bluuebunny/crossref_metadata_2025_split huggingface dataset:
Notch signaling regulates nuclear androgen receptor AR and membrane androgen receptor ZIP9 in mouse Sertoli cells
Authors: Kamińska A. , Pardyak L. , Marek S. , Wróbel K. , Kotula‐Balak M. , Bilińska B. , Hejmej A. 
Published: August 2019

AbstractBackgroundNotch signaling pathway is involved in contact‐dependent communication between the cells of seminiferous epithelium, and its proper activity is important for undisturbed spermatogenesis.ObjectivesThe aim was to assess the effect of Notch pathway inhibition on the expression of nuclear (AR) and membrane (ZIP9) androgen receptors and androgen‐regulated genes, claudin‐5 and claudin‐11, in TM4 mouse Sertoli cell line.Materials and methodsDAPT (γ‐secretase inhibitor) treatment and recombination signal binding protein silencing were employed to reduce Notch signaling, whereas immobilized ligands were used to activate Notch pathway in TM4 cells. To reveal specific effect of each androgen receptor, AR or ZIP9 silencing was performed.ResultsNotch pathway inhibition increased the expression of AR and ZIP9 mRNA and proteins (p < 0.01; p < 0.05) in TM4 cells, whereas incubation with Notch ligands, rDLL1 or rJAG1, reduced AR (p < 0.01; p < 0.001) and ZIP9 (p < 0.05; p < 0.01) expressions, respectively. Testosterone enhanced the expression of both receptors (p < 0.05; p < 0.01). Androgen‐regulated claudin‐5 and claudin‐11 (p < 0.01; p < 0.001) and cAMP (p < 0.001) were elevated in Notch‐inhibited cells, while activation of Notch signaling by DLL1 or JAG1 reduced claudin‐11 or claudin‐5 level (p < 0.01; p < 0.001), respectively.DiscussionOur findings indicate opposite effect of Notch and androgen signaling on the expression of androgen receptors in TM4 cells. We demonstrated that AR expression is regulated by DLL1‐mediated Notch signaling, whereas JAG1 is involved in the regulation of ZIP9. The expression of both claudins and cAMP production is under inhibitory influence of Notch pathway. The effects of Notch signaling on claudin‐5 and claudin‐11 expression are mediated by ZIP9 and AR, respectively.ConclusionNotch signaling may be considered as an important pathway controlling Sertoli cell physiology, and its alterations may contribute to disturbed response of Sertoli cells to androgens.
Impact of medicines regulatory risk communications in the UK on prescribing and clinical outcomes: Systematic review, time series analysis and meta‐analysis
Authors: Weatherburn Christopher J. , Guthrie Bruce , Dreischulte Tobias , Morales Daniel R. 
Published: August 2019

AimsRegulatory risk communications are important to ensure medication safety, but their impact is poorly understood. The aim was to quantify the impact of UK risk communications on medication use and other outcomes.MethodsWe conducted a systematic review of studies reporting prescribing/health outcome data relevant to UK regulatory risk communication. Data were reanalysed using interrupted time series regression 12 months after each regulatory intervention. Mean changes were pooled using random‐effects generic inverse variance examining the following subgroups: drug withdrawals; restrictions/changes in indications; be aware messages without specific recommendations for action; communication via direct healthcare practitioner communications; communication via drug bulletins.ResultsOf 11 466 articles screened, 40 studies examining 25 UK regulatory risk communications were included. Product withdrawals, restriction in indications and be aware communications were associated with relative mean changes of −78% (95% confidence interval [CI] −60 to −96%), −34% (95% confidence interval [CI] −12 to −55%) and −11% (95%CI −8 to −15%) in targeted drug prescribing respectively. Direct healthcare professional communications were associated with relative mean changes of −47% (95%CI −27 to −68%) compared to −13% (95%CI −6 to −20%) for drug bulletins. Of 7 studies examining unique health outcomes related to the safety concern, risk communications were associated with a mean −10% (95%CI −3 to −16%) decrease in intended and a 7% (95%CI 4 to 10%) increase in unintended health outcomes.DiscussionUK regulatory risk communications were associated with significant changes in targeted prescribing and potential changes in clinical outcomes. Further research is needed to systematically study the impact of regulatory interventions.
Ibrutinib monotherapy outside of clinical trial setting in Waldenström macroglobulinaemia: practice patterns, toxicities and outcomes
Authors: Abeykoon Jithma P. , Zanwar Saurabh , Ansell Stephen M. , Gertz Morie A. , Kumar Shaji , Manske Michelle , Novak Anne J. , King Rebecca , Greipp Patricia , Go Ronald , Inwards David , Muchtar Eli , Habermann Thomas , Witzig Thomas E. , Thompson Carrie A. , Dingli David , Lacy Martha Q. , Leung Nelson , Dispenzieri Angela , Gonsalves Wilson , Warsame Rahma , Kyle Robert A. , Rajkumar Vincent , Parikh Sameer A. , Kapoor Prashant 
Published: August 2019

SummaryIbrutinib‐related data in Waldenström macroglobulinaemia (WM) remain sparse, particularly outside of trials. We report on 80 patients [previously treated, n = 67 (84%), treatment‐naïve, n = 13 (16%)] with WM, evaluated consecutively at Mayo Clinic, who received ibrutinib off‐study after its approval in 2015 for WM. Overall response rate (ORR) was 91%; major‐response rate (MRR) was 78%. The median time to first response and best response was 2·9 [95% confidence interval (CI): 2–4] and 5·7 (95% CI: 4–12) months, respectively. The median follow‐up was 19 (95% CI: 14–21) months; 18‐month progression‐free survival (PFS) was 82%. The median time on therapy was 12·5 (95% CI: 9·3–16·7) months, and the median duration‐of‐response was 32 (range: 23–32) months. Twenty‐five patients (31%) had discontinued therapy at last follow‐up (68% due to treatment‐related toxicities) and 18% of patients required dose reduction. Fatigue (12%) and atrial‐fibrillation (11%) were common non‐haematological toxicities. IgM rebound occurred in 36% of patients who abruptly discontinued ibrutinib. Following ibrutinib discontinuation, 84% of patients received subsequent treatment, achieving an ORR of 57% and MRR of 50%. The median PFS from commencement of subsequent salvage therapy was 18 months. Ibrutinib therapy, outside of clinical trials, is effective in WM, but is associated with toxicities and challenges, including IgM rebound and a high drug discontinuation rate for reasons other than disease progression.
The role of extended venous thromboembolism prophylaxis for major urological cancer operations
Authors: Naik Rishi , Mandal Indrajeet , Hampson Alexander , Lane Tim , Adshead Jim , Rai Bhavan Prasad , Vasdev Nikhil 
Published: August 2019

ObjectivesVenous thromboembolism (VTE), consisting of both pulmonary embolism (PE) and deep vein thromboses (DVT), remains a well‐recognised complication of major urological cancer surgery. Several international guidelines recommend extended thromboprophylaxis (ETP) with LMWH, whereby the period of delivery is extended to the post‐discharge period, where the majority of VTE occurs. In this literature review we investigate whether ETP should be indicated for all patients undergoing major urological cancer surgery, as well procedure specific data that may influence a clinician's decision.MethodsWe performed a search of six databases (PubMed, Cochrane, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, and British Nursing Index (BNI)) from inception to June 2019, for studies looking at adult patients who received VTE prophylaxis after surgery for a major urological malignancy.ResultsEighteen studies were analysed. VTE risk is highest in open and robotic Radical Cystectomy (RC) (2.6–11.6%) and ETP demonstrates a significant reduction in risk of VTE, but not a significant difference in Pulmonary Embolism (PE) or mortality. Risk of VTE in open Radical Prostatectomy (RP) (0.8–15.7%) is comparable to RC, but robotic RP (0.2–0.9%), open partial/radical nephrectomy (1.0–4.4%) and robotic partial/radical nephrectomy (0.7–3.9%) were lower risk. It has not been shown that ETP reduces VTE risk specifically for RP or nephrectomy.ConclusionThe decision to use ETP is a fine balance between variables such as VTE incidence, bleeding risk and perioperative morbidity/mortality. This balance should be assessed for each specific procedure type. While ETP still remains of net benefit for open RP as well as open and robotic RC, the balance is closer for minimally invasive RP as well as radical and partial nephrectomy. Due to a lack of procedure specific evidence for the use of ETP, adherence with national guidelines remains poor. Therefore, we advocate further studies directly comparing ETP vs standard prophylaxis, for specific procedure types, in order to allow clinicians to make a more informed decision in future.
It's in your glass: a history of sea level and storminess from the Laphroaig bog, Islay (southwestern Scotland)
Authors: Kylander Malin E. , Söderlindh Jenny , Schenk Frederik , Gyllencreutz Richard , Rydberg Johan , Bindler Richard , Martínez Cortizas Antonio , Skelton Alasdair 
Published: August 2019

Severe winter windstorms have become an increasingly common occurrence over recent decades in northwestern Europe. Although there exists considerable uncertainty, storminess is projected to increase in the future. On centennial to millennial time scales in particular, the mechanisms forcing storminess remain unsettled. We contribute to available palaeostorm records by reconstructing changes over the last 6670 years using a coastal peat sequence retrieved from the ombrotrophic Laphroaig bog on Islay, southwestern Scotland. We use a combination of ash content, grain size and elemental chemistry to identify periods of greater storminess, which are dated to 6605, 6290–6225, 5315–5085, 4505, 3900–3635, 3310–3130, 2920–2380, 2275–2190, 2005–1860, 1305–1090, 805–435 and 275 cal. a BP. Storm signals in the first half of the record up to ~3000 cal. a BP are mainly apparent in the grain‐size changes. Samples from this time period also have a different elemental signature than those later in the record. We speculate that this is due to receding sea levels and the consequent establishment of a new sand source in the form of dunes, which are still present today. The most significant events and strongest winds are found during the Iron Ages Cold Epoch (2645 cal. a BP), the transition into, and in the middle of, the Roman Ages Warm Period (2235 and 1965 cal. a BP) and early in the Little Ice Age (545 cal. a BP). The Laphroaig record generally agrees with regionally relevant peat palaeostorm records from Wales and the Outer Hebrides, although the relative importance of the different storm periods is not the same. In general, stormier periods are coeval with cold periods in the region as evidenced by parallels with increased ice‐rafted debris in the North Atlantic, highlighting that sea‐ice conditions could impact future storminess and storm track position.
Therapeutics for dementia and Alzheimer's disease: New directions for precision medicine
Authors: Duce J.A. , Zhu X. , Jacobson L.H. , Beart P.M. 
Published: August 2019

Linked ArticlesThis article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc
Provider and community perspectives of dental therapists in Alaska’s Yukon‐Kuskokwim Delta: A qualitative programme evaluation
Authors: Chi Donald L. , Hopkins Scarlett , Zahlis Ellen , Randall Cameron L. , Senturia Kirsten , Orr Eliza , Mancl Lloyd , Lenaker Dane 
Published: August 2019

AbstractObjectivesDental therapists deliver preventive and basic restorative care and have been practicing since 2006 in Alaska's Yukon‐Kuskokwim (YK) Delta. In this qualitative programme evaluation, we documented health providers’ and community members’ experiences with dental therapy. The goal of the evaluation was to develop a conceptual model of dental care delivery in Alaska Native Communities centred on dental therapists.MethodsWe developed semi‐structured interview scripts and used snowball sampling to recruit 16 health providers with experience providing care in the YK Delta and 125 community members from six YK Delta Communities in 2017 and 2018. The six communities were a stratified convenience sample based on community‐level exposure to dental therapists (high, medium and no exposure). Interview data were digitally recorded, transcribed, verified for accuracy and coded inductively into conceptual domains using content analytic methods.ResultsProviders believed individuals living in the YK Delta have benefited from clinic‐based restorative care and community‐based education provided by dental therapists. The restricted scope of dental therapy practice limits the complexity of care that may be offered to patients. However, community members expressed high satisfaction with the quality of care provided by dental therapists. Community members noted more widespread knowledge and evolving norms about oral health and believed dental therapists are helping to prevent disease and improve quality of life. Participants believed access to dental care for children has improved over the years, but felt that many adults in the YK Delta continue to have unmet needs. A potential barrier to sustained programme effectiveness is low retention of dental therapists in the region, driven primarily by reports that dental therapists feel overworked, stressed and geographically isolated.ConclusionsDental therapists have contributed to the dental care delivery system in Alaska's YK Delta. Future opportunities remain within the system to address the needs of adults, develop strategies to retain dental therapists in the region and incorporate evidence‐based, prevention‐oriented strategies to improve oral health behaviours and reduce oral diseases.
Exploring intergenerational communication and stress in refugee families
Authors: McCleary Jennifer Simmelink , Shannon Patricia J. , Wieling Elizabeth , Becher Emily 
Published: August 2019

AbstractMore than half of the refugees who have resettled to the United States in recent years have been youth. Refugee youth have often witnessed or experienced violence and family separation prior to resettlement and face barriers to successful resettlement such as language and educational challenges. These factors elevate risk for mental and emotional distress, and protective factors like strong familial relationships are important to promoting mental well‐being. This study utilized focus groups with 36 refugees ages 18 to 25 from four ethnic groups to explore conceptualizations of and communication about mental and emotional distress within and outside of family systems. Youth reported a nuanced conceptualization of their premigration and postmigration stressors and their patterns of communication about distress in three domains: (a) exposure to traumatic stress prior to resettlement, (b) stressful experiences in resettlement, and (c) communication about mental health inside and outside of family groups.
The effects of correctional education on juvenile delinquents and the factors for their overall changes: Focusing on academic performance and family‐type environment
Authors: Ohara Takaharu , Matsuura Naomi , Hagiuda Nobuko , Wakasugi Natsuki 
Published: August 2019

AbstractThis study aimed to explore the effects of correctional education on juvenile delinquents at a children's self‐reliance support facility in Japan, which provides delinquents with familial environments and multidimensional, comprehensive education. The purpose of this study was to compare the youth's academic performance and resilience from the time of admission to discharge and to identify which interventions improved participants' academic performance and resilience. We examined juvenile database records and “juvenile diaries” of 283 male youth. Participants were categorized into either an Improvement Group (IG) or a No‐Improvement Group (No‐IG) based on their outcome at discharge. The results showed that their academic performance and resilient characteristics were significantly higher at discharge than at admission. Employing single logistic regression, we found that the length of stay, academic performance, and the number of visits by family and social workers were characteristics associated with membership in the IG. These findings can guide future clinical practices and measures implemented for juvenile delinquents.
Extracellular vesicles in urologic malignancies—Implementations for future cancer care
Authors: Wu Zhangsong , Zhang Zhiqiang , Xia Wuchao , Cai Jiajia , Li Yuqing , Wu Song 
Published: August 2019

AbstractExtracellular vesicles (EVs), a heterogeneous group of vesicles differing in size and shape, cargo content and function, are membrane‐bound and nano‐sized vesicles that could be released by nearly all variations of cells. EVs have gained considerable attention in the past decades for their functions in modulating intercellular signalling and roles as potential pools for the novel diagnostic and prognostic biomarkers, as well as therapeutic targets in several cancers including urological neoplasms. In general, human and animal cells both can release distinct types of EVs, including exosomes, microvesicles, oncosomes and large oncosomes, and apoptotic bodies, while the content of EVs can be divided into proteins, lipids and nucleic acids. However, the lack of standard methods for isolation and detection platforms rein the widespread usage in clinical applications warranted furthermore investigations in the development of reliable, specific and sensitive isolation techniques. Whether and how the EVs work has become pertinent issues. With the aid of high‐throughput proteomics or genomics methods, a fully understanding of contents contained in EVs from urogenital tumours, beyond all doubt, will improve our ability to identify the complex genomic alterations in the process of cancer and, in turn, contribute to detect potential therapeutic target and then provide personalization strategy for patient.
LncRNA LOXL1‐AS1 facilitates the tumorigenesis and stemness of gastric carcinoma via regulation of miR‐708‐5p/USF1 pathway
Authors: Sun Qi , Li Jian , Li Fan , Li Huanqin , Bei Songhua , Zhang Xiaohong , Feng Li 
Published: August 2019

AbstractObjectivesAs one of the most life‐threatening malignancies, gastric cancer is the third contributor of cancer mortalities globally. Increasing studies have proven the regulatory roles of lncRNAs in the development of diverse malignant tumours. But little is known about its function and molecular mechanism in gastric carcinoma.Materials and methodsRT‐qPCR was performed to measure the expression pattern of LOXL1‐AS1 in gastric cancer. To ascertain its definite role, CCK‐8, EdU, Western blot, transwell and sphere formation assays were adopted. RNA pull‐down, RIP, ChIP and luciferase reporter assays were carried out to investigate the molecular mechanism of LOXL1‐AS1 in gastric carcinoma.ResultsLOXL1‐AS1 was highly expressed in tissues and cells of gastric cancer. The upregulation of LOXL1‐AS1 predicted poor prognosis in gastric carcinoma. Our findings demonstrated that LOXL1‐AS1 accelerated the deterioration of gastric cancer by inducing cell proliferation, migration, EMT and stemness. Moreover, the expression of USF1 in gastric cancer was higher than in normal control and LOXL1‐AS1 negatively modulated USF1. Functionally, LOXL1‐AS1 acted as a ceRNA to upregulate USF1 via sponging miR‐708‐5p. Besides, we confirmed USF1 promoted the transcription of stemness marker SOX2. Rescue experiments testified the stimulative role of LOXL1‐AS1/miR‐708‐5p/USF1 pathway in gastric cancer progression. It was also validated that LOXL1‐AS1 facilitated cell growth of gastric carcinoma in vivo.ConclusionsOur study unravelled that LOXL1‐AS1/miR‐708‐5p/USF1 pathway contributed to the development of gastric cancer.
Tissue regeneration during lower jaw restoration in zebrafish shows some features of epimorphic regeneration
Authors: Ohgo Shiro , Ichinose Sayaka , Yokota Hinako , Sato‐Maeda Mika , Shoji Wataru , Wada Naoyuki 
Published: August 2019

AbstractZebrafish have the ability to regenerate skeletal structures, including the fin, skull roof, and jaw. Although fin regeneration proceeds by epimorphic regeneration, it remains unclear whether this process is involved in other skeletal regeneration in zebrafish. Initially in epimorphic regeneration, the wound epidermis covers the wound surface. Subsequently, the blastema, an undifferentiated mesenchymal mass, forms beneath the epidermis. In the present study, we re‐examined the regeneration of the zebrafish lower jaw in detail, and investigated whether epimorphic regeneration is involved in this process. We performed amputation of the lower jaw at two different positions; the proximal level (presence of Meckel's cartilage) and the distal level (absence of Meckel's cartilage). In both manipulations, a blastema‐like cellular mass was initially formed. Subsequently, cartilaginous aggregates were formed in this mass. In the proximal amputation, the cartilaginous aggregates were then fused with Meckel's cartilage and remained as a skeletal component of the regenerated jaw, whereas in the distal amputation, the cartilaginous aggregates disappeared as regeneration progressed. Two molecules that were observed during epimorphic regeneration, Laminin and msxb, were expressed in the regenerating lower jaw, although the domain of msxb expression was out of the main plain of the aggregate formation. Administration of an inhibitor of Wnt/β‐catenin signaling, a pathway associated with epimorphic regeneration, showed few effects on lower jaw regeneration. Our finding suggests that skeletal regeneration of the lower jaw mainly progresses through tissue regeneration that is dependent on the position in the jaw, and epimorphic regeneration plays an adjunctive role in this regeneration.
Characterizing psychiatric symptoms and neurocognitive functioning among substance‐naïve early adolescents: Associations with sleep problems
Authors: Peiper Nicholas C. , Ridenour Ty A. , Fishbein Diana H. 
Published: August 2019

AbstractAimEvidence consistently links psychiatric symptoms, reduced neurocognitive functioning (NCF) and sleep problems to the initiation of a wide range of risk behaviours. Less is known, however, about the associations between sleep problems with psychiatric symptoms and NCF among early adolescents yet to engage in substance use.MethodsThe present study examined baseline data from an ongoing prospective study of 529 youth aged 10‐12 years who completed a battery of instruments measuring symptom counts for four psychiatric disorders, performance on six tests of NCF and five types of sleep behaviour on week days. We used latent class analysis to classify the 473 substance‐naïve youth into subtypes characterized by probabilistic patterns of psychiatric symptoms and poorer NCF.ResultsFour subtypes emerged: normative (24% of the sample); nonspecific mental health symptoms (27%); lower neurocognitive function (24%) and comorbid psychiatric symptoms and lower neurocognitive function (25%). In a multivariable latent regression model, three or more sleep arousals per night, sleep phase of two or more hours and sleep latency of 20 minutes or more were significantly associated with the two classes having higher symptom counts. Lack of family support was significantly associated with the two classes having lower neurocognitive function and comorbid psychiatric symptoms.ConclusionsThe youth subtypes in this study provide an important baseline characterization to subsequently understand how these neuropsychiatric relationships may change when substance use and other risk behaviours develop during adolescence. Implications for preventing and treating sleep problems associated with psychiatric comorbidity and neurocognitive dysfunctions are discussed.