bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of the novel tubulin polymerization inhibitor PTC‐028 for myelodysplastic syndrome
Authors: Zhong Cheng , Kayamori Kensuke , Koide Shuhei , Shinoda Daisuke , Oshima Motohiko , Nakajima‐Takagi Yaeko , Nagai Yurie , Mimura Naoya , Sakaida Emiko , Yamazaki Satoshi , Iwano Satoshi , Miyawaki Atsushi , Ito Ryoji , Tohyama Kaoru , Yamaguchi Kiyoshi , Furukawa Yoichi , Lennox William , Sheedy Josephine , Weetall Marla , Iwama Atsushi 
Published: October 2020

AbstractMonomer tubulin polymerize into microtubules, which are highly dynamic and play a critical role in mitosis. Therefore, microtubule dynamics are an important target for anticancer drugs. The inhibition of tubulin polymerization or depolymerization was previously targeted and exhibited efficacy against solid tumors. The novel small molecule PTC596 directly binds tubulin, inhibits microtubule polymerization, downregulates MCL‐1, and induces p53‐independent apoptosis in acute myeloid leukemia cells. We herein investigated the efficacy of PTC‐028, a structural analog of PTC596, for myelodysplastic syndrome (MDS). PTC‐028 suppressed growth and induced apoptosis in MDS cell lines. The efficacy of PTC028 in primary MDS samples was confirmed using cell proliferation assays. PTC‐028 synergized with hypomethylating agents, such as decitabine and azacitidine, to inhibit growth and induce apoptosis in MDS cells. Mechanistically, a treatment with PTC‐028 induced G2/M arrest followed by apoptotic cell death. We also assessed the efficacy of PTC‐028 in a xenograft mouse model of MDS using the MDS cell line, MDS‐L, and the AkaBLI bioluminescence imaging system, which is composed of AkaLumine‐HCl and Akaluc. PTC‐028 prolonged the survival of mice in xenograft models. The present results suggest a chemotherapeutic strategy for MDS through the disruption of microtubule dynamics in combination with DNA hypomethylating agents.
TET2: A cornerstone in normal and malignant hematopoiesis
Authors: Kunimoto Hiroyoshi , Nakajima Hideaki 
Published: October 2020

AbstractRegulation of genome‐wide DNA methylation is fundamental for a variety of biological processes such as mammalian development, stem cell function, cellular proliferation/differentiation, and oncogenesis. Among the regulators of DNA methylation, ten‐eleven translocation 2 (TET2) is one of the most frequently mutated genes in clonal hematopoiesis of indeterminate potential and in various hematological malignancies, underscoring a pivotal role for TET2 in blood homeostasis and hematopoietic transformation. TET2 oxidizes methylated cytosines to further modify cytosines, which behave as intermediates in active/passive DNA demethylation processes. TET2 itself associates with histone modifiers, thereby regulating histone modifications and expression of target genes. A number of studies have reported pleiotropic effects of TET2 on hematopoietic stem cell self‐renewal, hematopoietic differentiation, genome instability and inflammatory response. Recent single‐cell genomics studies have identified gene promoters as well as transcription factor binding sites as TET2‐targeted genetic loci in which disruption of DNA methylation can fundamentally modify hematopoietic differentiation and promote leukemogenesis. TET2 mutations show convergent cooperativity with other disease alleles in signaling molecules, epigenetic modifiers, and spliceosome factors in hematopoietic transformation. Future studies focusing on the molecular basis of stem cell and immune regulation by TET2 loss will further deepen our understanding of the entire landscape of pathophysiology and molecular vulnerabilities of TET2‐mutated hematological malignancies.
The use of digital media: To support and enhance vulnerable children’s perspectives, voices and choices
Authors: Koch Anette Boye , Brandt Erika Zimmer 
Published: October 2020

AbstractThe article reports findings from a study that explored the potential of digital media to create new possibilities for professional caregivers to encounter 10 vulnerable children (7–17 years old) as subjects (rather than objects) and participants in their own lives. Five professionals received training in media pedagogy and experimented with new ways to communicate with children. Digital communication was found to expand the children's ability to engage in dialogue. Professionals need to find the courage to engage in digital communication on a child's terms as it helps generate a relationship that offers children new opportunities for raising their voices.
A meta‐analysis of anthropogenic impacts on physiological stress in wild primates
Authors: Kaisin Olivier , Fuzessy Lisieux , Poncin Pascal , Brotcorne Fany , Culot Laurence 
Published: October 2020

AbstractAs humanity continues to alter the environment extensively, comprehending the effect of anthropogenic disturbances on the health, survival, and fitness of wildlife is a crucial question for conservation science. Many primate populations occupy suboptimal habitats prone to diverse anthropogenic disturbances that may be sources of acute and chronic stress. Quantification of glucocorticoid (GC) concentrations has repeatedly been used to explore the impact of disturbances on physiological stress. Although it is still debated, prolonged elevation of GC levels may impair reproduction, growth, and immune system activity of individuals. We quantified the effect of anthropogenic disturbances on physiological stress in primates with a global meta‐analysis based on data from 26 articles, covering 24 distinct species in 13 different countries. Anthropogenic disturbances were classified into 6 distinct categories: habitat loss, habitat degradation, ongoing logging, hunting, tourism, and other human activities. We calculated effect sizes (Hedges’ g) with the standardized mean difference in GC concentrations between primates affected by human activity and their undisturbed conspecifics. We ran random‐effects models and subgroup analyses to estimate the overall effect as well as a cumulative effect size for each disturbance category. Overall, primates inhabiting sites subject to anthropogenic disturbances exhibited significantly higher GC levels (g = 0.60; 95% CI: 0.28–0.93). Habitat loss and hunting were overall associated with increased GC concentrations, whereas the cumulative effects of the other disturbances were not statistically significant. Biologically, high GC levels may increase fitness by enabling individuals to overcome the challenges linked to anthropogenic disturbances. However, primates in disturbed environments may have sustained elevated GC levels. To strengthen future research, it is necessary to control confounding factors systematically (e.g., diet, reproductive status, predatory pressure, and resource availability) and improve understanding of the link between GC levels and the health, fitness, and survival of animals.
Cultural Variation in the Development of Beliefs About Conservation
Authors: Busch Justin T. A. , Watson‐Jones Rachel E. , Legare Cristine H. 
Published: October 2020

AbstractExamining variation in reasoning about sustainability between diverse populations provides unique insight into how group norms surrounding resource conservation develop. Cultural institutions, such as religious organizations and formal schools, can mobilize communities to solve collective challenges associated with resource depletion. This study examined conservation beliefs in a Western industrialized (Austin, Texas, USA) and a non‐Western, subsistence agricultural community (Tanna, Vanuatu) among children, adolescents, and adults (N = 171;n = 58 7–12‐year‐olds,n = 53 13–17‐year‐olds, andn = 60 18–68‐year‐olds). Participants endorsed or rejected four types of justifications for engaging in land and animal conservation: sustainability, moral, religious, or permissible. In both populations, participants endorsed sustainability justifications most frequently. Religious justifications increased with age in Tanna and decreased with age in Austin. Tannese participants were also more likely to endorse multiple justifications for conservation than Austin participants. Data across all justification types show a main effect of age in both communities; endorsement of conservation decreased with age in Austin, but increased with age in Tanna. Across age groups, participants were more likely to endorse the conservation of animals than land in Austin, yet equally as likely to endorse the conservation of land and animals in Tanna. Overall, these results reveal similarities and differences in the beliefs that support the conservation of natural resources across populations.
The impact of donor and recipient diabetes on renal transplant outcomes
Authors: Singh Navdeep , Washburn Kenneth , Schenk Austin , El‐Hinnawi Ashraf , Bumgardner Ginny , Logan April , Rajab Amer 
Published: October 2020

AbstractThe use of diabetic kidneys is increasing worldwide with better outcome than being on waitlist and possible reversal of diabetic changes in transplanted kidneys. But particular caution is warranted in diabetic donor‐recipient combination. Total 1223 deceased donor kidney transplants were performed at our center between 2008 and 2018. 689 from non‐diabetic donor (NDD) to non‐diabetic recipient, 400 from non‐diabetic donor to diabetic recipient, 97 from diabetic to non‐diabetic recipient, and 32 from diabetic donor (DD) to diabetic recipient. The DD was older than NDDs (median age 48 vs 39 years, P < 0.0001). DD had higher BMI (35.6 vs 26.9, P < 0.0001), higher KDPI (74% vs 37%, P < 0.0001), and higher terminal creatinine (1.10 mg/dl vs 0.95 mg/dl, p 0.0046) than the NDD. Diabetes recipients were comparatively older (57 vs 54, P < 0.001). DD recipients had higher serum creatinine at 6 months (1.70 vs 1.50 mg/dl, p 0.00304) and 2 years post‐transplant (1.70 vs 1.50 mg/dl P < 0.0002). DD recipients had more favorable end CPRA than NDD recipients (77.5% at 0% vs 67.4% at 0, P = 0.0074). Ten‐year patient and graft survival was best in NDD‐recipient pair and worse in DD‐recipient pair. Diabetic donor kidneys to diabetic recipients have lower 1‐, 3‐, and 5‐year graft survival.
Induction immunosuppression and the risk of incident malignancies among older and younger kidney transplant recipients: A prospective cohort study
Authors: Wang Lingyu , Motter Jennifer , Bae Sunjae , Ahn JiYoon B. , Kanakry Jennifer A. , Jackson John , Schnitzler Mark A. , Hess Gregory , Lentine Krista L. , Stuart Elizabeth A. , Segev Dorry L. , McAdams‐DeMarco Mara 
Published: October 2020

AbstractBackgroundOlder (≥65) KT recipients differ from their younger counterparts in their immune response to immunosuppression (IS) and may have a different risk of malignancy after receiving induction.MethodsWe identified 66 700 adult KT recipients treated with anti‐thymocyte globulin (ATG) (n = 40 443) or interleukin‐2 receptor antagonist (IL‐2RA) (n = 26 327) induction (1/1/1999–12/31/2014) using USRDS/Medicare data. We estimated the risk of first‐diagnosed post‐KT malignancy associated with induction (ATG vs. IL‐2RA) using Cox proportional hazard models. We then tested whether these risks differed between older and younger recipients (Wald test for interaction). Models incorporated inverse probability of treatment weights to adjust for confounders.ResultsThe 3‐year cumulative incidences of any diagnosed malignancy were 11.5%. ATG was associated with a higher malignancy risk (HR = 1.12, 95%CI:1.06–1.18). This association differed (pinteraction = 0.04) between younger (HR = 1.12, 95%CI:1.06–1.18) and older recipients (HR = 1.03, 95%CI:0.96–1.09). ATG was also associated with higher risk of skin (HR = 1.18, 95%CI:1.08–1.29), lung (HR = 1.24, 95%CI:1.05–1.47), and ovary malignancies (HR = 1.94, 95%CI:1.08–3.48). However, only the association of ATG with post‐KT skin malignancy differed (pinteraction = 0.01) between younger (HR = 1.18; 95%CI:1.08–1.29) and older (HR = 1.01; 95%CI:0.93–1.09) recipients.ConclusionsCompared with IL‐2RA induction, ATG was associated with elevated post‐KT malignancy risk but only among younger recipients. Transplant centers may need to tailor induction IS for younger recipients to mitigate malignancy risk.
Edoxaban for the Long‐Term Therapy of Venous Thromboembolism: Should the Criteria for Dose Reduction be Revised?
Authors: Camporese Giuseppe , Simioni Paolo , Di Micco Pierpaolo , Fernández‐Capitán Carmen , Rivas Agustina , Font Carme , Sahuquillo Joan Carles , Villares Paula , Prandoni Paolo , Monreal Manuel ,   and the RIETE Investigators
Published: October 2020

Edoxaban is used for venous thromboembolism (VTE) treatment. Real‐life data are lacking about its use in long‐term therapy. We aimed to assess the efficacy and the safety of edoxaban for long‐term VTE treatment in a real‐life setting. Patients with VTE included in the Registro Informatizado Enfermedad TromboEmbólica (RIETE) registry, receiving edoxaban 60 or 30 mg daily were prospectively followed up to validate the benefit of using different dosages. The main outcome was the composite of VTE recurrences or major bleeding in patients with or without criteria for dose reduction. Multivariable analysis to identify predictors for the composite outcome was performed. From October 2015 to November 2019, 562 patients received edoxaban for long‐term therapy. Most (94%) of the 416 patients not meeting criteria for dose reduction received 60 mg daily, and 92 patients meeting criteria (63%) received 30 mg daily. During treatment, two patients developed recurrent VTE, six had major bleeding and nine died (2 from fatal bleeding). Among patients not meeting criteria for dose reduction, those receiving 30 mg daily had a higher rate of the composite event (hazard ratio (HR) 8.37; 95% confidence interval (CI) 1.12–42.4) and a significant higher mortality rate (HR 31.1; 95% CI 4.63–262) than those receiving 60 mg. Among patients meeting criteria for dose reduction, those receiving 60 mg daily had no events, and a nonsignificantly higher mortality rate (HR 5.04; 95% CI 0.54–133) than those receiving 30 mg daily. In conclusion, edoxaban seems to be effective and safe for long‐term VTE treatment in real life. Criteria for dose reduction should be reformulated.
Characterization of intragastric pressure waveform in endoscopic pressure study integrated system: Novel diagnostic device for gastroesophageal reflux disease
Authors: Shimamura Yuto , Inoue Haruhiro , Rodriguez de Santiago Enrique , Abad Mary Raina Angeli , Fujiyoshi Yusuke , Toshimori Akiko , Tanabe Mayo , Sumi Kazuya , Iwaya Yugo , Ikeda Haruo , Onimaru Manabu 
Published: October 2020

ObjectivesEndoscopic pressure study integrated system (EPSIS) is a novel diagnostic tool for gastroesophageal reflux disease (GERD). EPSIS has been developed to evaluate lower esophageal sphincter function by monitoring the intragastric pressure (IGP) while insufflating the stomach during gastroscopy. Based on previous data, EPSIS could diagnose GERD with good accuracy by assessing IGP waveform pattern. This study aimed to further characterize the waveform to improve the diagnostic yield of EPSIS.MethodsWe conducted a retrospective analysis of patients with typical GERD symptoms who underwent both EPSIS and 24‐h impedance‐pH monitoring (MII‐pH) at a single tertiary referral center from October 2018 to May 2020. EPSIS was performed by using a through‐the‐scope catheter connected to the pressure measuring system (TR‐W550, TR‐TeH08, AP‐C35; Keyence, Osaka, Japan) to monitor IGP. Abnormal acid reflux was defined as acid exposure time (AET) over 6.0%. Pressure waveform was characterized as follows: (i) Basal IGP, (ii) Maximum IGP, (iii) Pressure difference, (iv) Gradient of the waveform.ResultsA total of 57 patients with GERD symptoms were analyzed. Twenty‐one patients presented abnormal AET on MII‐pH. Among EPSIS parameters, pressure difference during insufflation correlated with AET (ρ = −0.66, P < 0.01) and showed the best diagnostic accuracy for AET with the cutoff value of 4.7 mmHg (area under the curve [AUC], 0.87). The gradient of EPSIS waveform also revealed good diagnostic accuracy for abnormal AET with the cutoff value of 0.07 mmHg/s (AUC, 0.81).ConclusionsEndoscopic pressure study integrated system waveform parameters, especially pressure difference, presented high diagnostic accuracy for the presence of abnormal acid reflux.
Money spider dietary choice in pre‐ and post‐harvest cereal crops using metabarcoding
Authors: Cuff Jordan P. , Drake Lorna E. , Tercel Maximillian P.T.G. , Stockdale Jennifer E. , Orozco‐terWengel Pablo , Bell James R. , Vaughan Ian P. , Müller Carsten T. , Symondson William O.C. 
Published: October 2020

Money spiders (Linyphiidae) are an important component of conservation biological control in cereal crops, but they rely on alternative prey when pests are not abundant, such as between cropping cycles. To optimally benefit from these generalist predators, prey choice dynamics must first be understood.
Money spiders and their locally available prey were collected from cereal crops 2 weeks pre‐ and post‐harvest. Spider gut DNA was amplified with two novel metabarcoding primer pairs designed for spider dietary analysis, and sequenced.
The combined general and spider‐exclusion primers successfully identified prey from 15 families in the guts of the 46 linyphiid spiders screened, whilst avoiding amplification of Erigone spp. The primers show promise for application to the diets of other spider families such as Agelenidae and Pholcidae.
Distinct invertebrate communities were identified pre‐ and post‐harvest, and changes in spider diet and, to a lesser extent, prey choice reflected this. Spiders were found to consume one another more than expected, indicating their propensity towards intraguild predation, but also consumed common pest families.
Changes in spider prey choice may redress prey community changes to maintain a consistent dietary intake. Consistent provision of alternative prey via permanent refugia should be considered to sustain effective conservation biocontrol.
Thematic content of obsessive and compulsive symptoms and conversion to psychosis in a clinical high‐risk cohort
Authors: Kennedy Leda , Brucato Gary , Lundgren Brooke , Califano Allegra , Dishy Gabriella , Hesson Hannah , Masucci Michael D. , Pia Tyler , Goldberg Pablo H. , Xu Qing , Wall Melanie M. , Girgis Ragy R. 
Published: October 2020

AbstractAimWe sought to explore the complex phenomenological overlap between obsessive and compulsive symptoms (OCS), and attenuated positive symptoms among 156 young people at clinical high‐risk (CHR) for psychosis.MethodsIn order to explore the hypothesis that OCS of an implausible nature might optimally predict future transition to syndromal psychosis, ideas associated with obsessive and compulsive experiences elicited by clinical measures were thematically categorized as “plausible” or “implausible.”ResultsWhile OCS were found to be common in our CHR sample, we did not find that implausible OCS themes were predictive of conversion.ConclusionGiven the absence of qualitative differences between OCS and early psychotic symptoms, we propose that clinicians encountering adolescent or young adult patients with new‐onset OCD or OCS in the past year should monitor such symptoms for a minimum of 2 years to assess for the possible emergence of psychosis.
Sleep in first‐episode schizophrenia patients, their unaffected siblings and healthy controls: A comparison
Authors: Fekih‐Romdhane Feten , Nefzi Houssem , Sassi Hadhami , Cherif Wissal , Cheour Majda 
Published: October 2020

AbstractBackgroundSleep disturbances in schizophrenia are common throughout its course including in the prodrome, and have been mainly attributed to severity of symptoms and antipsychotic use. We aimed to investigate whether early course patients with schizophrenia and young non‐psychotic siblings of patients with schizophrenia also show sleep disturbances and whether sleep correlates with symptoms and functioning.MethodsThree study groups, that is, adults newly diagnosed with schizophrenia (n = 54), young non‐psychotic siblings of schizophrenia patients (n = 56) and a sample of healthy controls matched to the patients and siblings (n = 61) were evaluated on Horne and Ostberg Morningness‐Eveningness Questionnaire, Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index. Severity of symptoms and functioning are assessed using the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale, respectively. Age, gender, occupation and marital status were regarded as covariates, and differences between the three groups were evaluated using analysis of covariance.ResultsEarly course schizophrenia patients and non‐psychotic siblings of schizophrenia patients showed significantly reduced sleep quality relative to healthy controls (P < .001). Schizophrenia patients had significantly higher daytime sleepiness compared to controls (P < .001). Chronotypes in schizophrenia patients and unaffected siblings did not significantly differ from those of the healthy controls.ConclusionsLike chronic medicated schizophrenia patients, early course schizophrenia patients and young non‐psychotic siblings of individuals with schizophrenia have sleep disturbances. These findings indicate that sleep markers can distinguish unaffected siblings of schizophrenia from healthy controls and serve as an endophenotype for schizophrenia.
Mechanical harvester removes invasive aquatic weeds to restore water quality and fish habitat values on the Burdekin floodplain
Authors: Waltham Nathan J. , Pyott Merv , Buelow Christina , Wearne Lynise 
Published: October 2020

Removal of approximately 5 ha of an aquatic weed in late 2016 rapidly improved water quality in a 7 km section of creek on the Burdekin floodplain, northern Queensland – one of many creeks feeding into the Bowling Green Bay RAMSAR wetland. Numbers of native fish species found in the creek increased from one species prior to treatment to 15 species within 2 years. This project concluded that removal of weed blocks to re‐oxygenate water and improve fish passage is one important action towards improving environmental conditions of floodplains in the Great Barrier Reef catchments, as long as there is ongoing weed follow up.
Bionomics and rearing of Miltotranes prosternalis (Lea, 1929) (Coleoptera: Curculionidae), a mutualistic cycad pollinator in Australia
Authors: Hsiao Yun , Oberprieler Rolf G. 
Published: October 2020

ABSTRACTPollination is the crucial stage for reproduction and survival of plants, therefore knowledge about the bionomics of pollinators is often critical for plant conservation. Bowenia spectabilis (Cycadales: Stangeriaceae) is a CITES‐protected cycad species endemic to the Wet Tropics Bioregion of Queensland, Australia. It is pollinated by a host‐specific weevil species, Miltotranes prosternalis (Lea, 1929) (Curculionidae: Molytinae), which breeds in its male cones but also visits its female cones and pollinates them. The association between the cycad and the weevil is an obligate brood‐site reward pollination system, in which the weevil is provided with food and a brood site by the plant in “return” for the service of pollinating it. To facilitate the knowledge of the natural history of this unique Bowenia pollinator, we developed a method for rearing mature larvae of M. prosternalis collected from the field in the laboratory. Furthermore, we summarize biological information of M. prosternalis gathered from previous studies and by firsthand observations in the wild and during rearing in captivity.