bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Islam impede development? A critical analysis
Authors: Sidani Yusuf
Published: November 2019

Purpose

This paper aims to investigate the relationship between Islam and economic underdevelopment that characterizes many Muslim societies. It examines the Weberian thesis regarding Islam and development, assessing the role of Islamic law, in addition to the concepts of rationality and fatalism.

Design/methodology/approach

The paper reviews the major theses regarding the link between Islam and development and makes an attempt at explaining economic underdevelopment by engaging the most prominent arguments in this regard.

Findings

Lack of development in most Muslim societies is a multidimensional problem, and it would not help to rely on explanations that are culturally deterministic or sociologically reductionist.

Practical implications

Development requires improvements at various regulatory, economic, educational, and social levels. It also requires a significant transformation in people’s value systems that guide their actions. This requires a process of self-examination, not only looking at exogenous factors to explain failures, but also to focus on one’s own responsibility to alleviate crisis situations.

Originality/value

This paper challenges many of the for-granted theses regarding the purported link between Islam and development. While not dispelling the need for internal reflection for Muslim societies, it puts some of the popular arguments regarding this link in proper perspective.
The effect of managing different types of work on open innovation
Authors: Peris-Ortiz Marta , Rueda-Armengot Carlos , Estelles-Miguel Sofia
Published: November 2019

Purpose

The purpose of this paper is to analyze the different types of work and to examine how they are related with open innovation, either by carrying out relationships with companies or external agents, or through the outsourcing of qualified and creative work.

Design/methodology/approach

After the theoretical analysis of the different types of work, the empirical study uses qualitative comparative analysis (QCA) to analyze the different variables and their relations which favor open innovation.

Findings

The combination of the variables in the QCA makes it possible to obtain three paths among the characteristics of the qualified work and open innovation, with a positive empirical result. The general conclusion is that the motivation level of the qualified work is relevant for open innovation.

Research limitations/implications

The study has some limitations, notably the reliability of the measurement of the variables, based on the subjective assessment of the respondent employee. The limited number of cases is always a question to be considered, although the statistical results show consistency in the results.

Practical implications

The most important implication for practice is the relevant connection between the internal efficiency in the management of the different types of work and open innovation.

Originality/value

The originality and value of this paper consist in relating the internal efficiency in the work management with the effectiveness and success of open innovation.
Long-run equity performance of firms that restate financial statements
Authors: Moon Gisung , Lee Hongbok , Waggle Doug
Published: November 2019

Purpose

The authors investigate how the stock market reacts to financial restatements using the restatements data from the United States Government Accountability Office (GAO-06-678). In particular, the purpose of this paper is to examine the long-run equity performance of the restating firms, for holding periods of one to five years after the announcements of restatements.

Design/methodology/approach

This paper measures the long-run stock performance of restating firms with the buy-and-hold abnormal returns and time-series regression analyses based on Fama–French’s (1993) three-factor model and Carhart’s (1997) four-factor model.

Findings

The authors find that restating firms significantly underperform in the long run compared with their peers matched by industry, size and book-to-market. Restating firms’ underperformance is confirmed with time-series regression analyses based on Fama–French’s (1993) three-factor model and Carhart’s (1997) four-factor model. Further, the authors find the negative long-run abnormal performance of restating firms is primarily driven by large firms. The authors also report that self-prompted restatements and improper revenue accounting-triggered restatements result in worse long-run abnormal performance.

Originality/value

This paper is the first paper that thoroughly investigates the long-run stock returns of the firms that restate financial statements by fully considering the size effect.
Limit elastic analysis of rotating annular disks having sigmoid-FGM composition based on MROM
Authors: Madan Royal , Saha Kashinath , Bhowmick Shubhankar
Published: November 2019

Purpose

The limit elastic speed of rotating disk is an important design criterion, as it defines the limit before onset of yielding initiates. The purpose of this paper is to establish the limit elastic speeds for S-FG disks and report the stresses induced at such speeds.

Design/methodology/approach

For S-FGM disk, effective Young’s modulus is calculated using modified rule of mixture and subsequently effective yield stress is also calculated by taking into consideration of stress-strain transfer ratio. The S-FGM disk is subject to centrifugal loading and the stress and deformation characteristics are investigated using variational principle wherein the solution is obtained by Galerkin’s error minimization principle. Based on von-Mises yield criteria, equivalent stress is calculated at different angular speeds till the equivalent stress at any given location in the disk attains the value of effective yield stress at the given location (location of yield initiation). This defines the limit elastic speed for the S-FGM disk (for given n).

Findings

The limit elastic speed of S-FGM disks for a range of grading index (n) and corresponding stresses within the disk are reported. Results are reported for uniform disks of different aspect ratio and the results reported could be used as practical design data.

Practical implications

Functional grading of material in structures opens a new horizon to explore the possibility of manufacturing high strength component at low weight. Material grading plays a significant role in achieving desired material properties, and literature review reveals reporting of numerous grading functions to approximate material distribution in structure.

Originality/value

The work has not been addressed earlier and findings provide a pioneering insight into the performance of S-FG disks.
Exploring bacterial pathogen community dynamics in freshwater beach sediments: A tale of two lakes
Authors: VanMensel Danielle , Chaganti Subba Rao , Droppo Ian G. , Weisener Christopher G.
Published: November 2019

Pathogenic bacteria associated with freshwater ecosystems can pose significant health risks particularly where recreational water use is popular. Common water quality assessments involve quantifying indicator Escherichia coli within the water column but neglect to consider physical and geochemical factors and contributions from the sediment. In this study, we used high‐throughput sequencing to investigate sediment microbial communities at four freshwater public beaches in southern Ontario, Canada and analysed community structure, function, and gene expression with relation to geographical characteristics. Our results indicate that beach sediments at the sediment–water interface could serve as potential sources of bacterial contamination under low‐energy environments with tightly packed small sediment particles compared with high‐energy environments. Further, the absence of pathogens but expression of pathogenic transcripts suggests occurrence of alternate gene acquisition. Pathogenicity at these locations included expression of Salmonella virulence factors, genes involved in pertussis, and antimicrobial resistance. Finally, we introduce a proposed universal bacterial pathogen model to consider the combined and synergistic processes used by these microbes. To our knowledge, this is the first study of its kind to investigate chemolithotrophic activity related to pathogens within bed sediment at freshwater beaches. This work helps advance current understanding of health risks in these environments.
The evolution of addiction treatment and harm reduction programs in Iran: a chaotic response or a synergistic diversity?
Authors: Ekhtiari Hamed , Noroozi Alireza , Farhoudian Ali , Radfar Seyed Ramin , Hajebi Ahmad , Sefatian Saeed , Zare‐bidoky Mehran , Razaghi Emran Mohammad , Mokri Azarakhsh , Rahimi‐Movaghar Afarin , Rawson Richard
Published: November 2019

Backgrounds and aims

Iran has 2.1 and 1.8% of its 15–64‐year‐old population living with illicit substance and opioid use disorders, respectively. To address these problems, Iran has been developing a large and multi‐modality addiction treatment system, spanning the time before and after the Islamic Revolution.

Methods

Iran's current drug treatment scene is a combination of services, ranging from medical/harm reduction services to punitive/criminal justice programs. Included in this array of services are drop‐in centers providing low‐threshold harm reduction services, such as distribution of sterile needles and syringes; opioid maintenance treatment clinics providing methadone, buprenorphine and opium tincture; and abstinence‐based residential centers. We will review the evolution of this system in four phases.

Results

In 1980, Iran's revolutionary government shut down all voluntary treatment programs and replaced them with residential correctional programs. The first shift in the addiction treatment policies came 15 years later after facing the negative consequences. Addiction is viewed as a disease, and new voluntary treatment centers offering non‐agonist medications and psychosocial services were established. With an increased number of people who inject drugs and HIV/AIDS epidemics, in the second shift an extensive move towards harm reduction strategies and opioid‐maintenance programs has been implemented to reduce HIV‐related high‐risk behavior. The emergence of a methamphetamine use crisis creating an increased number of socially marginalized addicted people resulted in public and political demands for stricter policies and ended in the third shift starting in 2010, with extended compulsory court‐based residential programs. Currently, there is a new shift towards reducing the severity of criminal penalties for drug use/sales and promoting proposals for opium legalization.

Conclusion

Iran's evolutionary experience in developing a large addiction treatment program in a complex combination of medical/harm reduction and punitive/criminal justice addiction treatment can be examined in its political, clinical and pragmatic context.
A clinical, pathological and immunohistochemical series of 9 cases of primary cutaneous apocrine carcinomas of the head and neck
Authors: Portelli Francesca , Salvati Lorenzo , Projetto Elisabetta , Gori Alessia , Scarfì Federica , Trane Luciana , Lo Russo Giulia , Innocenti Alessandro , De Giorgi Vincenzo
Published: November 2019

Background/Objectives

Primary cutaneous apocrine carcinoma is a rare malignant adnexal skin tumour that can recur locally, spread to regional lymph nodes and metastatize to visceral organs. Wide dissemination and death from disease are much less common. The axilla is the most common site of presentation. It is infrequently reported in the head and neck region.

Methods

All cases diagnosed as primary cutaneous apocrine carcinoma of the head and neck were retrospectively collected from the archives of the Division of Pathological Anatomy, University of Florence from 1996 to 2016. There was no history or clinical evidence of breast cancer. Clinical data and follow‐up were collected by the clinicians.

Results

Nine cases were found, with a mean age of 76 years, ranging in size between 0.3 and 3.5 cm. Clinically, they were frequently mistaken for basal cell carcinomas. Histopathologically, all the tumours showed decapitation secretion, a tubular, solid or mixed (tubulo‐papillary and solid‐tubular) growth pattern and were predominantly classified as grade 2 tumours. GCDFP‐15 and hormone receptors were variably expressed. HER2 and podoplanin were negative in all cases.

In one case, spreading to regional lymph nodes was observed. No cases were associated with death due to the disease.

Conclusion

As immunohistochemical analysis lacks specificity in distinguishing primary cutaneous apocrine carcinoma from a cutaneous metastasis of breast carcinoma, detailed clinical history, breast examination, adequate treatment and follow‐up are necessary to confirm a diagnosis of primary cutaneous apocrine carcinoma.
Using GRGDSPC peptides to improve re‐endothelialization of decellularized pancreatic scaffolds
Authors: Wan Jian , Wang Lei , Huang Yan , Fan Haowen , Chen Chunqiu , Yuan Xiaoqi , Guo Yibing , Yin Lu
Published: November 2019

Engineering of functional vascularized pancreatic tissues offers an alternative way to solve the perpetual shortage of organs for transplantation. However, revascularization remains a major bottleneck in biological engineering, which limited the further clinical applications of this strategy. In this study, an efficient approach for enhancing re‐endothelialization of rat decellularized pancreatic scaffolds (DPS) was presented, by conjugating with GRGDSPC peptide to maximize coverage of the vessel walls with human umbilical vein endothelial cells (HUVECs). First, pancreas was perfused with 1% Triton X‐100 and 0.1% ammonium hydroxide to remove the cellular components. Subsequently, GRGDSPC was covalently coupled to the vasculature of DPS and re‐seeded with HUVECs via perfusion of the portal vein in the bioreactor. After the re‐endothelialized scaffolds were created, in vitro and in vivo experiments were undertaken to evaluate the angiogenesis. Our results demonstrated that GRGDSPC‐conjugated scaffolds could support the survival and accelerated the proliferation of HUVECs; angiogenesis was also significantly improved over untreated scaffolds. In conclusion, GRGDSPC‐conjugated scaffolds showed great potential for the generation of functional bioengineered pancreatic tissue suitable for long‐term transplantation.
Comparison of macular buckling and vitrectomy for the treatment of macular schisis and associated macular detachment in high myopia: a randomized clinical trial
Authors: Liu Bingqian , Chen Shida , Li Yonghao , Lian Ping , Zhao Xiujuan , Yu Xiling , Li Tao , Jin Chenjin , Liang Xiaoling , Huang Suber S. , Lu Lin
Published: November 2019

Objective

To compare the efficacy and safety of macular buckling and vitrectomy for myopic traction maculopathy showing macular schisis (MS) and associated macular detachment (MD) but without full‐thickness macular hole (FTMH).

Design

Prospective, randomized, parallel, open‐label study.

Methods

Patients were randomly assigned to either buckling or vitrectomy group. Macular buckling and intravitreal C3F8 gas injection were performed in the buckling group. Small gauge vitrectomy, internal limiting membrane peeling (ILMP) and C3F8 gas tamponade were performed in the vitrectomy group. The patients were followed for 12 months.

Main outcome measures

Best‐corrected visual acuity (BCVA) at 12 months.

Results

A total of 85 patients were randomized, 80 eyes were included (41 receiving buckling, 39 received vitrectomy), and 78 patients completed the study. There were less eyes determined as surgical failure and required a second surgery in the buckling group than vitrectomy the group (2.4% versus 18.4%, p = 0.021). After surgery, macular buckling achieved more improvement in BCVA (+21.7 versus +4.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, p = 0.002). FTMH development was observed in only 1 (2.4%) eye, after removing of the implant due to recurrent conjunctival erosion, in the buckling group and 10 (26.3%) eyes (seven with‐, three without MD) in the vitrectomy group (p < 0.001). More eyes developed cataracts in the vitrectomy group than did in the buckling group (28.9% versus 7.5%, p = 0.014). Macular buckling‐associated strabismus (esotropia), binocular diplopia and implant exposure were observed in limited cases.

Conclusions and relevance

Macular buckling is superior to vitrectomy with ILM peeling plus gas injection for surgical treatment of MS and associated MD in high myopia.
Aqueous humour cytokine changes during a loading phase of intravitreal ranibizumab or dexamethasone implant in diabetic macular oedema
Authors: Podkowinski Dominika , Orlowski‐Wimmer Eva , Zlabinger Gerhard , Pollreisz Andreas , Mursch‐Edlmayr Anna‐Sophie , Mariacher Siegfried , Ring Michael , Bolz Matthias
Published: November 2019

Purpose

To determine the effect of intravitreal ranibizumab and a dexamethasone implant on aqueous humour cytokine, protein and enzyme levels and to correlate findings to morphologic and functional changes.

Methods

In a prospective, randomized, controlled, double‐blind study, patients with clinically significant diabetic macular oedema (CSME) were randomly allocated to receive either monthly intravitreal injections of ranibizumab (Lucentis, Novartis Pharma) or a single dexamethasone implant (Ozurdex, Pharm‐Allergan) at baseline (BL). Aqueous humour samples were collected at BL and weeks 2, 8 and 20.

Results

The study included 18 eyes of 18 patients. In the dexamethasone implant group, soluble intercellular adhesion molecule 1 (sICAM‐1) (weeks 2 and 8), CXCL9/monokine induced by gamma interferon (MIG) (weeks 2 and 8), soluble vascular cell adhesion protein 1 (sVCAM‐1) (weeks 2 and 8) and monocyte chemo‐attractant protein 1 (MCP‐1) (week 2) levels were significantly decreased compared with baseline. In the ranibizumab group, placental growth factor (PIGF) (week 2) and vascular endothelial growth factor (VEGF) (week 2 and 8) levels were significantly decreased compared with baseline. No significant changes in central retinal thickness (CRT) or Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA) were observed in the Ozurdex group at any time‐points. ETDRS scores significantly increased at week 20 (84.88 ± 8.88 letters) compared with baseline (74.78 ± 14.85 letters), and the CRT decreased significantly at week 4 (381.00 ± 114.64 μm) compared with baseline (440 ± 144 μm) in the Lucentis group.

Conclusion

The dexamethasone implant affected the aqueous cytokines and proteins MCP‐1, sICAM‐1, sVCAM‐1 and MIG, whereas ranibizumab treatments reduced VEGF and PIGF levels. Morphological changes may diverge from cytokine changes. Results may indicate a rationale for a combination therapy for CSME using both agents, the dexamethasone implant and repeatedly administered ranibizumab injections.
Multivariate hierarchical frameworks for modeling delayed reporting in count data
Authors: Stoner Oliver , Economou Theo
Published: November 2019

In many fields and applications, count data can be subject to delayed reporting. This is where the total count, such as the number of disease cases contracted in a given week, may not be immediately available, instead arriving in parts over time. For short‐term decision making, the statistical challenge lies in predicting the total count based on any observed partial counts, along with a robust quantification of uncertainty. We discuss previous approaches to modeling delayed reporting and present a multivariate hierarchical framework where the count generating process and delay mechanism are modeled simultaneously in a flexible way. This framework can also be easily adapted to allow for the presence of underreporting in the final observed count. To illustrate our approach and to compare it with existing frameworks, we present a case study of reported dengue fever cases in Rio de Janeiro. Based on both within‐sample and out‐of‐sample posterior predictive model checking and arguments of interpretability, adaptability, and computational efficiency, we discuss the relative merits of different approaches.
What are the costs of stillbirth? Capturing the direct health care and macroeconomic costs in Australia
Authors: Callander Emily J. , Thomas Joseph , Fox Haylee , Ellwood David , Flenady Vicki
Published: November 2019

Background

Reducing stillbirth rates is an international priority; however, little is known about the cost of stillbirth. This analysis sought to quantify the costs of stillbirth in Australia.

Methods

Mothers and costs were identified by linking a state‐based registry of all births between 2012 and 2015 to other administrative data sets. Costs from time of birth to 2 years postbirth were included. Propensity score matching was used to account for differences between women who had a stillbirth and those that did not. Macroeconomic costs were estimated using value of lost output analysis and value of lost welfare analysis.

Results

Cost to government was on average $3774 more per mother who had a stillbirth compared with mothers who had a live birth. After accounting for gestation at birth, the cost of a stillbirth was 42% more than a live birth (P < .001). Costs for inpatient services, emergency department services, services covered under Medicare (such as primary and specialist care, diagnostic tests and imaging), and prescription pharmaceuticals were all significantly higher for mothers who had a stillbirth. Mothers who had a stillbirth paid on average $1479 out of pocket, which was 52% more than mothers who had a live birth after accounting for gestation at birth (P < .001). The value of lost output was estimated to be $73.8 million (95% CI: 44.0 million‐103.9 million). The estimated value of lost social welfare was estimated to be $18 billion.

Discussion

Stillbirth has a sustained economic impact on society and families, which demonstrates the potential resource savings that could be generated from stillbirth prevention.
Extended experience with a non‐cytotoxic DNMT1‐targeting regimen of decitabine to treat myeloid malignancies
Authors: Awada Hassan , Mahfouz Reda Z. , Kishtagari Ashwin , Kuzmanovic Teodora , Durrani Jibran , Kerr Cassandra M. , Patel Bhumika J. , Visconte Valeria , Radivoyevitch Tomas , Lichtin Alan , Carraway Hetty E. , Maciejewski Jaroslaw P. , Saunthararajah Yogen
Published: November 2019

The nucleoside analogue decitabine can deplete the epigenetic regulator DNA methyltransferase 1 (DNMT1), an effect that occurs, and is saturated at, low concentrations/doses. A reason to pursue this molecular‐targeted effect instead of the DNA damage/cytotoxicity produced with high concentrations/doses, is that non‐cytotoxic DNMT1‐depletion can cytoreduce even p53‐null myeloid malignancies while sparing normal haematopoiesis. We thus identified minimum doses of decitabine (0·1–0·2 mg/kg) that deplete DNMT1 without off‐target anti‐metabolite effects/cytotoxicity, and then administered these well‐tolerated doses frequently 1–2X/week to increase S‐phase dependent DNMT1‐depletion, and used a Myeloid Malignancy Registry to evaluate long‐term outcomes in 69 patients treated this way. Consistent with the scientific rationale, treatment was well‐tolerated and durable responses were produced (~40%) in genetically heterogeneous disease and the very elderly.
Psychosis Therapy Project: A Psychoanalytic Project in the Community
Authors: Bonnigal‐Katz Dorothée
Published: November 2019

This paper discusses the benefits and the challenges of running a specialist psychoanalytic project in the community in the current economic and political climate. As the founder and clinical lead of the Psychosis Therapy Project, an Inner London service for people who experience psychosis, the author reflects on the pitfalls currently facing the psychoanalytic treatment of psychosis and exposes the ideological violence underlying the dominant model of recovery and rehabilitation in mental health care. From her frontline perspective, she recounts the devastating impact of social exclusion and discrimination on the welfare of those living with severe mental illness.
Water, No Fire … Leaning on Winnicott to Understand the Institution
Authors: Zachary Anne
Published: November 2019

Experience in institutions earlier in one's career informs work with psychotic patients in analytic practice. The author remembers the influence of Winnicott's work on understanding how institutions function. This is enhanced by a correspondence with Joel Kanter from Maryland and his unique experience in bringing the institution to the community.
Paradoxical Representation: The Royal Road to Creativity
Authors: Israeli Naftally
Published: November 2019

Creativity is connected to our experiences. But how are these represented in language? The concept of paradoxical representation is introduced here as a ‘solution’ to this problem. Two other solutions are focusing on the non‐representational and creating a ‘private’ language. Psychoanalysis and children's literature use these solutions in order to deal with representation of the ‘inner world’. However, when using paradoxical representation, the way in which this world is represented is unique. This is so because the relationship between language and experience is truly paradoxical in nature. It presents two different and contradictory manners of representation – one in which the word symbolizes – and does not symbolize – the experience; one that is separate – and not separate – from it; and one that serves as subjective expression and public communication. This representation is one in which successful representation, which symbolizes the thing, is a representation that fails, and therefore does not symbolize it. Although creativity can also stem from non‐verbal realms or from ‘private’ languages, using words as paradoxical representations – which in Winnicottian terms means using words as transitional objects – maximizes the creative process and is thus the ‘royal road’ to creativity.
Orbiting Planet Gemma: The Trajectory of a Two‐Year Infant Observation
Authors: Arthur Sally
Published: November 2019

This paper describes the author's reflections on an infant observation which took place at baby Gemma's home for an hour a week over two years. It describes the phenomenological experience of the weekly observation and the observer's progressive attempt to ‘feel into’ Gemma's developing mind. The author tracks Gemma's journey from her birth to the age of 2 years and witnesses the gradual emergence of a unique separate self. The paper attempts to untangle which feelings belong to the writer, which to Gemma and which to her mother, and it acknowledges ‘black holes’ of unknowable aspects. The astronomical headings reflect the family's interest in space exploration and also the writer's appreciation of the numinous quality of a close encounter with an infant.
Changes in cellular prion protein expression, processing and localisation during differentiation of the neuronal cell line CAD 5
Authors: Fremuntova Zuzana , Mosko Tibor , Soukup Jakub , Kucerova Johanka , Kostelanska Marie , Hanusova Zdenka Backovska , Filipova Marcela , Cervenakova Larisa , Holada Karel
Published: November 2019

Background information

Cellular prion protein (PrPC) is infamous for its role in prion diseases. The physiological function of PrPC remains enigmatic, but several studies point to its involvement in cell differentiation processes. To test this possibility, we monitored PrPC changes during the differentiation of prion‐susceptible CAD 5 cells, and then we analysed the effect of PrPC ablation on the differentiation process.

Results

Neuronal CAD 5 cells differentiate within 5 days of serum withdrawal, with the majority of the cells developing long neurites. This process is accompanied by an up to sixfold increase in PrPC expression and enhanced N‐terminal β‐cleavage of the protein, which suggests a role for the PrPC in the differentiation process. Moreover, the majority of PrPC in differentiated cells is inside the cell, and a large proportion of the protein does not associate with membrane lipid rafts. In contrast, PrPC in proliferating cells is found mostly on the cytoplasmic membrane and is predominantly associated with lipid rafts. To determine the importance of PrPC in cell differentiation, a CAD 5 PrP−/− cell line with ablated PrPC expression was created using the CRISPR/Cas9 system. We observed no considerable difference in morphology, proliferation rate or expression of molecular markers between CAD 5 and CAD 5 PrP−/− cells during the differentiation initiated by serum withdrawal.

Conclusions

PrPC characteristics, such as cell localisation, level of expression and posttranslational modifications, change during CAD 5 cell differentiation, but PrPC ablation does not change the course of the differentiation process.

Significance

Ablation of PrPC expression does not affect CAD 5 cell differentiation, although we observed many intriguing changes in PrPC features during the process. Our study does not support the concept that PrPC is important for neuronal cell differentiation, at least in simple in vitro conditions.
Endoscopic submucosal dissection in the rectum with a novel tissue retraction device
Authors: Sidhu Mayenaaz , Bourke Michael J.
Published: November 2019

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Clinical and genetic features in pyridoxine‐dependent epilepsy: a Chinese cohort study
Authors: Jiao Xianru , Xue Jiao , Gong Pan , Wu Ye , Zhang Yuehua , Jiang Yuwu , Yang Zhixian
Published: November 2019

Aim

To characterize the clinical and genetic characteristics of a large cohort of patients with pyridoxine‐dependent epilepsy (PDE).

Method

We retrospectively collected clinical and genetic information of 33 (15 males, 18 females; mean [SD] age 4y 11mo [2y 5mo]; 1y 3mo–10y 4mo) patients with PDE from 31 unrelated families at a single centre.

Results

There were many types of seizures, with focal seizures in 32 cases. Dravet syndrome was suspected clinically in two patients. Electroencephalogram (EEG) was normal in seven patients at the initial stage and then in 17 patients during pyridoxine maintenance therapy. Genetic studies revealed 26 kinds of variants in ALDH7A1 and four in PLPBP with 18 variants unreported previously, and 48 ALDH7A1 variants were located in exon 11, 12, 14, and 17 or intron 9 and 11. In addition, three patients carried different exons deletion. Among these, seizures could be controlled for several years in one patient by levetiracetam monotherapy. Another patient remained seizure free for up to 7 months without therapy. All patients received oral pyridoxine treatment, with only one case (with exon 8–13 deletion) showing poor control.

Interpretation

This study illustrates the range of clinical presentations and genetic causes in PDE, as well as responsiveness to antiepileptic drugs. A relationship between EEG and pyridoxine therapy could be seen in many cases. Seizure control was seen in all with pyridoxine monotherapy except for one patient.

What this paper adds

There is a parallel relationship between electroencephalogram and pyridoxine therapy in many patients.

Patients with pyridoxine‐dependent epilepsy may respond well to low‐dose pyridoxine.
Conditioning‐based outcomes after allogeneic transplantation for myeloma following a prior autologous transplant (1991‐2012) on behalf of EBMT CMWP
Authors: Hayden Patrick J. , Iacobelli Simona , Pérez‐Simón José Antonio , van Biezen Anja , Minnema Monique , Niittyvuopio Riitta , Schönland Stefan , Meijer Ellen , Blaise Didier , Milpied Noel , Márquez‐Malaver Francisco J. , Veelken Joan Hendrik , Maertens Johan , Michallet Mauricette , Cammenga Jörg , N'Guyen Stephanie , Niederwieser Dietger , Hunault‐Berger Mathilde , Bourhis Jean Henri , Passweg Jakob , Bermudez Arancha , Chalandon Yves , Yakoub‐Agha Ibrahim , Garderet Laurent , Kröger Nicolaus
Published: November 2019

Objectives

The aim of this study was to compare the effect of the intensity of conditioning approaches used in allogeneic transplantation in myeloma—reduced intensity conditioning (RIC), non‐myeloablative (NMA), myeloablative conditioning (MAC) or Auto‐AlloHCT—on outcomes in patients who had had a prior autologous transplant.

Methods

A retrospective analysis of the EBMT database (1991‐2012) was performed.

Results

A total of 344 patients aged between 40 and 60 years at the time of alloHCT were identified: 169 RIC, 69 NMA, 65 MAC and 41 Auto‐Allo transplants. At a median follow‐up of 54 months, the probabilities of overall survival (OS) at 5 years were 39% (95% CI 31%‐47%), 45% (95% CI 32%‐57%), 19% (95% CI 6%‐32%) and 34% (95% CI 17%‐51%), respectively. Status at allogeneic HCT other than CR or PR conferred a 70% higher risk of death and a 40% higher risk of relapse. OS was markedly lower in the MAC group (P = .004). MAC alloHCT was associated with a higher risk of death than RIC alloHCT until 2002 (HR = 4.1, P < .001) but not after 2002 (HR = 1.2, P = .276).

Conclusion

From 1991 to 2002, MAC was associated with poorer OS. Between 2003 and 2012, there were no significant differences in outcomes based on these different approaches.
Threat‐of‐shock decreases emotional interference on affective stroop performance in healthy controls and anxiety patients
Authors: Lago Tiffany R. , Blair Karina S. , Alvarez Gabriella , Thongdarong Amanda , Blair James R. , Ernst Monique , Grillon Christian
Published: November 2019

Patients with anxiety disorders suffer from impaired concentration, potentially as a result of stronger emotional interference on attention. Studies using behavioural measures provide conflicting support for this hypothesis. Elevated state anxiety may be necessary to reliably document differences in emotional interference in patients versus healthy controls. The present study examines the effect of experimentally induced state anxiety (threat‐of‐shock) on attention interference by emotional stimuli. Anxiety patients (n = 36) and healthy controls (n = 32) completed a modified affective Stroop task during periods of safety and threat‐of‐shock. Results indicated that in both patients and controls, threat decreased negative, but not positive or neutral, emotional interference on attention (both p < .001). This finding supports a threat‐related narrowing of attention whereby a certain level of anxiety decreases task‐irrelevant processing.
The active nuclear form of SREBP1 amplifies ER stress and autophagy via regulation of PERK
Authors: Hu Qin , Mao Yu , Liu Min , Luo Rui , Jiang Rong , Guo Fengjin
Published: November 2019

Endoplasmic reticulum (ER) stress and autophagy dysfunction contribute to the establishment and progression of diverse pathologies. Proteolytic activation of the transcription factor nSREBP1 is induced under ER stress; however, little is known about how SREBP1 and its nuclear active form nSREBP1 influence autophagy and unfolded protein response (UPR) activation in osteosarcoma cells. Our research focused on the effect of SREBP1/nSREBP1 upon apoptosis and autophagy during ER stress and the molecular mechanisms involved. Here, we showed that nSREBP1 binds to the promoter of protein kinase RNA‐like endoplasmic reticulum kinase (PERK) and then regulates ER stress, cell growth, cell apoptosis, and autophagy through the PERK signaling pathway. nSREBP1 increased PERK gene expression and phosphorylation. nSREBP1 was further demonstrated to activate ER stress response through stimulatory effects on PERK signaling. Overexpression of SREBP1 increased its cleavage and release of nSREBP1; therefore, the effect of SREBP1 is achieved through the enhancement of the expression of nSREBP1. Overexpression of SREBP1/nSREBP1 amplifies PERK‐associated cell cycle stagnation with G1 phase arresting, S phase reducing, and G2‐M phase delaying. LV‐SREBP1/nSREBP1 can also bolster PERK’s ER stress‐associated pro‐apoptotic effects. LV‐SREBP1/nSREBP1 and LV‐PERK can activate autophagy in ER stress response, along with the overexpression of SREBP1/nSREBP1 and PERK. This resulted in amplification of PERK‐related changes to cell proliferation and ER stress‐mediated apoptosis and autophagy, with the biological effect of nSREBP1 relying on PERK, which makes up one of the three branches of the UPR signaling pathway. This study reveals important roles for SREBP1/nSREBP1 in PERK signaling under ER stress. Furthermore, nSREBP1, the nuclear active form of SREBP1, is able to robustly augment the effects of PERK. Description of the link between PERK and SREBP1/nSREBP1 function offers an improved understanding of the ER stress response and insight into the biological function of SREBP1/nSREBP1.
Cholesterol impacts chemokine CCR5 receptor ligand‐binding activity
Authors: Calmet Pierre , Cullin Christophe , Cortès Sandra , Vang Maylou , Caudy Nada , Baccouch Rim , Dessolin Jean , Maamar Nada Taib , Lecomte Sophie , Tillier Bruno , Alves Isabel D.
Published: November 2019

The chemokine CCR5 receptor is target of maraviroc, a negative allosteric modulator of CCR5 that blocks the HIV protein gp120 from associating with the receptor, thereby inhibiting virus cellular entry. As noted with other G‐protein‐coupled receptor family members, the role of the lipid environment in CCR5 signaling remains obscure and very modestly investigated. Controversial literature on the impact of cholesterol (Chol) depletion in HIV infection and CCR5 signaling, including the hypothesis that Chol depletion could inhibit HIV infection, lead us to focus on the understanding of Chol impact in the first stages of receptor activation. To address this aim, the approach chosen was to employ reconstituted model lipid systems of controlled lipid composition containing CCR5 from two distinct expression systems: Pichia pastoris and cell‐free expression. The characterization of receptor/ligand interaction in terms of total binding or competition binding assays was independently performed by plasmon waveguide resonance and fluorescence anisotropy, respectively. Maraviroc, a potent receptor antagonist, was the ligand investigated. Additionally, coarse‐grained molecular dynamics simulation was employed to investigate Chol impact in the receptor‐conformational flexibility and dynamics. Results obtained with receptor produced by different expression systems and using different biophysical approaches clearly demonstrate a considerable impact of Chol in the binding affinity of maraviroc to the receptor and receptor‐conformational dynamics. Chol considerably decreases maraviroc binding affinity to the CCR5 receptor. The mechanisms by which this effect occurs seem to involve the adoption of distinct receptor‐conformational states with restrained structural dynamics and helical motions in the presence of Chol.
Stochastic Modeling of Groundwater Fluoride Contamination: Introducing Lazy Learners
Authors: Khosravi Khabat , Barzegar Rahim , Miraki Shaghayegh , Adamowski Jan , Daggupati Prasad , Alizadeh Mohammad Reza , Pham Binh Thai , Alami Mohammad Taghi
Published: November 2019

While it remains the primary source of safe drinking and irrigation water in northwest Iran's Maku Plain, the region's groundwater is prone to fluoride contamination. Accordingly, modeling techniques to accurately predict groundwater fluoride concentration are required. The current paper advances several novel data mining algorithms including Lazy learners [instance‐based K‐nearest neighbors (IBK); locally weighted learning (LWL); and KStar], a tree‐based algorithm (M5P), and a meta classifier algorithm [regression by discretization (RBD)] to predict groundwater fluoride concentration. Drawing on several groundwater quality variables (e.g.,concentrations), measured in each of 143 samples collected between 2004 and 2008, several models predicting groundwater fluoride concentrations were developed. The full dataset was divided into two subsets: 70% for model training (calibration) and 30% for model evaluation (validation). Models were validated using several statistical evaluation criteria and three visual evaluation approaches (i.e., scatter plots, Taylor and Violin diagrams). Although Na+and Ca2+showed the greatest positive and negative correlations with fluoride (r = 0.59 and −0.39, respectively), they were insufficient to reliably predict fluoride levels; therefore, other water quality variables, including those weakly correlated with fluoride, should be considered as inputs for fluoride prediction. The IBK model outperformed other models in fluoride contamination prediction, followed by KStar, RBD, M5P, and LWL. The RBD and M5P models were the least accurate in terms of predicting peaks in fluoride concentration values. Results of the current study can be used to support practical and sustainable management of water and groundwater resources.
Prognostic significance of nucleolar assessment in invasive breast cancer
Authors: Elsharawy Khloud A , Toss Michael S , Raafat Sara , Ball Graham , Green Andrew R , Aleskandarany Mohammed A , Dalton Leslie W , Rakha Emad A
Published: November 2019

Aims

Nucleolar morphometric features have a potential role in the assessment of the aggressiveness of many cancers. However, the role of nucleoli in invasive breast cancer (BC) is still unclear. The aims of this study were to investigate the optimal method for scoring nucleoli in IBC and their prognostic significance, and to refine the grading of breast cancer (BC) by incorporating nucleolar score.

Methods and results

Digital images acquired from haematoxylin and eosin‐stained sections from a large BC cohort were divided into training (n = 400) and validation (n = 1200) sets for use in this study. Four different assessment methods were evaluated in the training set to identify the optimal method associated with the best performance and significant prognostic value. These were: (i) a modified Helpap method; (ii) counting prominent nucleoli (size ≥2.5 µm) in 10 field views (FVs); (iii) counting prominent nucleoli in five FVs; and (iv) counting prominent nucleoli in one FV. The optimal method was applied to the validation set and to an external validation set, i.e. data from The Cancer Genome Atlas (n = 743). Scoring prominent nucleoli in five FVs showed the highest interobserver concordance rate (intraclass correlation coefficient of 0.8) and a significant association with BC‐specific survival (P < 0.0001). A high nucleolar score was associated with younger age, larger tumour size, and higher grade. Incorporation of nucleolar score in the Nottingham grading system resulted in a higher significant association with survival than the conventional grade.

Conclusions

Quantification of nucleolar prominence in five FVs is a cost‐efficient and reproducible morphological feature that can predict BC behaviour and can provide an alternative to pleomorphism to improve BC grading performance.
Phenological and physiological evaluation of first and second cropping periods of sorghum and maize crops
Authors: Barbosa Maria Antonia Machado , Kuki Kacilda Naomi , Bengala Pedro Santos Peno , Pereira Emilly dos Santos , de Barros Angélica Fátima , Montoya Sebastián Giraldo , Pimentel Leonardo Duarte
Published: November 2019

Environmental conditions influence phenology and physiological processes of plants. It is common for maize and sorghum to be sown at two different periods: the first cropping (spring/summer) and the second cropping (autumn/winter). The phenological cycle of these crops varies greatly according to the planting season, and it is necessary to characterize the growth and development to facilitate the selection of the species best adapted to the environment. The aim of this study was to characterize phenological phases and physiological parameters in sorghum and maize plants as a function of environmental conditions from the first cropping and second cropping periods. Two parallel experiments were conducted with both crops. The phenological characterization was based on growth analyses (plant height, leaf area and photoassimilate partitioning) and gas exchange evaluations (net assimilation rate, stomatal conductance, transpiration and water‐use efficiency). It was found that the vegetative stage (VS) for sorghum and maize plants was 7 and 21 days, respectively, longer when cultivated during the second cropping. In the first cropping, the plants were taller than in the second cropping, regardless of the crop. The stomatal conductance of sorghum plants fluctuated in the second cropping during the development period, while maize plants showed decreasing linear behaviour. Water‐use efficiency in sorghum plants was higher during the second cropping compared with the first cropping. In maize plants, in the second cropping, the water‐use efficiency showed a slight variation in relation to the first cropping. It was concluded that the environmental conditions as degree‐days, temperature, photoperiod and pluvial precipitation influence the phenology and physiology of both crops during the first and the second cropping periods, specifically cycle duration, plant height, leaf area, net assimilation rate, stomatal conductance and water‐use efficiency, indicating that both crops respond differentially to environmental changes during the growing season.
Fabrication of lightweight alumina with nanoscale intracrystalline pores
Authors: Fu Lvping , Gu Huazhi , Huang Ao , Zou Yongshun , Zhang Meijie
Published: November 2019

In this study, lightweight alumina containing nanoscale intracrystalline pores was fabricated by introducing zirconia sol and alumina sol into α‐Al2O3 micropowder. The effects of zirconia sol on the sintering behavior of lightweight alumina were also investigated. With the introduction of zirconia sol, the grain growth and phase transformation of nano‐alumina are delayed. Therefore, the structure of the nanoscale pores between nanoparticles can be stabilized during heat treatment, and numerous nanoscale intracrystalline pores with diameters in the range of 50‐300 nm are trapped in the alumina grains. Because of the existence of these nanoscale intracrystalline pores, the thermal conductivity of lightweight alumina decreases significantly. Lightweight alumina with the addition of 0.75 wt% zirconia sol exhibits 31% lower thermal conductivity compared to alumina without zirconia sol.
Causal attribution and coping with parental dominance and deprecation in youth with mild intellectual disability
Authors: Kurtek Paweł
Published: November 2019

Although interactions among parents and Youth with Mild Intellectual Disability (MID) may be stressful at times, most studies focus on the effects of stressful interactions on the parents. This study considers the Youth's perspective – particularly their beliefs about the reason for the parent's actions as well as how they would respond in the situation. The RA‐PD test (American Psychologist, 28, 2015, 107) was administered to 151 transition age youth with MID in Poland. The test includes vignettes that describe common situations in which the parent engages in Domination or Deprecation. The participants coping responses, based on a multi‐axial approach developed by Hobfoll (Stress, culture, and community. The psychology and philosophy of stress, 1998, Springer, New York, NY), and attributions toward the parental figure in the scenarios, based on Kelley (American Psychologist, 28, 2015, 107), were coded by judges. Correlations between causal attribution and coping response showed a consistent pattern where positive attributions were associated with prosocial coping and negative attributions were significantly related to antisocial coping. The implications for improving coping, especially for Youth with aggressive and passive tendencies, are discussed.