bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Background & Aims

Gemcitabine 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.

Methods

The 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.

Results

Fifty‐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.

Conclusions

Modified GS showed moderate efficacy with a favourable safety profile in ABTC patients, thus mandating further assessment.

ClinicalTrials.gov number: NCT02425137.
Becoming a physician involves learning to manage uncertainty and learning how to fail
Authors: Weurlander Maria
Published: May 2020

Management of uncertainty and failure are key health professional education competencies. To enable them Weurlander argues we need safe space and deliberate reflection on the realities of practice.
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

Aims

Neuroferritinopathy (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.

Methods

We carried out pathological and biochemical studies of six individuals with the same pathogenic FTL mutation.

Results

CNS 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.

Conclusions

HF 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

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

In 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.
The decline of FANCM immunohistochemical expression in prostate cancer stroma correlates with the grade group
Authors: Dzaparidze Georgi , Anion Evelin , Laan Maris , Minajeva Ave
Published: May 2020

Prostate adenocarcinoma (PCa) stromal markers have recently gained attention as complementary diagnostic tools. The DNA reparation complex protein FANCM has been shown to express in the normal prostate stroma and FANCM gene alterations to be associated with PCa susceptibility; this has led to the hypothesis that an insufficient level of FANCM expression may provide additional information for the evaluation of PCa. The study cohort comprised 60 radical prostatectomy specimens. The controls involved 11 autopsies (CTRL) and non‐cancerous tissue (NCT) areas from the prostatectomy specimen. The samples were stained with the FANCM antibody. The quantification of the stromal staining index (SSI) was made using ImageJ and QuPath. Overall, 655 regions of interest (ROI) were analyzed. FANCM expression appeared equally intense and stroma specific in both CTRL and NCT, indicating the absence of underlying baseline alterations. Within the age span of the cohort 47–89 years, no significant effect of the age of the patients on the FANCM expression was seen. FANCM demonstrated Gleason grade (G) dependent decline in PCa, being statistically significant in controls versus G1 and G2 versus G3. In other adjacent International Society of Urological Pathology (ISUP) groups, it remained insignificant, still being meaningful between high and low‐grade cancers.
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

Objective

To 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 design

Randomized clinical trial.

Animals

Twelve 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.

Methods

Horses 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).

Results

Time 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.

Conclusion

The 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 significance

The paravertebral nerve block can be readily performed and may be useful in surgical procedures.
Transthoracic ultrasound: an essential diagnostic tool in a very rare case of thoracic lymphangiomatosis
Authors: Chira Romeo Ioan , Florea Alina , Pârvu Doru , Chira Alexadra , Crişan Doiniţa , Popovici Bogdan
Published: May 2020

Thoracic lymphangiomatosis (proliferation of anastomosing lymphatic vessels, of different sizes, in pulmonary, pleural and mediastinal regions) is an extremely rare disorder occurring mostly in childhood. We present a diffuse pulmonary lymphangiomatosis (DPL) case in a young adult female patient in which repeated surgical biopsies were inconclusive and transthoracic ultrasound-guided (TUS) biopsy led to the diagnosis. Even histologically, DPL is very difficult to differentiate from other lymphatic diseases such as lymphangioma and lymphangiomyomatosis, requiring an experienced pathologist and proper immunohistochemistry staining. This case highlights the importance of TUS-guided biopsies in the armamentarium of imagistic techniques in this very rare case
Examining How Elite S&C Coaches Develop Coaching Practice Using Reflection Stimulated by Video Vignettes
Authors: Szedlak Christoph , Smith Matthew J. , Callary Bettina , Day Melissa C.
Published: May 2020

The purpose of this study was to identify narrative types that illuminate how strength and conditioning (S&C) coaches used video vignettes in a guided reflection process to support the development of effective coaching practices. At the beginning of each week, over a 4-week period, 11 elite S&C coaches were sent a short video vignette clip of an S&C coach’s practice. They subsequently engaged in daily reflections in which they were guided to explore how the topic of the vignette aligned (or not) with their coaching practice. After the intervention, each S&C coach was interviewed regarding their process of learning from the vignette and from their reflections. Using a holistic narrative analysis of form and structure, the results exemplified three narrative types: performance, achievement, and helper. The S&C coaches whose reflections fitted the performance narrative type focused on their own practice, with limited consideration of the athletes’ perspective or the vignette. The S&C coaches whose reflections fitted the achievement narrative type strove to accomplish goals with their athletes and were selective in considering the vignette. The S&C coaches whose reflections fit the helper narrative type found that the vignette helped them consider an athlete-centered coaching approach focusing on the athletes’ well-being, as well as athletic abilities. Thus, S&C coach developers should utilize a guided reflection process that focuses on encouraging a coaching approach based on the helper narrative type.
New tools aim to tame pandemic paper tsunami
Authors: Brainard Jeffrey
Published: May 2020

Researchers harness AI and old-fashioned expertise to glean findings, but face challenges.
Remote activation of cellular signaling
Authors: Brier Matthew I. , Dordick Jonathan S.
Published: May 2020

Electric fields stimulate genetically modified pancreatic β cells to secrete insulin in mice
Probing the tumor micro(b)environment
Authors: Atreya Chloe E. , Turnbaugh Peter J.
Published: May 2020

Bacteria are widespread in tumors, are found within cells, and differ by cancer type
Killer cells add fire to fuel immunotherapy
Authors: Nicolai Christopher J. , Raulet David H.
Published: May 2020

Cytotoxic lymphocytes induce inflammatory target cell death, amplifying antitumor immunity
Exotic plants get a little help from their friends
Authors: Urcelay Carlos , Austin Amy T.
Published: May 2020

Interactions with herbivores and microbes link exotic-plant success with carbon cycling
Legionella pneumophila Excludes Autophagy Adaptors from the Ubiquitin-Labeled Vacuole in Which It Resides
Authors: Omotade Titilayo O. , Roy Craig R.
Published: May 2020

Xenophagy targets intracellular pathogens for destruction by the host autophagy pathway. Ubiquitin chains are conjugated to xenophagic targets and recruit multiple autophagy adaptors. The intracellular pathogen
Legionella pneumophila
resides in a vacuole that is ubiquitinated; however, this pathogen avoids xenophagic detection. Here, the mechanisms by which
L. pneumophila
can prevent the host xenophagy pathway from targeting the vacuole in which it resides were examined.
Evaluation of a Novel Semiquantitative Cryptococcal Antigen Lateral Flow Assay in Patients with Advanced HIV Disease
Authors: Jarvis Joseph N. , Tenforde Mark W. , Lechiile Kwana , Milton Thandi , Boose Amber , Leeme Tshepo B. , Tawe Leabaneng , Muthoga Charles , Rukasha Ivy , Mulenga Fredah , Rulaganyang Ikanyeng , Molefi Mooketsi , Molloy Síle F. , Ngidi Julia , Harrison Thomas S. , Govender Nelesh P. , Mine Madisa
Published: May 2020

Higher cryptococcal antigen (CrAg) titers are strongly associated with mortality risk in individuals with HIV-associated cryptococcal disease. Rapid tests to quantify CrAg levels may provide important prognostic information and enable treatment stratification. We performed a laboratory-based validation of the IMMY semiquantitative cryptococcal antigen (CrAgSQ) lateral flow assay (LFA) against the current gold standard CrAg tests. We assessed the diagnostic accuracy of the CrAgSQ in HIV-positive individuals undergoing CrAg screening, determined the relationship between CrAgSQ scores and dilutional CrAg titers, assessed interrater reliability, and determined the clinical correlates of CrAgSQ scores.
Acute massive gastric dilatation: a rare, forgotten complication of fundoplication
Authors: Lau Sue Een , Boam Tristan , Parsons Simon , Motiwale Sandeep
Published: May 2020

An 8-year-old boy with a history of multiple neonatal laparotomies, including congenital diaphragmatic hernia repair and an open fundoplication, presented acutely with severe abdominal pain, distension, vomiting and shock. A large abnormal opacity in the left upper quadrant was visible on a plain abdominal radiograph. The patient was taken to the theatre for emergency laparotomy and was found to have a massively distended stomach, the fundus and body of which were necrotic. A subtotal gastrectomy was performed, sparing the viable tissue. The patient went on to make a full recovery. Acute massive gastric dilatation (AMGD) is a rare condition characterised by severe gastric distension. Gastric ischaemia results when intragastric pressure exceeds venous pressure, obstructing venous outflow. It is important to recognise AMGD as a severe complication of fundoplication due to closed-loop gastric obstruction. It should prompt consideration of an early laparotomy in cases where the diagnosis is suspected.
Cervicofacial actinomycosis of the mandible in a paediatric patient
Authors: Cho Jason J , Shupak Raymond Patrick
Published: May 2020

Cervicofacial actinomycosis remains a rare pathogenic finding in the paediatric population. Diagnosis is challenging, as findings are often non-specific andActinomycesspecies are generally difficult to culture. Treatment is a prolonged course of antibiotics, either intravenous and oral, often combined with a surgical procedure to remove the lesion. This patient had non-specific intermittent left mandibular pain for 8 months that was eventually attributed to anActinomyces odontolyticusinfection in the mandible. Diagnosis required incisional biopsy, and treatment involved 12 months of oral antibiotics.
Iatrogenic Cushing syndrome and multifocal osteonecrosis caused by the interaction between inhaled fluticasone and ritonavir
Authors: Figueiredo Joana , Serrado Margarida , Khmelinskii Nikita , do Vale Sónia
Published: May 2020

Inhaled corticosteroids are generally considered safe and do not usually lead to systemic adverse events since their plasma concentrations are low due to hepatic metabolism by the cytochrome P450 3A4. However, when associated with inhibitors of this cytochrome, such as ritonavir, they may lead to iatrogenic Cushing syndrome by the systemic accumulation of corticosteroids and consequent suppression of the hypothalamic-pituitary-adrenal axis. We present a case of iatrogenic Cushing syndrome complicated by multifocal osteonecrosis in a patient with HIV infection on antiretroviral therapy with protease inhibitors boosted with ritonavir, after the association of inhaled fluticasone. This clinical case highlights a relevant interaction between corticosteroids and inhibitors of the cytochrome P450 and the severe consequences that may occur.
Atypical case of Miller-Fisher syndrome presenting with severe dysphagia and weight loss
Authors: Patel Kishan , Nussbaum Eliezer , Sico Jason , Merchant Naseema
Published: May 2020

A 71-year-old man developed dysphagia, bilateral lower extremity muscle weakness and weight loss. He was admitted to the hospital after a failed formal swallow evaluation, nearly 3 weeks after symptom onset. In addition to dysphagia and weakness, physical examination was notable for hypophonia, dysarthria, diplopia, horizontal ophthalmoparesis, ptosis, ataxia and hyporeflexia. Cerebrospinal fluid was notable for albuminocytological dissociation and serum anti-GQ1b antibody titre was elevated (1:200). A diagnosis of Miller-Fisher syndrome (MFS) was made, and the patient was treated with intravenous immunoglobulin (0.4 g/kg/day) for 5 days, which resulted in resolution of symptoms. This is an atypical case of MFS, in that the presenting symptom was progressive dysphagia rather than the ophthalmoplegia and ataxia that are normally seen in MFS. Patients who present with dysphagia should receive a thorough neurological examination, with particular attention to extraocular movements, reflexes and gait stability, to rule out MFS as a potential cause.
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

Background

Acute 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.

Objective

To explore potential prognostic indicators associated with in-hospital mortality of AECOPD patients.

Setting

General medical ward and medical intensive care unit of a university-affiliated tertiary care centre.

Methods

A 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.

Results

A 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).

Conclusion

Six 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

Objective

The 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.

Methods

Prospective 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.

Results

Patients 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.

Conclusions

PS 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.
Rhizosphere soil affects pear fruit quality under rain-shelter cultivation
Authors: Chen Xiao-Ming , Zhang Qi , Zeng Shao-Min , Chen Yao , Guo Yong-Yan , Huang Xin-Zhong
Published: May 2020

The use of rain shelters in pear cultivation has been shown to improve yields and the appearance and quality of fruit, as well as reduce diseases and pests; however, how rain shelters affect soil chemical properties, soil enzyme activity, and soil microbial diversity remains unknown. Here, we studied pear trees under rain-shelter cultivation and open-field cultivation in the same orchard and compared fruit quality, soil chemical characteristics, soil enzyme activity, and soil microbial diversity. Results showed that rain shelters can significantly (p < 0.05) increase the sugar content (sweetness) of pear fruits and decrease the content of acids. The levels of available phosphorus, available potassium, organic matter, and water in soils under rain shelters were significantly (p < 0.05) lower than in soils in open fields. Rain-shelter treatment increased soil polyphenol oxidase activity and decreased phosphomonoesterase, urease, and sucrase activity. Analysis of microbial carbon-source utilization rates and microbial diversity showed that open-field cultivation is beneficial for microbial carbon-source utilization and microbial diversity in rhizosphere soil. Our study found that rain-shelter cultivation is not beneficial to soil fertility, microbial carbon-source metabolism and utilization, matter cycling, or microbial diversity and that the use of rain shelters may require appropriate nutrient and organic matter supplementation to maintain long-term cultivation of crops; whereas, the effects of environmental factors on open-field cultivation are greater, and more refined water and fertilizer management is required to improve fruit quality.
The scale factor potential approach to inflation
Authors: Benisty David , Guendelman Eduardo I. , Saridakis Emmanuel N.
Published: May 2020

We 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.
An Opamp-Less PVT Compensation Structure for Ramp Generator Circuit
Authors: Padash Mohsen , Yargholi Mostafa , Baghini Maryam Shojaei
Published: May 2020

Accurate ramp signal, with low power dissipation, is highly demanded, for applications like counter ADC. This paper presents a novel low power ramp generator circuit with a negative feedback loop for compensation of the variations in process, voltage, and temperature (PVT). While using an opamp for PVT compensation has been essential in the previous ramp generator structures, the proposed ramp generator is opamp-less. Derived equations of the proposed ramp generator circuit show that PVT compensation structure works effectively. In addition, the circuit design and simulations were done in TSMC 0.18[Formula: see text][Formula: see text]m CMOS technology. Corner analysis shows that integral non-linearity (INL) of the ramp signal is about 3.7[Formula: see text]mV, for a wide temperature range, while the power dissipation of the circuit is about 1.16[Formula: see text][Formula: see text]W.
Investigating the Sensing Activities in Strategic Planning with Multi-Dimensional Aspects: Timo
Authors: Joseph Cho Yonghee , Daim Tugrul U.
Published: May 2020

The purpose of this study is to enrich the stream of research on Technology Forecasting (TF) activities in a firm for practitioners and researchers, a unique context where TF could lead to technological innovation. This paper offers a classification of the approaches and presents technological, industrial, methodological and organizational (TIMO) aspects of TF methods that are inherent in TF activities. Furthermore, this study provides empirical evidences to support organizational and managerial implications regarding TF activities associated with technology planning in a firm. Finally, research findings in regimes of technological changes suggest insights on technological, organizational and managerial processes within the firm.
Glucocorticoid regulates mesenchymal cell differentiation required for perinatal lung morphogenesis and function
Authors: Bridges James P. , Sudha Parvathi , Lipps Dakota , Wagner Andrew , Guo Minzhe , Du Yina , Brown Kari , Filuta Alyssa , Kitzmiller Joseph , Stockman Courtney , Chen Xiaoting , Weirauch Matthew T. , Jobe Alan H. , Whitsett Jeffrey A. , Xu Yan
Published: May 2020

While antenatal glucocorticoids are widely used to enhance lung function in preterm infants, cellular and molecular mechanisms by which glucocorticoid receptor (GR) signaling influences lung maturation remain poorly understood. Deletion of the glucocorticoid receptor gene ( Nr3c1) from fetal pulmonary mesenchymal cells phenocopied defects caused by global Nr3c1 deletion, while lung epithelial- or endothelial-specific Nr3c1 deletion did not impair lung function at birth. We integrated genome-wide gene expression profiling, ATAC-seq, and single cell RNA-seq data in mice in which GR was deleted or activated to identify the cellular and molecular mechanisms by which glucocorticoids control prenatal lung maturation. GR enhanced differentiation of a newly defined proliferative mesenchymal progenitor cell (PMP) into matrix fibroblasts (MFBs), in part by directly activating extracellular matrix-associated target genes, including Fn1, Col16a4, and Eln and by modulating VEGF, JAK-STAT, and WNT signaling. Loss of mesenchymal GR signaling blocked fibroblast progenitor differentiation into mature MFBs, which in turn increased proliferation of SOX9+ alveolar epithelial progenitor cells and inhibited differentiation of mature alveolar type II (AT2) and AT1cells. GR signaling controls genes required for differentiation of a subset of proliferative mesenchymal progenitors into matrix fibroblasts, in turn, regulating signals controlling AT2/AT1progenitor cell proliferation and differentiation and identifying cells and processes by which glucocorticoid signaling regulates fetal lung maturation.
MitoTEMPOL, a mitochondrial targeted antioxidant, prevents sepsis-induced diaphragm dysfunction
Authors: Supinski Gerald S. , Wang Lin , Schroder Elizabeth A. , Callahan Leigh Ann P.
Published: May 2020

Clinical studies indicate that sepsis-induced diaphragm dysfunction is a major contributor to respiratory failure in mechanically ventilated patients. Currently there is no drug to treat this form of diaphragm weakness. Sepsis-induced muscle dysfunction is thought to be triggered by excessive mitochondrial free radical generation; we therefore hypothesized that therapies that target mitochondrial free radical production may prevent sepsis-induced diaphragm weakness. The present study determined whether MitoTEMPOL, a mitochondrially targeted free radical scavenger, could reduce sepsis-induced diaphragm dysfunction. Using an animal model of sepsis, we compared four groups of mice: 1) sham-operated controls, 2) animals with sepsis induced by cecal ligation puncture (CLP), 3) sham controls given MitoTEMPOL (10 mg·kg−1·day−1 ip), and 4) CLP animals given MitoTEMPOL. At 48 h after surgery, we measured diaphragm force generation, mitochondrial function, proteolytic enzyme activities, and myosin heavy chain (MHC) content. We also examined the effects of delayed administration of MitoTEMPOL (by 6 h) on CLP-induced diaphragm weakness. The effects of MitoTEMPOL on cytokine-mediated alterations on muscle cell superoxide generation and cell size in vitro were also assessed. Sepsis markedly reduced diaphragm force generation. Both immediate and delayed MitoTEMPOL administration prevented sepsis-induced diaphragm weakness. MitoTEMPOL reversed sepsis-mediated reductions in mitochondrial function, activation of proteolytic pathways, and decreases in MHC content. Cytokines increased muscle cell superoxide generation and decreased cell size, effects that were ablated by MitoTEMPOL. MitoTEMPOL and other compounds that target mitochondrial free radical generation may be useful therapies for sepsis-induced diaphragm weakness.
Normal-range urinary albumin excretion associates with blood pressure and renal electrolyte handling in pregnancy
Authors: Birukov Anna , Andersen Marianne Skovsager , Jørgensen Jan Stener , Kitlen Gitte , Rakova Natalia , Nielsen Julie Hougård , Andersen Louise Bjørkholt , Dechend Ralf , Jensen Boye L.
Published: May 2020

Albuminuria in the pathological range is a significant predictor of preeclampsia. In healthy persons, high normal urinary albumin predicts a later incidence of hypertension and is associated with salt sensitivity of blood pressure. We hypothesized that in pregnancy urinary albumin in the normal range associates with blood pressure through activation of distal Na+ reabsorption and renal salt retention by plasma factors cofiltered with albumin. We analyzed 24-h urine collections and plasma samples from gestational week 29 of 560 pregnant women from the Odense Child Cohort, a Danish population-based cohort. Plasma and urinary aldosterone were measured by ELISA. Plasma and urinary Na+, K+, Cl−, and creatinine were also determined. Predictive values of urinary albumin were assessed by linear mixed, multiple, and Cox regression analyses. Primary outcomes were blood pressure and renal electrolyte handling. Twenty-four-hour urinary albumin excretion at gestational week 29 associated with gestational blood pressure trajectory, with adjusted β coefficients (95% confidence intervals) for each 10-fold increase in urinary albumin as follows: 5.71 (1.60 to 9.81) mmHg for systolic blood pressure and 4.39 (1.41 to 7.38) mmHg for diastolic blood pressure. Urinary albumin was inversely associated with fractional excretion rates of Na+, K+, and Cl−, with adjusted β coefficients (95% confidence intervals) for each 10-fold increase in urine albumin as follows: −0.25 (−0.35 to −0.14), −5.06 (−6.81 to −3.30), and −0.28 (−0.41 to −0.15), respectively. In conclusion, at gestational week 29, urinary albumin excretion in the normal range associated with blood pressure and renal electrolyte handling independent of potential confounders.
Testosterone suppression does not exacerbate disuse atrophy and impairs muscle recovery that is not rescued by high protein
Authors: Hanson Erik D. , Betik Andrew C. , Timpani Cara A. , Tarle John , Zhang Xinmei , Hayes Alan
Published: May 2020

Low testosterone levels during skeletal muscle disuse did not worsen declines in muscle mass and function, although hypogonadism may attenuate recovery during subsequent reloading. Diets high in casein did not improve outcomes during immobilization or reloading. Practical strategies are needed that do not compromise caloric intake yet provide effective protein doses to augment these adverse effects.
Improved Quantum-Behaved Particle Swarm Algorithm Based on Levy Flight
Authors: Zheng Song , Zhou Xinwei , Zheng Xiaoqing , Ge Ming
Published: May 2020

To improve convergence speed and search accuracy, this paper proposes an improved quantum-behaved particle swarm optimization algorithm based on Levy flight. The improved algorithm reduces the probability of a local optimal solution through Levy flight and enhances the accuracy of the later search through a postsearch strategy. During the search process, the probability of quantum behavior is retained and the directivity of the particles is strengthened. According to the simulation comparison results, the improved quantum-behaved particle swarm algorithm exhibits faster convergence speed and higher accuracy.
Research on Modelling and Stability Characteristics of Electric Traffic Energy System Based on ZVS-DAB Converter
Authors: Tuluhong Ayiguzhali , Wang Weiqing , Li Yongdong , Wang Haiyun , Xu Lie
Published: May 2020

We study and describe mostly used traditional simplified circuits for full-bridge Zero Voltage Switching-Dual Active Bridge (ZVS-DAB) converter and deduce their mathematical model. On this basis, we propose a high-frequency (HF) mathematical model, which takes into account conduction loss and HF characteristics of the ZVS-DAB converter model. We compare the static and dynamic stabilities of the traditional and the proposed HF mathematical model by simulation. Finally, the high-frequency planar transformer (HFPT) with good heat dissipation and the wide band gap (WBG) semiconductor SiC switches with fast switching speed are employed to build a 4.4 kw, 40 KHz experimental prototype to verify the effectiveness of the improved HF circuit of ZVS-DAB converter. The results show that the proposed HF mathematical model is superior to the traditional one, and it fully considers the HF characteristics of the circuit and effectively improves the HF oscillation, DC bias, and waveform distortion of the ZVS-DAB converter.
Aliskiren Improved the Endothelial Repair Capacity of Endothelial Progenitor Cells from Patients with Hypertension via the Tie2/PI3k/Akt/eNOS Signalling Pathway
Authors: Yao Shun , Su Chen , Wu Shao-Hong , Hu Da-Jun , Liu Xing
Published: May 2020

Background. Studies show that aliskiren exerts favourable effects not only on endothelial progenitor cells (EPCs) but also on endothelial function. However, the mechanism of the favourable effect of aliskiren on EPCs from patients with hypertension is unclear and remains to be further studied. Methods. The object of this study was to investigate and assess the in vitro function of EPCs pretreated with aliskiren. After treated with aliskiren, the human EPCs were transplanted into a nude mouse model of carotid artery injury, and the in vivo reendothelialization of injured artery was estimated by staining denuded areas with Evans blue dye via tail vein injection. Results. We found that aliskiren increased the in vitro migration, proliferation, and adhesion of EPCs from patients with hypertension in a dose-dependent manner and improved the reendothelialization capability of these EPCs. Furthermore, aliskiren increased the phosphorylation of Tie2, Akt, and eNOS. After the blockade of the Tie2 signalling pathway, the favourable effects of aliskiren on the in vitro function and in vivo reendothelialization capability of EPCs were suppressed. Conclusions. This study demonstrates that aliskiren can improve the in vitro function and in vivo reendothelialization capability of EPCs from patients with hypertension via the activation of the Tie2/PI3k/Akt/eNOS signalling pathway. These findings further indicate that aliskiren is an effective pharmacological treatment for cell-based repair in hypertension-related vascular injury.
Sustained Release of Melatonin from GelMA Liposomes Reduced Osteoblast Apoptosis and Improved Implant Osseointegration in Osteoporosis
Authors: Xiao Long , Lin Jiayi , Chen Ruoyu , Huang Yu , Liu Yu , Bai Jiaxiang , Ge Gaoran , Shi Xiaopeng , Chen Yong , Shi Jiandong , Aiqing Lu , Yang Huilin , Geng Dechun , Wang Zhirong
Published: May 2020

A reduction in bone mass around an implant is the main cause of implant loosening, especially in postmenopausal osteoporosis patients. In osteoporosis, excessive oxidative stress, resulting in osteoblast apoptosis, largely contributes to abnormal bone remodeling. Melatonin (MT) synthesized by the pineal gland promotes osteoblast differentiation and bone formation and has been effectively used to combat oxidative stress. Therefore, we hypothesized that MT attenuates osteoblast apoptosis induced by oxidative stress, promotes osteogenesis in osteoporosis, and improves bone mass around prostheses. Moreover, considering the distribution and metabolism of MT, its systemic administration would require a large amount of MT, increasing the probability of drug side effects, so the local administration of MT is more effective than its systemic administration. In this study, we constructed a composite adhesive hydrogel system (GelMA-DOPA@MT) to bring about sustained MT release in a local area. Additionally, MT-reduced apoptosis caused by hydrogen peroxide- (H2O2-) induced oxidative stress and restored the osteogenic potential of MC3T3-E1 cells. Furthermore, apoptosis in osteoblasts around the implant was significantly attenuated, and increased bone mass around the implant was observed in ovariectomized (OVX) rats treated with this composite system. In conclusion, our results show that GelMA-DOPA@MT can inhibit osteoblast apoptosis caused by oxidative stress, thereby promoting osteogenesis and improving bone quality around a prosthesis. Therefore, this system of local, sustained MT release is a suitable candidate to address implant loosening in patients with osteoporosis.
Effect of Curcumol on the Fenestrae of Liver Sinusoidal Endothelial Cells Based on NF‐κB Signaling Pathway
Authors: Zheng Yang , Wang Jiahui , Wang Jiaru , Xie Haiyuan , Zhao Tiejian
Published: May 2020

Objective. To study the effect of curcumol on liver sinusoidal endothelial cells (LSECs) and to analyze the mechanism of antihepatic fibrosis. Methods. The effects of drug intervention on cell proliferation rates were detected by MTT assay. The expression of NF‐κB was detected by RT‐PCR and WB. The NF‐κB expression and entry into the nucleus were detected by immunofluorescence; scanning electron microscopy was used to observe the changes of LSECs fenestrae. Results. MTT results showed that the interference of cell proliferation in each group was small. RT‐PCR showed that the expression of NF‐κB in the curcumol intervention group was significantly lower than that in the positive control group (P < 0.05). The WB detection found that, in the curcumol intervention group, the expression of pNF‐κB in the NF‐κB signaling pathway was significantly lower than that in the positive control group (P < 0.05). Scanning electron microscopy showed that the LSEC fenestrae were significantly improved compared with the positive control group. Conclusion. Curcumol may be one of the mechanisms of antihepatic fibrosis by inhibiting the activity of the NF‐κB signaling pathway and increasing the fenestrae of LSECs.
Design of Real-Time Dynamic Reversible Lane in Intelligent Cooperative Vehicle Infrastructure System
Authors: Mao Lina , Li Wenquan , Hu Pengsen , Zhou Guiliang , Zhang Huiting , Dai Jin
Published: May 2020

The rapidly growing traffic demand and the slowly increasing traffic supply have produced an mounting contradiction, which is mainly manifested in cities as road congestion and unbalanced bidirectional traffic flow. Most of the reversible lanes are implemented on fixed sections and fixed times and are mainly guided by ground markings, road signs, railings, and traffic police officer. It requires a lot of human and material costs. And, the control effect is lagging and inaccurate. Aiming at these problems, a real-time dynamic reversible lane scheme in the Intelligent Cooperative Vehicle Infrastructure System (CVIS) was proposed. Traffic information was collected in real time through the CVIS, and a reversible lane scheme was established based on the real-time service level V/C and BRP functions. A lane change control model was applied to determine the number of lanes and the timing of lane changes. Then, the reversible lanes were managed in real time through intelligent road stud lights and light curtain walls. Buffer sections and no-entry sections were set to ensure reversible lanes operating safely and efficiently. VISSIM simulation was used for case analysis, and the results showed that compared with the traditional time-controlled reversible lane scheme, the real-time dynamic reversible lane scheme could reduce the average vehicle delay by 27.4% and decrease the vehicle VOC, CO and NOX emissions by 13.5%.
Historical Rainfall and Evapotranspiration Changes over Mpologoma Catchment in Uganda
Authors: Mubialiwo Ambrose , Onyutha Charles , Abebe Adane
Published: May 2020

Changes in the long-term (1948–2016) rainfall and evapotranspiration over Mpologoma catchment were analysed using gridded (0.25° × 0.25°) Princeton Global Forcing data. Trend and variability were assessed using a nonparametric approach based on the cumulative sum of the difference between exceedance and nonexceedance counts of data. Annual and March-May (MAM) rainfall displayed a positive trend (p<0.05), whereas October-December (OND) and June-September rainfall exhibited negative trends withp>0.05andp<0.05, respectively. Positive subtrends in rainfall occurred in the 1950s and from the mid-2000s till 2016; however, negative subtrends existed between 1960 till around 2005. Seasonal evapotranspiration exhibited a positive trend (p>0.05). For the entire period (1948–2016), there was no negative subtrend in the OND and MAM evapotranspiration. Rainfall and evapotranspiration trends and oscillatory variation in subtrends over multidecadal time scales indicate the need for careful planning of predictive adaptation to the impacts of climate variability on environmental applications which depend on water balance in the Mpologoma catchment. It is recommended that future studies quantify possible contributions of human factors on the variability of rainfall and evapotranspiration. Furthermore, climate change impacts on rainfall and evapotranspiration across the study area should be investigated.
Telomere DNA Damage Signaling Regulates Prostate Cancer Tumorigenesis
Authors: Wu Jianchun , Crowe David L.
Published: May 2020

Telomere 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.