bluuebunny/crossref_metadata_2025_split huggingface dataset:
CFTR promotes malignant glioma development via up‐regulation of Akt/Bcl2‐mediated anti‐apoptosis pathway
Authors: Zhao Mingyue , Zhang Jieting , Huang Wenqing , Dong Jianda , Guo Jinghui , U Kin Pong , Weng ZhiHui , Liu Si , Chan Hsiao Chang , Feng Hua , Jiang Xiaohua 
Published: May 2020

AbstractCystic fibrosis transmembrane conductance regulator (CFTR), a cAMP‐activated Cl‐ channel, is extensively expressed in the epithelial cells of various tissues and organs. Accumulating evidence indicates that aberrant expression or mutation of CFTR is related to carcinoma development. Malignant gliomas are the most common and aggressive intracranial tumours; however, the role of CFTR in the development of malignant gliomas is unclear. Here, we report that CFTR is expressed in malignant glioma cell lines. Suppression of CFTR channel function or knockdown of CFTR suppresses glioma cell viability whereas overexpression of CFTR promotes it. Additionally, overexpression of CFTR suppresses apoptosis and promotes glioma progression in both subcutaneous and orthotopic xenograft models. Cystic fibrosis transmembrane conductance regulator activates Akt/Bcl2 pathway, and suppression of PI3K/Akt pathway abolishes CFTR overexpression–induced up‐regulation of Bcl2 (MK‐2206 and LY294002) and cell viability (MK‐2206). More importantly, the protein expression level of CFTR is significantly increased in glioblastoma patient samples. Altogether, our study has revealed a mechanism by which CFTR promotes glioma progression via up‐regulation of Akt/Bcl2‐mediated anti‐apoptotic pathway, which warrants future studies into the potential of using CFTR as a therapeutic target for glioma treatment.
Clostridium perfringens epsilon toxin binds to erythrocyte MAL receptors and triggers phosphatidylserine exposure
Authors: Geng Zhijun , Huang Jing , Kang Lin , Gao Shan , Yuan Yuan , Li Yanwei , Wang Jing , Xin Wenwen , Wang Jinglin 
Published: May 2020

AbstractEpsilon toxin (ETX) is a 33‐kDa pore‐forming toxin produced by type B and D strains of Clostridium perfringens. We previously found that ETX caused haemolysis of human red blood cells, but not of erythrocytes from other species. The cellular and molecular mechanisms of ETX‐mediated haemolysis are not well understood. Here, we investigated the effects of ETX on erythrocyte volume and the role of the putative myelin and lymphocyte (MAL) receptors in ETX‐mediated haemolysis. We observed that ETX initially decreased erythrocyte size, followed by a gradual increase in volume until lysis. Moreover, ETX triggered phosphatidylserine (PS) exposure and enhanced ceramide abundance in erythrocytes. Cell shrinkage, PS exposure and enhanced ceramide abundance were preceded by increases in intracellular Ca2+ concentration. Interestingly, lentivirus‐mediated RNA interference studies in the human erythroleukaemia cell line (HEL) cells confirmed that MAL contributes to ETX‐induced cytotoxicity. Additionally, ETX was shown to bind to MAL in vitro. The results of this study recommend that ETX‐mediated haemolysis is associated with MAL receptor activation in human erythrocytes. These data imply that interventions affecting local MAL‐mediated autocrine and paracrine signalling may prevent ETX‐mediated erythrocyte damage.
Combined microwaves and fractional microablative CO2 laser treatment for postpartum abdominal laxity
Authors: Bonan Paolo , Verdelli Alice 
Published: May 2020

AbstractBackgroundPostpartum abdominal changes represent a major esthetic concern affecting women. As the abdomen stretches during pregnancy and some of the muscles lose tone, there is an increased skin laxity and a loss of abdominal elasticity. As a result, the abdomen becomes saggy.AimsTo evaluate the performance of a combined microwaves and fractional microablative CO2 laser treatment for reshaping and improvement of abdomen texture/laxity and striae distensae in postpartum women.Patients/MethodsFifteen women (median age 38 years) received three monthly abdomen treatments with a new microwaves platform, the ONDA Coolwaves® (DEKA) system, followed by a treatment with fractional microablative CO2 laser (SmartXide2; DEKA) a month thereafter. We followed up each patient's weight and nutritional habits. Outcome was assessed using reproducible circumference and abdominal measurements, digital and 3D photography, the laxity score as well as patient satisfaction index.ResultsThe overall mean circumferences reduction was 3.6 ± 1.2 cm. Significant improvement in skin laxity and tightening was noted by physicians and patients as well as a reduction of striae distensae. Interestingly, as a result of skin remodeling, repositioning of the umbilicus was also demonstrated. Treatments were well tolerated with no side effects.ConclusionsOur data showed a sustainable reduction in circumference and improvement in appearance of abdomen in postpartum women, without compromising patients' safety.
Freezing, Melting, and Light Stress on the Photophysiology of Ice Algae: Ex Situ Incubation of the Ice Algal diatom Fragilariopsis cylindrus (Bacillariophyceae) Using an Ice Tank
Authors: Yoshida Kazuhiro , Seger Andreas , Kennedy Fraser , McMinn Andrew , Suzuki Koji 
Published: May 2020

Sea ice algae contribute up to 25% of the primary productivity of polar seas and seed large‐scale ice‐edge blooms. Fluctuations in temperature, salinity, and light associated with the freeze/thaw cycle can significantly impact the photophysiology of ice‐associated taxa. The effects of multiple co‐stressors (i.e., freezing temperature and high brine salinity or sudden high light exposure) on the photophysiology of ice algae were investigated in a series of ice tank experiments with the polar diatom Fragilariopsis cylindrus under different light intensities. When algal cells were frozen into the ice, the maximum quantum yield of photosystem II photochemistry (PSII; Fv/Fm) decreased possibly due to the damage of PSII reaction centers and/or high brine salinity stress suppressing the reduction capacity downstream of PSII. Expression of the rbcL gene was highly up‐regulated, suggesting that cells initiated strategies to enhance survival upon freezing in. Algae contained within the ice‐matrix displayed similar levels of Fv/Fm regardless of the light treatments. Upon melting out, cells were exposed to high light (800 μmol photons · m−2 · s−1), resulting in a rapid decline in Fv/Fm and significant up‐regulation of non‐photochemical quenching (NPQ). These results suggest that ice algae employed safety valves (i.e., NPQ) to maintain their photosynthetic capability during the sudden environmental changes. Our results infer that sea ice algae are highly adaptable when exposed to multiple co‐stressors and that their success can, in part, be explained by the ability to rapidly modify their photosynthetic competence – a key factor contributing to algal bloom formation in the polar seas.
Multicentre, phase II study of gemcitabine and S‐1 in patients with advanced biliary tract cancer: TG1308 study
Authors: Chiang Nai‐Jung , Chen Ming‐Huang , Yang Shih‐Hung , Hsu Chiun , Yen Chia‐Jui , Tsou Hsiao‐Hui , Su Yung‐Yeh , Chen Jen‐Shi , Shan Yan‐Shen , Chen Li‐Tzong 
Published: May 2020

AbstractBackground & AimsGemcitabine plus cisplatin (GC) remains the standard, frontline therapy for advanced biliary tract cancer (ABTC). The JCOG1113 study suggested that gemcitabine plus S‐1 (GS) had noninferior median overall survival and comparable incidence of significant neutropenia as compared to GC treatments. This study evaluates the efficacy and safety of a modified GS regimen.MethodsThe eligible patients with chemonaive, measurable ABTC received 800 mg/m2 of gemcitabine on day 1 and 80 mg/m2/day of S‐1 (80/100/120 mg for patients with body surface <1.25/ ≥1.25 and <1.5/ ≥1.5 m2 respectively). The primary endpoint was the 12‐week disease control rate (12‐week DCR: objective response and stable disease ≥ 12 weeks). Per the p0 = 40% and p1 = 60% (α/β = 0.05/0.2) assumption, Simon's optimal two‐stage design indicated 12‐week DCR in ≥ 24 of 46 evaluable patients for significant activity. Tumour responses were assessed every 6 weeks.ResultsFifty‐one patients were enrolled and most of them had intrahepatic cholangiocarcinoma (64.7%), metastatic disease (84.3%) and disease‐related symptoms (82.4%). On intention‐to‐treat analysis, 11 (21.6%) patients showed partial response, whereas 21 (41.2%) showed stable disease ≥ 12 weeks. The progression‐free and overall survival were 5.4 months (95% confidence interval [CI]: 3.5‐7.0), and 12.7 months (95% CI: 6.1‐15.6) respectively. The study met its primary endpoint with a 12‐week DCR of 69.6% in 46 evaluable patients. Grade 3/4 treatment‐related adverse eventsoccurred in < 6% of patients of all individual items. The mean dose intensities of S‐1 and gemcitabine were 87.1% and 92.5% respectively.ConclusionsModified GS showed moderate efficacy with a favourable safety profile in ABTC patients, thus mandating further assessment.ClinicalTrials.gov number: NCT02425137.
Neuropathological and biochemical investigation of Hereditary Ferritinopathy cases with ferritin light chain mutation: Prominent protein aggregation in the absence of major mitochondrial or oxidative stress
Authors: Kurzawa‐Akanbi M. , Keogh M. , Tsefou E. , Ramsay L. , Johnson M. , Keers S. , WSA Ochieng L. , McNair A. , Singh P. , Khan A. , Pyle A. , Hudson G. , Ince P. G. , Attems J. , Burn J. , Chinnery P. F. , Morris C. M. 
Published: May 2020

AimsNeuroferritinopathy (NF) or hereditary ferritinopathy (HF) is an autosomal dominant movement disorder due to mutation in the light chain of the iron storage protein ferritin (FTL). HF is the only late‐onset neurodegeneration with brain iron accumulation disorder and study of HF offers a unique opportunity to understand the role of iron in more common neurodegenerative syndromes.MethodsWe carried out pathological and biochemical studies of six individuals with the same pathogenic FTL mutation.ResultsCNS pathological changes were most prominent in the basal ganglia and cerebellar dentate, echoing the normal pattern of brain iron accumulation. Accumulation of ferritin and iron was conspicuous in cells with a phenotype suggesting oligodendrocytes, with accompanying neuronal pathology and neuronal loss. Neurons still survived, however, despite extensive adjacent glial iron deposition, suggesting neuronal loss is a downstream event. Typical age‐related neurodegenerative pathology was not normally present. Uniquely, the extensive aggregates of ubiquitinated ferritin identified indicate that abnormal FTL can aggregate, reflecting the intrinsic ability of FTL to self‐assemble. Ferritin aggregates were seen in neuronal and glial nuclei showing parallels with Huntington’s disease. There was neither evidence of oxidative stress activation nor any significant mitochondrial pathology in the affected basal ganglia.ConclusionsHF shows hallmarks of a protein aggregation disorder, in addition to iron accumulation. Degeneration in HF is not accompanied by age‐related neurodegenerative pathology and the lack of evidence of oxidative stress and mitochondrial damage suggests that these are not key mediators of neurodegeneration in HF, casting light on other neurodegenerative diseases characterized by iron deposition.
NRT2.1 C‐terminus phosphorylation prevents root high affinity nitrate uptake activity in Arabidopsis thaliana
Authors: Jacquot Aurore , Chaput Valentin , Mauries Adeline , Li Zhi , Tillard Pascal , Fizames Cécile , Bonillo Pauline , Bellegarde Fanny , Laugier Edith , Santoni Véronique , Hem Sonia , Martin Antoine , Gojon Alain , Schulze Waltraud , Lejay Laurence 
Published: May 2020

Summary

In Arabidopsis thaliana, NRT2.1 codes for a main component of the root nitrate high‐affinity transport system. Previous studies revealed that post‐translational regulation of NRT2.1 plays an important role in the control of root nitrate uptake and that one mechanism could correspond to NRT2.1 C‐terminus processing.

To further investigate this hypothesis, we produced transgenic plants with truncated forms of NRT2.1. This revealed an essential sequence for NRT2.1 activity, located between the residues 494 and 513.

Using a phospho‐proteomic approach, we found that this sequence contains one phosphorylation site, at serine 501, which can inactivate NRT2.1 function when mimicking the constitutive phosphorylation of this residue in transgenic plants. This phenotype could neither be explained by changes in abundance of NRT2.1 and NAR2.1, a partner protein of NRT2.1, nor by a lack of interaction between these two proteins.

Finally, the relative level of serine 501 phosphorylation was found to be increased by ammonium nitrate in wild‐type plants, leading to the inactivation of NRT2.1 and to a decrease in high affinity nitrate transport into roots. Altogether, these observations reveal a new and essential mechanism for the regulation of NRT2.1 activity.
Salt stress and fluctuating light have separate effects on photosynthetic acclimation, but interactively affect biomass
Authors: Zhang Yuqi , Kaiser Elias , Marcelis Leo F. M. , Yang Qichang , Li Tao 
Published: May 2020

AbstractIn nature, soil salinity and fluctuating light (FL) often occur concomitantly. However, it is unknown whether salt stress interacts with FL on leaf photosynthesis, architecture, biochemistry, pigmentation, mineral concentrations, as well as whole‐plant biomass. To elucidate this, tomato (Solanum lycopersicum) seedlings were grown under constant light (C, 200 μmol m−2 s−1) or FL (5–650 μmol m−2 s−1), in combination with no (0 mM NaCl) or moderate (80 mM NaCl) salinity, for 14 days, at identical photoperiods and daily light integrals. FL and salt stress had separate effects on leaf anatomy, biochemistry and photosynthetic capacity: FL reduced leaf thickness as well as nitrogen, chlorophyll and carotenoid contents per unit leaf area, but rarely affected steady‐state and dynamic photosynthetic properties along with abundance of key proteins in the electron transport chain. Salt stress, meanwhile, mainly disorganized chloroplast grana stacking, reduced stomatal density, size and aperture as well as photosynthetic capacity. Plant biomass was affected interactively by light regime and salt stress: FL reduced biomass in salt stressed plants by 17%, but it did not affect biomass of non‐stressed plants. Our results stress the importance of considering FL when inferring effects of salt‐stress on photosynthesis and productivity under fluctuating light intensities.
Effectiveness of a paraverterbral nerve block versus local portal blocks for laparoscopic closure of the nephrosplenic space: A pilot study
Authors: Delli‐Rocili Massimo M. , Cribb Nicola C. , Trout Donald R. , Thomason Jeffrey J. , Valverde Alexander 
Published: May 2020

AbstractObjectiveTo compare the effectiveness of a paravertebral nerve block vs local portal blocks for laparoscopic closure of the nephrosplenic space in standing sedated research horses.Study designRandomized clinical trial.AnimalsTwelve horses were randomly allocated to two groups (n= 6 per group), paravertebral block of nerves T18, L1, and L2or local blocks of the three laparoscopic portals.MethodsHorses were sedated with dexmedetomidine (4 μg/kg IV and constant rate infusion [CRI] of 2.5 μg/kg/h) and morphine (50 μg/kg IV and CRI of 30 μg/kg/h). According to group allocation, 20 mL of either lidocaine or saline was injected into each paravertebral nerve site or into each local portal site to facilitate laparoscopy for closure of the nephrosplenic space. The overall quality of sedation, analgesia, behavior exhibited during surgery, and ease to perform the surgery were blindly scored by using a visual analog scale (VAS).ResultsTime to complete local anesthesia was similar for both blocks, and there was no difference in VAS scores between groups. Total duration of surgery was also similar between the paravertebral (79 ± 16 min) and local portal blocks (85 ± 25 min) groups.ConclusionThe paravertebral nerve block and the local portal blocks provided similar conditions during surgery and can be used interchangeably for closure of the nephrosplenic space.Clinical significanceThe paravertebral nerve block can be readily performed and may be useful in surgical procedures.
Prognostic indicators for in-hospital mortality in COPD with acute exacerbation in Thailand: a retrospective cohort study
Authors: Morasert Thotsaporn , Jantarapootirat Methus , Phinyo Phichayut , Patumanond Jayanton 
Published: May 2020

BackgroundAcute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common and deteriorating event leading to in-hospital morbidity and mortality. Identification of predictors for in-hospital mortality of AECOPD patients could aid clinicians in identifying patients with a higher risk of death during their hospitalisation.ObjectiveTo explore potential prognostic indicators associated with in-hospital mortality of AECOPD patients.SettingGeneral medical ward and medical intensive care unit of a university-affiliated tertiary care centre.MethodsA prognostic factor research was conducted with a retrospective cohort design. All admission records of AECOPD patients between October 2015 and September 2016 were retrieved. Stratified Cox’s regression was used for the primary analysis.ResultsA total of 516 admission records of 358 AECOPD patients were included in this study. The in-hospital mortality rate of the cohort was 1.9 per 100 person-day. From stratified Cox’s proportional hazard regression, the predictors of in-hospital mortality were aged 80 years or more (HR=2.16, 95% CI: 1.26 to 3.72, p=0.005), respiratory failure on admission (HR=2.50, 95% CI: 1.12 to 5.57, p=0.025), body temperature more than 38°C (HR=2.97, 95% CI: 1.61 to 5.51, p=0.001), mean arterial pressure lower than 65 mm Hg (HR=4.01, 95% CI: 1.88 to 8.60, p<0.001), white blood cell count more than 15 x 109/L (HR=3.51, 95% CI: 1.90 to 6.48, p<0.001) and serum creatinine more than 1.5 mg/dL (HR=2.08, 95% CI: 1.17 to 3.70, p=0.013).ConclusionSix independent prognostic indicators for in-hospital mortality of AECOPD patients were identified. All of the parameters were readily available in routine practice and can be used as an aid for risk stratification of AECOPD patients.
Spondylodiscitis complicating infective endocarditis
Authors: Carbone Andreina , Lieu Audrey , Mouhat Basile , Santelli Francesco , Philip Mary , Bohbot Yohann , Tessonnier Laetitia , Peugnet Fanny , D'Andrea Antonello , Cammilleri Serge , Delpierre Quentin , Gouriet Frédérique , Camoin-Jau Laurence , Gun Mesut , Casalta Jean-Paul , Riberi Alberto , Collart Frederic , Martel Hélène , Arregle Florent , Guedj Eric , Raoult Didier , Drancourt Michel , Tribouilloy Christophe , Habib Gilbert 
Published: May 2020

ObjectiveThe primary objective was to assess the characteristics and prognosis of pyogenic spondylodiscitis (PS) in patients with infective endocarditis (IE). The secondary objectives were to assess the factors associated with occurrence of PS.MethodsProspective case–control bi-centre study of 1755 patients with definite IE with (n=150) or without (n=1605) PS. Clinical, microbiological and prognostic variables were recorded.ResultsPatients with PS were older (mean age 69.7±18 vs 66.2±14; p=0.004) and had more arterial hypertension (48% vs 34.5%; p<0.001) and autoimmune disease (5% vs 2%; p=0.03) than patients without PS. The lumbar vertebrae were the most frequently involved (84 patients, 66%), especially L4–L5. Neurological symptoms were observed in 59% of patients. Enterococci and Streptococcus gallolyticus were more frequent (24% vs 12% and 24% vs 11%; p<0001, respectively) in the PS group. The diagnosis of PS was based on contrast-enhanced MRI in 92 patients, bone CT in 88 patients and 18F-FDG PET/CT in 56 patients. In-hospital (16% vs 13.5%, p=0.38) and 1-year (21% vs 22%, p=0.82) mortalities did not differ between patients with or without PS.ConclusionsPS is a frequent complication of IE (8.5% of IE), is observed in older hypertensive patients with enterococcal or S. gallolyticus IE, and has a similar prognosis than other forms of IE. Since PS is associated with specific management, multimodality imaging including MRI, CT and PET/CT should be used for early diagnosis of this complication of endocarditis.
The scale factor potential approach to inflation
Authors: Benisty David , Guendelman Eduardo I. , Saridakis Emmanuel N. 
Published: May 2020

AbstractWe propose a new approach to investigate inflation in a model-independent way, and in particular to elaborate the involved observables, through the introduction of the “scale factor potential”. Through its use one can immediately determine the inflation end, which corresponds to its first (and global) minimum. Additionally, we express the inflationary observables in terms of its logarithm, using as independent variable the e-folding number. As an example, we construct a new class of scalar potentials that can lead to the desired spectral index and tensor-to-scalar ratio, namely $$n_s \approx 0.965$$ns≈0.965 and $$r \sim 10^{-4}$$r∼10-4 for 60 e-folds, in agreement with observations.
Telomere DNA Damage Signaling Regulates Prostate Cancer Tumorigenesis
Authors: Wu Jianchun , Crowe David L. 
Published: May 2020

AbstractTelomere shortening has been demonstrated in benign prostatic hypertrophy (BPH), which is associated with prostate epithelial cell senescence. Telomere shortening is the most frequently observed genetic alteration in prostatic intraepithelial neoplasia, and is associated with poor clinical outcomes in prostate cancer. Gene expression database analysis revealed decreased TRF2 expression during malignant progression of the prostate gland. We reasoned that reduced TRF2 expression in prostate epithelium, by activating the telomere DNA damage response, would allow us to model both benign and malignant prostate disease. Prostate glands with reduced epithelial TRF2 expression developed age- and p53-dependent hypertrophy, senescence, ductal dilation, and smooth muscle hyperplasia similar to human BPH. Prostate tumors with reduced TRF2 expression were classified as high-grade androgen receptor–negative adenocarcinomas, which exhibited decreased latency, increased proliferation, and distant metastases. Prostate cancer stem cells with reduced TRF2 expression were highly tumorigenic and maintained telomeres both by telomerase and alternative lengthening (ALT). Telomerase inhibition in prostate glands with reduced TRF2 expression produced significant reduction in prostate tumor incidence by halting progression at intraepithelial neoplasia (PIN). These lesions were highly differentiated, exhibited low proliferation index, and high apoptotic cell fraction. Prostate tumors with reduced TRF2 expression and telomerase inhibition failed to metastasize and did not exhibit ALT.Implications:Our results demonstrate that the telomere DNA damage response regulates BPH, PIN, and prostate cancer and may be therapeutically manipulated to prevent prostate cancer progression.