risk. In addition, the rationale and methods adopted to determine sampling locations and frequency are described.
Neuroprotective effects of dexmedetomidine on the ketamine-induced disruption of the proliferation and differentiation of developing neural stem cells in the subventricular zone
Authors: Sha Huanhuan , Peng Peipei , Li Bing , Wei Guohua , Wang Juan , Wu Yuqing , huang he
Published: December 2020

Background: Recently, the number of neonatal patients receiving surgery under general anesthesia has increased. Ketamine disrupts the proliferation and differentiation of developing neural stem cells (NSCs). Therefore, the safe use of ketamine in pediatric anesthesia has been an issue of increasing concern among anesthesiologists and the children’s parents. Dexmedetomidine (DEX) is widely used in sedation, as an antianxiety agent and for analgesia. DEX has recently been shown to provide neuroprotection against anesthetic-induced neurotoxicity in the developing brain. The aim of this in vivo study was to investigate whether DEX exerted neuroprotective effects on the proliferation and differentiation of NSCs in the subventricular zone (SVZ) following neonatal ketamine exposure. Methods: Postnatal day 7 (PND-7) male Sprague-Dawley rats were equally divided into the following 5 groups: Control group (n=8), Ketamine group (n=8), 1 μg/kg DEX+Ketamine group (n=8), 5 μg/kg DEX+Ketamine group (n=8) and 10 μg/kg DEX+Ketamine group (n=8). The proliferation and differentiation of NSCs in the SVZ were assessed using immunostaining with BrdU incorporation. The levels of Nestin and β-tubulin III in the SVZ were measured using Western blot analyses. Apoptosis was assessed by detecting the levels of the cleaved caspase-3 protein using Western blotting. Results: Neonatal ketamine exposure significantly inhibited NSC proliferation and astrocytic differentiation in the SVZ, and neuronal differentiation was markedly increased. Furthermore, pretreatment with moderate (5 μg/kg) or high doses (10 μg/kg) of DEX reversed the ketamine-induced disturbances in the proliferation and differentiation of NSCs. Meanwhile, neonatal ketamine exposure significantly decreased the expression of Nestin and increased the expression of β-tubulin III in the SVZ compared with the Control group. Treatment with 10 μg/kg DEX notably reversed the ketamine-induced changes in the levels of Nestin and β-tubulin III. In addition, a pretreatment with 10 μg/kg DEX before ketamine anesthesia prevented apoptosis in the SVZ induced by neonatal ketamine exposure. Conclusions: Based on our findings, DEX may exert neuroprotective effects on the proliferation and differentiation of NSCs in the SVZ of neonatal rats in a repeated ketamine anesthesia model.
An 192 bp ERV Insertion in the First Intron of TLR6 Acts as an Enhancer to Increase TLR6 and TLR1 Expression
Authors: wang xiaoyan , Chen Zixuan , Murani Eduard , D'alessandro Enrico , An Yalong , Chen Cai , Li Kui , Galeano Grazia , Wimmers Klaus , Song Chengyi
Published: December 2020

BackgroundToll-like receptors (TLRs) play important roles in building innate immune and inducing adaptive immune responses. Associations of the TLR gene polymorphisms with diseases susceptibility, which are the basis of molecular breeding for disease resistant animals, have been reported extensively. Retrotransposon insertion polymorphisms (RIPs) were developed recently as a new type of molecular marker having great potential in population genetics and quantitative trait locus (QTL) mapping analysis. In this study, bioinformatics prediction combined with the PCR-based amplification was employed to screen for RIPs in porcine TLR genes. Their population distribution and impact on gene activity and phenotype of one RIP was been further evaluated. ResultsThe results showed that five RIPs, located at the 3' flank of TLR3, 5' flank of TLR5, intron 1 of TLR6, intron 1 of TLR7, and 3' flank of TLR8 respectively, was identified. These RIPs were detected in different breeds with an uneven distribution among them. By using the dual luciferase activity assay a 192 bp endogenous retrovirus (ERV) in the intron 1 of TLR6 was proven to act as an enhancer increasing the activities of TLR6 promoter and multiple mini-promoters. Furthermore, the real-time quantitative polymerase chain reaction (qPCR) analysis demonstrated that the ERV insertion significantly enhances the mRNA expressions of TLR6, the neighboring gene TLR1, and the downstream genes MyD88 (Myeloid differentiation factor 88), Rac1 (Rac family small GTPase 1), TIRAP (TIR domain containing adaptor protein), Tollip (Toll interacting protein) of TLR signaling pathway and the inflammatory factors IL6 (Interleukin 6), IL8 (Interleukin 8), and TNFα (Tumor necrosis factor alpha) in 30-day piglet tissues. In addition, the serum IL-6 and TNFα was also significantly upregulated by ERV insertion. ConclusionsOverall, five RIPs were been identified in several TLRs, and the 192 bp ERV insertion in the first intron of TLR6 can improve the expressions of TLR6, TLR1, their downstream genes, and the inflammatory factors by acting as an enhancer affecting the regulation of TLR pathways, which may be applicable in the molecular breeding of disease resistant animals.
Pt/TiO2 Catalyzed Hydrogenation of Benzoic Acid with Unprecedented High Activity
Authors: Guo Miao , Kong Xiangtao , Li Chunzhi , Yang Qihua
Published: December 2020

The hydrogenation of benzoic acid (BA) to corresponding cyclohexanecarboxylic acid has important industry and academia significance, however, the electron deficient aromatic ring and the catalyst “poison” by carboxyl group make BA hydrogenation as one of the most challenging transformations. Herein, we found that Pt NPs deposited on TiO2 were very effective for BA hydrogenation with a record TOF of 4490 h− 1 under 80 oC and 50 bar H2 in hexane, one order higher than the reported results. DFT calculation showed that Pt NPs had a weaker interaction with BA than Ru and Pd NPs commonly used for BA hydrogenation, which improved the toxicity resistance of catalyst to BA. Pt/TiO2 catalysts with electron deficient and electron enriched Pt sites were successfully synthesized by modifying the electron transfer direction between Pt and TiO2. Isotopic experiments suggested the participation of dissociated H from carboxyl group in BA hydrogenation. Consequently, the electron deficient Pt sites with stronger adsorption of BA were more active than electron rich Pt sites in BA hydrogenation. In addition to BA, terephthalic acid, iso-phthalic acid, trimesic acid and other BA derivatives could also be efficiently converted to corresponding aromatic saturated products, demonstrating the wide substrate scope of Pt/TiO2.
Infection Was Associated With Intensive Care Unit Pediatric Delirium in Children Younger Than 2 Years Old: A Single-Center Observational Study
Authors: Ge Xiaohua , Wei Wanrui , Zheng Qingru , Xu Lili , Hu Yaqin , Yuan Changrong
Published: December 2020

Objective: The primary objective of this study was to investigate the prevalence of intensive care unit (ICU) pediatric delirium in Shanghai, China. Secondary objectives were to determine the association of hypoxia and infection with ICU pediatric delirium, and the impact between different age. Design: Prospective single-center observational study. Setting: Two pediatric intensive care unit (PICU) within a tertiary-A general hospital. Patients: Patients age between 1 month to 7 years in PICU who stayed at least 1 day were included. Convenance sampling was used. Interventions: None. Measurements and Main Results: Pediatric patients (n=639) were screened twice a day for the prevalence of ICU pediatric delirium by Cornell Assessment of Pediatric Delirium, 300 (46.95%) of them had infection and 213 (33.33%) had hypoxia in PICU. Children who suffered hypoxia remained more than three times likely to be delirious during their hospitalization compared with children who were not hypoxia, after controlling other covariates, the odds of pediatric delirium for subjects with hypoxia was 3.26 times (95% CI, 1.98-5.38) the odds without hypoxia. Also, the odds of pediatric delirium for subjects with infection was 2.55 times (95% CI, 1.58-4.11) the odds without infection adjusting for other covariates. After subgrouping by age, the occurrence of ICU pediatric delirium with infection for children younger than two years old was 5.37 times (95% CI, 3.09-9.33) compared with patients who were never infection, while that for the children equal to or older than two years old was no statistically significant relationship. Conclusions: The prevalence of ICU pediatric delirium was 31.30%, while there is an independent association of infection and hypoxia with ICU pediatric delirium. Furthermore, children younger than two years old took more risks on pediatric delirium when they were infected in this study, while there was no relationship between infection and pediatric delirium who aged 2 years or older.
Identification of Driver Genes and Key Pathways of Osteosarcoma Shows K-7174 As a Novel Anti-osteosarcoma Drug by Inhibiting VCAM1
Authors: Fu Zhaoyu , Yu Jing , Liu Yan , Wu Bo , Cheng Long , Zhou Pengcheng , Zhu Dong
Published: December 2020

BackgroundOsteosarcoma is one of the leading causes in cancer-related death of children and adolescents. However current standard therapeutic strategy, surgery combined with neoadjuvant chemotherapy is very limited in effects. As big data mining and analysis using bioinformatics method has been applied in the diagnosis and treatment of many cancers, we want to use bioinformatic combined with experimental assays to found new molecular targets and test new drug for osteosarcoma.MethodsThe gene chip of osteosarcoma samples constructed by Richter GH et al were downloaded from the Gene Expression Omnibus (GEO) database, Gene Ontology analysis (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on differential expression genes which screened by bioinformatics methods.Protein-protein interaction network was constructed by suing STRING database to found hub gene. Combined with pertinent literature, genes of interest and corresponding drug was selected. Series of experiments were performed on the osteosarcoma cell lines in vitro, involved cell viability test, colony formation assay, migratory and invasive tests, western blot as well.ResultsA total of 1069 DEGs were obtained from data, including 375 up-regulated genes and 694 down-regulated genes. Differentially expressed genes mainly involve biological processes such as cellular immune function, such as interferon-gamma-mediated signaling pathway and antigen processing and presentation of peptide. Among top 20-ranked degree hug gene evaluated by PPI network, vascular cell adhesion molecule-1(VCAM1) was picked out. An VCAM1 inhibitor K-7174 was treated in U2OS and MG63 cell lines. In vitro experiments have shown that K-7174 can inhibit the proliferation, migration and invasion of osteosarcoma, the protein expression of VCAM1was also decreased by K-7174.ConclusionsVCAM1 could be a potential target for osteosarcoma and K-7174 promises to be a therapeutic drug after more nuanced evaluation in animal and clinical trials.
Energy Transfer to the Phonons of A Macromolecule Through Light Pumping
Authors: Faraji Elham , Franzosi Roberto , Mancini Stefano , Pettini Marco
Published: December 2020

In the present paper we address the problem of the energy downconversion of the light absorbed by a protein into its internal vibrational modes. We consider the case in which the light receptors are fluorophores either naturally co-expressed with the protein or artificially covalently bound to some of its amino acids. In a recent work [Phys. Rev. X 8, 031061 (2018)], it has been experimentally found that by shining a laser light on the fluorophores attached to a protein the energy fed to it can be channeled into the normal mode of lowest frequency of vibration thus making the subunits of the protein coherently oscillate. Even if the phonon condensation phenomenon has been theoretically explained, the first step - the energy transfer from electronic excitation into phonon excitation - has been left open. The present work is aimed at filling this gap.
Oral pH Value Predicts the Incidence of Radiotherapy Related Caries in Nasopharyngeal Carcinoma Patients
Authors: LI Zheng , WU Qiuji , MENG Xiangyu , YU Haijun , JIANG Dazhen , CHEN Gaili , HU Xiaoyan , HUA Xinying , WANG Xiaoyong , WANG Dajiang , ZHAO Hongli , ZHONG Yahua
Published: December 2020

Purpose: Radiotherapy-related caries is a complication of radiotherapy for nasopharyngeal carcinoma; however, factors influencing the occurrence, accurate prediction of onset, and protective factors of radiotherapy-related caries remain unclear. This study analyzed risk factors, disease predictors, and protective factors for radiotherapy-related caries in nasopharyngeal carcinoma. Methods and Materials: This prospective study included 138 nasopharyngeal carcinoma patients receiving radical radiotherapy at our hospital during June 2012-December 2016 and were followed up for dental caries. Patients’ clinical data on radiotherapy were collected, dynamic monitoring was performed to assess changes in oral pH values, and a questionnaire survey was administered to collect patients’ lifestyle habits. Time-dependent cox regression tress, event-free Kaplan-Meier curve, Mann-Whitely U test were used to analysis the results.Results: The median follow-up time was 30 (12-60) months. Radiotherapy-related caries occurred in 28 cases (20.3%). Univariate analyses showed that radiotherapy-related caries was associated with patient’s age, oral saliva pH value, green tea consumption, and radiation dose to sublingual glands, but not with the radiation dose to the parotid and submandibular glands. Multivariate analysis showed that oral saliva pH value (hazard ratio [HR]=0.390, 95% confidence interval=0.204-0.746) was an independent prognostic factor for radiotherapy-related caries. Patients with oral saliva pH values ≤5.3 in the 9th month after radiotherapy a significantly higher risks for radiotherapy-related caries (HR=33.68, p<0.001). Conclusions: Green tea consumption was associated with the occurrence of radiotherapy-related caries, and oral saliva pH values could predict the occurrence of radiotherapy-related caries. Limiting radiation doses to sublingual glands can reduce the occurrence of radiotherapy-related caries.
Hyperhomocysteinemia and its Relations to Conventional Risk Factors for Cardiovascular Diseases in Adult Nigerians: The REMAH Study.
Authors: Chori Babangida , Danladi Benjamin , Inyang Bassey , Okoh Michael , Nwegbu Maxwell , Alli Adewale , Odili Augustine
Published: December 2020

Background: Evidence linking homocysteine (Hcy) with cardiovascular diseases (CVD) or its risk factors are insufficient in a Sub-Saharan black population. Objective: We set out to evaluate the association between Hcy and hypertension and other CVD risk factors in a population of adult Nigerians. Methods: Data of 156 adults aged 18-70years was accessed from the North Central study site of the REmoving the MAsk on Hypertension (REMAH) study. Homocysteine, blood glucose and lipid profile in whole blood/serum were measured using standard laboratory methods. Hypertension was diagnosed if average of 5 consecutive blood pressure (BP) measurements obtained using a mercury sphygmomanometer was equal to or higher than 140 systolic and/or 90 mmHg diastolic or the individual is on antihypertensive medication. Hyperhomocysteinemia (HHcy) was defined as Hcy>10µmol/L. Results: Of the 156 participants, 72 (43.5%) were hypertensive, of whom 18 had HHcy. Subjects with HHcy were significantly (p<0.05) older (41.5 vs 40.6yrs), had lower HDL-cholesterol (0.6 vs 0.8mmol/L) and higher systolic (145.5 vs 126.0mmHg) and diastolic BP (92.9 vs 79.6mmHg), compared to those without HHcy. Intake of alcohol and a 1yr increase in age were respectively and significantly (p<0.05) associated with a 1.54 and 0.10 µmol/L increase in Hcy. In a multivariable model adjusted for age, sex and body mass index, a 1µmol/L increase in Hcy, was associated with a 1.69 mmHg and 1.34 mmHg increase in systolic and diastolic pressure (p< 0.0001) respectively; and a 0.01mmol/L decrease in HDL-cholesterol (p<0.05). Conclusion: HHcy occurs among hypertensive Nigerians and it is independently associated with age, HDL-cholesterol, systolic and diastolic BP.
High-Depth Viral Blood Metagenomics Reveals Extensive Anellovirus Diversity in Healthy Humans
Authors: Cebriá-Mendoza María , Arbona Cristina , Larrea Luís , Díaz Wladimiro , Arnau Vicente , Peña Carlos , Bou Juan , Sanjuán Rafael , Cuevas José
Published: December 2020

Human blood metagenomics has revealed the presence of different types of viruses in apparently healthy subjects. By far, anelloviruses constitute the viral family that is more frequently found in human blood, although amplification biases and contaminations pose a major challenge in this field. To investigate this further, we subjected pooled plasma samples from 120 healthy donors in Spain to high-speed centrifugation, RNA and DNA extraction, random amplification, and massive parallel sequencing. Our results confirm the abundance of anelloviruses in such samples, which represented >98% of the total viral sequence reads obtained. We assembled 114 different viral genomes belonging to this family, revealing remarkable diversity. Phylogenetic analysis of ORF1 suggested 28 potentially novel anellovirus species, 24 of which were validated by Sanger sequencing to discard artifacts. These findings underscore the importance of implementing more efficient purification procedures that enrich the viral fraction as an essential step in virome studies and question the suggested pathological role of anelloviruses.
Three-Dimensional and Two-Dimensional Relationships of Gangliogenesis With Folliculogenesis in Mature Mouse Ovary: A Golgi-Cox Staining Approach
Authors: Zarch Mohammad Ebrahim Asadi , Afshar Alireza , Rahmanifar Farhad , Shirazi Mohammad Reza Jafarzadeh , Baghban Mandana , Dadpasand Mohammad , Rezazadeh Farzad Mohammad , Khoradmehr Arezoo , Baharvand Hossein , Tamadon Amin
Published: December 2020

The present study was set out to investigate two-dimensional (2D) and three-dimensional (3D) evaluations of ovarian nervous network development and the structural relationship between folliculogenesis and gangliogenesis in mouse ovary. Adult mice ovarian tissue samples were collected from diestrus and estrus stages after cardiac perfusion. Ovarian samples were stained by a Golgi-Cox protocol. Following staining, tissues were serially sectioned for imaging. Neural filaments and ganglia were present in the ovaries. In both 2D and 3D studies, an increase in the number and area of ganglia was seen during the follicular growth. The same pattern was also seen in corpora lutea development. However, in some cases such as ratio of ganglia number to follicle area, the ratio of ganglia area to follicular area, 2D findings were different compared with the 3D results. 3D analysis of ovarian gangliogenesis showed the possible direct effect of them on folliculogenesis. Golgi-Cox staining was used in this study for 3D evaluation in non-brain tissue. The results of 3D analysis of the present study showed that, in some cases, the information provided by 2D analysis does not match the reality of ovarian neuronal function. This confirmed the importance of 3D analysis for evaluation of ovarian function.
Comparison Between Deep Inspiration Breath Hold and Shallow Breathing for Prone Photon or Proton Irradiation of the Breast and Regional Lymph Nodes
Authors: Speleers Bruno , Schoepen Max , Belosi Francesca , Vakaet Vincent , De Neve Wilfried , Deseyne Pieter , Paelinck Leen , Vercauteren Tom , Parkes Michael , Lomax Tony , Greveling Annick Van , Bolsi Alessandra , Weber Damien , Veldeman Liv , De Gersem Werner
Published: December 2020

We report on a comparative dosimetrical study between deep inspiration breath hold (DIBH) and shallow breathing (SB) in prone crawl position for photon and proton radiotherapy of whole breast (WB) and locoregional lymph node regions, including the internal mammary chain (LN_IM). We investigate the dosimetrical effects of DIBH in prone crawl position on organs-at-risk for both photon and proton plans. For each modality, we further estimate the effects of lung and heart doses on the mortality risks of different risk profiles of patients. Thirty-one patients with invasive carcinoma of the left breast and pathologically confirmed positive lymph node status were included in this study. DIBH significantly decreased dose to heart for photon and proton radiotherapy. DIBH also decreased lung doses for photons, while increased lung doses were observed using protons because the retracting heart is displaced by low-density lung tissue. For other organs-at-risk, DIBH resulted in significant dose reductions using photons while minor differences in dose deposition between DIBH and SB were observed using protons. In high-risk patients for cardiac and lung cancer mortality, average thirty-year mortality rates from radiotherapy-related cardiac injury and lung cancer were estimated at 3.12% (photon DIBH), 4.03% (photon SB), 1.80% (proton DIBH) and 1.66% (proton SB). The radiation-related mortality risk could not outweigh the ~8% disease-specific survival benefit of WB + LN_IM radiotherapy in any of the assessed treatments. Trial registration: No trial registration was performed because there were no therapeutic interventions.
Radiologic-Pathologic Analysis of Increased Ethanol Localization and Ablative Extent Achieved by Ethyl Cellulose
Authors: Chelales Erika , Morhard Robert , Nief Corrine , Crouch Brian , Sag Alan , Ramanujam Nirmala
Published: December 2020

PurposeEthanol provides a rapid, low-cost ablative solution for liver tumors with a small technological footprint but suffers from uncontrolled diffusion in target tissue, limiting treatment precision and accuracy. The authors demonstrate that incorporating the gel-forming polymer ethyl cellulose to ethanol localizes the distribution. This therapy may have a low barrier of entry for cancer care in low- and middle- income countries.Materials and MethodsThe relationship of radiodensity to ethanol concentration was characterized with water-ethanol surrogates. Ex vivo EC-ethanol ablations were performed to optimize the formulation (n=6). In vivo ablations were performed to compare the optimal EC-ethanol formulation to pure ethanol (n=6). Ablations were monitored with CT and ethanol distribution volume was quantified. Livers were explanted, sectioned and stained with NADH-diaphorase to determine the ablative extent.ResultsCT imaging of ethanol-water surrogates demonstrated the ethanol concentration-radiodensity relationship is approximately linear. A concentration of 12% EC in ethanol created the largest distribution volume, more than 8-fold that of pure ethanol, ex vivo. In vivo, 12% EC-ethanol was superior to pure ethanol, yielding a distribution volume 3 times greater and an ablation zone 6 times greater than pure ethanol.Conclusions EC-ethanol, a novel gel formulation injectable ablative injectate, safely increases distribution and necrosis compared to pure ethanol.
PHAIR – A Biosensor for pH Measurement in Air-liquid Interface
Authors: Dabaghi Mohammadhossein , Saraei Neda , Xu Gang , Chandiramohan Abiram , Yeung Jonas , Nguyen Jenny , Vukmirovic Milica , Selvaganapathy Ponnambalam Ravi , Hirota Jeremy
Published: December 2020

In many biological systems, pH can be used as a parameter to understand and study cell dynamics. However, measuring pH in live cell culture is limited by the sensor ion specificity, proximity to the cell surface, and scalability. Commercially available pH sensors are difficult to integrate into a small-scale cell culture system due to their size and are not cost-effective for disposable use. We made PHAIR - a new pH sensor that uses a micro-wire format to measure pH in vitro human airway cell culture. Tungsten micro-wires were used as the working electrodes, and silver micro-wires with a silver/silver chloride coating were used as a pseudo reference electrode. pH sensitivity, in a wide and narrow range, and stability of these sensors were tested in common standard buffer solutions as well as in culture media of human airway epithelial cells grown at the air-liquid interface in a 24 well cell culture plate. When measuring the pH of cells grown under basal and challenging conditions using PHAIR, cell viability and cytokine responses were not affected. Our results confirm that micro-wires-based sensors have the capacity for miniaturization, and detection of diverse ions while maintaining sensitivity. This suggests the broad application of PHAIR in various biological experimental settings.
Unravelling the Differential Expression of Potential microRNAs in Bacterial Wilt-resistant and Susceptible Ginger Species
Authors: Snigdha M , Prasath D
Published: December 2020

MicroRNAs (miRNA) have been shown to regulate plant pathogen interaction, by silencing genes, destructing or blocking of the translation of mRNA. However, their role in bacterial wilt, caused by Ralstonia solanacearum in ginger, has not been studied. In the present study, we utilized the transcriptome data from ginger-Ralstonia solanacearum interactions to characterize miRNAs from bacterial wilt-susceptible ginger (Zingiber officinale) and resistant mango ginger (Curcuma amada). The assembled mRNAs were utilized to generate miRNA targets and miRNAs. Considering the alignment results, we located a total of 2926 potential miRNA targets out of which 1551 were upregulated and 1419 were downregulated in ginger. In case of mango ginger, out of 2145 potential miRNA targets, 1506 were upregulated and 1594 were downregulated. In the resistance interactions with mango ginger, 1068 unique target genes were upregulated when compared to control. Gene Ontology (GO) analysis of differentially expressed target genes showed highest enrichment in response to cold, chloroplast and ATP binding in biological, cellular and molecular functions respectively. Nine target genes and their corresponding miRNAs were experimentally validated, which shows significant difference in expression with ginger-Ralstonia solanacearum interactions. The results will be very useful to disease resistant varieties of ginger.
Snow Supervision in Digital Pathology: Managing Imperfect Annotations for Segmentation in Deep Learning
Authors: Foucart Adrien , Debeir Olivier , Decaestecker Christine
Published: December 2020

In digital pathology, image segmentation algorithms are usually ranked on clean, benchmark datasets. However, annotations in digital pathology are hard, time-consuming and by nature imperfect. We expand on the SNOW (Semi-, Noisy and/or Weak) supervision concept introduced in an earlier work to characterize such data supervision imperfections. We analyse the effects of SNOW supervision on typical DCNNs, and explore learning strategies to counteract those effects. We apply those lessons to the real-world task of artefact detection in whole-slide imaging. Our results show that SNOW supervision has an important impact on the performances of DCNNs and that relying on benchmarks and challenge datasets may not always be relevant for assessing algorithm performance. We show that a learning strategy adapted to SNOW supervision, such as “Generative Annotations", can greatly improve the results of DCNNs on real-world datasets.
Spatiotemporal Variations Dictate Stable and Resilient Microbiome Interactions in the Chesapeake Bay
Authors: Wang Hualong , Chen Feng , Zhang Chuanlun , Wang Min , Kan Jinjun
Published: December 2020

Background: Annually reoccurring microbial populations with strong spatial and temporal variations have been identified in estuarine environments, especially in those with long residence time such as the Chesapeake Bay (CB). However, it is unclear how microbial taxa interact with each other (e.g., mutualistic and competitive interactions) and how these interactions respond to their surrounding environments. Specifically, there is a lack of understanding of how these interactions influence microbiome population dynamics, and its adaptability and resilience to estuarine gradients. Results: Here, we constructed co-occurrence networks on prokaryotic microbial communities in the Bay, which included seasonal samples from seven spatial stations along the salinity gradients for three consecutive years. Our results showed that spatiotemporal variations of planktonic microbiomes promoted differentiations of the characteristics and stability of prokaryotic microbial networks in the CB estuary. Prokaryotic microbial networks are more stable seasonally than spatially, and microbes were more strongly connected during warm season compared to the associations during cold season. In addition, microbial interactions were more stable in the lower Bay (ocean side) than those in the upper Bay (freshwater side). Interestingly, compared to the abundant groups, the rare taxa such as SAR116 clade, SAR11 clade III, and OM182 clade contributed greatly to the stability and resilience of prokaryotic microbial interactions in the Bay. Modularity and cluster structures of microbial networks varied spatiotemporally, which provided valuable insights into the ‘small world’ (a group of more interconnected species), network stability, and habitat partitioning/preferences. Multivariate regression tree (MRT) analysis and Piecewise structural equation modeling (SEM) indicated that temperature, salinity and total suspended substances directly or indirectly (through nutrient availability, particulate carbon and Chl a) affected the distribution and associations of microbial groups, such as Actinobacteria, Bacteroidetes, Cyanobacteria, Planctomycetes, Proteobacteria, and Verrucomicrobia.Conclusion: Our results shed light on how spatiotemporal variations alter the nature and stability of prokaryotic microbial networks in the estuarine ecosystem, as well as the ability of planktonic microbiomes and their interactions to resist future disturbances.
Acidified Pepsin Promotes Laryngeal Precancerosis by Upregulating H+/K+-ATPase and Activating Mitophagy in Laryngeal Epithelial Cells
Authors: Cheng Ke-Jia , Xu Qiong , Li Zhi-Mei , Zhou Shui hong , Bao Yang-Yang , Chen Zhe , Fan Jun
Published: December 2020

Background: Although laryngopharyngeal reflux (LPR) has been implicated in various upper aerodigestive tract and laryngeal diseases, the underlying mechanisms remain elusive. In this study, we investigated the role of gastric acidified pepsin in laryngeal precancerosis. Methods: The in vitro and in vivo effects of acidified pepsin on H+/K+-ATPase expression and autophagy/mitophagy induction in mouse laryngeal epithelial cells were assessed by hematoxylin and eosin staining, immunohistochemistry, CCK-8 assay, flow cytometry, Western blotting, and quantitative real-time PCR. Additionally, the levels of pepsin and H+/K+-ATPase α and β subunits in 31 human laryngeal mucosal specimens were assessed by immunohistochemical staining. Results: Acidified pepsin (pH=3) enhanced the growth and survival of mouse laryngeal epithelial cells in vitro and promoted laryngeal mucosal thickening and laryngeal epithelial cell growth in vivo. Furthermore, acidified pepsin promoted autophagy/mitophagy induction, accompanied by a significant decrease in mitochondrial membrane potential (MMP). Inhibition of autophagy by chloroquine abolished the ability of acidified pepsin to promote mitophagy and cell growth in laryngeal epithelial cells. Additionally, chloroquine promoted cell apoptosis and further reduced MMP in laryngeal epithelial cells treated with acidified pepsin. The expression levels of pepsin and H+/K+-ATPase α and β subunits in 31 human laryngeal mucosa specimens were 51.6%, 48.4%, and 48.4%, respectively. Importantly, the pepsin level was correlated with the H+/K+-ATPase β subunit level. H+/K+-ATPase upregulation in laryngeal epithelial cells in response to acidified pepsin was essential for the mitophagy-promoting effect of acidified pepsin. H+/K+-ATPase knockout or inhibition further reduced MMP in the presence of acidified pepsin. Conclusions: Our findings suggest that in an acidic environment, pepsin promotes laryngeal epithelial cell growth and survival by upregulating H+/K+-ATPase and activating mitophagy, potentially leading to laryngeal precancerosis.
The Clinical Value of Regional Lymphadenectomy for Intrahepatic Cholangiocarcinoma: Results of A Retrospective Cohort Study
Authors: YANG Facai , WU Changkang , CHEN Taian , DUAN Anqi , XU Jian , BO Zhiyuan , LI Jingdong , Qiu Yinghe , YI Bin
Published: December 2020

Objective: The aim of this study was to explore the clinical value of lymph node dissection (LND) for intrahepatic cholangiocarcinoma (ICC). Methods: Clinical and pathological data were collected from 147 ICC patients who attended two tertiary centers over the past 5 years. The patients were classified into two groups: the LND group (group A) and the no-performance LND (NLND) group (group B). Clinical and pathological parameters were compared between the two groups to analyze the impact of LND on the prognosis of ICC patients. Results: Of the 147 patients, 54.4% (80) received LND and 42.5% (34/80) of these were found to have lymph node metastasis (LNM) in postoperative pathological diagnosis. Patients undergoing LND usually have a larger surgical range, including hemihepatectomy and enlarged hemihepatectomy (P = 0.001). LND did not increase postoperative complications (27.5%, P = 0.354), but postoperative hospital stays were longer (12.2 ± 6.3 d, P = 0.005) in group A compared with group B (20.9%, 9.5 ± 3.5 d). The 5-year survival rates of groups A and B are almost similar (21% vs 29%, P=0.905). The overall survival rate of cN0 (diagnosis obtained by imaging) is better than pN1 (diagnosis obtained by histopathology), but lower than pN0. (all P < 0.05). Elevated CA19-9 level (HR = 1.764, 95% CI: 1.113 ~ 2.795 , P = 0.016), vascular invasion (HR = 2.697, 95% CI: 1.103 ~ 6.599, P = 0.030), and T staging (HR = 1.848, 95% CI: 1.059 ~ 3.224, P = 0.031) were independent risk factors for poor ICC prognosis (all P values > 0.05).Conclusion: ICC patients with cN0 may have LNM, and the prognosis of LNM patients is usually poor. Our data may support routine lymphadenectomy for ICC.
Association of Gravity Drainage and Complications Following Whipple: An Analysis of the ACS-NSQIP Targeted Database
Authors: BR Hall , Egr Zachary H , Krell Robert W , Padussis James C , Shostrom Valerie K , Are Chandrakanth , Reames Bradley N
Published: December 2020

Background: The optimal type of operative drainage following pancreaticoduodenectomy (PD) remains unclear. Our objective is to investigate risk associated with closed drainage techniques (passive [gravity] vs. suction) after PD.Methods: We assessed operative drainage techniques utilized in patients undergoing PD in the ACS-NSQIP Pancreas-Targeted database from 2016-2018. Using multivariable logistic regression to adjust for characteristics of the patient, procedure, and pancreas, we examined the association between use of gravity drainage and postoperative outcomes.Results: We identified 9,665 patients with drains following PD from 2016-2018, of which 12.7% received gravity drainage. 61.0% had a diagnosis of adenocarcinoma or pancreatitis, 26.5% had a duct <3 mm, and 43.5% had a soft or intermediate gland. After multivariable adjustment, gravity drainage was associated with decreased rates of postoperative pancreatic fistula (odds ratio [OR] 0.804, 95% Confidence Interval [CI] 0.659-0.981, P= 0.031), delayed gastric emptying (OR 0.830, 95%CI 0.693-0.988, P= 0.036), superficial SSI (OR: 0.741, 95% CI: 0.572-0.959, P=0.023), organ space SSI (OR: 0.791, 95% CI: 0.658-0.951, P=0.012), and readmission (OR: 0.807, 95% CI: 0.679-0.958, P=0.014) following PD.Conclusions: Gravity drainage is independently associated with decreased rates of CR-POPF, DGE, SSI, and readmission following PD. Additional prospective research will help determine which method is preferred.
Feeding Ecology and Host Preferences of Mosquitoes in two Zoological Gardens in the United Kingdom
Authors: Hernandez-Colina Arturo , Gonzalez-Olvera Merit , Lomax Emily , Townsend Freya , Maddox Amber , Hesson Jenny C. , Sherlock Kenneth , Ward Dawn , Eckley Lindsay , Lopez Javier , Baylis Matthew
Published: December 2020

Background: Zoological gardens contain unique configurations of exotic and endemic animals and plants that create a diverse range of developing sites and potential sources of blood meals for local mosquitoes. This may imply unusual interspecific pathogen transmission risks involving zoo animals, like avian malaria to captive penguins. Understanding mosquito ecology and host preferences is necessary to improve mosquito control and disease prevention measures in these environments. Methods: Mosquito sampling took place in Chester Zoo for three years (2017 to 2019) and for one year in Flamingo Land (2017) using different trapping methods. Blood-fed mosquitoes were identified and their bloodmeal was amplified by PCR, sequenced, and blasted for host species identification.Results: In total, 640 blood-fed mosquitoes were collected (Culex pipiens (n = 497), Culiseta annulata (n = 81), Anopheles maculipennis s.l. (n = 7), An. claviger (n = 1) and unidentifiable (n = 55)). Successful identification of the host species was achieved from 159 of the 640 blood-fed mosquitoes. Mosquitoes fed on birds (n = 74), non-human mammals (n = 20) and humans (n = 71). There were mixed bloodmeals from two hosts (n = 6). The proportions of blood-fed mosquitoes varied across sampling seasons and sites within the zoos. The use of resting traps and aspiration of vegetation were more efficient techniques for capturing blood-fed mosquitoes than traps for host-seeking or gravid mosquitoes. By relating the locations of zoo animals to where fed mosquitoes were trapped, the minimum travelling distances were calculated (13.7 to 366.7 meters). Temperature, precipitation, relative humidity, proximity to zoo animal exhibits and vegetation level were found to be significantly associated with the proportion of captured blood-fed mosquitoes by generalized linear modelling.Conclusions: Mosquito feeding behaviour in zoos is influenced by environmental variables and host availability, which highlights the value of mosquito monitoring in complex settings to plan control strategies and potentially reduce inherent disease transmission risks for humans and threatened zoo animals.