bluuebunny/crossref_metadata_2025 huggingface dataset:
Semisolid Compression Brazing of Al50Si Alloy Using Zn-Al-Cu Filler Metal Assisted by SiC Particles
Authors: Xiao Jing , Li Shun , Bai Shuxin , Xiong Degan , Tang Yu
Published: December 2019

Semisolid compression brazing of Al50Si alloy using Zn-Al-Cu filler metal assisted by SiC particles coating has been developed. The effects of the size and concentration of SiC particles on the microstructure and mechanical properties of the joints were studied. By using 1 μm SiC particles and the concentration of SiC particles increased to 3 g/m2, oxide film on the surface of base metal was completely disrupted and a good bonding strength was obtained. As SiC concentration further increased to 4 g/m2, colonies of SiC particle with nonwetting areas of filler metal formed at the interface, resulting in a decrease in the bonding strength. By using 5 μm SiC particles, the bonding strength was enhanced as SiC concentration increased from 1 g/m2 to 3 g/m2 due to the removal of the oxide film. By further increasing SiC concentration to 16 g/m2, the strength was constantly improved because of the dislocation strengthening effect generated at the SiC particle layer/filler metal interface. When SiC concentration increased to 32 g/m2, nonwetting area appeared inside the SiC particles layer, causing a decrease in the bonding strength.
A Randomized Placebo-Controlled N-of-1 Trial: The Effect of Proton Pump Inhibitor in the Management of Gastroesophageal Reflux Disease
Authors: Sierra-Arango Fernando , Castaño D. M. , Forero Jennifer D. , Pérez-Riveros Erika D. , Ardila Duarte Gerardo , Botero Maria L. , Cárdenas Andres , De la Hoz-Valle Jose
Published: December 2019

Background. Gastroesophageal reflux disease (GERD) is the most frequent chronic gastrointestinal disorder. It is defined as a condition developed when the reflux of gastric contents causes troublesome symptoms (heartburn and regurgitation). This requires adequate treatment since it can lead to long-term complications including esophagus adenocarcinoma. Proton pump inhibitors (PPI) are generally used to treat GERD due to their high-security profile and efficiency on most patients. However, recurrent reflux despite initial treatment is frequent. N-of-1 trial is a study that allows the identification of the best treatment for each patient. The objective of this study is to compare the efficacy of standard dose with double dosage of esomeprazole, to improve the GERD symptoms in a single patient. Methods. A single-patient trial, placebo-controlled, randomized, double-blind, was carried out from September 25th, 2012, to April 26th, 2013. It included one outpatient at the gastroenterology service in a fourth-level hospital, diagnosed with nonerosive reflux disease (NERD). Yet, his symptoms were heartburn and reflux, and his endoscopic results were normal esophageal mucosa, without hiatal hernia, though pathological pH values. A no-obese male without any tobacco or alcohol usage received esomeprazole 40 mg/day and 40 mg/bid for 24 weeks. A standardized gastroesophageal reflux disease questionnaire (GerdQ) was used weekly to evaluate symptom frequency and severity. The consumption of 90% of the capsules was considered as an adequate treatment adherence. D’agostino–Pearson and Wilcoxon test were used to determine normal or nonnormal distribution and compare both treatments, respectively, both with a significant statistical difference of p<0.05. Results. The patient completed the study with 96% of adherence. The double dosage of esomeprazole did not improve the control of symptoms compared with the standard dosage. Mean symptomatic score was 9.5±0.5 and 10.2±0.6 for each treatment, respectively (p>0.05). Conclusion. There was no significant improvement in the patient GERD symptoms increasing the dose of oral esomeprazole during the 6 months of study. N-of-1 trials in chronic pathologies including GERD are recommended due to their potential value as systematic methods that evaluate therapies without strong scientific evidence.
New Predictive Equations for Resting Energy Expenditure in Normal to Overweight and Obese Population
Authors: Almajwal Ali M. , Abulmeaty Mahmoud M. A.
Published: December 2019

Background and Aims. The unique demographic and dietary characteristics of modern Arabic population require development of a new predictive equation for the estimation of resting energy expenditure (REE). This study presented new equations characteristic to Saudi population. Methods. A set of predictive equations for REE was derived for 427 healthy male and female subjects (aged 18–57 ± 14 years). REE was measured (REEm) by indirect calorimetry (IC) and predicted (REEp) using nine equations. REEp was compared with REEm to determine the predictive accuracy of these equations. Using IC and anthropometrics for stepwise linear regression analysis, a new set of equations to predict REE of men and women was developed. Accuracy of the new main equations was further tested in an external sample of 48 subjects (men = 50%). Results. Using a number of parameters (bias, underprediction, overprediction, and % accurate prediction), our results suggested that almost all (9/9 in men and 7/9 in women) equations either underpredicted or overpredicted (2/9) REE. None of the already existing equations showed an acceptable REEp/REEm difference as low as 5% and an accurate prediction (∼55%) at the individual level. Based on these findings, a new prediction equation (hereafter referred to as the Almajwal–Abulmeaty (AA) equation) was developed using this study’s data, after a rigorous stepwise regression analysis using the following formula: REE = 3832.955 + AdjWt (kg) × 48.037 − Ht (cm) × 30.642 + gender × 141.268 − age (years) × 4.525 [AdjWt is Adjusted body weight = (Wt − IBW)/4 + IBW. IBW is Ideal body weight; for men IBW = (Ht(cm) − 152.4) × 1.0714) + 45.36 and for women IBW = (Ht(cm)−152.4) × 0.8928) + 45.36]. The regression model accounted for approximately 70% of the variance in REEm (R2 = 0.702). Conclusion. Previous equations likely over- or underpredicted REE. Therefore, the new predictive AA equations developed in this study are recommended for the estimation of REE in young to middle-aged Saudi men and women with different body mass indexes. Future research is also required for further clinical and cross-validation of these new equations.
Subchronic Exposure to Cadmium Causes Persistent Changes in the Reproductive System in Female Wistar Rats
Authors: Nasiadek Marzenna , Danilewicz Marian , Klimczak Michał , Stragierowicz Joanna , Kilanowicz Anna
Published: December 2019

Cadmium (Cd) is an environmental toxicant and endocrine disruptor in humans and animals, and recent studies have illustrated that the uterus is exceedingly sensitive to Cd toxicity. The aim of the study was to investigate the influence of subchronic (90 days) oral Cd exposure in daily doses of 0.09-4.5 mg/kg b.w. on the balance of sex hormones by estimating estradiol (E2) and progesterone (P) concentrations in the uterus and plasma in comparison with the effects of 17β-E2. Additionally, the uterine weight, histopathological changes in the uterus and ovaries, the regularity of the estrous cycle, Cd bioaccumulation in uterine tissue, and selected biochemical parameters of oxidative stress were determined. A long period of observation (three and six months following the administration period) was used to assess whether the existing effects are reversible. The lowest dose of Cd caused effects similar to 17β-E2: an increase of E2concentration in the uterus, endometrial epithelium thickness, and disturbed estrous cycle with estrus phase prolongation. The obtained results suggest that Cd causes nonlinear response. Higher doses of Cd caused a significant decrease in E2concentration in the uterus and plasma, estrous cycle disturbances, endometrium atrophy, and structural damage in the ovaries. This dose additionally induces lipid peroxidation in the uterine tissues. It is noteworthy that a prolonged time of observation after terminating the exposure showed persistent changes in the concentration of E2in uterine tissue, as well as alterations in estrous cycle phases, and an increase in lipid peroxidation in the uterus. Moreover, significant positive correlations between the plasma E2concentration and endometrial epithelium thickness in all studied groups were found. In summary, subchronic oral Cd exposure of female rats may result in impaired fertility processes.
Multiobjective Optimization Model of Production Planning in Cloud Manufacturing Based on TOPSIS Method with Combined Weights
Authors: Li Zhiru , Xu Wei , Shi Huibin , Zhang Qingshan , He Fengyi
Published: December 2019

Combined with the research of mass customization and cloud manufacturing mode, this paper discussed the production planning of mass customization enterprises in the context of cloud manufacturing in detail, analyzed the attribute index of manufacturing resource combination, and given a system considering the characteristics of batch production in mass customization and the decentralization of manufacturing resources in cloud manufacturing environment. Then, a multiobjective optimization model has been constructed according to the product delivery date, product cost, and product quality that customers care most about. The Pareto solution set of production plan has been obtained by using NSGA‐II algorithm. This paper established a six‐tier attribute index system evaluation model for the optimization of production planning scheme set of mass customization enterprises in cloud manufacturing environment. The weight coefficients of attribute indexes were calculated by combining subjective and objective weights with analytic hierarchy process (AHP) and entropy weight method. Finally, the combined weights calculated were applied to the improved TOPSIS method, and the optimal production planning scheme has been obtained by ranking. This paper validated the effectiveness and feasibility of the multiobjective model and NSGA‐II algorithm by the example of company A. The Pareto effective solution has been obtained by solving the model. Then the production plan set has been sorted synthetically according to the comprehensive evaluation model, and the optimal production plan has been obtained.
Effect of an Acupuncture Technique of Penetrating through Zhibian (BL54) to Shuidao (ST28) with Long Needle for Pain Relief in Patients with Primary Dysmenorrhea: A Randomized Controlled Trial
Authors: Wang Haijun , Cao Yuxia , Jin Xiaofei , Yan Min , Wang Jianchao , Li Rangqian , Ji Laixi
Published: December 2019

Background. Primary dysmenorrhea (PD) is the commonest gynecological disorder in young women of reproductive age, and there is not always satisfactory relief of pain treated by common medications. Therefore, acupuncture has been used as an alternative therapy to relieve the symptoms of PD. In clinical practice, a penetrating method of acupuncture with long needle has been shown to be particularly effective for improving primary dysmenorrhea. This study was conducted to evaluate the effectiveness of this technique for pain relief in patients with primary dysmenorrhea as compared with a conventional pain medication. Methods. The present study is a perspective, randomized, ibuprofen-controlled trial. Sixty-two eligible participants were randomly assigned in a 1 : 1 ratio to receive either acupuncture treatment or ibuprofen administration. The treatment lasted for three menstrual cycles for both groups. The primary outcome was the intensity of menstrual pain measured by using the visual analogue scale at the completion of treatment. Secondary outcomes included the severity of symptoms associated with menstrual pain, responder rate, and safety of acupuncture treatment. The clinical outcomes were measured on each menstrual cycle at baseline, treatment course (3 cycles), and follow-up period. Results. Sixty-four patients of primary dysmenorrhea were recruited, and 62 subjects were included in the final analysis. At trial completion, acupuncture was shown to be associated with a significantly lower pain intensity and decreased symptom severity of primary dysmenorrhea as compared with ibuprofen (p<0.05). A significantly higher responder rate was found in the acupuncture group as compared with the control group (p<0.05). No serious adverse events were reported by patients in either group. Conclusions. The penetrating method of acupuncture with long needle may be an effective and safe therapy for pain relief in patients with primary dysmenorrhea. This trial was registered with the Chinese Clinical Trial Registry (ChiCTR-IOR-17012621).
Delayed Bone Age Might Accelerate the Response to Human Growth Hormone Treatment in Small for Gestational Age Children with Short Stature
Authors: Moon Jung-Eun , Ko Cheol Woo
Published: December 2019

Purpose. Growth hormone (GH) treatment is recommended to improve growth and psychosocial problems in short stature children born small for gestational age (SGA). Although GH therapy in these patients has been extensively studied, the impact of therapy according to delays in bone age (BA) is not known well.Objective.To investigate the effects of GH therapy in SGA patients with short stature according to BA delay.Methods. We retrospectively analyzed changes in height SD score (SDS) and BA/chronological age (CA) after 6 and 12 months of GH therapy in patients grouped according to BA delay. We studied 27 SGA children with short stature in the pediatric endocrinology clinic of Kyungpook National University Children’s Hospital.Results. Of the 27 patients, 9 had <2 years of BA delay, while 18 had >2 years of delay. There were no significant differences between the two groups in terms of gestational age and weight at birth, height SDS, IGF-1 SDS, and growth hormone dosage at the beginning of therapy. However, height SDS increased significantly in the group with >2 years of BA delay after 6 months of GH therapy (−2.50 ± 0.61 vs −1.87 ± 0.82;p=0.037) and 12 months (−2.27 ± 0.70 vs −1.63 ± 0.65;p=0.002). When height SDS was compared between with and without GHD, there were no significant differences.Conclusions. Delayed BA (>2 years) may impact the response to GH treatment in SGA children with short stature.
Ultrasound Measurements of Fetal Thyroid: Reference Ranges from a Cohort of Low-Risk Pregnant Women
Authors: Barbosa R. M. , Andrade K. C. , Silveira C. , Almeida C. M. , Souza R. T. , Oliveira P. F , Cecatti Jose Guilherme
Published: December 2019

Background. Adequate thyroid function is essential for normal growth and development of the fetus. Sonographic recognition of alterations in fetal thyroid dimensions may be the first sign of thyroid dysfunction, permitting early diagnosis and intervention. The main goal of this study was to build curves with reference values for ultrasound measurements of the fetal thyroid from 14 to 40 weeks of gestation. Methods. This is a prospective longitudinal study of 90 Brazilian pregnant women, complementary to a cohort multicentre study named “WHO multicentre study for the development of growth standards from fetal life to childhood: the fetal component.” Pregnant women without any pre-existing conditions that might affect fetal growth received antenatal care from the first trimester until childbirth, undergoing serial ultrasound evaluations of the fetus, including the thyroid. Longitudinal, anteroposterior, and transverse diameters of both thyroid lobes were measured in the fetus. Fetal thyroid lobe volume was also estimated. By quantile regression analysis, reference curves of measurements were fitted according to the gestational age. Results. A reference standard of thyroid growth was defined during pregnancy by fitting curves of its measurements. Reference values for the 10th, 50th, and 90th centiles of fetal thyroid measurements (longitudinal, anteroposterior, transverse diameters, and lobe volume) were defined, from 14 to 40 weeks of gestation. Conclusion. We provided a reference curve of optimal thyroid development in a low-risk population that can be used as a standard of comparison to diagnose deviations from the norm. In addition, we demonstrated an alternative and simplified method for early recognition of thyroid morphological alterations by an individualized technique to evaluate the thyroid lobes.
Genomic and Phenotypic Characterization of a Broad Panel of Patient-Derived Xenografts Reflects the Diversity of Glioblastoma
Authors: Vaubel Rachael A. , Tian Shulan , Remonde Dioval , Schroeder Mark A. , Mladek Ann C. , Kitange Gaspar J. , Caron Alissa , Kollmeyer Thomas M. , Grove Rebecca , Peng Sen , Carlson Brett L. , Ma Daniel J. , Sarkar Gobinda , Evers Lisa , Decker Paul A. , Yan Huihuang , Dhruv Harshil D. , Berens Michael E. , Wang Qianghu , Marin Bianca M. , Klee Eric W. , Califano Andrea , LaChance Daniel H. , Eckel-Passow Jeanette E. , Verhaak Roel G. , Sulman Erik P. , Burns Terry C. , Meyer Fredrick B. , O'Neill Brian P. , Tran Nhan L. , Giannini Caterina , Jenkins Robert B. , Parney Ian F. , Sarkaria Jann N.
Published: December 2019

Purpose:

Glioblastoma is the most frequent and lethal primary brain tumor. Development of novel therapies relies on the availability of relevant preclinical models. We have established a panel of 96 glioblastoma patient-derived xenografts (PDX) and undertaken its genomic and phenotypic characterization.

Experimental Design:

PDXs were established from glioblastoma, IDH-wildtype (n = 93), glioblastoma, IDH-mutant (n = 2), diffuse midline glioma, H3 K27M-mutant (n = 1), and both primary (n = 60) and recurrent (n = 34) tumors. Tumor growth rates, histopathology, and treatment response were characterized. Integrated molecular profiling was performed by whole-exome sequencing (WES, n = 83), RNA-sequencing (n = 68), and genome-wide methylation profiling (n = 76). WES data from 24 patient tumors was compared with derivative models.

Results:

PDXs recapitulate many key phenotypic and molecular features of patient tumors. Orthotopic PDXs show characteristic tumor morphology and invasion patterns, but largely lack microvascular proliferation and necrosis. PDXs capture common and rare molecular drivers, including alterations of TERT, EGFR, PTEN, TP53, BRAF, and IDH1, most at frequencies comparable with human glioblastoma. However, PDGFRA amplification was absent. RNA-sequencing and genome-wide methylation profiling demonstrated broad representation of glioblastoma molecular subtypes. MGMT promoter methylation correlated with increased survival in response to temozolomide. WES of 24 matched patient tumors showed preservation of most genetic driver alterations, including EGFR amplification. However, in four patient–PDX pairs, driver alterations were gained or lost on engraftment, consistent with clonal selection.

Conclusions:

Our PDX panel captures the molecular heterogeneity of glioblastoma and recapitulates many salient genetic and phenotypic features. All models and genomic data are openly available to investigators.
EGFRAmplification Induces Increased DNA Damage Response and Renders Selective Sensitivity to Talazoparib (PARP Inhibitor) in Glioblastoma
Authors: Wu Shaofang , Gao Feng , Zheng Siyuan , Zhang Chen , Martinez-Ledesma Emmanuel , Ezhilarasan Ravesanker , Ding Jie , Li Xiaolong , Feng Ningping , Multani Asha , Sulman Erik P. , Verhaak Roel G. , de Groot John F. , Heffernan Tim P. , Yung W.K. Alfred , Koul Dimpy
Published: December 2019

Purpose:

Exploration of novel strategies to extend the benefit of PARP inhibitors beyond BRCA-mutant cancers is of great interest in personalized medicine. Here, we identified EGFR amplification as a potential biomarker to predict sensitivity to PARP inhibition, providing selection for the glioblastoma (GBM) patient population who will benefit from PARP inhibition therapy.

Experimental Design:

Selective sensitivity to the PARP inhibitor talazoparib was screened and validated in two sets [test set (n = 14) and validation set (n = 13)] of well-characterized patient-derived glioma sphere-forming cells (GSC). FISH was used to detect EGFR copy number. DNA damage response following talazoparib treatment was evaluated by γH2AX and 53BP1 staining and neutral comet assay. PARP–DNA trapping was analyzed by subcellular fractionation. The selective monotherapy of talazoparib was confirmed using in vivo glioma models.

Results:

EGFR-amplified GSCs showed remarkable sensitivity to talazoparib treatment. EGFR amplification was associated with increased reactive oxygen species (ROS) and subsequent increased basal expression of DNA-repair pathways to counterelevated oxidative stress, and thus rendered vulnerability to PARP inhibition. Following talazoparib treatment, EGFR-amplified GSCs showed enhanced DNA damage and increased PARP–DNA trapping, which augmented the cytotoxicity. EGFR amplification–associated selective sensitivity was further supported by the in vivo experimental results showing that talazoparib significantly suppressed tumor growth in EGFR-amplified subcutaneous models but not in nonamplified models.

Conclusions:

EGFR-amplified cells are highly sensitive to talazoparib. Our data provide insight into the potential of using EGFR amplification as a selection biomarker for the development of personalized therapy.
The Cytosolic DNA-Sensing cGAS–STING Pathway in Cancer
Authors: Kwon John , Bakhoum Samuel F.
Published: December 2019

The recognition of DNA as an immune-stimulatory molecule is an evolutionarily conserved mechanism to initiate rapid innate immune responses against microbial pathogens. The cGAS–STING pathway was discovered as an important DNA-sensing machinery in innate immunity and viral defense. Recent advances have now expanded the roles of cGAS–STING to cancer. Highly aggressive, unstable tumors have evolved to co-opt this program to drive tumorigenic behaviors. In this review, we discuss the link between the cGAS–STING DNA-sensing pathway and antitumor immunity as well as cancer progression, genomic instability, the tumor microenvironment, and pharmacologic strategies for cancer therapy.

Significance:

The cGAS–STING pathway is an evolutionarily conserved defense mechanism against viral infections. Given its role in activating immune surveillance, it has been assumed that this pathway primarily functions as a tumor suppressor. Yet, mounting evidence now suggests that depending on the context, cGAS–STING signaling can also have tumor and metastasis-promoting functions, and its chronic activation can paradoxically induce an immune-suppressive tumor microenvironment.
CD40 Enhances Type I Interferon Responses Downstream of CD47 Blockade, Bridging Innate and Adaptive Immunity
Authors: de Silva Suresh , Fromm George , Shuptrine Casey W. , Johannes Kellsey , Patel Arpita , Yoo Kyung Jin , Huang Kaiwen , Schreiber Taylor H.
Published: December 2019

Disrupting the binding of CD47 to SIRPα has emerged as a promising immunotherapeutic strategy for advanced cancers by potentiating antibody-dependent cellular phagocytosis (ADCP) of targeted antibodies. Preclinically, CD47/SIRPα blockade induces antitumor activity by increasing the phagocytosis of tumor cells by macrophages and enhancing the cross-presentation of tumor antigens to CD8+ T cells by dendritic cells; both of these processes are potentiated by CD40 signaling. Here we generated a novel, two-sided fusion protein incorporating the extracellular domains of SIRPα and CD40L, adjoined by a central Fc domain, termed SIRPα-Fc-CD40L. SIRPα-Fc-CD40L bound CD47 and CD40 with high affinity and activated CD40 signaling in the absence of Fc receptor cross-linking. No evidence of hemolysis, hemagglutination, or thrombocytopenia was observed in vitro or in cynomolgus macaques. Murine SIRPα-Fc-CD40L outperformed CD47 blocking and CD40 agonist antibodies in murine CT26 tumor models and synergized with immune checkpoint blockade of PD-1 and CTLA4. SIRPα-Fc-CD40L activated a type I interferon response in macrophages and potentiated the activity of ADCP-competent targeted antibodies both in vitro and in vivo. These data illustrated that whereas CD47/SIRPα inhibition could potentiate tumor cell phagocytosis, CD40-mediated activation of a type I interferon response provided a bridge between macrophage- and T-cell–mediated immunity that significantly enhanced durable tumor control and rejection.
Influence of the Covering Area of Major Connectors of Mandibular Dentures on the Accuracy of Speech Production: A Pilot Study
Authors: Wada Junichiro , Hideshima Masayuki , Uchikura Keiichiro , Shichiri Yuka , Inukai Shusuke , Matsuura Hiroshi , Wakabayashi Noriyuki
Published: December 2019

Background/Objectives: Speech impairment during the initial phase of removable partial denture (RPD) treatment can prevent patient adaptation to RPDs. This quasi-experimental study aimed to investigate the influence of the covering area of major connectors located in the mandibular anterior region on the accuracy of speech production. Methods: Fifteen adults (12 men and 3 women aged 26–40 years) with healthy dentition were recruited. Four target syllables were used for the assessments: [ʃi], [ʧi], [çi], and [ki]. There were four speaking conditions: without a connector (control), wearing lingual bar (5 mm width), wearing lingual plates (12 mm width), and wearing connectors covering the occlusal surface of lower dentition (16 mm width; CO). The accuracy of speech production was evaluated by mean appearance ratio of correct labels (MARC) and incorrect labels (MARIC) of the phonetic segments which were calculated with a speech evaluation system (VoiceAnalyzer). Results: The MARC in the 3 target syllables [ʃi], [ʧi], and [ki] significantly decreased with CO. For the target syllable [ʃi], the MARICs of [ʧi], [ʤi], and [çi] with CO were significantly lower than that in the control. For the target syllable [ʧi], the MARIC of [ki] with CO was significantly higher than that in the control. For the target syllable [çi], the MARIC of [gi] with CO was significantly higher than that in the control. Conclusion: RPDs with major connectors covering the lower dentition could disturb speech production during the initial phase of RPD treatment. Prosthodontic treatment with such RPD designs requires further consideration regarding the information given to patients before starting the treatment.
Intradialytic Hypotension: Mechanisms and Outcome
Authors: Sars Benedict , van der Sande Frank M. , Kooman Jeroen P.
Published: December 2019

Intradialytic hypotension (IDH) occurs in approximately 10–12% of treatments. Whereas several definitions for IDH are available, a nadir systolic blood pressure carries the strongest relation with outcome. Whereas the relation between IDH may partly be based on patient characteristics, it is likely that also impaired organ perfusion leading to permanent damage, plays a role in this relationship. The pathogenesis of IDH is multifactorial and is based on a combination of a decline in blood volume (BV) and impaired vascular resistance at a background of a reduced cardiovascular reserve. Measurements of absolute BV based on an on-line dilution method appear more promising than relative BV measurements in the prediction of IDH. Also, feedback treatments in which ultrafiltration rate is automatically adjusted based on changes in relative BV have not yet resulted in improvement. Frequent assessment of dry weight, attempting to reduce interdialytic weight gain and prescribing more frequent or longer dialysis treatments may aid in preventing IDH. The impaired vascular response can be improved using isothermic or cool dialysis treatment which has also been associated with a reduction in end organ damage, although their effect on mortality has not yet been assessed. For the future, identification of vulnerable patients based on artificial intelligence and on-line assessment of markers of organ perfusion may aid in individualizing treatment prescription, which will always remain dependent on the clinical context of the patient.
Diagnosis of Acute Kidney Injury in Children Hospitalized in a Sub-Saharan African Unit by Saliva Urea Nitrogen Dipstick Test
Authors: Hussein Rasha H. , Calice-Silva Viviane , Evans Rhys , Levin Nathan W. , Ellidir Rashid A. , Ali Elitigani M. , Bakhiet Yassir , Ahmed Amna , Abdelkareem Asmaa , Abdelraheem Mohamed B. , Kotanko Peter , Pecoits-Filho Roberto , Raimann Jochen G. ,   the International Society of Nephrology (ISN) 0by25 Initiative
Published: December 2019

Introduction: Acute kidney injury in pediatric patients (pAKI) is common in developing countries and leads to significant morbidity and mortality. Most nephrology services in developing countries are only in larger cities and for that reason many cases remain undiagnosed. We evaluated the performance of a saliva urea nitrogen (SUN) dipstick to diagnose pAKI in Sudan. Methods: We collected demographic and clinical information, serum creatinine (SCr), blood urea nitrogen (BUN), SUN, and urine output (UO) in children with pAKI. pAKI was diagnosed based on different criteria (Risk, Injury, Failure, Loss of kidney function, and end-stage kidney disease, Acute Kidney Injury Network and Kidney Disease Improving Global Outcomes). We also recorded hospital and 3-months’ mortality and progression to chronic kidney disease (CKD) as outcomes. Results: We studied 81 patients (mean age 10.7 ± 7 years, 51.9% females) and divided them by age into (a) neonates (<120 days; n = 21; 25.9%); (b) ­infants (120–365 days; n = 18; 25.9%); and (c) children (>365 days; n = 42; 53.1%). Diagnosis using different pAKI definitions resulted in differences in AKI staging. SUN reliably reflected BUN over the entire study period, regardless of treatment modality or pAKI severity. Neither pAKI staging, SUN, BUN, nor SCr were associated with mortality or progression to CKD. UO predicted all-cause mortality during the 3-months follow-up. Conclusion: Diagnosis of pAKI using different criteria differs in triage and staging. SUN reflects BUN particularly at higher BUN levels and allows monitoring of treatment responses. Despite the lack of predictive power of SUN to predict hard outcomes, measurement of SUN by dipstick can be used to identify, screen, and monitor pediatric patients with pAKI.
Itch and Ache on Dialysis: New Approaches to Manage Uremic Pruritus and Restless Legs
Authors: Arzhan Soraya , Roumelioti Maria-Eleni , Unruh Mark L.
Published: December 2019

Background: Uremic pruritus (UP) and restless legs syndrome (RLS) are highly prevalent complaints among patients with end-stage renal disease (ESRD) undergoing chronic dialysis. These chronic troublesome symptoms lead to a significant decrease in quality of life (QOL) and increase in mortality rate. Despite their distressing characteristics, these symptoms usually remain under-recognized by healthcare providers. Therefore, careful history intake, and stepwise treatment are essential. Numerous pharmacological and non-pharmacological treatments have been demonstrated to help in controlling these 2 conditions. Summary: In this review, we discuss the latest findings regarding UP and RLS among ESRD patients on maintenance dialysis. We also examine different treatment options in this group of patients. The majority of these patients do not have the opportunity to receive a kidney transplant and need other treatments for these burdensome symptoms in order to improve their QOL and prognosis. Key Messages: UP and RLS are common but underdiagnosed conditions in ESRD patients on maintenance dialysis that are related to a decline in patients’ QOL and poor prognosis. The pathophysiology of these conditions remains not well understood. Therefore, controversies still exist on treatment options. Treating these conditions provides an opportunity to improve the health-related QOL and outcomes of dialysis patients.
Non-Caloric Artificial Sweeteners Modulate the Expression of Key Metabolic Genes in the Omnipresent Gut Microbe Escherichia coli
Authors: Mahmud Rizwan , Shehreen Saadlee , Shahriar Shayan , Rahman Md Siddiqur , Akhteruzzaman Sharif , Sajib Abu Ashfaqur
Published: December 2019

The human gut is inhabited by several hundred different bacterial species. These bacteria are closely associated with our health and well-being. The composition of these diverse commensals is influenced by our dietary intakes. Non-caloric artificial sweeteners (NAS) have gained global popularity, particularly among diabetic patients, due to their perceived health benefits, such as reduction of body weight and maintenance of blood glucose level compared to caloric sugars. Recent studies have reported that these artificial sweeteners can alter the composition of gut microbiota and, thus, affect our normal physiological state. Here, we investigated the effect of aspartame and acesulfame potassium (ace-K), two popular NAS, in a commercial formulation on the growth and metabolic pathways of omnipresent gut commensal Escherichia coliby analyzing the relative expression levels of the key genes, which control over twenty important metabolic pathways. Treatment with NAS preparation (aspartame and ace-K) modulates the growth of E. colias well as inducing the expression of important metabolic genes associated with glucose (pfkA, sucA, aceE, pfkB, lpdA), nucleotide (tmk, adk, tdk, thyA), and fatty acid (fabI) metabolisms, among others. Several of the affected geneswere previously reported to be important for the colonization of the microbes in the gut. These findings may shed light on the mechanism of alteration of gut microbes and their metabolism by NAS.
Asymmetric Slow-Spike-Wave Patterns with Maximal Discharges Contralateral to MRI Lesions Predict Better Surgical Prognosis in Symptomatic Lennox-Gastaut Syndrome or Lennox-Gastaut Phenotypes
Authors: Yang Mei-Hua , Liu Juan , Zhou Yi-Ling , Yang Hui , Cai Fang-Cheng , Zempel  John , Yang Qing-Wu , Liu Shi-Yong
Published: December 2019

Introduction: Lennox-Gastaut syndrome (LGS) is a severe subtype of childhood-onset epileptic encephalopathy with drug-resistant and poor surgical prognosis. However, electroencephalogram (EEG) patterns of symptomatic LGS or LG phenotypes with structural brain lesions including focal abnormalities or asymmetric slow-spike-wave (SSW) patterns remain largely unknown. Due to the contradictory lateralization difference between MRI lesions and EEG pattern in symptomatic LGS or LG phenotypes, it is difficult to determine the precise lateralization of epileptic lesions, which is crucial to better surgical prognosis. This study is aim to ascertain the clinical characteristics of the EEG patterns, and its relationship with MRI lesions and to evaluate its prognostic value of surgical treatment in symptomatic LGS or LG phenotypes. Methods: Twenty-four symptomatic LGS cases with asymmetric EEG SSW patterns and contralaterally independent or contralaterally dominant MRI lesions were collected, and their clinical features were analyzed retrospectively. Results: In this cohort, most of lesions were perinatal or acquired during the first 6 months of life. The most common etiology was intracerebral hemorrhage. The LGS patients with both asymmetric SSW and focal sporadic epileptic waves (SEW) patterns showed the best surgical outcome with Engel class I level. Asymmetric SSW patterns with maximal discharges contralateral to MRI lesions were frequently observed in most of symptomatic LGS or LG phenotypes. Predominantly diffuse destructive lesions led to an attenuated voltage of ipsilateral scalp EEG producing an asymmetric SSW pattern in those patients with symptomatic LGS or LG phenotypes. Conclusions: Our study reveals a special SEW EEG pattern in symptomatic LG patients with asymmetric SSW and MRI lesions contralateral to the dominant EEG patterns. Contradictory lateralization difference between MRI and EEG probably arises from the relative voltage attenuation presenting in EEG ipsilateral to huge destructive lesions from early life. Our study suggests that the independent focal SEW activity remaining ipsilateral to the MRI lesion can potentially predict better surgical prognosis in symptomatic LGS or LG phenotypes.
Hearing Improvement after Sudden Sensorineural Hearing Loss as a Predictor of Vestibular Schwannoma
Authors: Ungar Omer J. , Wengier Anat , Cavel Oren , Handzel Ophir , Oron Yahav
Published: December 2019

Introduction: Sudden sensorineural hearing loss (SSNHL) can be the presenting symptom of vestibular schwannoma (VS). Usually, steroidal treatment is given before magnetic resonance imaging (MRI) is performed. Objectives: The aim of this study was to investigate whether there is a different pattern of steroidal treatment response after SSNHL in patients with and without a VS, in order to determine whether rapid hearing improvement can serve as a predictor of the presence of VS. Methods: Charts of patients with SSNHLs were reviewed. Analysis of the presenting symptoms of patients with an SSNHL with and without a coexisting VS and comparison of the response to steroids of the two groups of patients was performed. Results: A total of 420 patients were treated for SSNHLs during the study period. Treatment consisted of intraoral prednisone 1 mg/kg/day. The male-to-female ratio was 1.00:1.17, and the median age at diagnosis was 38 years (range 18–82); neither parameter correlated with the presence of VS. MRI scans demonstrated a VS in 20 patients (4.76%). Audiometric testing 7 days after steroidal treatment initiation revealed that the pure-tone average of 240 patients (60%) without VS improved, and that of the 16 (80%) patients with VS improved by the same audiometric criteria (p = 0.0007). Conclusions:Improvement of hearing within 1 week after steroidal treatment initiation in patients with SSNHLs may suggest the presence of a VS.
New Drugs, Old Toxicities: Pneumonitis Related to Palbociclib – A Case Report
Authors: Felip Eudald , Llobera Laia , Perez-Mañá Clara , Quintela David , Guasch Ignacio , Margelí Mireia , Teruel Iris , Cirauqui Beatriz , Centeno Carmen , Romeo Margarita , Ballana Ester , Quiroga Vanesa
Published: December 2019

Background: Palbociclib is a specific inhibitor of cyclin-dependent kinases 4 and 6 that is approved for the treatment of advanced or metastatic breast cancer patients. Despite a good toxicity profile in pivotal trials, where asymptomatic neutropenia was the main adverse effect, its wider use in clinical practice may show less prevalent but serious toxicities. Case Presentation: Here, we describe a case of pneumonitis due to palbocicblib. A 57-year-old female with breast cancer with bone metastasis presented dyspnea at rest 3 months after beginning treatment with palbociclib and letrozole. Palbociclib-induced pneumonitis was considered the most probable cause after ruling out all alternatives, and the patient was successfully treated with steroids and showed complete remission. Conclusions: In summary, we present a well-documented case report of pneumonitis related to palbociclib. However, the mechanism of toxicity is still unknown, and there are as yet no reliable biomarkers to predict toxicity with cyclin-dependent kinase 4/6 inhibitors. In this case report, we alert physicians about new drugs that can provoke old toxicities.
Comparison of the Perioperative and Postoperative Outcomes of Ileal Conduit and Cutaneous Ureterostomy: A Propensity Score-Matched Analysis
Authors: Suzuki Kotaro , Hinata Nobuyuki , Inoue Taka-aki , Nakamura Ichiro , Nakano Yuzo , Fujisawa Masato
Published: December 2019

Introduction: To compare perioperative and postoperative outcomes related to urinary diversion (UD) between ileal conduit and cutaneous ureterostomy following open radical cystectomy (ORC). Methods: This retrospective study included 232 patients with bladder cancer who underwent ORC and subsequent UD (ileal conduit, n = 123; cutaneous ureterostomy, n = 109) at Kobe University and related hospitals between January 2007 and December 2016. A propensity score method was used to adjust the preoperative status of the two groups, and the perioperative and postoperative outcomes were compared between matched cohorts. In addition, we evaluated several factors predicting renal deterioration. Results: In the matched cohorts, 87 patients were included in each group. While the operative time and postoperative fasting periods were significantly longer in patients with ileal conduit in comparison to those with cutaneous ureterostomy (both p < 0.001), there were no differences in blood loss or duration of hospitalization. Although the incidence of grade ≥III perioperative complications was similar between the two groups, the incidence of postoperative recurrent pyelonephritis in the cutaneous ureterostomy group was significantly higher than that in the ileal conduit group (25.3 and 11.4%, respectively; p = 0.030), and cutaneous ureterostomy was identified as a significant predictor of a decrease in the estimated glomerular filtration rate with an odds ratio of 2.13 (95% confidence interval, 1.19–3.85; p = 0.010). Conclusions: The perioperative safety of ileal conduit was comparable to that of cutaneous ureterostomy, and cutaneous ureterostomy was a significant risk factor for pyelonephritis and subsequent renal deterioration, suggesting that ileal conduit may be preferable to cutaneous ureterostomy.
Characterization of Alanine Dehydrogenase and Its Effect on Streptomyces coelicolorA3(2) Development in Liquid Culture
Authors: Van Wieren Arie , Cook Ryan , Majumdar Sudipta
Published: December 2019

Streptomyces, the most important group of industrial microorganisms, is harvested in liquid cultures for the production of two-thirds of all clinically relevant secondary metabolites. It is demonstrated here that the growth of Streptomyces coelicolor A3(2) is impacted by the deletion of the alanine dehydrogenase (ALD), an essential enzyme that plays a central role in the carbon and nitrogen metabolism. A long lag-phase growth followed by a slow exponential growth of S. coelicolor due to ALD gene deletion was observed in liquid yeast extract mineral salt culture. The slow lag-phase growth was replaced by the normal wild-type like growth by ALD complementation engineering. The ALD enzyme from S. coelicolor was also heterologously cloned and expressed in Escherichia coli for characterization. The optimum enzyme activity for the oxidative deamination reaction was found at 30°C, pH 9.5 with a catalytic efficiency, kcat/KM, of 2.0 ± 0.1 mM–1 s–1. The optimum enzyme activity for the reductive amination reaction was found at 30°C, pH 9.0 with a catalytic efficiency, kcat/KM, of 1.9 ± 0.1 mM–1 s–1.
Isolated Ocular Sarcoidosis Mimicking Ring Melanoma
Authors: Faber Carsten , Ejstrup Rasmus , Madsen Karine , Heegaard Steffen , Scheie David , Kiilgaard Jens Folke
Published: December 2019

We report the case of a 25-year-old female, who presented with a large, pale tumor of her ciliary body that extended to >180° of the anterior chamber angle. All preoperative examinations including ultrasound biomicroscopy, scleral transillumination, and MRI indicated melanoma. A thorough systemic work-up was negative. A diagnosis of ring melanoma was suspected, and the patient was scheduled for enucleation. However, perioperative frozen section indicated granulomatous inflammation. The enucleation was cancelled, and a subtenon injection of triamcinolone was administered, which resulted in the disappearance of the tumor. Together, the findings meet the criteria for the diagnosis of isolated ocular sarcoidosis. This case demonstrates that a sarcoid granuloma can mimic all clinical features of a ring melanoma. Therefore, a biopsy should be done before destructive surgery is carried out.
Causes that Contribute to the Excess Mortality Risk in Multiple Sclerosis: A Population-Based Study
Authors: Kingwell Elaine , Zhu Feng , Evans Charity , Duggan Thomas , Oger Joel , Tremlett Helen
Published: December 2019

Background: Lifespan is 6–10 years shorter in multiple sclerosis (MS), but the reasons remain unclear. Using linked clinical- and population-based administrative health databases, we compared cause-specific mortality in an MS cohort to the general population. Methods: MS patients in British Columbia (BC), Canada, were followed from the later of first MS clinic visit or January 1, 1986, to the earlier of death, emigration, or December 31, 2013. Comprehensive mortality information was obtained by linkage to BC’s multiple-cause-of-death mortality data. Causes were grouped using International Classification of Disease codes. Standardized mortality ratios (SMRs) were calculated for underlying cause, and relative mortality ratios (RMRs) for any mention cause, by comparison to mortality rates in the age-, sex-, and calendar year-matched general population. Cause-specific relative mortality was explored by sex and disease course (relapsing onset and primary progressive). Results: Among 6,629 MS patients with 104,236 patient-years of follow-up, 1,416 died. The all-cause mortality risk was increased relative to the general population (SMR 2.71; 95% CI 2.55–2.87). MS was the underlying cause in 50.4%, and a mentioned cause in 77.9%, of deaths. Mortality by underlying cause was higher than expected for genitourinary disorders/infections (SMR 3.55; 95% CI 2.25–5.32), respiratory diseases/infections (SMR 2.69; 95% CI 2.17–3.28), suicide (SMR 2.40; 95% CI 1.61–3.45), cardiovascular disease (SMR 1.57; 95% CI 1.36–1.81), and other infections/septicemia (SMR 1.83; 95% CI 1.15–2.78). Risks of death due to overall cancer, accidents, digestive system disorders, and endocrine/nutritional diseases as underlying causes were similar to the general population. However, mortality with any mention of accidents (RMR 2.71; 95% CI 2.22–3.29) or endocrine/nutritional diseases (RMR 1.75; 95% CI 1.46–2.09) was greater. Bladder cancer mortality was increased in women (SMR 3.87; 95% CI 1.42–8.42) but not men. No notable differences were observed by disease course. Conclusions: MS itself was the most frequent underlying cause of death. Infections (genitourinary, respiratory, and septicemia), suicides, cardiovascular disease, and accidents contributed significantly to the increased risk of death. Some findings differed by sex, but not disease course. Multiple-cause death data offer advantages over “traditional” use of underlying cause only.
СИСТЕМНІ ВЗАЄМОДІЇ В МІКРОРНК У ПАТОГЕНЕЗІ СЕРЦЕВО-СУДИННИХ ЗАХВОРЮВАНЬ
Authors: Mintser O. P. , Zaliskyi V. M.
Published: December 2019

Оглядово-аналітична стаття присвячена аналізу ролі мікроРНК (miRNAs) у модуляції експресії генів у біологічних подіях, у першу чергу, при серцево-судинних захворюваннях. Наведено окремі мікроРНК, що спричиняють системний регулюючий вплив на експресію цільових генів таких процесів, як гіпертонія міокарда, фіброз і апоптоз. Аналізується група мікроРНК, що може мати особливе значення в онтогенезі серцево-судинних захворювань (ССЗ), оскільки вони модулюють експресію генів цільових кластерів, ділянок багатьох патологічних серцево-судинних реакцій. Огляд ілюструє залучення мікроРНК у мережеву взаємодію внутрішньоклітинних сигнальних шляхів і позиціонує важливу регуляторну кооперацію мікроРНК у ССЗ. Постулюється, що накопичені дані про роль мікроРНК у патогенезі хвороб, у першу чергу, в патогенезі серцево-судинних захворювань є основою для подальших інноваційних рішень в області розроблення методів діагностики та системної терапії на основі використання посттрансляційних регуляторів. Підкреслюється, що циркулюючі мікроРНК можуть бути запропоновані в якості перспективних діагностичних і прогностичних біомаркерів ССЗ, таких як інфаркт міокарда, атеросклероз, ішемічна хвороба серця, серцева недостатність тощо.