bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metastatic melanoma patient outcomes since introduction of immune checkpoint inhibitors in England between 2014 and 2018
Authors: Board Ruth , Smittenaar Rebecca , Lawton Sarah , Liu Hanhua , Juwa Bukky , Chao David , Corrie Pippa 
Published: August 2020

AbstractImmune checkpoint inhibitors (CPIs) have radically changed outcomes for patients diagnosed with metastatic melanoma globally in the last 10 years, based on evidence of overall survival (OS) benefits generated from international randomised controlled trials (RCTs). Since RCTs do not always reflect real‐world prescribing, we interrogated established national databases to track prescribing of CPIs approved for first line treatment of metastatic melanoma patients in England since 2014 and determined patient outcomes associated with OS, as well as treatment‐related toxicity. Between April 2014 and March 2018, 5465 melanoma patients were diagnosed and treated with systemic anticancer therapy (SACT), 2322 of which received first‐line CPIs. There was good 3‐year OS concordance with RCT outcomes for ipilimumab (32%), ipinivo (56%) and nivolumab (51%), but OS was lower than expected for pembrolizumab (40%). Comparing patients prescribed ipinivo with those prescribed pembrolizumab, ipinivo‐treated patients were younger (88% vs 49% patients <70 years, P < .001) and fitter (60% vs 38% patients with Eastern Cooperative Oncology Group [ECOG] performance status 0, P < .0001). Emergency hospital admission rates from the earliest and last treatment dates were higher for patients prescribed ipinivo (37% and 55%) compared to those prescribed pembrolizumab (17% and 29%). The 30‐day mortality rates favoured ipinivo patients (3.8% ipinivo, 9.1% pembrolizumab, P < .0001) and likely reflected marked differences in median treatment durations: 63 (range 7‐440) days for ipinivo and 192 (range 5‐943) days for pembrolizumab. The dominant treatment‐related condition linked to hospital admission was colitis, recorded for 25% of patients prescribed ipinivo compared to 4% of patients prescribed pembrolizumab. Our population data has demonstrated that RCT outcomes can be achieved in routine care settings with careful patient selection.
Nonclinical safety testing of imaging agents, contrast agents and radiopharmaceuticals
Authors: Baldrick Paul 
Published: August 2020

AbstractDrug development includes imaging agents, contrast agents and radiopharmaceuticals; these materials differ from therapeutic drugs in that they are largely used to diagnose and/or monitor diseases and not treat them. Consequently, nonclinical safety testing needs are different. An examination of testing packages supporting clinical entry and/or marketing of these materials has shown a common approach to some study types (eg, imaging, biodistribution and toxicity testing). Recent regulatory guidelines to support development are the United States Food and Drug Administration (FDA)’s “Guidance for Industry Microdose Radiopharmaceutical Diagnostic Drugs: Nonclinical Study Recommendations” and the European Medicines Agency (EMA)’s “Guideline on the Non‐Clinical Requirements for Radiopharmaceuticals” (currently draft). It is hoped that these documents will allow developers to only perform nonclinical studies that are necessary to support functionality, follow distribution of the material and examine general safety/toxicity. However, as they are mainly focused on radiopharmaceuticals, companies are likely to apply knowledge of established testing packages to other new imaging agents and/or follow principles given in older regulatory guidelines, namely FDA’s “Guidance for Industry Developing Medical Imaging Drug and Biological Products Part I Conducting Safety Assessments”. Thus, in some cases, the need for regulatory agency interaction is still vital to avoid development surprises and delays due to an incomplete or badly performed testing package.
Short‐ and Long‐Term Reciprocal Bone‐Muscle Relationships in the Upper and Lower Extremity of Afro‐Caribbean Men by DXA: A Longitudinal Analysis of the Tobago Bone Health Study
Authors: Wong Andy KO , Pokhoy Anthony , Chandrakumar Abinaa , Cvejkus Ryan K , Zmuda Joseph M 
Published: August 2020

ABSTRACTLittle is known about the time course of muscle–bone effects and whether a reciprocal clinical effect of bone on muscle is present. We hypothesized that lean mass (LM) measures at the arms and legs have a stronger relationship with BMD measured within the same region than the reciprocal effect. The Tobago Bone Health Study was used to address this hypothesis, examining body composition data from total body DXA scans obtained at 0, 48‐, and 120‐month visits. A longitudinal analysis of LM, LM/height2 (LMI), and LM/BMI was conducted at the upper and lower extremities separately, in relation to BMD within the corresponding region. A cross‐lagged panel model was used to study pathways from 0 to 120 months for muscle–bone and bone–muscle effects within the same visit, and across each lagged period. Models accounted for age, height, weight, race, arthritis, prior nontraumatic fracture after age 40, number of units of alcohol consumed per week, current smoking, diagnosis of diabetes mellitus, amount of walking in the last week, grip strength, and hospitalizations. Significant models demonstrating parsimony, and meeting absolute and relative fit criteria were retained. Among 1286 Afro‐Caribbean men (mean age: 53 ± 9 years, BMI: 27.43 ± 4.23 kg/m2) with data available for all visits, LM, LMI, and LM/BMI had modest contemporaneous relationships with BMD, which dissipated with lagged time. The size of these effects was stronger at the legs than at the arms. These lagged effects were primarily mediated through indirect same time‐point muscle–bone relations rather than a true directly lagged effect. Bone density showed only a small effect on LM arm measures across lagged time, but this was impossible to tease‐out from same time‐point relations. These results suggest muscle–bone relationships are not long‐lasting at least beyond 48 months. Efforts to maintain muscle and bone strength should focus on shorter‐term interventions. More studies are needed with serial bone–muscle imaging over shorter periods. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Risedronate to Prevent Bone Loss After Sleeve Gastrectomy: Study Design and Feasibility Report of a Pilot Randomized Controlled Trial
Authors: Swafford Ashlyn A , Ard Jamy D , Beavers Daniel P , Gearren Peri C , Fernandez Adolfo Z , Ford Sherri A , Greene Katelyn A , Kammire Daniel E , Nesbit Beverly A , Reed Kylie K , Weaver Ashley A , Beavers Kristen M 
Published: August 2020

ABSTRACTMounting evidence implicates bariatric surgery as a cause of increased skeletal fragility and fracture risk. Bisphosphonate therapy reduces osteoporotic fracture risk and may be effective in minimizing bone loss associated with bariatric surgery. The main objective of this pilot randomized controlled trial (RCT; Clinical Trial No. NCT03411902) was to determine the feasibility of recruiting, treating, and following 24 older patients who had undergone sleeve gastrectomy in a 6 month RCT examining the efficacy of 150‐mg once‐monthly risedronate (versus placebo) in the prevention of surgical weight‐loss–associated bone loss. Feasibility was defined as: (i) >30% recruitment yield, (ii) >80% retention, (iii) >80% pills taken, (iv) <20% adverse events (AEs), and (v) >80% participant satisfaction. Study recruitment occurred over 17 months. Seventy participants were referred, with 24 randomized (34% yield) to risedronate (n = 11) or placebo (n = 13). Average age was 56 ± 7 years, 83% were female (63% postmenopausal), and 21% were black. The risedronate group had a higher baseline BMI than the placebo group (48.1 ± 7.2 versus 41.9 ± 3.8 kg/m2). The 10‐year fracture risk was low (6.0% major osteoporotic fracture, 0.4% hip fracture); however, three individuals (12.5%, all risedronate group) were osteopenic at baseline. Twenty‐one participants returned for 6‐month follow‐up testing (88% retention) with all (n = 3) loss to follow‐up occurring in the risedronate group. Average number of pills taken among completers was 5.9 ± 0.4 and 6.0 ± 0.0 in the risedronate and placebo groups, respectively (p = 0.21), with active participants taking >80% of allotted pills. Five AEs (3.7% AE rate) were reported; one definitely related, four not related, and none serious. All participants reported high satisfaction with participation in the study. Use of bisphosphonates as a novel therapeutic to preserve bone density in patients who had undergone a sleeve gastrectomy appears feasible and well‐tolerated. Knowledge gained from this pilot RCT will be used to inform the design of an appropriately powered trial.Clinical Trial Registrationhttp://clinicaltrials.gov/show/NCT03411902. Weight Loss With Risedronate for Bone Health. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
ECP as additional immunomodulation in idiopathic hyperammonemia and recurrent hypercapnic respiratory failure early post lung transplantation
Authors: Steinack Carolin , Robinson Cécile A. , Nägeli Mirjam , Inci Ilhan , Benden Christian 
Published: August 2020

AbstractExtra‐corporeal photopheresis (ECP) is known as safe ultimate treatment option for chronic lung allograft dysfunction (CLAD). Here, we report the first case of ECP as “second‐line” immunomodulatory therapy early post‐transplant in an adult patient undergoing lung transplantation for severe chronic thromboembolic pulmonary hypertension, complicated by impaired consciousness due to idiopathic hyperammonemia resulting in recurrent hypercapnic respiratory failure. ECP was initiated twice weekly on post‐transplant day 25 and standard triple immunosuppression reduced. Within 2 weeks, the clinical status improved. ECP has been continued every 4 weeks after discharge. At 1 year post‐transplant, ECP was stopped as maintenance immunosuppression was reached. We recommend to consider the immunomodulatory effect of ECP as “second line” immunomodulatory therapy in cases where standard immunosuppression causes severe collateral damage. ECP is able to assist prevention of allograft rejection in conjunction with reduced levels of standard immunosuppression, even in the early period following lung transplantation.
Neonatal and Childhood Outcomes in Offspring of Pregnant Women Using Antidepressant Medications: A Critical Review of Current Meta‐Analyses
Authors: Uguz Faruk 
Published: August 2020

AbstractThis article reviewed the results of 21 recent meta‐analyses examining the relationship between maternal use of antidepressants during pregnancy and negative outcomes in newborns and children. PubMed was searched for meta‐analyses published in English between January 1, 2011, and November 30, 2019, by using combinations of the keywords pregnancy, antidepressants, review, meta‐analysis, selective serotonin reuptake inhibitors, selective serotonin‐norepinephrine reuptake inhibitors, tricyclic antidepressants, neonatal outcomes, autism spectrum disorders, attention deficit hyperactivity disorder (ADHD), preterm birth, low birth weight, spontaneous abortion, persistent pulmonary hypertension, infant, newborn, children, and offspring. The present review included a total of 21 relevant meta‐analyses that met the inclusion criteria. Most of the meta‐analyses reported that compared to non‐users, the risks of preterm birth, low birth weight, spontaneous abortion, persistent pulmonary hypertension, autism spectrum disorders, and ADHD in offspring of antidepressant users were significantly higher. Some meta‐analyses also noted that the elevated risks were no longer statistically significant when pregnant women with psychiatric diagnoses treated with an antidepressant were compared with control patients who remained untreated. Although this review of current meta‐analyses suggests a moderately increased risk of neonatal and childhood outcomes assessed with maternal use of antidepressants, it is difficult to ascertain whether these outcomes are independent of underlying maternal psychiatric disorders.
Long non‐coding RNA SNHG6 increases JAK2 expression by targeting the miR‐181 family to promote colorectal cancer cell proliferation
Authors: Lai Fangfang , Deng Wei , Fu Chunhua , Wu Pengbo , Cao Mingwei , Tan Shiyun 
Published: August 2020

AbstractBackgroundLong non‐coding RNA (lncRNA) small nucleolar RNA host gene 6 (SNHG6) exerts a regulatory role in cancer biology, although its detailed functions and mechanisms in colorectal cancer (CRC) still remain unclear.MethodsA quantitative reverse transcriptase‐polymerase chain reaction was implemented to investigate the expression of SNHG6, miR‐181 family and Janus kinase 2 (JAK2) in CRC tissues and cell lines. The proliferation of CRC cells was detected by a cell counting kit‐8 assay, and the apoptosis of CRC cells was determined by flow cytometry analysis. The interaction of the miR‐181 family with SNHG6 or with the 3'‐untranslated region of JAK2 was validated by the luciferase reporter gene method. The effects of SNHG6 and the miR‐181 family on JAK2 expression were analyzed by western blotting.ResultsSNHG6 was significantly up‐regulated in CRC samples. The knockdown of SNHG6 reduced the proliferation of CRC cells and promoted the apoptosis, whereas the over‐expression of SNHG6 had the opposite effect. SNHG6 could bind with all the four members of the miR‐181 family, and expression in miR‐181 family members was significantly down‐regulated in CRC samples. SNHG6 expression was negatively correlated with the miR‐181 family member expression in CRC samples. Moreover, over‐expressed SNHG6 significantly counteracted the inhibitory effect of miR‐181 mimics on CRC cell proliferation, as well as the promoting effect on apoptosis. Furthermore, SNHG6 over‐expression and knockdown can promote and inhibit JAK2 expression, respectively, and miR‐181 family member function is opposite to that of SNHG6 by repressing JAK2.ConclusionsSNHG6 can exert a cancer‐promoting effect in CRC by targeting miR‐181 family members and up‐regulating JAK2.
Decitabine mildly attenuates MLL‐rearranged acute lymphoblastic leukemia in vivo, and represents a poor chemo‐sensitizer
Authors: Schneider Pauline , Castro Patricia Garrido , Pinhanços Sandra M. , Kerstjens Mark , van Roon Eddy H. , Essing Anke H.W. , Dolman M. Emmy M. , Molenaar Jan J. , Pieters Rob , Stam Ronald W. 
Published: August 2020

AbstractMLL‐rearranged acute lymphoblastic leukemia (ALL) represents a highly aggressive ALL subtype, characterized by aberrant DNA methylation patterns. DNA methyltransferase inhibitors, such as decitabine have previously been demonstrated to be effective in eradicating MLL‐rearranged ALL cells in vitro.Here, we assessed the in vivo anti‐leukemic potential of low‐dose DNA methyltransferase inhibitor decitabine using a xenograft mouse model of human MLL‐rearranged ALL. Furthermore, we explored whether prolonged exposure to low‐dose decitabine could chemo‐sensitize MLL‐rearranged ALL cells toward conventional chemotherapy as well as other known epigenetic‐based and anti‐neoplastic compounds.Our data reveal that decitabine prolonged survival in xenograft mice of MLL‐rearranged ALL by 8.5 days (P = .0181), but eventually was insufficient to prevent leukemia out‐growth, based on the examination of the MLLAF4 cell line SEM. Furthermore, we observe that prolonged pretreatment of low‐dose decitabine mildly sensitized toward the conventional drugs prednisolone, vincristine, daunorubicin, asparaginase, and cytarabine in a panel of MLL‐rearranged cell lines. Additionally, we assessed synergistic effects of decitabine with other epigenetic‐based or anticancer drugs using high‐throughput drug library screens. Validation of the top hits, including histone deacetylase inhibitor panobinostat, BCL2 inhibitor Venetoclax, MEK inhibitor pimasertib, and receptor tyrosine kinase foretinib, revealed additive and moderate synergistic effects for the combination of each drug together with decitabine in a cell line‐dependent manner.
How do Crocodylian embryos process yolk? Morphological evidence from the American alligator,Alligator mississippiensis
Authors: Blackburn Daniel G. , Barnes Madeline S. , Reimers Charles D. , Appiah Farahana A. , Lestz Luisa L. , Bonneau Laurie J. , Hanson Michael , Smith‐Paredes Daniel , Bhullar Bhart‐Anjan 
Published: August 2020

AbstractRecent studies have demonstrated a mechanism of embryonic yolk processing in lizards, snakes and turtles that differs markedly from that of birds. In the avian pattern, cells that line the inside of the yolk sac take up products of yolk digestion and deliver nutrients into the vitelline circulation. In contrast, in squamates and turtles, proliferating endodermal cells invade and fill the yolk sac cavity, forming elongated strands of yolk‐filled cells that surround small blood vessels. This arrangement provides a means by which yolk material becomes cellularized, digested, and transported for embryonic use. Ultrastructural observations on late‐stageAlligator mississippiensiseggs reveal elongated, vascular strands of endodermal cells within the yolk sac cavity. The strands of cells are intermixed with free yolk spheres and clumps of yolk‐filled endodermal cells, features that reflect early phases in the yolk‐processing pattern. These observations indicate that yolk processing inAlligatoris more like the pattern of other reptiles than that of birds.
Seeking and finding justice: Why and when managers' feedback seeking enhances justice enactment
Authors: Sherf Elad N. , Gajendran Ravi S. , Posner Barry Z. 
Published: August 2020

SummaryThere is growing recognition that justice enactment is a complex activity and that managers face significant contextual and situational roadblocks when attempting to enact justice. However, research has not fully examined how managers, in the course of their jobs, can (a) identify and respond to justice‐related issues and (b) assemble and synthesize relevant information required to act in a manner consistent with justice rules. To begin addressing these concerns, we posit feedback seeking as a key managerial behavior that can facilitate greater justice enactment because it promotes the flow of both solicited and unsolicited information from employees to managers. Such information flows enhance the saliency of fairness goals and allow managers to learn about employees' contextualized needs in ways that facilitate increased justice enactment. However, we argue that these effects are less likely to occur when feedback‐seeking managers have lower generalized self‐efficacy. An analysis of archival data (NManagers = 8,706, NEmployees = 40,830), a study with manager–employee dyads (N = 181), and a time‐separated study of managers (N = 196) provide preliminary evidence in line with these arguments. We discuss the implications of our theory and findings with respect to the justice and feedback‐seeking literature.
Review of some adulteration detection techniques of edible oils
Authors: Salah Wael A , Nofal Mays 
Published: August 2020

AbstractEdible oils have economical and nutritional benefits. These oils offer nutrients that are essential to human health because they are the primary source of mono‐ and poly‐unsaturated fats. Moreover, edible oils are used in home cooking and industrial food manufacturing. Therefore, edible oils have a considerable demand worldwide. However, some edible oils, such as olive oil, are more expensive than any other vegetable oils. Thus, oils such as olive oil are mixed with cheap edible oils as a result of the high price difference. Accordingly, adulteration in edible oils to obtain additional profit for the producer becomes a major issue of high concern for consumers. Moreover, adulteration in edible oils can cause several problems that affect consumer health. Therefore, the need for a sensitive, accurate and suitable method to detect the adulteration is highly considered. We provide a brief review of the different methods and techniques used to detect adulteration in edible oils, especially olive oil, with the aim of promoting consumer awareness of the authenticity of edible oils. © 2020 Society of Chemical Industry
Sanitizer efficacy in reducing microbial load on commercially grown hydroponic lettuce
Authors: Dankwa Adwoa S , Machado Robson M , Perry Jennifer J 
Published: August 2020

AbstractBACKGROUNDMost hydroponic lettuce growers harvest and package their marketable‐size lettuces with an intact root ball. With a high microbial load on the peat moss substrate, there is a risk of microbial transfer onto the edible portion during packaging and throughout the product's shelf life. Since the produce is believed to have no contact with the substrate, no sanitizer wash is performed before packaging and storage.RESULTSAerobic plate count (APC) results suggested that reduction in count was influenced by both sanitizer application and storage time. Peroxyacetic acid significantly reduced APC count on leaves, roots, and substrate, with a 1.8 log CFU g−1 initial reduction on the leaf. Fungi and APC levels increased with storage time, with the greatest APC increase in the roots. Leaves had the lowest coliform bacteria (CB), with chlorine slightly reducing CB count. Unlike APC, CB levels decreased during storage on the substrate and root samples. No Listeria positive was confirmed by agglutination test. Further evaluation of different commercial substrates reveals that Com4, a drier‐compacted plug, had the least ability to support growth/survival of all microbial populations enumerated relative to the spongy, wet black plugs.CONCLUSIONThe ability of peat moss substrates to host microorganisms is influenced by the physical properties of the product. Sanitizer wash efficacy is dependent on the initial microbial load and the length of storage. Chlorine and peroxyacetic acid are effective in reducing microbial populations on the leaves of hydroponically grown lettuce without affecting visual quality during shelf life. © 2020 Society of Chemical Industry
A new strategy of studying protein–protein interactions: Integrated strong anion exchange/reversed‐phase chromatography/immunoprecipitation coupled with mass spectrometry for large‐scale identification of proteins interact with immunoglobulin G in HeLa cells
Authors: Qin Feng , Wang Xuantang , Yan Guoquan , Gao Mingxia , Zhang Xiangmin 
Published: August 2020

AbstractRecently, significant research efforts have been devoted to the development of technology for large‐scale analysis of protein–protein interactions. Herein, a comprehensive method by coupling the first‐dimension strong anion exchange chromatography with the second‐dimension reversed‐phase liquid chromatography via immunoprecipitation technique and high‐resolution mass spectrometry analysis was developed for analyzing protein–protein interactions. After two‐dimensional liquid chromatography separation, 108 fractions were obtained in one experiment. Immunoglobulin G from human serum was used as a model of an interacting protein. As a result, 919 proteins in these fractions were identified to interact with immunoglobulin G. By searching STRING database and data analysis, 27 of 919 proteins were inferred to directly interact with immunoglobulin G. Moreover, important target proteins that interacted with immunoglobulin G were mapped in the two‐dimensional liquid chromatography system, which facilitated selection of these proteins from specific fractions. These results demonstrated that the proposed method can be useful for large‐scale investigation of protein–protein interactions and as an advanced tool for the isolation of target proteins.