bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in background parenchymal enhancement in HER2-positive breast cancer before and after neoadjuvant chemotherapy
Authors: Dong Jing-Min , Wang Hong-Xia , Zhong Xiao-Fei , Xu Kun , Bian Jia , Feng Yan , Chen Liang , Zhang Lin , Wang Xia , Ma De-Jing , Wang Bin
Published: October 2018

This study aimed to analyze the relationship between pathologic complete response (pCR) and changes in background parenchymal enhancement (BPE) levels in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer and who received neoadjuvant chemotherapy (NAC).

The pre- and post-NAC magnetic resonance imaging results of 51 patients with confirmed unilateral HER2-positive breast cancer were retrospectively analyzed by 2 experienced radiologists. Pre- and post-NAC of contralateral BPE levels were classified into 4 categories (1 = minimal, 2 = mild, 3 = moderate, and 4 = marked). The 4 categories of BPE were defined by the visually estimated enhancement of fibroglandular tissue of the breast. Changes in BPE before and after NAC were compared between the premenopausal and postmenopausal groups and between the pCR and non-pCR groups. The associations between BPE and pCR and between BPE and tumor size were analyzed before and after NAC.

Twenty-three patients achieved pCR, and 28 patients achieved non-pCR. Premenopausal patients had significantly higher baseline BPE levels than postmenopausal women (P = .023). The post-NAC BPE levels of premenopausal patients significantly decreased relative to those of postmenopausal patients (P = .027). The baseline BPE levels of the pCR group were not significantly different from those of the non-pCR group (P = .892). However, the decrease in BPE levels in the pCR group was more drastic than that in the non-pCR group (P < .001). Decreased BPE levels were directly associated with pCR and tumor size reduction (P < .05). Women with hormone receptor (HR)-negative tumors were more likely to exhibit pCR than those with HR-positive tumors (P = .007).

Decreased BPE of patients with HER2-positive breast cancer may serve as an indicator of NAC effectiveness. Furthermore, women with HR-negative tumors were more likely to exhibit pCR than women with HR-positive tumors.
Choosing between ticagrelor and clopidogrel following percutaneous coronary intervention
Authors: Guan Wenjun , Lu Hongtao , Yang Keping
Published: October 2018

Background:

Limitations have been observed with the use of clopidogrel following percutaneous coronary intervention (PCI) indicating the urgent need of a more potent anti-platelet agent. We aimed to compare the efficacy and safety of ticagrelor versus clopidogrel following PCI.

Methods:

Online databases were searched for relevant studies (published between the years 2007 and 2017) comparing ticagrelor versus clopidogrel following coronary stenting. Primary outcomes assessed efficacy whereas secondary outcomes assessed safety. Odds ratios (OR) with 95% confidence intervals (CIs) based on a random effect model were calculated and the analysis was carried out by the RevMan 5.3 software.

Results:

A total number of 25,632 patients with acute coronary syndrome (ACS) [12,992 patients with ST segment elevation myocardial infarction (STEMI) and 14,215 patients with non-ST segment elevation myocardial infarction (NSTEMI)] were included in this analysis, of whom 23,714 patients were revascularized by PCI. Results of this analysis did not show any significant difference in all-cause mortality, major adverse cardiac events (MACEs), myocardial infarction, stroke and stent thrombosis observed between ticagrelor and clopidogrel with (OR: 0.83, 95% CI: 0.67–1.03; P = .09), (OR: 0.64, 95% CI: 0.41–1.01; P = .06), (OR: 0.77, 95% CI: 0.57–1.03; P = .08), (OR: 0.85, 95% CI: 0.57–1.26; P = .42) and (OR: 0.70, 95% CI: 0.47–1.05; P =.09).

However, ticagrelor was associated with a significantly higher minor and major bleeding with (OR: 1.57, 95% CI: 1.30–1.89; P = .00001) and (OR: 1.52, 95% CI: 1.01–2.29; P = 0.04) respectively. Dyspnea was also significantly higher in the ticagrelor group (OR: 2.64, 95% CI: 1.87–3.72; P = .00001).

Conclusion:

Ticagrelor and clopidogrel were comparable in terms of efficacy in these patients with ACS. However, the safety outcomes of ticagrelor should further be investigated.
Patterns of nystagmus conversion in sudden sensorineural hearing loss with vertigo
Authors: Kim Chang-Hee , Choi Hye Rang , Choi Seongjun , Lee Yong Sik , Shin Jung Eun
Published: October 2018

The patients with sudden sensorineural hearing loss (SSNHL) may complain of vertigo. Although there have been many reports on SSNHL with vertigo (SSNHL_V), changes in the pattern of nystagmus have not been studied as yet. This study is a retrospective study and aims to investigate the characteristic changes in type of nystagmus and clinical features in patients with SSNHL_V who experienced a change in their nystagmus pattern during follow-up. Among 50 patients with SSNHL_V between January 2012 and December 2015, we identified 15 patients with SSNHL_V whose pattern of nystagmus changed. Initial nystagmus was classified into 5 subgroups: paretic type, irritative type, persistent geotropic direction-changing positional nystagmus (PG-DCPN), persistent apogeotropic direction-changing positional nystagmus (PA-DCPN), and posterior semicircular canal benign paroxysmal positional vertigo. The most common pattern of initial nystagmus was PG-DCPN (n = 7). The change of initial nystagmus pattern occurred on day 2 to 75 from symptom onset, and 2 (of 15) patients showed further conversion. The most common pattern of final nystagmus was PA-DCPN (n = 9). Hearing improvement after treatment was not significantly different (P = .59) between SSNHL_V patients with nystagmus change (25 ± 17 dB, n = 15) and those without nystagmus change (28 ± 18 dB, n = 35). In conclusion, clinician's attention is required in evaluating the vertigo symptom in patients with SSNHL_V because the initial patterns of nystagmus can be converted to another type of nystagmus. The presence of nystagmus change during follow-up may not be a prognosticator for hearing recovery in patients with SSNHL_V.
Pulmonary infection caused by Nocardia cyriacigeorgica in a patient with allergic bronchopulmonary aspergillosis
Authors: Wu Jianyong , Wu Yingping , Zhu Zhiqiang
Published: October 2018

Rationale:

Nocardia species is known as conditional pathogenic bacteria. Among Nocardia species, pulmonary infection caused by Nocardia cyriacigeorgica associated with Aspergillus fumigatus complex lung disease is rarely reported.

Patient concerns:

A 55-year-old female with a history of productive cough with recurrent expectoration for 20 years presented with increasing cough for 12 months. The patient presented complaining of respiratory symptoms including increasing cough with yellow phlegm, poor appetite, and generalized fatigue for a week prior to admission.

Diagnoses:

Nocardia cyriacigeorgica pneumonia was identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing.

Interventions:

Combined treatments (trimethoprim-sulfamethoxazole and meropenem) were administered after identification of N cyriacigeorgica.

Outcomes:

The respiratory symptoms of the patient had improved both clinically and radiologically after 4 weeks of antibacterial therapy.

Lessons:

Early precise diagnosis and prompt combined therapy are of vital importance in severe Nocardia pulmonary infection.
Frequency distribution and risk factors of hepatitis B virus and hepatitis C virus infections among thalassemia patients: a regional study
Authors: Shah Tariq , Hussain Wajid , Ali Niyaz , Sardar Sadia , Ishaq Muhammad , Ur Rahman Mujaddad , Ding Luming , Qayyum Sadia , Khan Ibrar
Published: October 2018

Background

Thalassemia is a group of inherited hematological disorders caused by mutation in globin’s genes. Regular blood transfusion lengthens the life of thalassemia patients but it carries a definite risk of the infections of blood-borne diseases.

Aim/Objective

The current study was carried out for the frequency distributions and risk factors of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among thalassemia patients in Hazara regions, Pakistan.

Methods

A total of 324 enrolled thalassemia major patients were diagnosed in five different centers of Hazara regions. The study participants were screened for HBV and HCV using the immunochromatographic techniques test and real-time PCR for immunochromatographic technique-positive specimens.

Results

Out of the 324 major thalassemia patients, 24 (7.41%) were diagnosed with HBV and HCV infections. In total, 206 were male patients and the rate of HBV and HCV infections was 0.97% (two patients) and 3.88% (eight patients), respectively. Similarly, 118 were female patients and the rate of HBV-positive patients was 3.39% (four patients) and HCV was 8.47% (10 patients). The results also showed that 50% of HBV and HCV infections were found in the age group of 26–30 years, while 1.81% was found in the age group of 11–15 years. The positive HBV and HCV samples were also verified with the band size of 242 and 227 bp, respectively.

Conclusion

Thus, to reduce the incidence of HBV and HCV in thalassemia patients, we must call for critical look on the transfusion practices as well as adoption of stricter donor selection.
Are All Breast‐fed Infants Equal? Clustering Metabolomics Data to Identify Predictive Risk Clusters for Childhood Obesity
Authors: Kirchberg Franca Fabiana , Grote Veit , Gruszfeld Dariusz , Socha Piotr , Closa‐Monasterolo Ricardo , Escribano Joaquin , Verduci Elvira , Mariani Benedetta , Langhendries Jean‐Paul , Poncelet Pascale , Koletzko Berthold , Hellmuth Christian ,   European Childhood Obesity Trial Study Group
Published: October 2018

Objectives:

Fetal and early life represent a period of developmental plasticity during which metabolic pathways are modified by environmental and nutritional cues. Little is known on the pathways underlying this multifactorial complex. We explored whether 6 months old breast‐fed infants could be clustered into metabolically similar groups and that those metabotypes could be used to predict later obesity risk.

Methods:

Plasma samples were obtained from 183 breast‐fed infants aged 6 months participating in the European multicenter Childhood Obesity Project study. We measured amino acids along with polar lipid concentrations (acylcarnitines, lysophosphatidylcholines, phosphatidylcholines, sphingomyelins). We determined the metabotypes using a Bayesian agglomerative clustering method and investigated the properties of these clusters with respect to clinical, programming, and metabolic factors up to 6 years of age.

Results:

We identified 20 metabolite clusters comprising 1 to 39 children. Phosphatidylcholines predominantly influenced the clustering process. In the largest clusters (n ≥ 14), large differences existed for birth length (unadjusted P < 0.0001) and length and weight at 6 months (unadjusted P < 0.0001 and P = 0.012, respectively). Infants tended to cluster together by country (unadjusted P < 0.001). The body mass index (BMI) z score at 6 years of age tended to differ (unadjusted P = 0.07).

Conclusions:

Our exploratory study provided evidence that breast‐fed infants are not metabolically homogeneous and that variation in metabolic profiles among infants may provide insight into later development and health. This work highlights the potential of metabotypes for identifying inter‐individual differences that may form the basis for developing personalized early preventive strategies.
Insulinoma-associated Protein 1 (INSM1) in Thoracic Tumors is Less Sensitive but More Specific Compared With Synaptophysin, Chromogranin A, and CD56
Authors: Kriegsmann Katharina , Zgorzelski Christiane , Kazdal Daniel , Cremer Martin , Muley Thomas , Winter Hauke , Longuespée Rémi , Kriegsmann Jörg , Warth Arne , Kriegsmann Mark
Published: October 2018

Objective:

Recognition of neuroendocrine differentiation is important for tumor classification and treatment stratification. To detect and confirm neuroendocrine differentiation, a combination of morphology and immunohistochemistry is often required. In this regard, synaptophysin, chromogranin A, and CD56 are established immunohistochemical markers. Insulinoma-associated protein 1 (INSM1) has been suggested as a novel stand-alone marker with the potential to replace the current standard panel. In this study, we compared the sensitivity and specificity of INSM1 and established markers.

Materials and Methods:

A cohort of 493 lung tumors including 112 typical, 39 atypical carcinoids, 77 large cell neuroendocrine carcinomas, 144 small cell lung cancers, 30 thoracic paragangliomas, 47 adenocarcinomas, and 44 squamous cell carcinomas were selected and tissue microarrays were constructed. Synaptophysin, chromogranin A, CD56, and INSM1 were stained on all cases and evaluated manually as well as with an analysis software. Positivity was defined as ≥1% stained tumor cells in at least 1 of 2 cores per patient.

Results:

INSM1 was positive in 305 of 402 tumors with expected neuroendocrine differentiation (typical and atypical carcinoids, large cell neuroendocrine carcinomas, small cell lung cancers, and paraganglioma; sensitivity: 76%). INSM1 was negative in all but 1 of 91 analyzed non-neuroendocrine tumors (adenocarcinomas, squamous cell carcinomas; specificity: 99%). All conventional markers, as well as their combination, had a higher sensitivity (97%) and a lower specificity (78%) for neuroendocrine differentiation compared with INSM1.

Conclusions:

Although INSM1 might be a meaningful adjunct in the differential diagnosis of neuroendocrine neoplasias, a general uncritical vote for replacing the traditional markers by INSM1 may not be justified.
Diagnostic Approach to Traumatic Axonal Injury of the Optic Radiation in Mild Traumatic Brain Injury
Authors: Jang Sung Ho , Lee Han Do
Published: October 2018

We describe a diffusion tensor tractography–based diagnostic approach to traumatic axonal injury of the optic radiation in a patient who showed visual field defect after mild traumatic brain injury. A 43-yr-old female patient experienced head trauma during a motor vehicle accident. After the head trauma, she noticed visual disturbance. Peripheral field defects were detected in both eyes on the Humphrey visual field test. After diffusion tensor tractography–based reconstruction of the optic radiation, We determined the fractional anisotropy and fiber number of each whole optic radiation. Four regions of interest were placed on the optic radiations based on diffusion tensor tractography configuration. The right optic radiation showed narrowing, and the left optic radiation revealed partial tearing in the posterior portion. The fiber number of the right optic radiation was more than two standard deviations lower than the control mean. The fractional anisotropy values of the regions of interest 2 (the narrowed area of the right optic radiation) and regions of interest 3 (the partially torn area of the left optic radiation) were more than two standard deviations lower than the control mean. Our results suggest that analysis of the configuration and parameters of the optic radiation based on three-dimensionally reconstructed diffusion tensor tractography results is a useful technique in the detection of traumatic axonal injury of the optic radiation in individual patients with mild traumatic brain injury.
Reverse Anterolateral Thigh Flap for Complex Scalp Reconstruction
Authors: Spitz Jamie A. , Payne Rachael M. , Ellis Marco F.
Published: October 2018

It is common for patients diagnosed with severe traumatic brain injury or intracranial tumors to undergo multiple craniotomy and cranioplasty procedures. In the setting of infection, these patients can develop scalp wounds with no local options. A reverse flow anterolateral thigh (ALT) flap for coverage of a complex multifocal scalp wound in a patient with exposed cranioplasty mesh and multiple prior operations without necessitating vein grafts was presented. This might be the first reverse flow free ALT flap to be reported in head and neck reconstruction.
Innovations and Contributions to Craniofacial Surgery in Japan
Authors: Fujino Toyomi
Published: October 2018

I look back at my decades in the field of plastic and reconstructive and craniofacial surgery, knowing I was the driving force behind its inception in Japan. However, behind me in turn, supporting me, teaching me, and encouraging me during my formative plastic surgery years in the United States and Europe have been many of the true giants in this field, and I will always accord them my total respect and deepest gratitude. Without their knowledge and technique, which they selflessly taught me and my peers, I would certainly never have been able to accomplish so much in the field of plastic and reconstructive surgery, and in particular, craniofacial surgery.
Parent Cognitive Satisfaction and Demand Research of Neonatal Hearing Screening
Authors: Chen Qia-Xin , Liu Yi , Huang Ping-Ting , Deng Meng-Xia , Zhang Xin-Li , Mai Fei , Zhang Tao
Published: October 2018

The primary aim of the present study was to investigate parent cognitive satisfaction and demand by using a valid and reliable questionnaire developed for this purpose (Parent Cognitive Satisfaction and Demand Questionnaire with Neonatal Hearing Screening Program, PCSDQ-NHSP). About 1000 parents whose children received hearing screening participated in this study. The satisfaction questionnaire was found to be a useful instrument for identifying service shortfalls, and the routine use of the PCSDQ-NHSP in other neonatal hearing screening programs is recommended. Overall, parents focused their attention to the neonatal hearing screening results and had high levels of expectations. They also longed for more information about relevant knowledge. Screening ability differed in different areas of Guangdong province where grass-roots hospitals had poor ability to perform this well. More preappointment information leaflets or brochures should be sent to parents. Regular training for neonatal hearing screening test is needed in primary hospitals. We can establish a neonatal hearing screening network to link as many hospitals as possible, and develop a standardized neonatal hearing screening system.
The incidence and associations of acute kidney injury in trauma patients admitted to critical care: A systematic review and meta-analysis
Authors: Haines Ryan W. , Fowler Alex J. , Kirwan Christopher J. , Prowle John R.
Published: October 2018

BACKGROUND

As more patients are surviving the initial effects of traumatic injury clinicians are faced with managing the systemic complications of severe tissue injury. Of these, acute kidney injury (AKI) may be a sentinel complication contributing to adverse outcomes.

OBJECTIVE

To establish the incidence of AKI in patients admitted to critical care after major trauma, to explore any risk factors and to evaluate the association of AKI with outcomes.

DATA SOURCES

Systematic search of MEDLINE, Excerpta Medica database and Cochrane library from January 2004 to April 2018.

STUDY SELECTION

Studies of adult major trauma patients admitted to critical care that applied consensus AKI criteria (risk injury failure loss end stage [RIFLE], AKI network, or kidney disease improving global outcomes) and reported clinical outcomes were assessed (PROSPERO Registration: CRD42017056781). Of the 35 full-text articles selected from the screening, 17 (48.6%) studies were included.

DATA EXTRACTION AND SYNTHESIS

We followed the PRISMA guidelines and study quality was assessed using the Newcastle-Ottawa score. The pooled incidence of AKI and relative risk of death were estimated using random-effects models.

MAIN OUTCOMES AND MEASURES

Incidence of AKI was the primary outcome. The secondary outcome was study-defined mortality.

RESULTS

We included 17 articles describing AKI outcomes in 24,267 trauma patients. The pooled incidence of AKI was 20.4% (95% confidence interval [CI], 16.5–24.9). Twelve studies reported the breakdown of stages of AKI with 55.7% of patients classified as RIFLE-R or stage 1, 30.3% as RIFLE-I or stage 2, and 14.0% as RIFLE-F or stage 3. The pooled relative risk of death with AKI compared was 3.6 (95% CI, 2.4–5.3). In addition, there was a concordant increase in odds of death among six studies that adjusted for multiple variables (adjusted odds ratio, 2.7; 95% CI, 1.9–3.8; p = <0.01).

CONCLUSION

Acute kidney injury is common after major trauma and associated with increased mortality. Future research is warranted to reduce the potential for harm associated with this subtype of AKI.

LEVEL OF EVIDENCE

Systematic review and meta-analysis, level III.
Optimal timing of delayed excretory phase computed tomography scan for diagnosis of urinary extravasation after high-grade renal trauma
Authors: Keihani Sorena , Putbrese Bryn E. , Rogers Douglas M. , Patel Darshan P. , Stoddard Gregory J. , Hotaling James M. , Nirula Raminder , Luo-Owen Xian , Mukherjee Kaushik , Morris Bradley J. , Majercik Sarah , Piotrowski Joshua , Dodgion Christopher M. , Schwartz Ian , Elliott Sean P. , DeSoucy Erik S. , Zakaluzny Scott , Sherwood Brenton G. , Erickson Bradley A. , Baradaran Nima , Breyer Benjamin N. , Fick Cameron N. , Smith Brian P. , Okafor Barbara U. , Askari Reza , Miller Brandi , Santucci Richard A. , Carrick Matthew M. , Kocik Jurek F. , Hewitt Timothy , Burks Frank N. , Heilbrun Marta E. , Myers Jeremy B.
Published: October 2018

BACKGROUND

Excretory phase computed tomography (CT) scan is used for diagnosis of renal collecting system injuries and accurate grading of high-grade renal trauma. However, optimal timing of the excretory phase is not well established. We hypothesized that there is an association between excretory phase timing and diagnosis of urinary extravasation and aimed to identify the optimal excretory phase timing for diagnosis of urinary extravasation.

METHODS

The Genito-Urinary Trauma Study collected data on high-grade renal trauma (grades III-V) from 14 Level I trauma centers between 2014 and 2017. The time between portal venous and excretory phases at initial CT scans was recorded. Poisson regression was used to measure the association between excretory phase timing and diagnosis of urinary extravasation. Predictive receiver operating characteristic analysis was used to identify a cutoff point optimizing detection of urinary extravasation.

RESULTS

Overall, 326 patients were included; 245 (75%) had excretory phase CT scans for review either initially (n = 212) or only at their follow-up (n = 33). At initial CT with excretory phase, 46 (22%) of 212 patients were diagnosed with urinary extravasation. Median time between portal venous and excretory phases was 4 minutes (interquartile range, 4–7 minutes). Time of initial excretory phase was significantly greater in those diagnosed with urinary extravasation. Increased time to excretory phase was positively associated with finding urinary extravasation at the initial CT scan after controlling for multiple factors (risk ratio per minute, 1.15; 95% confidence interval, 1.09–1.22; p < 0.001). The optimal delay for detection of urinary extravasation was 9 minutes.

CONCLUSION

Timing of the excretory phase is a significant factor in accurate diagnosis of renal collecting system injury. A 9-minute delay between the early and excretory phases optimized detection of urinary extravasation.

LEVEL OF EVIDENCE

Diagnostic tests/criteria study, level III.
Targeting endogenous retrovirus gene transcription in human cancers
Authors: Lin Audrey T. , Santander Cindy G. , Marchi Emanuele , Karamitros Timokratis , Katzourakis Aris , Magiorkinis Gkikas
Published: October 2018

Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections that make up to 8% of the human genome. Although these elements are mostly fragmented and inactive, many proviruses belonging to the HERV-K (HML-2) family, the only lineage still proliferating in the genome after the human-chimpanzee split, have intact open reading frames, some encoding for accessory genes callednp9andrecthat interact with oncogenic pathways. Many studies have established that the transient expression of ERVs are in both stem cells and cancers results in aberrant self-renewal and uncontrolled proliferation.

The wealth of high-quality genomic and transcriptomic Illumina sequence data available from The Cancer Genome Atlas (TCGA) that are sequenced from a diversity of different tumour types makes it a valuable resource in cancer research. However, there is currently no universal computational method for inferring expression of specific repetitive elements from RNA-seq data, such as genes encoded by HERV-K (HML-2).

This study presents a novel and a highly specific pipeline that is able to capture and measure transcription ofnp9andrecencoded by proviruses that share great sequence similarity, and are transcribed at very low levels. We show by using our novel methodology thatnp9andrecare overexpressed in breast cancer, germ cell tumours, skin melanoma, lymphoma, ovarian cancer, and prostate cancer compared to non-diseased tissues. We also show thatnp9andrecare specifically expressed in the 8 and 16-cell stage in human preimplantation embryos.
Automated optimized parameters for t-distributed stochastic neighbor embedding improve visualization and allow analysis of large datasets
Authors: Belkina Anna C. , Ciccolella Christopher O. , Anno Rina , Halpert Richard , Spidlen Josef , Snyder-Cappione Jennifer E.
Published: October 2018

Accurate and comprehensive extraction of information from high-dimensional single cell datasets necessitates faithful visualizations to assess biological populations. A state-of-the-art algorithm for non-linear dimension reduction, t-SNE, requires multiple heuristics and fails to produce clear representations of datasets when millions of cells are projected. We developed opt-SNE, an automated toolkit for t-SNE parameter selection that utilizes Kullback-Liebler divergence evaluation in real time to tailor the early exaggeration and overall number of gradient descent iterations in a dataset-specific manner. The precise calibration of early exaggeration together with opt-SNE adjustment of gradient descent learning rate dramatically improves computation time and enables high-quality visualization of large cytometry and transcriptomics datasets, overcoming limitations of analysis tools with hard-coded parameters that often produce poorly resolved or misleading maps of fluorescent and mass cytometry data. In summary, opt-SNE enables superior data resolution in t-SNE space and thereby more accurate data interpretation.
Different Munc18 Proteins Mediate Baseline and Stimulated Airway Mucin Secretion
Authors: Jaramillo Ana M. , Piccotti Lucia , Velasco Walter V. , Huerta Delgado Anna Sofia , Azzegagh Zoulikha , Chung Felicity , Nazeer Usman , Farooq Junaid , Brenner Josh , Parker-Thornburg Jan , Scott Brenton L. , Evans Christopher M. , Adachi Roberto , Burns Alan R. , Kreda Silvia M. , Tuvim Michael J. , Dickey Burton F.
Published: October 2018

Airway mucin secretion is necessary for ciliary clearance of inhaled particles and pathogens, but can be detrimental in pathologies such as asthma and cystic fibrosis. Exocytosis in mammals requires a Munc18 scaffolding protein, and airway secretory cells express all three Munc18 isoforms. Using conditional airway epithelial deletant mice, we found that Munc18a has the major role in baseline mucin secretion, Munc18b has the major role in stimulated mucin secretion, and Munc18c does not function in mucin secretion. In an allergic asthma model, Munc18b deletion reduced airway mucus occlusion and airflow resistance. In a cystic fibrosis model, Munc18b deletion reduced airway mucus occlusion and emphysema. Munc18b deficiency in the airway epithelium did not result in any abnormalities of lung structure, particle clearance, inflammation, or bacterial infection. Our results show that regulated secretion in a polarized epithelial cell may involve more than one exocytic machine at the apical plasma membrane, and that the protective roles of mucin secretion can be preserved while therapeutically targeting its pathologic roles.
Transitions in cell potency during early mouse development are driven by Notch
Authors: Menchero Sergio , Lopez-Izquierdo Antonio , Rollan Isabel , Sainz de Aja Julio , Andreu Maria Jose , Kang Minjung , Adan Javier , Benedito Rui , Rayon Teresa , Hadjantonakis Anna-Katerina , Manzanares Miguel
Published: October 2018

The Notch signalling pathway plays fundamental roles in diverse developmental processes in metazoans, where it is important in driving cell fate and directing differentiation of various cell types. However, we still have limited knowledge about the role of Notch in early preimplantation stages of mammalian development, or how it interacts with other signalling pathways active at these stages such as Hippo. By using genetic and pharmacological tools in vivo, together with image analysis of single embryos and pluripotent cell culture, we have found that Notch is active from the 4-cell stage. Transcriptomic analysis in single morula identified novel Notch targets, such as early naïve pluripotency markers or transcriptional repressors such as TLE4. Our results reveal a previously undescribed role for Notch in driving transitions during the gradual loss of potency that takes place in the early mouse embryo prior to the first lineage decisions.
Genetic transformation of the dinoflagellate chloroplast
Authors: Nimmo Isabel C. , Barbrook Adrian C. , Chen Jit Ern , Geisler Katrin , Smith Alison G. , Aranda Manuel , Saul Purton , Waller Ross F. , Nisbet R. Ellen R. , Howe Christopher J.
Published: October 2018

Coral reefs are some of the most important and ecologically diverse marine environments. At the base of the reef ecosystem are dinoflagellate algae, living in symbiosis with coral. Efforts to understand the relationship between alga and coral have been greatly hampered by the lack of an appropriate dinoflagellate genetic transformation technology. By making use of the plasmid-like fragmented chloroplast genome, we have introduced novel genetic material into the dinoflagellate chloroplast genome. We have shown that the introduced genes are expressed and confer the expected phenotypes. Genetically modified cultures have been grown for five months with subculturing, maintaining the introduced genes and phenotypes. This indicates that cells continue to divide after transformation and that the transformation is stable.
Loss of SATB1 Induces a p21 Dependent Cellular Senescence Phenotype in Dopaminergic Neurons
Authors: Riessland Markus , Kolisnyk Benjamin , Kim Tae Wan , Cheng Jia , Ni Jason , Pearson Jordan A. , Park Emily J. , Dam Kevin , Acehan Devrim , Ramos-Espiritu Lavoisier S. , Wang Wei , Zhang Jack , Shim Jae-won , Ciceri Gabriele , Brichta Lars , Studer Lorenz , Greengard Paul
Published: October 2018

Cellular senescence is a mechanism used by mitotic cells to prevent uncontrolled cell division. As senescent cells persist in tissues, they cause local inflammation and are harmful to surrounding cells, contributing to aging. Generally, neurodegenerative diseases, such as Parkinson‘s, are disorders of aging. The contribution of cellular senescence to neurodegeneration is still unclear. SATB1 is a DNA binding protein associated with Parkinson’s disease. We report that SATB1 prevents cellular senescence in post-mitotic dopaminergic neurons. Loss of SATB1 causes activation of a cellular senescence transcriptional program in dopamine neurons, both in human stem cell-derived dopaminergic neurons and in mice. We observed phenotypes which are central to cellular senescence in SATB1 knockout dopamine neurons in vitro and in vivo. Moreover, we found that SATB1 directly represses expression of the pro-senescence factor, p21, in dopaminergic neurons. Our data implicate senescence of dopamine neurons as a contributing factor to the pathology of Parkinson’s disease.
Interplay of protein disorder in retinoic acid receptor heterodimer and its corepressor regulates gene expression
Authors: Cordeiro Tiago N. , Sibille Nathalie , Germain Pierre , Barthe Philippe , Boulahtouf Abdel , Allemand Fréderic , Bailly Rémy , Vivat Valérie , Ebel Christine , Barducci Alessandro , Bourguet William , le Maire Albane , Bernadó Pau
Published: October 2018

The retinoic acid receptors (RARs) form heterodimers with retinoid X receptors (RXRs) and control gene transcription in response to ligand binding and via allosteric activation of the C-termini helix (helix H12) of its ligand-binding domain. Herein we show that in the absence of ligand, helices H12 of RXR and RAR are disordered. The selective RAR agonist, Am580, induces folding of H12, whereas in the presence of the inverse agonist BMS493, H12 stays mostly disordered. These results substantiate a link between the structural dynamics of H12 and RXR/RAR heterodimer biological functions, and highlight disordered-to-order transition as an essential mechanism for retinoic acid mediated regulation. Unliganded RAR exerts a strong repressive activity allowed by the recruitment of transcriptional corepressors and establishment of a corepressor complex in the promoter region of target genes. The human regulatory complex of the RARα bound to the full-length interaction domain of the corepressor N-CoR was studied by integrating several experimental (SAXS, X-ray crystallography, NMR, CD, AUC) and computational data. Unexpectedly, we found that, while mainly intrinsically disordered, the N-CoR presents partially evolutionary conserved structured regions that are involved in transient intramolecular contacts. In the presence of RXR/RAR, we show that N-CoR exploits its multivalency to form a multi-site complex that diplays an equilibrium between different conformational states. This conformational equilibrium is modulated by cognate ligands, RAR point mutation and RXR H12 deletion. Now, we can state that, in addition to NR conformation and ligand-induced allosteric changes, intrinsic disorder is substantially embedded in the synergetic regulation of RXR/RAR activity and its resulting abilities to communicate with the intracellular components.
Testing the Gene Expression Classification of the EMT Spectrum
Authors: Jia Dongya , George Jason T. , Tripathi Satyendra C. , Kundnani Deepali L. , Lu Mingyang , Hanash Samir M. , Onuchic José N. , Jolly Mohit Kumar , Levine Herbert
Published: October 2018

The epithelial-mesenchymal transition (EMT) plays a central role in cancer metastasis and drug resistance – two persistent clinical challenges. Epithelial cells can undergo a partial or full EMT, attaining either a hybrid epithelial/mesenchymal (E/M) or mesenchymal phenotype, respectively. Recent studies have emphasized that hybrid E/M cells may be more aggressive than their mesenchymal counterparts. However, mechanisms driving hybrid E/M phenotypes remain largely elusive. Here, to better characterize the hybrid E/M phenotype(s) and tumor aggressiveness, we integrate two computational methods – (a) RACIPE – to identify the robust gene expression patterns emerging from the dynamics of a given gene regulatory network, and (b) EMT scoring metric - to calculate the probability that a given gene expression profile displays a hybrid E/M phenotype. We apply the EMT scoring metric to RACIPE-generated gene expression data generated from a core EMT regulatory network and classify the gene expression profiles into relevant categories (epithelial, hybrid E/M, mesenchymal). This categorization is broadly consistent with hierarchical clustering readouts of RACIPE-generated gene expression data. We show that the EMT scoring metric can be used to distinguish between samples composed of exclusively hybrid E/M cells and those containing mixtures of epithelial and mesenchymal subpopulations using the RACIPE-generated gene expression data.
Asymmetric redundancy of ZERZAUST and ZERZAUST HOMOLOG in different accessions of Arabidopsis thaliana
Authors: Vaddepalli Prasad , Fulton Lynette , Schneitz Kay
Published: October 2018

Divergence among duplicate genes is one of the important sources of evolutionary innovation. But, the contribution of duplicate divergence to variation in Arabidopsis accessions is sparsely known. Recently, we studied the role of a cell wall localized protein, ZERZAUST (ZET), in Landsberg erecta (Ler) accession. Here, we present the study of ZET in Columbia (Col) accession, which not only showed differential expression patterns in comparison to Ler, but also revealed its close homolog, ZERZAUST HOMOLOG (ZETH). Although, genetic analysis implied redundancy, expression analysis revealed divergence, with ZETH showing minimal expression in both Col and Ler. In addition, ZETH shows relatively higher expression levels in Col compared to Ler. Our data also reveal compensatory up-regulation of ZETH in Col, but not in Ler, implying it is perhaps dispensable in Ler. However, a novel CRISPR/Cas9-induced zeth allele confirmed that ZETH has residual activity in Ler. The results provide genetic evidence for accession-specific differences in compensation mechanism and asymmetric gene contribution. Thus, our work reveals a novel example for how weakly expressed homologs contribute to diversity among accessions.
ILEX PARAGUARIENSIS, EXERCISE AND CARDIOPROTECTION: A retrospective analysis
Authors: Cahuê Fábio , Matheus Nascimento José Hamilton , Barcellos Luciane , Salerno Veronica P.
Published: October 2018

Studies on strategies to generate cardioprotective effects have been on the rise. Previous work by our group with an ex vivo model of ischemia/reperfusion has shown that both the short-term consumption of yerba mate and exercise can each induce protection of cardiac function independently. Surprising, the two strategies together do not, with an apparent loss of their respective cardioprotection activity. To improve our understanding of the mechanisms involved without reperforming the experiments, we have conducted a retrospective data science-analysis that have produced new insights. The analysis shows that yerba mate generated reductive stress. Alone, this stress increased redox damage in the heart that appears to have led to a protective conditioning. In combination with exercise, the effects of mate inhibited the intermittent ROS generation promoted by exercise alone, which diminished the adaptive response in the heart. These results suggest that an understanding of the molecular mechanisms involved with the yerba mate-promoted reductive stress in cardiac tissue could lead to improved strategies to induce cardioprotection.
Split Selectable Markers
Authors: Jillette Nathaniel , Du Menghan , Cheng Albert
Published: October 2018

Selectable markers are widely adopted in transgenesis and genome editing for selecting engineered cells with desired genotype but are limited in choices. We present here split selectable markers each allowing for selection of multiple “unlinked” transgenes in the context of lentivirus-mediated transgenesis as well as CRISPR/Cas-mediated biallelic knock-ins. Future development of split selectable markers may support enrichment or selection of “hyper-engineered” cells containing tens of transgenes or genetic modifications.
Total quality management practices and organizational performance in the construction chemicals companies in Jordan
Authors: Androwis Neven , Sweis Rateb J. , Tarhini Ali , Moarefi Alireza , Hosseini Amiri Mahmood
Published: October 2018

Purpose

The purpose of this paper is to investigate the relationship between total quality management practices and the organizational performance in the Jordanian construction chemicals companies.

Design/methodology/approach

In this research, ten constructs were used to measure TQM practices, whereas six constructs were used to measure the organizational performance. A total of 160 questionnaires were distributed to 28 companies. Of these 131 questionnaires were completed and used for the analysis, representing a response rate of 81.9 percent.

Findings

Analysis has shown that TQM practices positively affect the organizational performance, with a significant value for top management commitment, customer focus, supplier management, process control and continuous improvement.

Research limitations/implications

Results were based on perceptual data provided by participants working in different sectors of the organization, which may not provide a clear picture. It would be appropriate to consider collecting information from several stakeholders such as customers and suppliers. Willingness of respondents and delivering data within time were a big challenge though efforts were made to guarantee the confidentiality of the respondents.

Practical implications

Results from this research points out that TQM is considered as a key-contributing factor to firm’s survival. It also provides empirical support that TQM implementation in manufacturing organizations contributes to the performance and survival of such organizations. This research also provides an understanding of the dynamic role of TQM practices that would help managers pay attention to the fundamental practices that have a direct impact on the firms’ performance. This will help the organizations to dedicate efforts and allocate resources to get the best long-term outcomes and to figure out their strengths and weaknesses to develop and implement a new strategy to enhance their competitive position.

Originality/value

Construction sector in Jordan is a competitive sector. Therefore, quality in such industry is vital. Many companies in Jordan have much interest in implementing TQM practices. However, research efforts related to this field are rare. No research papers investigating the relationship between TQM practices and performance in Jordanian construction chemicals companies have been found. This research, therefore, seeks to examine the relationship between TQM practices and the construction chemicals firms’ performance in Jordan.
Mapping the TQM implementation
Authors: Kumar Vimal , Sharma R.R.K. , Verma Pratima , Lai Kuei-Kuei , Chang Yu-Hsin
Published: October 2018

Purpose

Culture is considered as one of the variables that influence the total quality management (TQM) adoption process. The purpose of this paper is to explore the relationship between cultural dimensions and the strategy of the firms in TQM implementation. These relationships are the subject of prior research. Furthermore, the authors make a comparative analysis of cultural dimensions on strategic choices of the firms, i.e. innovators, prospectors and defenders in TQM implementation.

Design/methodology/approach

From the existing literature review on TQM practices and organizational culture, 14 cultural dimensions were employed with organizational strategy in this present study. By using survey data collection method, 111 Indian firms were selected. The authors considered three strategy parameters and six structural attributes to identify the strategy of the firms, namely innovators, prospectors and defenders identified using cluster analysis. Furthermore, the relationship between organizational culture and strategy was examined using one-way ANOVA approach.

Findings

The results of the study revealed that eleven of the fourteen hypotheses supported which relating the cultural dimensions to TQM implementation with the strategic orientation. With the help of significant related values of cultural dimensions to the particular strategic firms, it is also found that implementation of TQM is easy or not. Some of the organizations with a particular strategic orientation will be able to implement TQM easily and successfully but some organizations will have difficulty to implement it successfully.

Practical implications

The firms hold their importance with respect to the different strategic orientation toward the various aspects of organizational cultures and TQM approaches in its implementation. Managerially, due to increased business competitiveness and economic pressures, top management sees the way in adopting TQM practices to achieve a competitive advantage. Apparently, it is evident that matching of TQM practices for a different strategy of the firms with various cultural dimensions leads to the smooth functioning of the organization. This study helps to the current organizations in implementing TQM with their respective culture.

Originality/value

This research can be useful for three strategic firms, namely innovators, prospectors and defenders to achieve effective implementation of TQM practices with consideration and understanding of the advantage of each culture dimension. The framework of the current study represents the effectiveness in assessing the TQM practices in individual cultural dimensions and its significant role.
Sustainability assessment in the manufacturing industry: a review of recent studies
Authors: Ahmad Shamraiz , Wong Kuan Yew
Published: October 2018

Purpose

The purpose of this paper is to review and analyze the recent sustainability assessment studies in the manufacturing industry from the triple-bottom-line (TBL) perspective. This paper aims to depict the status quo of practical sustainability assessment, summarize the different levels and boundaries of evaluation, and highlight the difficulties and further improvements needed to make the assessment more effective in the manufacturing industry.

Design/methodology/approach

Four keywords, namely, sustainability assessment, sustainable manufacturing, TBL and green production, were used to explore and find the relevant articles. First, this paper systematically reviewed the studies and analyzed the different levels and boundaries of sustainability assessment. Following this, the reviewed studies were critically discussed along with their merits and shortcomings.

Findings

The review showed that most of the sustainability assessment studies were conducted on product, company and process levels in the manufacturing industry. Nevertheless, there is still a need to focus more on plant and process level assessments to achieve the TBL objectives. Environmental assessment is comparatively matured in manufacturing industries. However, from the economic and social viewpoints, only cost analysis and workers’ safety, respectively, were considered in most of the studies. The economic and social indicators need to be more inclusive and should be validated and standardized for manufacturing industries.

Originality/value

Unlike previous sustainability assessment reviews in manufacturing industries which were mostly based on life cycle assessment, this paper has included environmental, social and economic aspects in one comprehensive review and focused on recent studies published from 2010 to 2017. This paper has explored the recent sustainability assessment trends and provided insights into the development of sustainability assessment in the manufacturing sector.