bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pragmatic use of short‐course radiotherapy, chemotherapy and surgery for stage IV rectal cancer with locally advanced or symptomatic primary tumours
Authors: Higgins Martin J , Mulsow Jurgen , Staunton Oonagh , Aird John , Cronin Carmel , Dunne Mary T , Burke John , Shields Conor , Faul Eleanor , McCawley Niamh , Toomey Des , Conneely John , O’Neill Brian 
Published: August 2021

AbstractIntroductionWe assessed management of patients with de novo metastatic rectal cancer, referred for radiotherapy to the rectum, who were candidates for short‐course radiotherapy (SCRT) and chemotherapy, followed by resection of all disease. We assessed surgical outcomes, overall survival (OS) and progression‐free survival (PFS).MethodsRetrospective review of patients meeting criteria: (i) treatment with SCRT to rectum; (ii) locally advanced primary rectal cancer; and (iii) resectable distant metastases at diagnosis. Data were collected from charts, correspondence and electronic patient records. OS and PFS were calculated using the Kaplan–Meier method.ResultsBetween 2016 and 2020, 48 patients with stage IV rectal cancer at diagnosis were treated with SCRT. Only 15 patients (31%) had resectable metastatic disease and were intended for SCRT (25 Gy/5#), then chemotherapy, followed by resection of all sites of disease and are included in our study. 12 of the 15 surgical candidates (80%) had rectal surgery as planned, and 11 of the 15 (73%) had resection of the rectal primary and all metastatic disease. One patient had a pathological complete response (pCR), and 50% of surgical patients had a Mandard TRG of 1 or 2. Median PFS and OS for the 15 surgical candidates were 12.6 and 25.2 months, respectively, with a median FU of 21.2 months.ConclusionFor this cohort of patients, our treatment paradigm is pragmatic and results in excellent pathological response. However, the effectiveness of this approach should be the subject of future prospective studies.
Trends in the bushmeat market trade in North Sulawesi and conservation implications
Authors: Bailey C. , Hilser H. , Siwi Y. , Lawe Z. , Waterman J. , Loffeld T. A. C. , Sampson H. , Tasirin J. , Melfi V. , Bowkett A. E. 
Published: August 2021

AbstractThe bushmeat trade, or the trade in wild animals for meat, is a primary threat to wildlife and ecosystems in Sulawesi, Indonesia. Hunting for trade and consumption can hasten the local extirpation of vulnerable species, such as fruit bats and the protected babirusa and Sulawesi crested black macaque. This study provides a much‐needed step in understanding the bushmeat trade by describing longitudinal trends in the amount of bushmeat (animal carcasses) observed for sale in markets in North Sulawesi, a particularly biodiversity‐rich area. Surveys were conducted in 10 markets in 2011, 2015, 2018 and 2019. At each market, total counts of all taxa for sale were noted, and encounter rates per market sample were derived to account for variable sampling effort across years and markets. Generalized Linear Mixed Models were used to compare encounter rates across years, months and markets. Our results show that although animal carcasses are still sold in high numbers, there has been an overall decrease between 2011 and 2019, particularly between 2011 and 2018 (encounter rate fell by 99%). However, bats, rats and Sulawesi warty pigs were still present at high levels, indicating a persistent demand for bushmeat in North Sulawesi. The encounter rate of protected taxa for sale was low, but steady throughout the study period. We identified which markets sold the greatest amount of bushmeat to inform future conservation actions and management. Based on our results, the persistent demand for bushmeat in the region, and the continued presence of protected taxa in the markets, we recommend further research to establish the sustainability of the bushmeat trade at its current rate.
Effect of fruit fly protein bait on the red scale parasitoid, Aphytis lingnanensis (Hymenoptera: Aphelinidae): attraction and toxicity
Authors: Mahat Kiran , Drew R A I 
Published: August 2021

AbstractProtein bait spray is a tool used widely in tephritid fruit fly pest (Diptera: Tephritidae) control and eradication programs. However, this technique might have a negative effect on non‐target, beneficial insects. Aphytis lingnanensis is a very successful parasitoid of the California red scale, Aonidiella aurantii, a worldwide pest of citrus. Though A. lingnanensis is widely used in augmentative release programs, the impact of protein bait‐insecticide mixtures on the parasitoid is not documented. In this study, we investigated the attraction of A. lingnanensis to Pinnacle® protein, a fruit fly protein bait commonly used in Australia. Following this, the contact toxicity of field weathered residues of protein bait mixed with the insecticides spinosad, fipronil, malathion and chlorpyrifos to A. lingnanensis were evaluated. Finally, the non‐lethal impact of these residues on the capacity of A. lingnanensis to parasitize its host was investigated. Food‐deprived parasitoids were not attracted to protein but were significantly attracted to honey. The lack of attraction of protein, however, increased when sugar was added to it. Relative to a control of only protein, protein bait‐insecticide mixtures applied on citrus leaves and weathered outdoors for 2 h, 3 days, 7 days and 12 days caused high mortality of A. lingnanensis. The residual toxicity of the four weathering periods, for all the protein bait‐insecticide mixtures, produced high mortality rates varying between 90% and 100%. In addition, the capacity of A. lingnanensis to parasitize its host after exposure to weathered residues containing an insecticide was severely affected. The results suggest that A. lingnanensis is highly susceptible to the insecticides evaluated here when used in fruit fly protein baits. Therefore, the use of these insecticides in protein bait sprays, as part of an area wide fruit fly management, should be carefully considered in areas where augmentative release and conservation of A. lingnanensis are also applied.
Addressing the crisis of congenital syphilis: Key findings from an evaluation of the management of syphilis in pregnancy and the newborn in South‐East Queensland
Authors: Wu Mandy , Seel Mandy , Britton Sumudu , Dean Judith A. , Lazarou Mattea , Safa Huda , Griffin Paul , Nourse Clare 
Published: August 2021

BackgroundSyphilis in pregnancy and congenital syphilis (CS) are increasing in Australia. Prevention of adverse outcomes requires adherence to management guidelines.AimsThe aim is to evaluate the management of syphilis in pregnant women and their newborns.Materials and MethodsA retrospective study of public health notifications, clinical records and testing results of women with positive syphilis serology in pregnancy requiring treatment from 2016 to 2018 inclusive across South‐East Queensland was conducted. Management was described and compared with contemporary guidelines from the Australasian Society of Infectious Diseases, the Communicable Diseases Network Australia and the United States Centers for Disease Control and Prevention.ResultsOf 30 women identified, 22 (73%) had management consistent with the guidelines (stage‐appropriate penicillin regimen, appropriate dosing interval and treatment completed greater than 30 days before delivery). Only 14 (47%) women had documentation of partner testing and/or treatment. Of 26 mother–infant pairs with complete data, 16 (62%) had investigations at delivery consistent with recommendations (parallel maternal–infant rapid plasma reagin, infant syphilis immunoglobulin M, placental histopathology +/– syphilis polymerase chain reaction and infant clinical examination). One infant met the criteria for confirmed CS. Five infants received penicillin therapy. Only seven (27%) infants had serological monitoring after discharge.ConclusionsManagement can be optimised with timely maternal testing and treatment, comprehensive partner screening and treatment, strict adherence to seven‐day penicillin dosing for late latent syphilis and thorough maternal and infant testing after treatment and delivery. If maternal treatment was inadequate in pregnancy, consideration needs to be given to close evaluation and empiric treatment of the infant.
The risk of chronic diseases and congenital malformations during childhood and adolescence after in utero exposure to thiopurines
Authors: Jølving Line Riis , Anru Pavithra Laxsen , Nielsen Jan , Friedman Sonia , Nørgård Bente Mertz 
Published: August 2021

SummaryBackgroundWomen with autoimmune diseases, particularly inflammatory bowel disease (IBD), often need to continue immunomodulatory therapies during pregnancy. While the evidence of birth and short‐term outcomes in children exposed in utero to these medicines is reassuring, long‐term safety data are lacking.AimTo assess any association between in utero exposure to thiopurines and diagnoses of chronic diseases (type 1 diabetes, coeliac disease, thyroid disease, rheumatoid arthritis, IBD and asthma) and congenital malformations during childhood and adolescence.MethodsThis nationwide cohort study was based on information using Danish registers and comprised all live‐born children from 1995 to 2015 (N = 1 308 778). Children exposed in utero to thiopurines were followed for a median of 8.9 years (25%‐75% percentiles 5.5‐12.4 years); children not exposed were followed for 13.9 years (25%‐75% percentiles 8.7‐19.0 years). Analyses were adjusted for a number of confounders including the type of maternal underlying disease.ResultsA total of 1047 children had been exposed to thiopurines in utero; 96 developed a chronic disease and 126 were diagnosed with congenital malformations during follow‐up. The adjusted hazard ratio for rheumatoid arthritis was 0.78 (95% CI 0.35‐1.73); for IBD, it was 1.45 (95% CI 0.64‐3.27); for asthma 0.94 (95% CI 0.73‐1.21), and for congenital malformations, it was 0.95 (95% CI 0.78‐1.15). For type 1 diabetes, coeliac disease, thyroid disease and ulcerative colitis, we had insufficient data to perform adjusted analysis.ConclusionWe found no increased risk of seven common chronic diseases or congenital malformations during childhood and adolescence after gestational exposure to thiopurines.
An early proinflammatory transcriptional response to tau pathology is age‐specific and foreshadows reduced tau burden
Authors: Rasmussen Jay , Ewing Adam D. , Bodea Liviu‐Gabriel , Bodea Gabriela O. , Gearing Marla , Faulkner Geoffrey J. 
Published: August 2021

AbstractAge is one of the strongest risk factors for the development of neurodegenerative diseases, the majority of which involve misfolded protein aggregates in the brain. These protein aggregates are thought to drive pathology and are attractive targets for the development of new therapies. However, it is unclear how age influences the onset of pathology and the accompanying molecular response. To address this knowledge gap, we used a model of seeded tau pathology to profile the transcriptomic changes in 3 and 12 month old mice in response to developing tau hyperphosphorylation and aggregation. First, we found the burden of hyperphosphorylated tau pathology in mice injected at 12 months of age was moderately reduced compared to animals injected at 3 months. On a molecular level, we found an inflammation‐related subset of genes, including C3 and the disease‐associated microglia genes Ctsd, Cst7, and Clec7a, were more expressed early in disease in 12 but not 3 month old mice. These findings provide evidence of an early, age‐specific response to tau pathology, which could serve as a marker for the severity of downstream pathology.
Child protection in British Columbia: Moving toward primary prevention
Authors: Vaghri Ziba , De Souza Lauren 
Published: August 2021

AbstractBritish Columbia lacks sufficient legislation to support Canada's commitments to protect the rights of young children. Of particular concern is the child's right to be free from violence, which requires stronger structural commitments to be fulfilled. This research note presents findings from the review and analysis of provincial child protection legislation and corresponding knowledge translation activities. It highlights three legislative gaps that must be addressed in order to meet BC's commitments under the Convention on the Rights of the Child. It concludes with the recommendation that BC develop a comprehensive child protection strategy prioritizing primary prevention of violence against children.
CD146 is a potential immunotarget for neuroblastoma
Authors: Obu Satoshi , Umeda Katsutsugu , Ueno Hiroo , Sonoda Mari , Tasaka Keiji , Ogata Hideto , Kouzuki Kagehiro , Nodomi Seishiro , Saida Satoshi , Kato Itaru , Hiramatsu Hidefumi , Okamoto Tatsuya , Ogawa Eri , Okajima Hideaki , Morita Ken , Kamikubo Yasuhiko , Kawaguchi Koji , Watanabe Kenichiro , Iwafuchi Hideto , Yagyu Shigeki , Iehara Tomoko , Hosoi Hajime , Nakahata Tatsutoshi , Adachi Souichi , Uemoto Shinji , Heike Toshio , Takita Junko 
Published: August 2021

AbstractNeuroblastoma, the most common extracranial solid tumor of childhood, is thought to arise from neural crest‐derived immature cells. The prognosis of patients with high‐risk or recurrent/refractory neuroblastoma remains quite poor despite intensive multimodality therapy; therefore, novel therapeutic interventions are required. We examined the expression of a cell adhesion molecule CD146 (melanoma cell adhesion molecule [MCAM]) by neuroblastoma cell lines and in clinical samples and investigated the anti‐tumor effects of CD146‐targeting treatment for neuroblastoma cells both in vitro and in vivo. CD146 is expressed by 4 cell lines and by most of primary tumors at any stage. Short hairpin RNA‐mediated knockdown of CD146, or treatment with an anti‐CD146 polyclonal antibody, effectively inhibited growth of neuroblastoma cells both in vitro and in vivo, principally due to increased apoptosis via the focal adhesion kinase and/or nuclear factor‐kappa B signaling pathway. Furthermore, the anti‐CD146 polyclonal antibody markedly inhibited tumor growth in immunodeficient mice inoculated with primary neuroblastoma cells. In conclusion, CD146 represents a promising therapeutic target for neuroblastoma.
Connecting inside out: Development of the social brain in infants and toddlers with a focus on myelination as a marker of brain maturation
Authors: Schneider Nora , Greenstreet Elizabeth , Deoni Sean C. L. 
Published: August 2021

AbstractEarly childhood is a sensitive period for learning and social skill development. The maturation of cerebral regions underlying social processing lays the foundation for later social‐emotional competence. This study explored myelin changes in social brain regions and their association with changes in parent‐rated social‐emotional development in a cohort of 129 children (64 females, 0–36 months, 77 White). Results reveal a steep increase in myelination throughout the social brain in the first 3 years of life that is significantly associated with social‐emotional development scores. These findings add knowledge to the emerging picture of social brain development by describing neural underpinnings of human social behavior. They can contribute to identifying age‐/stage‐appropriate early life factors in this developmental domain.
Young children’s ability to make predictions about novel illnesses
Authors: DeJesus Jasmine M. , Venkatesh Shruthi , Kinzler Katherine D. 
Published: August 2021

AbstractUnderstanding disease transmission is a complex problem highlighted by the COVID‐19 pandemic. These studies test whether 3‐ to 6‐year‐old children in the United States use information about social interactions to predict disease transmission. Before and during COVID‐19, children predicted illness would spread through close interactions. Older children outperformed younger children with no associations between task performance and pandemic experience. Children did not predict that being hungry or tired would similarly spread through close interactions. Participants include 196 three‐ to six‐year‐olds (53% girls, 47% boys; 68% White, 9% Black, 7% Asian, 6% Hispanic or Latinx), with medium‐sized effects (d = .6, = .3). These findings suggest that thinking about social interaction supports young children's predictions about illness, with noted limitations regarding children's real‐world avoidance of disease‐spreading behaviors.
Preparation of three‐notochord explants for imaging analysis of the cell movements of convergent extension during early Xenopus morphogenesis
Authors: Goto Toshiyasu , Keller Ray 
Published: August 2021

AbstractWe describe a method of generating three‐notochord explants to analyze the cell movements of convergent extension (CE) during Xenopus laevis gastrulation and neurulation. This method uses standard microsurgical techniques under a fluorescence stereomicroscope to combine notochordal sectors of gastrulae, side by side (lateral surfaces apposed) into a single explant. Three‐notochord explants cultured on bovine serum albumin (BSA)‐coated glass converged mediolaterally and extended in the anterior–posterior direction. The individual notochordal cells showed the mediolaterally oriented, bipolar tractional motility and the resulting mediolaterally oriented cell intercalation characteristic of CE, thereby reproducing both the in vivo tissue and the cell movements in an explant. Image analysis of three‐notochord explants reveals the effects of overexpressions or knockdowns of genes, of manipulation of the extracellular matrix, and of exposure to chemical reagents on morphogenesis during gastrulation and neurulation, compared with control explants. Moreover, since three‐notochord explants provide two zones of cell intercalation between notochords, individual cell behaviors between notochords of different characteristics and experimental treatments can be observed at the same time.
Potential contribution of haemoconcentration to changes in lipid variables with empagliflozin in patients with type 2 diabetes: A post hoc analysis of pooled data from four phase 3 randomized clinical trials
Authors: Lund Søren S. , Sattar Naveed , Salsali Afshin , Neubacher Dietmar , Ginsberg Henry N. 
Published: August 2021

AbstractAimTo examine the association between changes in lipids and markers of haemoconcentration (haematocrit and serum albumin) with empagliflozin, a sodium‐glucose co‐transporter‐2 inhibitor, in patients with type 2 diabetes (T2D) using pooled data from four phase 3 randomized trials.Materials and MethodsPatients with T2D received placebo (n = 825), empagliflozin 10 mg (n = 830) or 25 mg (n = 822) for 24 weeks. In post hoc mediation analyses, we assessed total changes in LDL‐cholesterol, HDL‐cholesterol, triglycerides, apolipoprotein (Apo) B, and Apo A‐I, and changes in these variables associated with, and independent of, changes in haematocrit and serum albumin at week 24 using ANCOVA models.ResultsEmpagliflozin versus placebo increased serum LDL‐cholesterol, HDL‐cholesterol, and Apo A‐I, decreased triglycerides (empagliflozin 10 mg only), and (non‐significantly) increased Apo B. Empagliflozin modestly increased haematocrit and serum albumin. In mediation analyses, haematocrit changes (increases) with empagliflozin were associated with significant changes (increases) in all lipid variables, including Apo B. Except for triglycerides (non‐significant), similar lipid variable associations were observed with serum albumin changes. Haematocrit‐ and serum albumin‐independent changes in lipids with empagliflozin were significant for HDL‐cholesterol (increases), mostly significant for triglycerides (decreases), and less so for other lipid fractions.ConclusionHaematocrit and serum albumin increases were associated with increases in lipid fractions with empagliflozin. Empagliflozin‐associated changes in serum lipids, particularly LDL‐cholesterol increases, may be partly attributable to haemoconcentration resulting from increased urinary volume and subsequent volume contraction.
Orexin receptors: Targets and applications
Authors: Subramanian Subhiksha , Ravichandran Mirunalini 
Published: August 2021

AbstractOver the years, elucidating targets from the neural circuits that can be used to treat disorders pertaining to the nervous system and extending their scope to other systems have always proved interesting to researchers. The role of various peptides and neurotransmitters has been elucidated and is being developed as therapeutic targets. Out of these, orexins are neuropeptides produced in the hypothalamus that stimulate a specific type of G‐Protein coupled receptors (GPCR) called orexin receptors and bring about various physiological and pathological roles. Orexin receptors are of interest not only because of their wide applications such as insomnia, obesity, and inflammatory disorders but also because of their contribution to promising aspects of drug discovery such as optogenetics and their tremendous growth from the stage of being orphans to orexins. This review will discuss in detail the structure of orexin receptors, their physiological role, and various applications in disease states adding a note on agonists and antagonists and finally summarizing the recent drug approvals in the field.
Analysis of residual stress relaxation of aluminum alloys EN AW 6061/‐82 T6 under cyclic loading
Authors: Repplinger Christian , Sellen Stephan , Kedziora Slawomir , Zürbes Arno , Maas Stefan 
Published: August 2021

AbstractStress relaxation describes the reduction of stress under static or cyclic loading at a constant strain level. Several processes induce intentionally residual stresses, for example, autofrettage of thick‐walled pressurized tubes to improve their fatigue life. This well‐known process induces residual compressive stresses at the critical inner surface by using a single static but controlled overloading internal pressure. Relaxation of residual stresses due to cyclic loading in service would endanger the effectiveness of autofrettage and could finally lead to unexpected fatigue failure. In this study, strain‐controlled experiments up to 500,000 load cycles and amending nonlinear finite element simulations were done for the aluminum alloys EN AW 6061 T6 and EN AW 6082 T6 to study potential cyclic stress relaxation in four‐point bending tests after controlled single static plasticization for residual stress generation. This analysis identifies almost stable residual stresses for both materials under different cyclic strain‐controlled load levels.