bluuebunny/crossref_metadata_2025 huggingface dataset:
The efficacy of amrubicin third‐line chemotherapy in patients with relapsed extensive‐disease small‐cell lung cancer: A retrospective and historical study in a single institute
Authors: Sonehara Kei , Tateishi Kazunari , Fukushima Toshirou , Komatsu Masamichi , Yamamoto Hiroshi , Koizumi Tomonobu , Hanaoka Masayuki
Published: July 2019

Background

The efficacy of amrubicin for relapsed small‐cell lung cancer (SCLC) has been reported in previous studies. Few reports, however, describe the efficacy and survival benefit of third‐line amrubicin chemotherapy in patients with extensive disease (ED)‐SCLC.

Methods

We retrospectively analyzed the clinical records of ED‐SCLC patients treated with amrubicin salvage chemotherapy as a third‐line chemotherapy between January 2005 and July 2016 (salvage amrubicin group). The efficacy and toxicities of amrubicin were evaluated. Overall survival (OS) in the amrubicin salvage group was compared with OS among ED‐SCLC patients treated with at least second‐line chemotherapy between May 2000 and July 2016 and without subsequent amrubicin salvage chemotherapy.

Results

A total of 18 patients with a median age of 70 years were analyzed in the amrubicin salvage group. The median number of treatment cycles of amrubicin was four. The response rate was 27.8% (95% confidence interval (CI), 7.1%–48.5%), and the disease control rate (DCR) was 66.7% (95% CI, 44.9%–88.4%). Median progression‐free survival was 2.9 months (95% CI, 1.0–4.9 months), and median OS after an initial chemotherapy was 18.1 months (95% CI, 10.2–26.0 months). OS in the amrubicin salvage group was significantly longer than in the no‐amrubicin group (n = 19; 12.6 months, 95% CI, 11.5–13.8 months, P = 0.005). The frequency of neutropenia greater than grade 3 was 72.2%, with febrile neutropenia developing in 38.9% of patients in the amrubicin salvage group.

Conclusions

Despite a high frequency of febrile neutropenia, amrubicin salvage chemotherapy may improve OS in patients with relapsed ED‐SCLC.
Epithelial‐to‐mesenchymal transition (EMT) to sarcoma in recurrent lung adenosquamous carcinoma following adjuvant chemotherapy
Authors: Poh Mau Ern , Liam Chong Kin , Mun Kein Seong , Chai Chee Shee , Wong Chee Kuan , Tan Jiunn Liang , Loh Thian Chee , Chin Ka Kiat
Published: July 2019

Adjuvant chemotherapy has long been indicated to extend survival in completely resected stage IB to IIIA non‐small cell lung cancer (NSCLC). However, there is accumulating evidence that chemotherapy or chemoradiotherapy can induce epithelial‐to‐mesenchymal transition (EMT) in disseminated or circulating NSCLC cells. Here, we describe the first case of EMT as the cause of recurrence and metastasis in a patient with resected stage IIB lung adenosquamous carcinoma after adjuvant chemotherapy. We review the literature and explore the possible mechanisms by which EMT occurs in disseminated tumor cells (DTC) or circulating tumor cells (CTC) in response to adjuvant chemotherapy (cisplatin) as a stressor. We also explore the possible therapeutic strategies to reverse EMT in patients with recurrence. In summary, although adjuvant cisplatin‐based chemotherapy in resected NSCLC does extend survival, it may lead to the adverse phenomenon of EMT in disseminated tumor cells (DTC) or circulating tumor cells (CTC) causing recurrence and metastasis.
Risky driving behaviours among stimulant drug users and the role of aggression: findings from a national survey
Authors: Hayley Amie C. , Hart Carl L. , O'Malley Kate Y. , Stough Con K. K. , Downey Luke A.
Published: July 2019

Background and Aims

Stimulant drug users have a greater prevalence of risky driving behaviour. This study aimed to assess how far this association remains after adjusting for aggressiveness.

Design

Cross‐sectional interview study assessing associations between measures of risky driving behaviours as outcomes, measures of stimulant drug use as predictors and a measure of aggressiveness as a covariate.

Setting

United States.

Participants

Data were drawn from wave 3 (2012–13) of the National Epidemiological Survey on Alcohol and Related Conditions (NESARC‐III) (n = 36 309 aged ≥ 18 years).

Measurements

Stimulant drug use, past‐year DSM‐5 stimulant use disorder, aggression and measures of risky driving were assessed using face‐to‐face interviews conducted using the Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS‐5) and the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM‐5).

Findings

Overall, 2714 (8.3%) respondents indicated life‐time stimulant use, and 112 (0.3%) met criteria for past‐year DSM‐5 stimulant use disorder. More than 10% of ongoing stimulant users and one‐third of respondents with DSM‐5 stimulant use disorder reported stimulant‐specific driving under the influence of drugs (DUID) in the past‐year (both P < 0.0001). Adjusted for demographics and independent of aggression, life‐time stimulant users reported increased likelihood of driving [adjusted odds ratio (aOR) = 3.00, 95% confidence interval (CI) = 2.63–3.42] or speeding under the influence of drugs (aOR = 3.39, 95% CI = 3.01–3.82) and licence revocation (aOR = 2.16, 95% CI = 1.87–2.50) (all P < 0.0001). Past‐year DSM‐5 stimulant use disorder was associated with all outcomes (aOR = 5.48, 95% CI = 2.95–10.18 and aOR = 3.87, 95% CI = 2.23–6.70, respectively, all P < 0.0001), except licence revocation (aOR = 1.72).

Conclusions

Stimulant use appears to be positively associated with risky driving behaviours after adjusting for aggressiveness.
Incidence and long‐term outcomes of surgically treated childhood hepatic malignancies in Finland
Authors: Tiusanen Toivo , Hukkinen Maria , Leskinen Outi , Soini Tea , Kanerva Jukka A. , Jahnukainen Timo , Mäkisalo Heikki , Heikinheimo Markku , Pakarinen Mikko P.
Published: July 2019

Aim

To analyse incidence, treatment and outcomes of paediatric liver malignancies in Finland during 1987‐2017.

Methods

Medical records and national cancer registry data of 47 children with liver malignancies were reviewed. Survival was calculated with the Kaplan‐Meier method.

Results

During follow‐up, liver malignancy incidence remained stable at 1.1:106. Altogether, 42 patients with hepatoblastoma (n = 24), hepatocellular carcinoma (n = 11) and undifferentiated embryonal sarcoma (n = 7) underwent surgery at median age 4.6 (interquartile range, 2.0‐9.6) years and were followed up for 13 (7.0‐19) years. Cumulative 5‐year survival was 86% for hepatoblastoma, 41% for hepatocellular carcinoma and 67% for undifferentiated embryonal sarcoma. Five‐year survival was decreased among hepatoblastoma patients aged ≥ 2.4 years (73% versus 100%, P = .040), with PRETreatment EXTent of disease IV (PRETEXT, 60% vs 100%, P = .004), and with recurrent disease (67% vs 88%, P = .029). Recurrent/residual disease associated with decreased 5‐year survival in hepatocellular carcinoma (0% vs 83%, P = .028). Survival was similar among 19 transplanted and 23 resected patients. In total, 14 deaths occurred either for the underlying malignancy (n = 8), adverse effects of chemotherapy (n = 5) or unrelated reasons (n = 1).

Conclusion

Outcomes for PRETEXT I‐III hepatoblastoma and un‐metastasized hepatocellular carcinoma were encouraging. Adverse effects of chemotherapy significantly contributed to mortality.
Systematic review of sensory processing in preterm children reveals abnormal sensory modulation, somatosensory processing and sensory‐based motor processing
Authors: Niutanen Ulla , Harra Toini , Lano Aulikki , Metsäranta Marjo
Published: July 2019

Aim

Preterm birth poses concerns in daily functioning and behaviour in childhood, possibly connected to sensory processing disorder. This review aimed to systematically identify assessments, incidence and nature of sensory processing disorder in preterm‐born infants and children.

Methods

We searched literature through CINAHL‐EBSCOhost, Cochrane, Ovid/PsychINFO, PubMed/Medline, Scopus and Google Scholar, published until November 2018. We included electronically available, peer‐reviewed studies of preterm‐born children that applied standardised sensory processing assessments. We excluded studies of preterm‐born children with major neurodevelopmental impairments.

Results

We identified 27 studies of premature children, aged from birth to 9 years 7 months. The assessments represented three versions of Sensory Profile questionnaires and three clinical tests, Test of Sensory Functions in Infants, the Miller Assessment for Preschoolers, and the Sensory Integration and Praxis Test. The studies revealed wide variation of atypical sensory processing: 28%‐87% in sensory modulation, 9%‐70% in somatosensory processing and 20%‐70% in sensory‐based motor processing.

Conclusion

Preterm‐born children exhibited elevated risk for sensory processing disorder from infancy into school age. Routine screening of sensory processing, intervention intervals and parental consultations should be considered in ameliorating sensory processing and neurocognitive development. Moreover, a larger body of intervention studies is needed.
Cochlear implants before 9 months of age led to more natural spoken language development without increased surgical risks
Authors: Karltorp Eva , Eklöf Martin , Östlund Elisabet , Asp Filip , Tideholm Bo , Löfkvist Ulrika
Published: July 2019

Aim

Evidence suggests that cochlear implants are beneficial for language development, but there is no consensus about the ideal age for surgery. We investigated how language development and surgical safety were affected by patients’ ages.

Methods

This study comprised 103 children (52 boys) aged 4.3‐16 years who received cochlear implants at 5‐29 months at the Karolinska University Hospital, Stockholm, Sweden, between 2002 and 2013. All showed typical development and were from monolingual homes. Bilateral implants were common (95%). The children were regularly assessed on language understanding, vocabulary and speech recognition by a multi‐disciplinary team for 10.0 ± 3.7 (4.7‐16.0) years.

Results

There were no associations between complications after surgery and the age when children had their first implant. Children implanted at 5‐11 months reached an age‐equivalent level of language understanding and better vocabulary outcome sooner than subgroups implanted later. Children who had surgery at 12‐29 months demonstrated more atypical and delayed language abilities over time. Early implantation, preferably before 9 months, may lead to a more typical trajectory of spoken language development.

Conclusion

Our findings showed that cochlear implantation before 9 months was safe. Early implantation may reduce the negative effects of auditory deprivation and promotes more natural and synchronised language development.
Swedish national guideline for prevention and treatment of neonatal hypoglycaemia in newborn infants with gestational age ≥35 weeks
Authors: Wackernagel Dirk , Gustafsson Anna , Edstedt Bonamy Anna‐Karin , Reims Annika , Ahlsson Fredrik , Elfving Maria , Domellöf Magnus , Hansen Pupp Ingrid
Published: July 2019

Aim

Postnatal hypoglycaemia in newborn infants remains an important clinical problem where prolonged periods of hypoglycaemia are associated with poor neurodevelopmental outcome. The aim was to develop an evidence‐based national guideline with the purpose to optimise prevention, diagnosis and treatment of hypoglycaemia in newborn infants with a gestational age ≥35 + 0 weeks.

Methods

A PubMed search‐based literature review was used to find actual and applicable evidence for all incorporated recommendations. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used for grading the evidence of the recommendations.

Results

Recommendations for the prevention of neonatal hypoglycaemia were extended and updated, focusing on promotion of breastfeeding as one prevention strategy. Oral dextrose gel as a novel supplemental therapy was incorporated in the treatment protocol. A new threshold‐based screening and treatment protocol presented as a flow chart was developed.

Conclusion

An updated and evidence‐based national guideline for screening and treatment of neonatal hypoglycaemia will support standardised regimes, which may prevent hypoglycaemia and the risk for hypoglycaemia‐related long‐term sequelae.
Quantifying artefacts over time: Interval estimation of a Poisson distribution using the Jeffreys prior
Authors: Collins‐Elliott S. A.
Published: July 2019

This paper presents a new method for estimating the amount of an artefact class in use at a given moment in the past from a random assemblage of archaeological finds. The method is based on the use of simulation, since an analytical solution is computationally impractical. Estimating the number of artefacts in use at any time t is shown to follow a Poisson distribution, which allows for credible intervals to be established using the Jeffreys prior. This estimator works from minimal assumptions about the dating and duration of finds, as well as the intensity of collection, and is applied to coinage from four Roman‐period sites excavated by the Roman Peasant Project (2009–14). The result provides an estimation of the abundance of material according to an interval of certainty.
Anatomy and histology of the gastrointestinal tract of the neo‐tropical opossum (Didelphis marsupialis insularis, Allen 1902)
Authors: Tardieu Laura , Sundaram Venkatesan , Adogwa Andrew O. , Garcia Gary W.
Published: July 2019

The morphology of the gastrointestinal tract (GI) is a strong indicator of the dietary habits of a species. The goal of this study was to describe the gross and microanatomy of the digestive tract of the neo‐tropical opossum (Didelphis marsupialis insularis) and relate them to the animals’ food habits. GI tracts from 12 adult animals were used for this study. Results found the small intestine made up 65.9% of the GI tract, and the stomach was simple with a prominent caecum. Histologically, the oesophageal mucosa was non‐keratinized and glands were found throughout the oesophagus. The large intestine showed a great number of goblet cells, the jejunum possessed well‐developed villi, and Peyer's patches were absent in the ileum. The absence of keratinization of the epithelial lining of the oesophagus and stomach and a high lymphocytic infiltration throughout the small and large intestine reflected a more carnivorous diet, whereas the presence of a well‐developed caecum in the large intestine indicated the ability to digest plant matter. Overall, the morphology of GI tract of D. m. insularis displayed both carnivorous and herbivorous features, allowing us to conclude that it is an omnivorous animal.
Functional outcomes of artificial urinary sphincter implantation with distal bulbar double cuff in men with and without a history of external beam radiotherapy: an analysis of a prospective database
Authors: Maurer Valentin , Marks Phillip , Dahlem Roland , Rosenbaum Clemens M. , Meyer Christian P. , Riechardt Silke , Fisch Margit , Ludwig Tim
Published: July 2019

Objectives

To analyse functional outcomes and complication rates of artificial urinary sphincter (AUS) implantation with a distal bulbar double cuff (DC) for the treatment of stress urinary incontinence (SUI) in men with and without a history of external beam radiotherapy (RT).

Patients and Methods

Data of all patients undergoing AUS implantation with a distal bulbar DC (DC‐AUS) were collected prospectively from 2009 to 2015. Indications for DC implantation were based on urethral risk factors in terms of RT and previous proximal bulbar urethral interventions including, endoscopic or open surgery for urethral stricture or SUI. Implantation was carried out to a standardised protocol. Activation of the AUS was performed 6 weeks after implantation. Further follow‐up (FU) included pad test, uroflowmetry, post‐void residual urine measurements, radiography, and a standardised questionnaire. Continence and complication rates were compared between patients with a history of RT and non‐RT patients. Explantation‐free survival was estimated using Kaplan–Meier curves and the log‐rank test. Firth's penalized Cox‐regression analyses were performed to analyse proportional hazard ratios for explantation.

Results

In all, 150 men (median age 70 years, interquartile range [IQR] 66–74) after DC‐AUS implantation were available for analysis. Overall, 73 men (48.7%) had a history of RT. The median (IQR) FU was 24 (7.25–36) months. Baseline clinical characteristics only differed regarding previous open SUI surgery (P = 0.016). Social and objective continence was achieved in 94.8% and 84.3% of all patients treated by implantation of a DC‐AUS, respectively. Between the RT and non‐RT patients there were no statistically significant differences in continence rates [social continence: 100% vs 90.2% (P = 0.194); objective continence: 87% vs 82% (P = 0.877)]. For complications rates there were no significant differences between RT and non‐RT patients after DC‐AUS implantation [infection (P = 0.09), erosion (P = 0.31), mechanical failures (P = 0.14)]. According to Kaplan–Meier analysis explantation rates in patients with a history of RT (26.0%) vs non‐RT patients (20.8%), estimated explantation‐free survival, and AUS durability, did not differ significantly (log‐rank P = 0.219).

Conclusion

Our data from a large institutional series indicate DC‐AUS implantation to be an effective and safe treatment strategy in men with SUI and a history of RT.
Effects of the FGF receptor‐1 inhibitor, infigratinib, with or without sildenafil, in experimental pulmonary arterial hypertension
Authors: Felix Nathane Santanna , de Mendonça Lucas , Braga Cassia Lisboa , da Silva Jaqueline Soares , Samary Cynthia dos Santos , Vieira Juliana Borges , Cruz Fernanda , Rocha Nazareth de Novaes , Zapata‐Sudo Gisele , Rocco Patricia Rieken Macedo , Silva Pedro Leme
Published: July 2019

Background and Purpose

Pulmonary arterial hypertension (PAH) is a progressive disease associated with high morbidity and mortality, despite advances in medical therapy. We compared the effects of infigratinib (NVP‐BGJ398), a new FGF receptor‐1 inhibitor, with or without the PDE‐5 inhibitor sildenafil, on vascular function and remodelling as well as on gene expression of signal transducers for receptors of TGF‐β (Smads‐1/2/4) and transcription factor of endothelial–mesenchymal transition (Twist‐1) in established experimental PAH. Types I and III pro‐collagen and TGF‐β expressions in lung fibroblasts were analysed in vitro after the different treatments.

Experimental Approach

PAH was induced in male Wistar rats with monocrotaline. 14 days later, treatments [sildenafil (SIL), infigratinib (INF) or their combination (SIL+INF)] were given for another 14 days. On Day 28, echocardiography and haemodynamic assays were performed, and lungs and pulmonary vessels were removed for analysis by histology, immunohistochemistry and RT‐PCR. Fibroblasts prepared from PAH lungs were also analysed for TGF‐β and pro‐collagen.

Key Results

Only the combination of infigratinib and sildenafil significantly improved right ventricular systolic pressure and vascular remodelling parameters (right ventricular hypertrophy, smooth muscle α‐actin, vessel wall thickness, and vascular collagen content). Infigratinib may act by reducing gene expression of Smads‐1/4 and Twist‐1 in lung tissue, as well as TGF‐β and types I and III pro‐collagen in lung fibroblasts.

Conclusions and Implications

In this model of monocrotaline‐induced PAH, the combination of the new inhibitor of FGF receptor‐1, infigratinib, and sildenafil effectively improved haemodynamics and decreased vascular remodelling.
Inhibition of the hyaluronan matrix enhances metabolic anticancer therapy by dichloroacetate in vitro and in vivo
Authors: Twarock Sören , Reichert Christina , Bach Katharina , Reiners Oliver , Kretschmer Inga , Gorski Daniel J. , Gorges Katharina , Grandoch Maria , Fischer Jens W.
Published: July 2019

Background and Purpose

Aerobic glycolysis is a unique feature of tumour cells that entails several advantages for cancer progression such as resistance to apoptosis. The low MW compound, dichloroacetate, is a pyruvate dehydrogenase kinase inhibitor, which restores oxidative phosphorylation and induces apoptosis in a variety of cancer entities. However, its therapeutic effectiveness is limited by resistance mechanisms. This study aimed to examine the role of the anti‐apoptotic hyaluronan (HA) matrix in this context and to identify a potential add‐on treatment option to overcome this limitation.

Experimental Approach

The metabolic connection between dichloroacetate treatment and HA matrix augmentation was analysed in vitro by quantitative PCR and affinity cytochemistry. Metabolic pathways were analysed using Seahorse, HPLC, fluorophore‐assisted carbohydrate electrophoresis, colourimetry, immunoblots, and immunochemistry. The effects of combining dichloroacetate with the HA synthesis inhibitor 4‐methylumbelliferone was evaluated in 2D and 3D cell cultures and in a nude mouse tumour xenograft regression model by immunoblot, immunochemistry, and FACS analysis.

Key Results

Mitochondrial reactivation induced by dichloroacetate metabolically activated HA synthesis by augmenting precursors as well as O‐GlcNAcylation. This process was blocked by 4‐methylumbelliferone, resulting in enhanced anti‐tumour efficacy in 2D and 3D cell culture and in a nude mouse tumour xenograft regression model.

Conclusions and Implications

The HA rich tumour micro‐environment represents a metabolic factor contributing to chemotherapy resistance. HA synthesis inhibition exhibited pronounced synergistic actions with dichloroacetate treatment on oesophageal tumour cell proliferation and survival in vitro and in vivo suggesting the combination of these two strategies is an effective anticancer therapy.
Biological effects of aromatic bis[aminomethylidenebis(phosphonic)] acids in osteoclast precursors in vitro
Authors: Nasulewicz‐Goldeman Anna , Goldeman Waldemar , Mrówczyńska Ewa , Wietrzyk Joanna
Published: July 2019

Nitrogen‐containing bisphosphonates (N‐BPs) inhibit bone resorption by preventing osteoclast activity. Most clinically used BPs are hydroxybisphosphonates with the exception of incadronate, which belongs to the class of aminomethylidenebisphosphonic acids. The aim of this study was to evaluate the antiproliferative activity of two previously reported aminobisphosphonates (WG8185B2 and WG9001B) in combination with doxorubicin and cisplatin toward J774E cells (a model of osteoclast precursors in vitro). WG8185B2 and WG9001B BPs enhanced the cytotoxic activity of doxorubicin and cisplatin, especially when applied 24 hr prior to cytostatics. The antiproliferative effect of studied BPs was related to the changes in cell cycle progression. WG8185B2 leads to significant accumulation of J774E cells in S phase, whereas WG9001B causes transient arrest in G2/M phase, followed by an increase in the percentage of cells in S phase. Moreover, WG8185B2 and WG9001B BPs showed enhanced proapoptotic activity in osteoclast precursors, which was manifested by an increase in caspase‐3 activity and percentage of apoptotic cells. In addition, both compounds influenced the motility of J774E cells. The exact molecular mechanism of action of examined BPs remains to be determined; however, results show an interesting biological activity of these compounds, which may be of interest in the context of antiresorptive therapy.
Neuropathological features of “non‐motor” symptoms in multiple sclerosis and neuromyelitis optica
Authors: Kawachi Izumi
Published: July 2019

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are the two main autoimmune demyelinating disorders of the central nervous system. MS is defined as autoimmune oligodendrocytopathy (unknown autoantigens), and NMOSD is defined as autoimmune astrocytopathy or aquaporin‐4 channelopathy. Both diseases can occur throughout the central nervous system, and do often cause various “motor” and “non‐motor” symptoms. “Non‐motor” symptoms, including cognitive impairment, fatigue, pain and neuropsychological symptoms (e.g. depression, loneliness and anxiety), have gained renewed attention in MS and NMOSD since the past three decades, because they influence a patient's competence in daily life activities, including the participation in social activities and their employment status. Herein, we summarize the current concepts of the neuropathological processes of these “non‐motor” symptoms in MS and NMOSD. These concepts help to define the novel disease‐specific mechanisms of the two diseases, and to improve the quality of daily life of patients with MS and NMOSD.
The child in child protection: Invisible and unheard
Authors: Bastian Carmela
Published: July 2019

The paper presents findings from a qualitative study of four child death reviews published in Australia. The study was informed by the theoretical concept of childism. A critical social research methodology facilitated the exposure of childist dynamics in statutory child protection. The transformation of child protection practices and systems has traditionally relied on the imposition of never‐ending structural changes, policies, and procedures. This paper proposes that transformation and the erosion of childist dynamics is contingent on humane and ethical statutory child protection agencies.
Patterns of individual change and program satisfaction in a positive parenting program for parents at psychosocial risk
Authors: Álvarez Míriam , Byrne Sonia , Rodrigo María José
Published: July 2019

Despite the evidence of effectiveness of positive parenting programs, little is known about the typology of changes that parents at psychosocial risk undergo after an intervention. We compared individual patterns of change in three parenting outcomes in 256 at risk parents with young children attending the group‐based Growing Up Happily in the Family program delivered in municipal social services. We identified four clusters of individual change: Cluster 1 (30.6%) had negative changes in parental child‐rearing attitudes and parenting stress, Cluster 2 (27.7%) had positive changes in child‐rearing attitudes and negative results in parental perceived competence, and Cluster 3 (24.1%) and Cluster 4 (17.6%) showed overall better results. Residential area, type of social support, and quality of implementation characterized cluster membership. Participants in clusters with better results were more satisfied with the program than those with worse results. Practical recommendations are provided for the successful implementation of group parenting programs in family preservation services.
“A girl's place is in the home”: Spatial gendered scripts in narratives of girls who have left or been pushed out of home
Authors: Peled Einat , Komem Michal
Published: July 2019

Little is known about the unique gendered experiences of runaway and homeless girls. This feminist study approaches the body and movement of these girls as potential sites of social control. We explored whether and how social values and directives that view the home as the proper place for girls are reflected in the narratives of 17 Israeli girls who have left or been pushed out of their homes, based on a critical interpretive analysis. We found evidence of the impact of gendered social control mechanisms in three key experiences of the girls: (a) delaying leaving home, even when suffering within it; (b) maintaining normativity after leaving home; and (c) help and supervision in encounters with professionals. The discussion further explores the impact of gendered social scripts on the girls' experiences both before and after leaving home and on the way in which they are offered and receive professional help. We call on helping professionals to examine critically how hegemonic gendered discourses about domestic and public spaces shape the experiences of these girls and the helping relationship and use these understandings to improve the services offered to them.
Single crown restorations supported by 6‐mm implants in the resorbed posterior mandible: A five‐year prospective case series
Authors: Guljé Felix L. , Raghoebar Gerry M. , Vissink Arjan , Meijer Henny J. A.
Published: July 2019

Purpose

To assess clinical performance of single restorations supported by 6‐mm long implants in the posterior mandible after 5 years in function.

Materials and Methods

Twenty‐one consecutive patients with the absence of premolars or molars in the posterior mandible and an estimated bone volume of at least 6 mm in width and an estimated height of 8 mm between the top of the ridge and alveolar nerve were included. Each patient received one or more 6‐mm implants. Custom‐made titanium abutments with cemented zirconia‐based porcelain crowns were placed after a 3‐month osseointegration period. Data of clinical examinations and radiographs were assessed at placement of the restoration and 12 and 60 months thereafter. The patients answered a questionnaire to score the satisfaction before treatment and after 12 and 60 months with the restoration in function.

Results

Implant survival was 100%. Five‐years' mean marginal bone loss was 0.14 mm (SD: 0.4). Indices scores for plaque, calculus, gingiva, and bleeding were low as well as mean pocket‐probing depth. Patients' satisfaction was high.

Conclusion

Five‐year follow‐up data of this limited case series study revealed that 6‐mm dental implants inserted in the resorbed posterior mandible provide a solid basis for single tooth restoration.
Early loading of splinted implants in posterior mandible: Three‐year results of a prospective multicenter study
Authors: Liu Jianzhang , Huang Qingfeng , Wang Xiaodong , Li Yan , Zhou Jianfeng , Zeng Deliang , Jiang Xinquan , Zhao Ke , Zhou Yongsheng
Published: July 2019

Objective

To evaluate the clinical outcomes of an early loading protocol of splinted implants with a fluoride‐modified nanostructure surface and a tapered apex design for the therapy of posterior partial edentulism of mandible.

Materials and Methods

One hundred and seven implants were placed in the mandible of 45 subjects at three centres in China. A minimum of two and a maximum of three implants were placed in an edentulous region using a one‐stage protocol. Each subject received a screw‐retained, splinted and fixed permanent prosthesis 6–8 weeks after surgery. Marginal bone level (MBL) change, implant survival and soft tissue health were assessed at 6, 12, 24 and 36 months after loading. A total of 92 implants from 40 subjects were recalled and investigated in this clinical trial.

Results

After three‐year loading, the survival rate of implant was 100%. On a subject level, there was a mean (±SD) marginal bone gain of 0.23 ± 0.48 mm at 36‐month recall and the change in MBL was statistically significant (p = .00061) compared with time of loading. On an implant level, the change in MBL was statistically significant (p = .03914, p = .01494, p = .00000) at 12, 24 and 36 months of loading compared with time of loading.

Conclusion

Three‐year data indicate that early loading protocol of splinted implants with a fluoride‐modified nanostructure surface and a tapered apex design is feasible and safe for the therapy of partial edentulism in posterior mandible, which may contribute to bone gain when the suitable occlusal load and oral hygiene maintenance are kept.
Uncovering the Genomic Landscape in Newly Diagnosed and Relapsed Pediatric Cytogenetically Normal FLT3‐ITD AML
Authors: Buelow Daelynn R. , Pounds Stanley B. , Wang Yong‐Dong , Shi Lei , Li Yongjin , Finkelstein David , Shurtleff Sheila , Neale Geoffrey , Inaba Hiroto , Ribeiro Raul C. , Palumbo Reid , Garrison Dominique , Orwick Shelley J. , Blachly James S. , Kroll Karl , Byrd John C. , Gruber Tanja A. , Rubnitz Jeffrey E. , Baker Sharyn D.
Published: July 2019

Fms‐like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations, common in pediatric acute myeloid leukemia (AML), associate with early relapse and poor prognosis. Past studies have suggested additional cooperative mutations are required for leukemogenesis in FLT3‐ITD+ AML. Using RNA sequencing and a next‐generation targeted gene panel, we broadly characterize the co‐occurring genomic alterations in pediatric cytogenetically normal (CN) FLT3‐ITD+ AML to gain a deeper understanding of the clonal patterns and heterogeneity at diagnosis and relapse. We show that chimeric transcripts were present in 21 of 34 (62%) of de novo samples, 2 (6%) of these samples included a rare reoccurring fusion partner BCL11B. At diagnosis, the median number of mutations other than FLT3 per patient was 1 (range 0–3), which involved 8 gene pathways; WT1 and NPM1 mutations were frequently observed (35% and 24%, respectively). Fusion transcripts and high variant allele frequency (VAF) mutants, which included WT1, NPM1, SMARCA2, RAD21, and TYK2, were retained from diagnosis to relapse. We did observe reduction in VAF of simple or single mutation clones, but VAFs were preserved or expanded in more complex clones with multiple mutations. Our data provide the first insight into the genomic complexity of pediatric CN FLT3‐ITD+ AML and could help stratify future targeted treatment strategies.
Musical Adventures: Extending the Museum Through Interdisciplinary Educational Programming and Tangible Takeaways
Authors: Botts Nathan , Palmer Katherine
Published: July 2019

The mission of the Musical Instrument Museum (MIM) in Phoenix, AZ, USA aims to support guests as they explore diverse musical cultures from across the globe. Participatory programming for youth, nicknamed MIMkids, a central part of the museum’s education mission, educates children ages 6–10 about world cultures through music. The program engages children in hands‐on experiences with musical cultures from around the world by providing opportunities for in‐class group music making, cultural exploration, and crafting. The authors present a set of case studies to offer an overview of the interdisciplinary pedagogical approach of the program, the affordances it provides for experiential learning, and its limitations. The authors conclude with recommendations for museum professionals to better conceptualize musically educative programming that encourages post‐visit learning and culturally themed learning objectives.
Bacterial communities of the reproductive organs of virgin and mated common bedbugs, Cimex lectularius
Authors: Bellinvia Sara , Johnston Paul R. , Reinhardt Klaus , Otti Oliver
Published: July 2019

1. Microbes associated with reproductive organs of animals are either sexually transmitted or opportunistic. Both can affect host defence, immunity, and future colonisation with other microbes. There are only few studies on the microbiota of reproductive organs in insects and how they are affected by copulation.

2. This study examines the bacterial communities associated with reproductive organs in the common bedbug Cimex lectularius, a well‐established insect model for the effects of microbes on male and female reproduction. Combining a metagenomic approach with a controlled mating scheme, we found 31 sequence variants (SVs) across 55 organ samples, with on average three SVs in each sample. Male and female reproductive organs harboured distinct bacterial communities in terms of present SVs.

3. Using a community ecology approach, we found three potential indications of sexual transmission of bacteria in the common bedbug: (i) copulation increased the similarity of the communities of male and female organs; (ii) mated individuals harboured bacteria that were found in non‐mated individuals of the opposite sex but not in non‐mated individuals of the same sex; and (iii) bacterial communities showed a high SV turnover between non‐mated and mated individuals, suggesting a mating‐induced replacement of bacteria.

4. Our findings show that the community ecology approach is useful to examine the bacterial dynamics on reproductive organs, especially when combined with studies that quantify the frequency of transmission and/or estimate the effect of the transmitted microbes on the host immune system and the host endosymbionts.
Population analysis reveals genetic structure of an invasive agricultural thrips pest related to invasion of greenhouses and suitable climatic space
Authors: Cao Li‐Jun , Gao Yong‐Fu , Gong Ya‐Jun , Chen Jin‐Cui , Chen Min , Hoffmann Ary , Wei Shu‐Jun
Published: July 2019

Biological invasions of pests into climatically unsuitable areas can be facilitated by human‐regulated environments, in which case there may be an impact on genetic structure through population processes and/or adaptation. Here, we investigated the population genetic structure of an invasive agricultural pest, Thrips palmi, in China, which has expanded its distribution range through using greenhouses. Early invaded populations showed a relatively higher level of genetic diversity than recently expanded greenhouse populations. Strong population genetic structure corresponded to a pattern of isolation by distance, with no recent gene flow and low historical gene flow among populations, reflecting limited ongoing dispersal. A genetic signature of population expansion was detected in early invaded populations and three northern populations from greenhouses, suggesting that the greenhouse environments facilitated expansion of this species. Redundancy analysis showed that the independent effects of environment and geography could explain 51.68% and 32.06% of the genetic variance, respectively. These findings point to climate‐ and greenhouse‐related spatial expansion, with the potential for adaptation by T. palmi. They emphasize the contribution of human‐regulated environments on the successes of this invasive species, a situation likely to apply to other invasive species that use greenhouse environments.
Single nucleotide polymorphisms reveal a genetic cline across the north‐east Atlantic and enable powerful population assignment in the European lobster
Authors: Jenkins Tom L. , Ellis Charlie D. , Triantafyllidis Alexandros , Stevens Jamie R.
Published: July 2019

Resolving stock structure is crucial for fisheries conservation to ensure that the spatial implementation of management is commensurate with that of biological population units. To address this in the economically important European lobster (Homarus gammarus), genetic structure was explored across the species' range using a small panel of single nucleotide polymorphisms (SNPs) previously isolated from restriction‐site‐associated DNA sequencing; these SNPs were selected to maximize differentiation at a range of both broad and fine scales. After quality control and filtering, 1,278 lobsters from 38 sampling sites were genotyped at 79 SNPs. The results revealed a pronounced phylogeographic break between the Atlantic and Mediterranean basins, while structure within the Mediterranean was also apparent, partitioned between lobsters from the central Mediterranean and the Aegean Sea. In addition, a genetic cline across the north‐east Atlantic was revealed using both putatively neutral and outlier SNPs, but the precise driver(s) of this clinal pattern—isolation by distance, secondary contact, selection across an environmental gradient, or a combination of these factors—remains undetermined. Putatively neutral markers differentiated lobsters from Oosterschelde, an estuary on the Dutch coast, a finding likely explained by past bottlenecks and limited gene flow with adjacent North Sea populations. Building on the findings of our spatial genetic analysis, we were able to test the accuracy of assigning lobsters at various spatial scales, including to basin of origin (Atlantic or Mediterranean), region of origin and sampling location. The predictive model assembled using 79 SNPs correctly assigned 99.7% of lobsters not used to build the model to their basin of origin, but accuracy decreased to region of origin and again to sampling location. These results are of direct relevance to managers of lobster fisheries and hatcheries, and provide the basis for a genetic tool for tracing the origin of European lobsters in the food supply chain.
Cutaneous extramedullary haematopoiesis: Implications in human disease and treatment
Authors: Khalil Shadi , Ariel Gru Alejandro , Saavedra Arturo P.
Published: July 2019

The skin and bone marrow are two of the most dynamic organ systems of the human body. While the skin is only transiently involved in haematopoiesis in utero, cutaneous extramedullary haematopoiesis (CEMH) has been appreciated in various neonatal and adult diseases. The mechanism by which CEMH occurs remains poorly understood, but may be associated with the plasticity of blood and skin tissues. Extensive studies have documented expansion and differentiation of haematopoietic lineages from cutaneous tissues and vice versa. This review will discuss CEMH, potential mechanisms and laboratory findings that shed light on the interaction between both tissues. Further, we will discuss the implications of understanding the role of the skin in haematopoiesis, including the potential therapeutic function of manipulating either organ system in the treatment of pathologic processes in the other.
Targeting cellular cholesterol for anticancer therapy
Authors: Gu Liang , Saha Sourav Taru , Thomas Jodie , Kaur Mandeep
Published: July 2019

Cholesterol dyshomeostasis in cancer cells leads to intracellular cholesterol accumulation, which imparts drug resistance and allows these cells to evade apoptotic signalling processes and maintain continuous cell division and proliferation. Therefore, cholesterol lowering in cancer cells has been envisaged as a potential anticancer strategy. In this direction, two therapeutic strategies have been proposed: (a) to inhibit the biosynthesis of cholesterol in the cells and (b) to deplete excess cholesterol from cancer cells. In the first phase of this review, we collate the cancer signalling pathways (particularly in breast cancer) that are perturbed by cholesterol dyshomeostasis and highlight recent drug discovery efforts to develop cholesterol‐lowering compounds, some of which are currently under clinical trials. In the second phase, based on the analysis of the available scientific evidence, we conceptualize and argue that the depletion of excess cholesterol could sensitize cancer cells to available therapeutics and may also help to alleviate cancer drug resistance.
Primal and Dual Access
Authors: Cui Mengying , Levinson David
Published: July 2019

Accessibility, measuring the ease of reaching potential destinations, is increasingly being considered as an effective indicator to evaluate the performance of transport and land use interactions. Primal accessibility, a generalization of the first accessibility formulation proposed by Hansen, has been widely used in many studies and demonstrated to be a reliable tool for project, program, and policy evaluation. The dual of accessibility, measuring the time required to reach a given number of opportunities, is less often considered but can be used for optimization in location covering‐type problems. This article, hence, clarifies the definitions of primal and dual access, and applies both measures to the Minneapolis—St. Paul metropolitan area for auto and transit to demonstrate their practicality as a metropolitan‐level measurement. We explore the correlations and differences between the primal and dual access to better understand the relative strengths of the measures. It is found that, as with primal accessibility, dual accessibility is an efficient approach to evaluate accessibility, which is straightforward to calculate and to explain to policy‐makers and the public.
Impact of pulsed electric field pretreatment on yield and quality of lipid extracted from cephalothorax of Pacific white shrimp (Litopenaeus vannamei) by ultrasound‐assisted process
Authors: Gulzar Saqib , Benjakul Soottawat
Published: July 2019

Pacific white shrimp cephalothorax was subjected to pulsed electric field (PEF) pretreatment at different electric field strengths (4, 8, 12 and 16 kV cm−1) and pulse numbers (120, 160, 200 and 240) to enhance the extraction yield of lipids. PEF‐treated samples were subsequently subjected to lipid extraction using ultrasound‐assisted extraction (UAE) process at ultrasound amplitude of 80% for 25 min in continuous mode. PEF‐pretreated samples subjected to UAE rendered the highest lipid yield (30.34 g 100 g−1 solids). PEF pretreatment resulted in reduced lipid oxidation as evidenced by the decreases in peroxide value (PV) and thiobarbituric acid reactive substances (TBARS). Lipids from PEF‐pretreated samples extracted using UAE had higher content of PUFAs and carotenoids, including astaxanthin, astaxanthin monoester, astaxanthin diester, canthaxanthin and β‐carotene. Overall, PEF pretreatment helped in enhancing the extraction yield of lipids and carotenoids from shrimp cephalothorax and reduce lipid oxidation to some extent.
Immunobiology of chimeric antigen receptor T cells and novel designs
Authors: Walsh Zachary , Yang Yinmeng , Kohler M. Eric
Published: July 2019

Advances in the development of immunotherapies have offered exciting new options for the treatment of malignant diseases that are refractory to conventional cytotoxic chemotherapies. The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) has demonstrated dramatic results in clinical trials and highlights the promise of novel immune‐based approaches to the treatment of cancer. As experience with CAR T cells has expanded with longer follow‐up and to a broader range of diseases, new obstacles have been identified which limit the potential lifelong benefits of CAR T cell therapy. These obstacles highlight not only the gaps in knowledge of the optimal clinical application of this “living drug”, but also gaps in our understanding of the fundamental biology of CAR T cells themselves. In this review, we discuss the obstacles facing CAR T cell therapy, how these relate to our current understanding of CAR T cell biology and approaches to enhance the clinical efficacy of this therapy.
The Mali Elephant Project: protecting elephants amidst conflict and poverty
Authors: Canney S. M.
Published: July 2019

This short report shows how it has been possible to protect a small yet important, highly vulnerable, remnant population of desert‐adapted African elephants Loxodonta africana that roams through a vast, populated area of Mali, which in recent years has become lawless and subject to an aggressive jihadist insurgency. Initial studies showed how ecosystem trends threatened elephant survival and local livelihoods, and exacerbated human–human and human–elephant conflict. A combination of adaptive management and action research methods was used to understand the social, economic, political and environmental aspects of this complex system. This knowledge served to derive intervention strategies that attempted to tackle the underlying drivers of threat to elephant survival. Central to this approach was the reinforcement of existing attitudes towards elephants and the use of collaborative methods. Local communities were empowered to counter resource over‐exploitation and degradation by devising resource‐management systems that were rooted in existing practice and provided tangible livelihood benefits from elephant conservation. When lawlessness overtook the elephant range in 2012, it became subject to attacks by armed groups, a deepening insurgency and elephant poaching. The existing community work proved key to respond to the escalation of poaching in 2015, as it had engaged local people in the conservation effort, improving their lives and securing local ‘buy‐in’. This facilitated the work of the newly created anti‐poaching unit, which was trained to operate according to an ‘intelligent’ and ethical doctrine that used local information to cope with the insecurity and target its efforts.