bluuebunny/crossref_metadata_2025_split huggingface dataset:
UBE2C triggers HIF‐1α‐glycolytic flux in head and neck squamous cell carcinoma
Authors: Yang Yi‐Fang , Chang Yu‐Chan , Tsai Kuo‐Wang , Hung Ming‐Hsin , Kang Bor‐Hwang 
Published: May 2022

AbstractHead and neck squamous cell carcinoma (HNSCC) is the most common malignancy in Taiwan. Therefore, refining the diagnostic sensitivity of biomarkers for early‐stage tumours and identifying therapeutic targets are critical for improving the survival rate of HNSCC patients. Metabolic reprogramming contributes to cancer development and progression. Metabolic pathways, specifically, play a crucial role in these diverse biological and pathological processes, which include cell proliferation, differentiation, apoptosis and carcinogenesis. Here, we investigated the role and potential prognostic value of the ubiquitin‐conjugating enzyme E2 (UBE2) family in HNSCC. Gene expression database analysis followed by tumour comparison with non‐tumour tissue showed that UBE2C was upregulated in tumours and was associated with lymph node metastasis in HNSCC patients. Knockdown of UBE2C significantly reduced the invasion/migration abilities of SAS and CAL27 cells. UBE2C modulates glycolysis pathway activation and HIF‐1α expression in SAS and CAL27 cells. CoCl2 (HIF‐1α inducer) treatment restored the expression of glycolytic enzymes and the migration/invasion abilities of UBE2C knockdown cells. Based on our findings, UBE2C expression mediates HIF‐1α activation, increasing glycolysis pathway activation and the invasion/migration abilities of cancer cells. UBE2C may be an independent prognostic factor and a therapeutic target in HNSCC.
Carbohydrate quantity is more closely associated with glycaemic control than weight in pregnant women with type 1 diabetes: Insights from the Diabetes and Pre‐eclampsia Intervention Trial (DAPIT)
Authors: Hill Alyson J. , Patterson C. C. , Young I. S. , Holmes V. A. , McCance D. R. 
Published: May 2022

AbstractBackgroundThe present study aimed to explore the relationships between carbohydrate intake, body mass index (BMI) and glycaemic control (HbA1c) in pregnant women with type 1 diabetes mellitus (T1DM)MethodsSecondary analysis of data was undertaken to assess dietary intake in a cohort of women who participated in a randomised controlled trial (RCT) of antioxidant supplementation to prevent preeclampsia (DAPIT10). Study‐specific peripheral venous blood samples were obtained for HbA1c at 26 and 34 weeks. Diet was collected using a validated semiquantitative food frequency questionnaire at 26–28 weeks of gestation which assessed dietary intake over 2 weeks. Mean daily average nutrient intakes were analysed using Q Builder nutritional software and SPSS, version 25.ResultsDietary data were available for 547 pregnant women (72% of cohort) aged 29 years (95% confidence interval [CI] = 28.9–29.9) with average diabetes duration 11.8 years (95% confidence interval = 11.1–12.6). Average body mass index (BMI) (<16 weeks of gestation) was 26.7 kg/m2 (95% CI = 26.3 −27, range 18.8–45.6 kg/m2); 43% (n = 234) were overweight (BMI = 25.0−29.9 kg/m2) and 20% (n = 112) were obese (BMI ≥ 30 kg/m2). Differences in HbA1c and carbohydrate quantity and quality were found when adjusted for age and insulin dose. No differences between BMI group were observed for total carbohydrate and glycaemic control; however, differences were noted in fibre and glycaemic index.ConclusionsAverage quantity of dietary carbohydrate influenced HbA1c when adjusted for insulin dose however, BMI had less impact. More research is required on the relationship between carbohydrate consumption and glycaemic control in pregnancy.
Disseminated intravascular coagulation complicated by amniotic band syndrome associated with deceased fetal umbilical cord following fetoscopic laser surgery
Authors: Ogoyama Manabu , Takahashi Hironori , Kagawa Keiko , Shimozawa Hironori , Yada Yukari , Wada Seiji , Sago Haruhiko , Fujiwara Hiroyuki 
Published: May 2022

AbstractFetoscopic laser surgery occasionally causes amniotic band syndrome, in which the disrupted amniotic membrane constricts fetal body parts, leading to functional or morphological loss. We report a case of fetal distress at 31 weeks of gestation in the larger surviving twin after fetoscopic laser surgery for selective intrauterine growth restriction, necessitating emergent cesarean section. Physical examination of the infant showed constriction rings caused by a disrupted amniotic membrane on the digits, and the distal part of the right index finger was necrotic because of tight strangulation by an amniotic band with the umbilical cord of the deceased smaller twin. Laboratory data showed severe coagulopathy, and the infant was diagnosed with disseminated intravascular coagulation (DIC). Immediate treatment improved his condition. DIC may have been associated with the necrotic finger, which was strangulated by the umbilical cord of the deceased fetus, because neither maternal coagulopathy nor an underlying neonatal disorder was detected.
L‐arginine stimulates the proliferation of mouse mammary epithelial cells and the development of mammary gland in pubertal mice by activating the GPRC6A/PI3K/AKT/mTOR signalling pathway
Authors: Ge Yusong , Li Feng , He Yuan , Cao Yu , Guo Wenjin , Hu Guiqiu , Liu Juxiong , Fu Shoupeng 
Published: May 2022

AbstractAmino acids have been shown to affect the development of mammary gland (MG). However, it is unclear whether L‐arginine promotes the development of pubertal MG. Therefore, our study aims to explore the effect of L‐arginine on the development of MG in pubertal mice. To investigate its internal mechanism of action, we will use mouse mammary epithelial cells (mMECs) line. Whole‐mount staining showed that L‐arginine can promote the extension of MG duct. In vitro, 0.4 mM L‐arginine could activate the G protein‐coupled receptor family C, group 6, subtype A (GPRC6A)/phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway and increase the phosphorylation of eukaryotic initiation factor 4E binding protein 1 (4EBP1) to promote the synthesis of cell cycle regulatory protein D1 (Cyclin D1), leading to the dissociation of the retinoblastoma tumour suppressor protein (Rb)‐E2F1 transcription factor (E2F1) complex in mMECs and releasing E2F1 to promote cell proliferation. Furthermore, GPRC6A was knocked down or inhibition of the PI3K/AKT/mTOR signalling pathway with corresponding inhibitors completely abolished the arginine‐induced promotion of mMECs proliferation. In vivo, it was further confirmed that 0.1% L‐arginine can activate the PI3K/AKT/mTOR signalling pathway in the MG of pubertal mice. These results were able to indicate that L‐arginine stimulates the development of MG in pubertal mice through the GPRC6A/PI3K/AKT/mTOR signalling pathway.
Influence of weaning management at 30, 75 and 180 days of age on non‐esterified fatty acids and reproductive performance in beef cows
Authors: Alforma Antónia Mendes Paizano , Pereira Gabriel Ribas , da Rocha Marcela Kuczynski , Teixeira Odilene de Souza , de Oliveira Maria Carolina Muniz , Lima Júlia Abud , Cumbe Télis Adolfo , Barcellos Júlio Otávio Jardim 
Published: May 2022

AbstractThis study aimed to investigate the effect of age at weaning of calves on non‐esterified fatty acids (NEFA) and reproductive parameters of beef cows. Animals (n = 65) were randomly assigned to three treatments after calving: hyper‐early weaning (W30) at 32 ± 0.89 days, early weaning (W75) at 77 ± 0.95 days, and conventional weaning (W180) at 183 ± 0.82 days. Body weight (BW) and body condition score (BCS) were evaluated at parturition (AP) and at 30, 45, 64, 81, 100 and 115 days postpartum (dPP). Blood samples were collected to analyze NEFA levels and progesterone (P4) at 30, 45, 64 and 81 dPP. Higher BW and BCS were observed from 64 to 115 dPP in W30 cows than W180 ones (p < 0.05). Cows subjected to W30 condition had higher levels of NEFA at 30 dPP compared to 64 and 81 dPP (p < 0.05). We also observed that cows from W180 group showed decreased levels of NEFA at 30 dPP compared to 45 (p < 0.01) and 64 dPP (p < 0.05). The highest P4 level was observed at 64 dPP in W30 cows compared to W75 and W180 (p < 0.05). We also observed higher CR of W30 (86%) compared to W180 (47%) at 45 dPP (p < 0.05). The overall pregnancy rate (PR) was higher for W30 (95.5%) than W180 (73.9%). In addition, higher BW at calving and P4 levels at 30 dPP were positively correlated with the possibility of pregnancy (p < 0.05). Improvement in BW and BCS were observed in cows subjected to hyper‐early weaning management. However, levels of NEFA decreased as the postpartum period progressed. We concluded that cows who weaned calves hyper‐early have greater chances of increasing cyclicity and PRs.
Effect of parity on non‐esterified fatty acid, oxidant/antioxidant status, and zinc and copper levels around periparturient period in Beetal goats of Himalayan Region
Authors: Singh Rajiv , Singh Virampal , Beigh Shafayat A. 
Published: May 2022

AbstractThe study was conducted to evaluate the effect of parity and physiological status on non‐esterified fatty acid (NEFA), oxidative stress, and zinc and copper levels among the Beetal breed of goat. Thirty dual‐purpose Beetal goats reared under the semi‐intensive system were selected and based on parity were divided into three groups with 10 animals each viz. Early parity (EP; ≤2 parity), mid parity (MP; 3–6 parity), and late parity (LP; ≥7 parity). Blood samples were collected 3 weeks and 1 week pre‐kidding followed by 1, 2, 4, and 8 weeks post‐kidding for the estimation of NEFA, oxidant (malondialdehyde [MDA], antioxidant (superoxide dismutase [SOD], catalase [CAT], glutathione [GSH], glutathione peroxidase [GSH‐Px], and glutathione S‐transferase [GST]), and zinc and copper levels. Significant (p < 0.01) increase was observed in NEFA and MDA levels as the goats approached kidding and continued till 2 weeks post‐kidding in MP and LP and 1 week post‐kidding in EP goats. Significant decrease in SOD (p < 0.05), CAT (p < 0.05), GSH‐Px (p < 0.01), GSH (p < 0.01), and GST (p < 0.05) activities were observed as goats approached kidding and continued to decrease up to 2 weeks post‐kidding. Zinc and copper levels showed a significant decline from 3 weeks pre‐kidding to 2 weeks post‐kidding in MP and LP and 1 week post‐kidding in EP goats. A significant effect of parity was observed on MDA (p < 0.05), GSH (p < 0.05), and GSH‐Px (p < 0.05) activities only; however, parity × sampling time interaction was observed in all the parameters. Findings highlight a different metabolic, trace mineral (zinc and copper), and oxidative response around the periparturient period in Beetal goats, with the EP goats, responding first to increased metabolic and oxidative stress and also first to recover from oxidant/antioxidant imbalance.
Pharmacokinetics of isavuconazole in healthy cats after oral and intravenous administration
Authors: Woerde Dennis J. , Wittenburg Luke A. , Dear Jonathan D. 
Published: May 2022

AbstractBackgroundIsavuconazole is a triazole antifungal drug that has shown good efficacy in human patients. Absorption and pharmacokinetics have not been evaluated in cats.ObjectivesTo determine the pharmacokinetics of isavuconazole in cats given a single IV or PO dose.AnimalsEight healthy, adult research cats.MethodsFour cats received 100 mg capsules of isavuconazole PO. Four cats received 5 mg/kg isavuconazole solution IV. Serum was collected at predetermined intervals for analysis using ultra‐high performance liquid chromatography‐tandem mass spectrometry. Data were analyzed using a 2‐compartment uniform weighting pharmacokinetic analysis with lag time for PO administration and a 2 compartment, 1/y2 weighting for IV administration. Predicted 24 and 48‐hour dosing intervals of 100 mg isavuconazole administered PO were modeled and in vitro plasma protein binding was assessed.ResultsBoth PO and IV drug administration resulted in high serum concentrations. Intravenous and PO formulations of isavuconazole appear to be able to be used interchangeably. Peak serum isavuconazole concentrations occurred 5 ± 3.8 hours after PO administration with an elimination rate half‐life of 66.2 ± 55.3 hours. Intersubject variability was apparent in both the PO and IV groups. Two cats vomited 6 to 8 hours after PO administration. No adverse effects were observed in the IV group. Oral bioavailability was estimated to be approximately 88%. Serum protein binding was calculated to be approximately 99.0% ± 0.03%.Conclusions and Clinical ImportanceIsavuconazole might prove to be useful in cats with fungal disease given its favorable pharmacokinetics. Additional studies on safety, efficacy, and tolerability of long‐term isavuconazole use are needed.
Characterization of a small tRNA‐binding protein that interacts with the archaeal proteasome complex
Authors: Hogrel Gaëlle , Marino‐Puertas Laura , Laurent Sébastien , Ibrahim Ziad , Covès Jacques , Girard Eric , Gabel Frank , Fenel Daphna , Daugeron Marie‐Claire , Clouet‐d'Orval Béatrice , Basta Tamara , Flament Didier , Franzetti Bruno 
Published: May 2022

AbstractThe proteasome system allows the elimination of functional or structurally impaired proteins. This includes the degradation of nascent peptides. In Archaea, how the proteasome complex interacts with the translational machinery remains to be described. Here, we characterized a small orphan protein, Q9UZY3 (UniProt ID), conserved in Thermococcales. The protein was identified in native pull‐down experiments using the proteasome regulatory complex (proteasome‐activating nucleotidase [PAN]) as bait. X‐ray crystallography and small‐angle X‐ray scattering experiments revealed that the protein is monomeric and adopts a β‐barrel core structure with an oligonucleotide/oligosaccharide‐binding (OB)‐fold, typically found in translation elongation factors. Mobility shift experiment showed that Q9UZY3 displays transfer ribonucleic acid (tRNA)‐binding properties. Pull‐downs, co‐immunoprecipitation and isothermal titration calorimetry (ITC) studies revealed that Q9UZY3 interacts in vitro with PAN. Native pull‐downs and proteomic analysis using different versions of Q9UZY3 showed that the protein interacts with the assembled PAN–20S proteasome machinery in Pyrococcus abyssi (Pa) cellular extracts. The protein was therefore named Pbp11, for Proteasome‐Binding Protein of 11 kDa. Interestingly, the interaction network of Pbp11 also includes ribosomal proteins, tRNA‐processing enzymes and exosome subunits dependent on Pbp11's N‐terminal domain that was found to be essential for tRNA binding. Together these data suggest that Pbp11 participates in an interface between the proteasome and the translational machinery.
No Evidence of Induced Skin Cancer or Other Skin Abnormalities after Long‐Term (66 week) Chronic Exposure to 222‐nm Far‐UVC Radiation
Authors: Welch David , Kleiman Norman J. , Arden Peter C. , Kuryla Christine L. , Buonanno Manuela , Ponnaiya Brian , Wu Xuefeng , Brenner David J. 
Published: May 2022

AbstractFar‐UVC radiation, typically defined as 200–235 nm, has similar or greater anti‐microbial efficacy compared with conventional 254‐nm germicidal radiation. In addition, biophysical considerations of the interaction of far‐UVC with tissue, as well as multiple short‐term safety studies in animal models and humans, suggest that far‐UVC exposure may be safe for skin and eye tissue. Nevertheless, the potential for skin cancer after chronic long‐term exposure to far‐UVC has not been studied. Here, we assessed far‐UVC induced carcinogenic skin changes and other pathological dermal abnormalities in 96 SKH‐1 hairless mice of both sexes that were exposed to average daily dorsal skin doses of 400, 130 or 55 mJ cm−2 of 222 nm far‐UVC radiation for 66 weeks, 5 days per week, 8 h per day, as well as similarly‐treated unexposed controls. No evidence for increased skin cancer, abnormal skin growths or incidental skin pathology findings was observed in the far‐UVC‐exposed mice. In addition, there were no significant changes in morbidity or mortality. The findings from this study support the long‐term safety of long‐term chronic exposure to far‐UVC radiation, and therefore its potential suitability as a practical anti‐microbial approach to reduce airborne viral and bacterial loads in occupied indoor settings.
Beyond polarization and priming: Public agenda diversity and trust in government
Authors: Meirick Patrick C. , Edy Jill A. 
Published: May 2022

AbstractObjectiveThe study set out to examine how diversity and volatility in the public's issue agenda are related to trust in government and congressional approval.MethodData from 1975 through 2014 for public agenda issue concerns, agenda diversity, agenda volatility, congressional polarization, trust in government, and congressional approval were transformed into a quarterly time series and analyzed with ridge regression.ResultsA more diverse public agenda is associated with less trust in government. When agenda volatility is higher, congressional approval is higher, perhaps because the government is perceived as dealing effectively with public problems —or perhaps because the public is distracted. Diversity and volatility interact: When many evenly matched issues are on a public agenda that is turning over quickly, congressional approval is higher than when a similarly diverse agenda is stagnant.ConclusionThe American public's evaluations of government are affected not only by the issue content of the public agenda but also by the character of the public agenda.
Pig‐to‐human kidney transplantation using brain‐dead donors as recipients: One giant leap, or only one small step for transplantkind?
Authors: Ganchiku Yoshikazu , Riella Leonardo V. 
Published: May 2022

AbstractPig kidney xenotransplantation is increasingly regarded as a realistic solution to the current shortage of human organ donors for patients with end‐stage organ failure. Recently, the news of three pig‐to‐human transplantation cases has awakened public interest. Notably, the case by the Alabama team reported detailed and important findings for the xenotransplantation field. Using a genetically modified pig, two porcine kidneys were transplanted into a brain‐dead recipient. They applied several approaches established in the preclinical NHP study, including gene‐edited pig kidney graft and preoperative laboratory inspection such as crossmatching and infection screening. The pig‐to‐human kidney xenotransplantation had no unexpected events during surgery or evidence of hyperacute rejection. Unfortunately, the grafts did not work appropriately, and the study had to be terminated due to the decompensation of the recipient. While this study demonstrated the outstanding achievement in this research area, it also revealed remaining gaps to move xenotransplantation to the clinic. While brain‐dead human recipients could reinforce the compatibility achievements of gene‐edited pigs in NHP, their pro‐inflammatory and pro‐coagulant environment, in combination with short‐duration of experiments will limit the assessment of kidney function, infection and rejection risk post‐transplant, in particular antibody‐mediated rejection. The use of successful immunosuppressive protocols of non‐human primates xenotransplant experiments including anti‐CD154 antibody will be critical to maximize the success in the first in‐human trials.
Addition of a Cognitive Task During Walking Alters Lower Body Muscle Activity
Authors: Vienneau Jordyn , Nigg Sandro , Nigg Benno M. 
Published: May 2022

This study compared electromyography of five leg muscles during a single walking task (WALK) to a dual task (walking + cognitive task; COG) in 40 individuals (20 M and 20 F) using a wavelet analysis technique. It was hypothesized that muscle activation during the dual task would differ significantly from the walking task with respect to both timing (H1) and frequency (H2). The mean overall intensity for the COG trials was 4.1% lower for the tibialis anterior and 5.5% higher for the gastrocnemius medialis than in the WALK trials. The changes between the WALK and COG trials were short 50 ms bursts that occurred within 100 ms of heel strike in the tibialis anterior, and longer activation periods during the stance phase in the gastrocnemius medialis. No changes in overall intensity were observed in the peroneus longus, gastrocnemius lateralis, or soleus. Furthermore, no clear frequency bands within the signal could further characterize the overall changes in muscle activity during the COG task. This advances our understanding of how the division of attentional resources affects muscle activity in a healthy population of adults.
Efficacy of pembrolizumab in patients with advanced cancer of unknown primary (CUP): a phase 2 non-randomized clinical trial
Authors: Raghav Kanwal P , Stephen Bettzy , Karp Daniel D , Piha-Paul Sarina A , Hong David S , Jain Dipti , Chudy Onwugaje Dilichukwu O , Abonofal Abdulrahman , Willett Anneleis F , Overman Michael , Smaglo Brandon , Huey Ryan W , Meric-Bernstam Funda , Varadhachary Gauri R , Naing Aung 
Published: May 2022

BackgroundCancer of unknown primary (CUP) is an aggressive rare malignancy with limited treatment options. Data regarding clinical activity of immune checkpoint inhibitors in CUP is lacking. Therefore, we evaluated the efficacy of pembrolizumab, a programmed cell death-1 inhibitor, in patients with CUP.MethodsThe study was designed as a phase 2 basket trial for independent rare tumor cohorts including CUP. Adult patients with CUP who had progressed on previous systemic therapy, performance status 0/1 and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST V.1.1) were eligible. Patients received pembrolizumab (200 mg) intravenously every 21 days. Twenty-nine patients were enrolled and treated between August 2016 and June 2020. The primary endpoint was non-progression rate (NPR) at 27 weeks (NPR-27) per immune-related RECIST. Key prespecified secondary endpoints were confirmed objective response rate (ORR), safety, duration of response (DoR), progression-free survival (PFS) and overall survival (OS). Pretreatment biopsies were examined for biomarkers of response (programmed cell death ligand-1 (PD-L1) expression and tumor infiltrating lymphocytes (TILs)).ResultsAmong 25 (of 29 enrolled) eligible and evaluable patients, 14 (56%) had poorly differentiated carcinoma. Patients received a median of two lines of therapy prior to enrollment. Median follow-up was 27.3 months. NPR-27 was observed in seven patients (28.0% (95% CI: 12.1 to 49.4)). ORR was 20.0% (95% CI: 6.8 to 40.7) with five patients achieving immune-related partial response with median DoR of 14.7 months (95% CI: 9.8 to 19.6). Median PFS and OS were 4.1 (95% CI: 3.1 to 5.1) and 11.3 (95% CI: 5.5 to 17.1) months, respectively. Treatment-related adverse events of any and grade ≥3 were seen in 19 (76%) and 4 (16%) patients, respectively. One (4%) patient had grade 3 immune-related acute kidney injury requiring treatment discontinuation. Neither PD-L1 nor TILs were associated with NPR-27. Both positive PD-L1 staining (44.4% vs 6.3%; p=0.040) and intense TIL infiltration (44.4% vs 6.3%; p=0.040) were associated with response.ConclusionPembrolizumab showed encouraging efficacy in patients with CUP with acceptable safety profile.Trial registration numberNCT02721732.