bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early detection of chronic kidney disease in low-income and middle-income countries: development and validation of a point-of-care screening strategy for India
Authors: Bradshaw Christina , Kondal Dimple , Montez-Rath Maria E , Han Jialin , Zheng Yuanchao , Shivashankar Roopa , Gupta Ruby , Srinivasapura Venkateshmurthy Nikhil , Jarhyan Prashant , Mohan Sailesh , Mohan Viswanathan , Ali Mohammed K , Patel Shivani , Narayan K M Venkat , Tandon Nikhil , Prabhakaran Dorairaj , Anand Shuchi 
Published: September 2019

IntroductionAlthough deaths due to chronic kidney disease (CKD) have doubled over the past two decades, few data exist to inform screening strategies for early detection of CKD in low-income and middle-income countries.MethodsUsing data from three population-based surveys in India, we developed a prediction model to identify a target population that could benefit from further CKD testing, after an initial screening implemented during home health visits. Using data from one urban survey (n=8698), we applied stepwise logistic regression to test three models: one comprised of demographics, self-reported medical history, anthropometry and point-of-care (urine dipstick or capillary glucose) tests; one with demographics and self-reported medical history and one with anthropometry and point-of-care tests. The ‘gold-standard’ definition of CKD was an estimated glomerular filtration rate <60 mL/min/1.73 m2or urine albumin-to-creatinine ratio ≥30 mg/g. Models were internally validated via bootstrap. The most parsimonious model with comparable performance was externally validated on distinct urban (n=5365) and rural (n=6173) Indian cohorts.ResultsA model with age, sex, waist circumference, body mass index and urine dipstick had a c-statistic of 0.76 (95% CI 0.75 to 0.78) for predicting need for further CKD testing, with external validation c-statistics of 0.74 and 0.70 in the urban and rural cohorts, respectively. At a probability cut-point of 0.09, sensitivity was 71% (95% CI 68% to 74%) and specificity was 70% (95% CI 69% to 71%). The model captured 71% of persons with CKD and 90% of persons at highest risk of complications from untreated CKD (ie, CKD stage 3A2 and above).ConclusionA point-of-care CKD screening strategy using three simple measures can accurately identify high-risk persons who require confirmatory kidney function testing.
Reducing unnecessary delays during the transfer of patients from the paediatric intensive care unit to the general ward: a quality improvement project
Authors: Alali Hamza , Kazzaz Yasser , Alshehri Ali , Antar Mohannad , Alhamouieh Ousaima , Hasan Zahra , Al-Surimi Khaled 
Published: September 2019

IntroductionDelaying the discharge of paediatric intensive care unit (PICU) patients is directly proportional to increased occupancy rate and cost. We aimed to study the process of transferring patients from the PICU to the general ward in order to improve the timeliness of this process while guaranteeing patient safety.MethodsA multidisciplinary quality improvement (QI) team was formed to analyse the transfer process. Several Plan Do Study Act cycles were tested, targeting all steps of the transfer process, and applying turnaround time (TAT)—the duration from the time of clinical transfer decision until the physical transfer of the patient—as an outcome measure, aiming for a TAT of 4 hours.ResultsBaseline results showed that medical transfer decisions by PICU attending physicians were taken late for most patients: only 19% of decisions were made by 08:00 by the on-call team. Average TAT of the transfer process was over 7 hours, with duration ranging from 7 to 17 hours. After implementing all suggested improvement interventions, early decision compliance improved to 59%. TAT improved gradually, starting in January 2017, until it approached our target (284–261 min≈4 hours) in February–May 2017.ConclusionPICU patient transfer process delays can be reduced by early evaluation, timely team communication and proper preparation. It is recommended that all personnel with early involvement avoid unnecessary delays by paying more attention to all process steps, starting with the clinical decision, until the physical transfer. Standardising transfer processes might lead to a decrease in the length of PICU stay, which is a desirable outcome, but this observation needs further exploration.
Home initiation of chronic non-invasive ventilation in COPD patients with chronic hypercapnic respiratory failure: a randomised controlled trial
Authors: Duiverman Marieke L , Vonk Judith M , Bladder Gerrie , van Melle Joost P , Nieuwenhuis Jellie , Hazenberg Anda , Kerstjens Huib A M , van Boven Job F M , Wijkstra Peter J 
Published: September 2019

IntroductionChronic non-invasive ventilation (NIV) has become evidence-based care for stable hypercapnic COPD patients. While the number of patients increases, home initiation of NIV would greatly alleviate the healthcare burden. We hypothesise that home initiation of NIV with the use of telemedicine in stable hypercapnic COPD is non-inferior to in-hospital NIV initiation.MethodsSixty-seven stable hypercapnic COPD patients were randomised to initiation of NIV in the hospital or at home using telemedicine. Primary outcome was daytime arterial carbon dioxide pressure (PaCO2) reduction after 6 months NIV, with a non-inferiority margin of 0.4 kPa. Secondary outcomes were health-related quality of life (HRQoL) and costs.ResultsHome NIV initiation was non-inferior to in-hospital initiation (adjusted mean difference in PaCO2change home vs in-hospital: 0.04 kPa (95% CI −0.31 to 0.38 kPa), with both groups showing a PaCO2reduction at 6 months compared with baseline (home: from 7.3±0.9 to 6.4±0.8 kPa (p<0.001) and in-hospital: from 7.4±1.0 to 6.4±0.6 kPa (p<0.001)). In both groups, HRQoL improved without a difference in change between groups (Clinical COPD Questionnaire total score-adjusted mean difference 0.0 (95% CI −0.4 to 0.5)). Furthermore, home NIV initiation was significantly cheaper (home: median €3768 (IQR €3546–€4163) vs in-hospital: median €8537 (IQR €7540–€9175); p<0.001).DiscussionThis is the first study showing that home initiation of chronic NIV in stable hypercapnic COPD patients, with the use of telemedicine, is non-inferior to in-hospital initiation, safe and reduces costs by over 50%.Trial registration numberNCT02652559.
Evaluating smoking control policies in the e-cigarette era: a modelling study
Authors: Doan Thi Thanh Tra , Tan Ken Wei , Dickens Borame Sue Lee , Lean Yin Ai , Yang Qianyu , Cook Alex R 
Published: September 2019

BackgroundIn jurisdictions in which electronic cigarettes are currently prohibited, policy makers must weigh the potentially lower risk compared with conventional cigarettes against the risk of initiation of e-cigarettes among non-smokers.MethodsWe simulated a synthetic population over a 50-year time horizon with an open cohort model using data from Singapore, a country where e-cigarettes are currently prohibited, and data from the USA, the UK and Japan. Using the smoking prevalence and the quality-adjusted life year gained calculated, we compared tobacco control policies without e-cigarettes—namely, raising the minimum legal age (MLA), introducing a smoke-free generation (SFG) and tax rises on tobacco consumption—with policies legalising e-cigarettes, either taking a laissez-faire approach or under some form of restriction. We also evaluated combinations of these policies.ResultsRegardless of the country informing the transition probabilities to and from e-cigarette use in Singapore, a laissez-faire e-cigarette policy could reduce the smoking prevalence in the short term, but it is not as effective as other policies in the long term. The most effective single policies evaluated were SFG and aggressive tax rises; the most effective combination of policies considered was MLA plus moderate tax rises and e-cigarettes on prescription.ConclusionPolicy makers in jurisdictions in which e-cigarettes are not yet established may be advised not to prioritise e-cigarettes in their tobacco end-game strategy, unless their use can be restricted to current smokers seeking to quit.
EXPERIMENTAL COMPARISON OF MCF7 AND MCF10A RESPONSE TO LOW INTENSITY ULTRASOUND
Authors: IVONE MARIANTONIETTA , LAMBERTI LUCIANO , PAPPALETTERE CARMINE , CARATOZZOLO MARIANO FRANCESCO , TULLO APOLLONIA 
Published: September 2019

The low-intensity ultrasound effects on MCF7 (human breast adenocarcinoma) and MCF10A (healthy breast cells) have been investigated at different sonication protocol to probe the effectiveness and the selectivity of the ultrasound (US) treatment and to understand the implications between cell mortality, biomechanical interactions and cell elastic modulus. Experiments performed at fixed and variable frequency demonstrated the effectiveness of some protocols in killing carcinogenic cells and the healthy cells insensitivity. Variation of elastic properties of MCF7 cells exposed to US under varying sonication conditions was examined. Sonication was carried out at fixed frequency (as it is usually done in therapy protocols), between 400[Formula: see text]kHz and 620[Formula: see text]kHz, following two protocols: (i) at fixed power output; (ii) at fixed voltage of the US generator. Evolution of cell stiffness during the US treatment was monitored via atomic force spectroscopy (AFS). It was found that cell mortality has a similar trend of variation with respect to sonication frequency regardless of the way specimens are exposed to US. Mechanical properties do not show a uniform trend with respect to frequency, but variations of Young’s modulus are more marked near the very low (400–480) kHz or very high frequencies (580–620) kHz. The observed variations may be related to mechanical interactions occurring in the cell culture, suggesting a primacy of the environment on other factors.
Lactobacillus reuteriDSM 17938 feeding of healthy newborn mice regulates immune responses while modulating gut microbiota and boosting beneficial metabolites
Authors: Liu Yuying , Tian Xiangjun , He Baokun , Hoang Thomas K. , Taylor Christopher M. , Blanchard Eugene , Freeborn Jasmin , Park Sinyoung , Luo Meng , Couturier Jacob , Tran Dat Q. , Roos Stefan , Wu Guoyao , Rhoads J. Marc 
Published: September 2019

Early administration of Lactobacillus reuteri DSM 17938 (LR) prevents necrotizing enterocolitis and inhibits regulatory T-cell (Treg)-deficiency-associated autoimmunity in mice. In humans, LR reduces crying time in breastfed infants with colic, modifies severity in infants with acute diarrheal illnesses, and improves pain in children with functional bowel disorders. In healthy breastfed newborns with evolving microbial colonization, it is unclear if early administration of LR can modulate gut microbiota and their metabolites in such a way as to promote homeostasis. We gavaged LR (107colony-forming units/day, daily) to C57BL/6J mice at age of day 8 for 2 wk. Both male and female mice were investigated in these experiments. We found that feeding LR did not affect clinical phenotype or inflammatory biomarkers in plasma and stool, but LR increased the proportion of Foxp3+regulatory T cells (Tregs) in the intestine. LR also increased bacterial diversity and the relative abundance of p_Firmicutes, f_Lachnospiraceae, f_Ruminococcaceae, and genera Clostridium and Candidatus arthromitus, while decreasing the relative abundance of p_Bacteriodetes, f_Bacteroidaceae, f_Verrucomicrobiaceae, and genera Bacteroides, Ruminococcus, Akkermansia, and Sutterella. Finally, LR exerted a major impact on the plasma metabolome, upregulating amino acid metabolites formed via the urea, tricarboxylic acid, and methionine cycles and increasing tryptophan metabolism. In conclusion, early oral administration of LR to healthy breastfed mice led to microbial and metabolic changes which could be beneficial to general health.NEW & NOTEWORTHY Oral administration of Lactobacillus reuteri DSM 17938 (LR) to healthy breastfed mice promotes intestinal immune tolerance and is linked to proliferation of beneficial gut microbiota. LR upregulates plasma metabolites that are involved in the urea cycle, the TCA cycle, methionine methylation, and the polyamine pathway. Herein, we show that LR given to newborn mice specifically increases levels of tryptophan metabolites and the purine nucleoside adenosine that are known to enhance tolerance to inflammatory stimuli.
Electrical microstimulation evokes saccades in posterior parietal cortex of common marmosets
Authors: Ghahremani Maryam , Johnston Kevin D. , Ma Liya , Hayrynen Lauren K. , Everling Stefan 
Published: September 2019

The common marmoset ( Callithrix jacchus) is a small-bodied New World primate increasing in prominence as a model animal for neuroscience research. The lissencephalic cortex of this primate species provides substantial advantages for the application of electrophysiological techniques such as high-density and laminar recordings, which have the capacity to advance our understanding of local and laminar cortical circuits and their roles in cognitive and motor functions. This is particularly the case with respect to the oculomotor system, as critical cortical areas of this network such as the frontal eye fields (FEF) and lateral intraparietal area (LIP) lie deep within sulci in macaques. Studies of cytoarchitecture and connectivity have established putative homologies between cortical oculomotor fields in marmoset and macaque, but physiological investigations of these areas, particularly in awake marmosets, have yet to be carried out. Here we addressed this gap by probing the function of posterior parietal cortex of the common marmoset with electrical microstimulation. We implanted two animals with 32-channel Utah arrays at the location of the putative area LIP and applied microstimulation while they viewed a video display and made untrained eye movements. Similar to previous studies in macaques, stimulation evoked fixed-vector and goal-directed saccades, staircase saccades, and eyeblinks. These data demonstrate that area LIP of the marmoset plays a role in the regulation of eye movements, provide additional evidence that this area is homologous with that of the macaque, and further establish the marmoset as a valuable model for neurophysiological investigations of oculomotor and cognitive control. NEW & NOTEWORTHY The macaque monkey has been the preeminent model for investigations of oculomotor control, but studies of cortical areas are limited, as many of these areas are buried within sulci in this species. Here we applied electrical microstimulation to the putative area LIP of the lissencephalic cortex of awake marmosets. Similar to the macaque, microstimulation evoked contralateral saccades from this area, supporting the marmoset as a valuable model for studies of oculomotor control.
Synthesis and Study of an Efficient Metal-Organic Framework Adsorbent (MIL-96(Al)) for Fluoride Removal from Water
Authors: Wang Xingang , Zhu Hui , Sun Tongshuai , Liu Yinbo , Han Ting , Lu Jingxian , Dai Hongliang , Zhai Linzhi 
Published: September 2019

Long-term consumption of drinking water that contains excessive amounts of fluoride can endanger human health; therefore, the preparation and application of a high-efficiency defluorination adsorbent for advanced purification of drinking water are of significant interest. This study presents a metal-organic framework adsorbent (MIL-96(Al)) with the granular structure of rice, which was generated by hydrothermal reaction. The specific surface area of MIL-96(Al) was ~220 m2 g-1, and it showed a good thermal stability. Several experiments were conducted wherein conditions, including adsorbent dosage, initial concentration, pH, and coexisting anions, were varied to understand the defluorination performance of the material. Results showed that pH (6–9) and coexisting anions had little effect on the removal efficiency of fluoride. The adsorption isotherm can be described by the Langmuir model, and the theoretical fluoride adsorption capacity of MIL-96(Al) was up to 42.19 mg Fg-1 at 298 K, which is much higher than that of the commonly used activated alumina. The adsorption process of fluoride is endothermic and follows pseudo second-order kinetics. In addition, MIL-96(Al) was shown to still achieve ~61.8% of the adsorption capacity after seven regenerations. This study shows that MIL-96(Al) is a good application prospect and could be widely used to remove fluoride from water.
Clonal Mutations Activate the NF-κB Pathway to Promote Recurrence of Nasopharyngeal Carcinoma
Authors: You Rui , Liu You-Ping , Lin De-Chen , Li Qing , Yu Tao , Zou Xiong , Lin Mei , Zhang Xiao-Long , He Gui-Ping , Yang Qi , Zhang Yi-Nuan , Xie Yu-Long , Jiang Rou , Wu Chen-Yan , Zhang Chao , Cui Cheng , Wang Jing-Qi , Wang Yue , Zhuang Ai-Hua , Guo Gui-Fang , Hua Yi-Jun , Sun Rui , Yun Jing-Ping , Zuo Zhi-Xiang , Liu Ze-Xian , Zhu Xiao-Feng , Kang Tie-Bang , Qian Chao-Nan , Mai Hai-Qiang , Sun Ying , Zeng Mu-Sheng , Feng Lin , Zeng Yi-Xin , Chen Ming-Yuan 
Published: September 2019

AbstractThe genetic events occurring in recurrent nasopharyngeal carcinoma (rNPC) are poorly understood. Here, we performed whole-genome and whole-exome sequencing in 55 patients with rNPC and 44 primarily diagnosed NPC (pNPC), with 7 patients having paired rNPC and pNPC samples. Previously published pNPC exome data were integrated for analysis. rNPC and pNPC tissues had similar mutational burdens, however, the number of clonal mutations was increased in rNPC samples. TP53 and three NF-κB pathway components (TRAF3, CYLD, and NFKBIA) were significantly mutated in both pNPC and rNPC. Notably, mutations in TRAF3, CYLD, and NFKBIA were all clonal in rNPC, however, 55.6% to 57.9% of them were clonal in pNPC. In general, the number of clonal mutations in NF-κB pathway–associated genes was significantly higher in rNPC than in pNPC. The NF-κB mutational clonality was selected and/or enriched during NPC recurrence. The amount of NF-κB translocated to the nucleus in samples with clonal NF-κB mutants was significantly higher than that in samples with subclonal NF-κB mutants. Moreover, the nuclear abundance of NF-κB protein was significantly greater in pNPC samples with locoregional relapse than in those without relapse. Furthermore, high nuclear NF-κB levels were an independent negative prognostic marker for locoregional relapse-free survival in pNPC. Finally, inhibition of NF-κB enhanced both radiosensitivity and chemosensitivity in vitro and in vivo. In conclusion, NF-κB pathway activation by clonal mutations plays an important role in promoting the recurrence of NPC. Moreover, nuclear accumulation of NF-κB is a prominent biomarker for predicting locoregional relapse-free survival.Significance:This study uncovers genetic events that promote the progression and recurrence of nasopharyngeal carcinoma and has potential prognostic and therapeutic implications.See related commentary by Sehgal and Barbie, p. 5915
Deoxycytidine Release from Pancreatic Stellate Cells Promotes Gemcitabine Resistance
Authors: Dalin Simona , Sullivan Mark R. , Lau Allison N. , Grauman-Boss Beatrice , Mueller Helen S. , Kreidl Emanuel , Fenoglio Silvia , Luengo Alba , Lees Jacqueline A. , Vander Heiden Matthew G. , Lauffenburger Douglas A. , Hemann Michael T. 
Published: September 2019

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer deaths in the United States. The deoxynucleoside analogue gemcitabine is among the most effective therapies to treat PDAC, however, nearly all patients treated with gemcitabine either fail to respond or rapidly develop resistance. One hallmark of PDAC is a striking accumulation of stromal tissue surrounding the tumor, and this accumulation of stroma can contribute to therapy resistance. To better understand how stroma limits response to therapy, we investigated cell-extrinsic mechanisms of resistance to gemcitabine. Conditioned media from pancreatic stellate cells (PSC), as well as from other fibroblasts, protected PDAC cells from gemcitabine toxicity. The protective effect of PSC-conditioned media was mediated by secretion of deoxycytidine, but not other deoxynucleosides, through equilibrative nucleoside transporters. Deoxycytidine inhibited the processing of gemcitabine in PDAC cells, thus reducing the effect of gemcitabine and other nucleoside analogues on cancer cells. These results suggest that reducing deoxycytidine production in PSCs may increase the efficacy of nucleoside analog therapies.

Significance:
This study provides important new insight into mechanisms that contribute to gemcitabine resistance in PDAC and suggests new avenues for improving gemcitabine efficacy.
Mitohormesis, UPRmt, and the Complexity of Mitochondrial DNA Landscapes in Cancer
Authors: Kenny Timothy C. , Gomez Maria L. , Germain Doris 
Published: September 2019

Abstract
The discovery of the Warburg effect, the preference of cancer cells to generate ATP via glycolysis rather than oxidative phosphorylation, has fostered the misconception that cancer cells become independent of the electron transport chain (ETC) for survival. This is inconsistent with the need of ETC function for the generation of pyrimidines. Along with this misconception, a large body of literature has reported numerous mutations in mitochondrial DNA (mtDNA), further fueling the notion of nonfunctional ETC in cancer cells. More recent findings, however, suggest that cancers maintain oxidative phosphorylation capacity and that the role of mtDNA mutations in cancer is likely far more nuanced in light of the remarkable complexity of mitochondrial genetics. This review aims at describing the various model systems that were developed to dissect the role of mtDNA in cancer, including cybrids, and more recently mitochondrial–nuclear exchange and conplastic mice. Furthermore, we put forward the notion of mtDNA landscapes, where the surrounding nonsynonymous mutations and variants can enhance or repress the biological effect of specific mtDNA mutations. Notably, we review recent studies describing the ability of some mtDNA landscapes to activate the mitochondrial unfolded protein response (UPRmt) but not others. Furthermore, the role of the UPRmt in maintaining cancer cells in the mitohormetic zone to provide selective adaptation to stress is discussed. Among the genes activated by the UPRmt, we suggest that the dismutases SOD2 and SOD1 may play key roles in the establishment of the mitohormetic zone. Finally, we propose that using a UPRmt nuclear gene expression signature may be a more reliable readout than mtDNA landscapes, given their diversity and complexity.