bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study
Authors: Antonarakis Emmanuel S. , Piulats Josep M. , Gross-Goupil Marine , Goh Jeffrey , Ojamaa Kristiina , Hoimes Christopher J. , Vaishampayan Ulka , Berger Ranaan , Sezer Ahmet , Alanko Tuomo , de Wit Ronald , Li Chunde , Omlin Aurelius , Procopio Giuseppe , Fukasawa Satoshi , Tabata Ken-ichi , Park Se Hoon , Feyerabend Susan , Drake Charles G. , Wu Haiyan , Qiu Ping , Kim Jeri , Poehlein Christian , de Bono Johann Sebastian 
Published: November 2019

PURPOSE Pembrolizumab has previously shown antitumor activity against programmed death ligand 1 (PD-L1)–positive metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed the antitumor activity and safety of pembrolizumab in three parallel cohorts of a larger mCRPC population. METHODS The phase II KEYNOTE-199 study included three cohorts of patients with mCRPC treated with docetaxel and one or more targeted endocrine therapies. Cohorts 1 and 2 enrolled patients with RECIST-measurable PD-L1–positive and PD-L1–negative disease, respectively. Cohort 3 enrolled patients with bone-predominant disease, regardless of PD-L1 expression. All patients received pembrolizumab 200 mg every 3 weeks for up to 35 cycles. The primary end point was objective response rate per RECIST v1.1 assessed by central review in cohorts 1 and 2. Secondary end points included disease control rate, duration of response, overall survival (OS), and safety. RESULTS Two hundred fifty-eight patients were enrolled: 133 in cohort 1, 66 in cohort 2, and 59 in cohort 3. Objective response rate was 5% (95% CI, 2% to 11%) in cohort 1 and 3% (95% CI, < 1% to 11%) in cohort 2. Median duration of response was not reached (range, 1.9 to ≥ 21.8 months) and 10.6 months (range, 4.4 to 16.8 months), respectively. Disease control rate was 10% in cohort 1, 9% in cohort 2, and 22% in cohort 3. Median OS was 9.5 months in cohort 1, 7.9 months in cohort 2, and 14.1 months in cohort 3. Treatment-related adverse events occurred in 60% of patients, were of grade 3 to 5 severity in 15%, and led to discontinuation of treatment in 5%. CONCLUSION Pembrolizumab monotherapy shows antitumor activity with an acceptable safety profile in a subset of patients with RECIST-measurable and bone-predominant mCRPC previously treated with docetaxel and targeted endocrine therapy. Observed responses seem to be durable, and OS estimates are encouraging.
Superior Intellectual Outcomes After Proton Radiotherapy Compared With Photon Radiotherapy for Pediatric Medulloblastoma
Authors: Kahalley Lisa S. , Peterson Rachel , Ris M. Douglas , Janzen Laura , Okcu M. Fatih , Grosshans David R. , Ramaswamy Vijay , Paulino Arnold C. , Hodgson David , Mahajan Anita , Tsang Derek S. , Laperriere Normand , Whitehead William E. , Dauser Robert C. , Taylor Michael D. , Conklin Heather M. , Chintagumpala Murali , Bouffet Eric , Mabbott Donald 
Published: November 2019

PURPOSE Proton radiotherapy (PRT) may lessen the neuropsychological risk traditionally associated with cranial radiotherapy for the treatment of pediatric brain tumors by reducing the dose to normal tissue compared with that of photon radiotherapy (XRT). We examined the change in intellectual scores over time in patients with pediatric medulloblastoma treated with craniospinal PRT versus XRT. METHODS Intelligence test scores were obtained for a sample of pediatric patients treated between 2007 and 2018 on the same medulloblastoma protocols that differed only in radiotherapy modality (PRT v XRT). Growth curve analyses compared change in scores over time since diagnosis between groups. RESULTS Longitudinal intelligence data from 79 patients (37 PRT, 42 XRT) were examined. Groups were similar on most demographic/clinical variables, including sex (67.1% male), age at diagnosis (mean, 8.6 years), craniospinal irradiation dose (median, 23.4 Gy), length of follow-up (mean, 4.3 years), and parental education (mean, 14.3 years). Boost dose ( P < .001) and boost margin ( P = .001) differed between groups. Adjusting for covariates, the PRT group exhibited superior long-term outcomes in global intelligence quotient (IQ), perceptual reasoning, and working memory compared with the XRT group (all P < .05). The XRT group exhibited a significant decline in global IQ, working memory, and processing speed (all P < .05). The PRT group exhibited stable scores over time in all domains with the exception of processing speed ( P = .003). CONCLUSION To our knowledge, this is the first study to compare intellectual trajectories between pediatric patients treated for medulloblastoma with PRT versus those treated with XRT on comparable, contemporary protocols. PRT was associated with more favorable intellectual outcomes in most domains compared with XRT, although processing speed emerged as a vulnerable domain for both groups. This study provides the strongest evidence to date of an intellectual sparing advantage with PRT in the treatment of pediatric medulloblastoma.
Art | Adrift
Authors: Cervone Einor K. 
Published: November 2019

Abstract
A floating gallery, a drifting studio where sprawling waterscapes set off artwork on display and inspire original creation—the painting-and-calligraphy boat (shuhua chuan) may sound like a postmodern experimental installation. For its Ming patrons, however, it was nothing of the sort. Traceable to Mi Fu's floating gallery-cum-studio, the “art boat” was perceived as a beacon of cultural orthodoxy by generations of aesthetes like Mi Wanzhong, Dong Qichang, and Li Rihua. A nod to antiquity, it situated them in the continuum of long-standing tradition. The practice reached its acme in the mid- and late Ming, against currents of growing social mobility and dynamic imbalance that gave rise to a culture of connoisseurship as part of a fierce competition for social distinction. This paper examines the lure of waterborne art connoisseurship as cultural capital. Unique to the art boat is the act of collecting pieces for display and appraisal—an act akin to modern curatorial discernment. The selection of works that accompanied the patron onboard became an expressive medium. The painting-and-calligraphy boat also privileged a sense of fortuity. Chance encounters and spontaneous inspiration complemented the boats' movement along their free-form routes. Yet, the most prominent feature distinguishing the art boat was its visibility. Open panoramas of outstretched waterscape conjured a new creative avenue, a self-aestheticizing of both participant and vessel. This paper extricates the painting-and-calligraphy boat from its perception as a passing curiosity and shows it to be an enduring phenomenon that permeated premodern Jiangnan—the choice of the waterscape as a space of creation and recreation.
A nested randomised trial of the effect of tranexamic acid on intracranial haemorrhage and infarction in traumatic brain injury (CRASH-3 trial intracranial bleeding mechanistic study): Statistical analysis plan
Authors: Mahmood Abda , Roberts Ian , Shakur-Still Haleema 
Published: November 2019

Background: The CRASH-3 trial is a randomised trial on the effect of tranexamic acid (TXA) versus placebo on death and disability in traumatic brain injury (TBI). The CRASH-3 intracranial bleeding mechanistic study (IBMS) is a randomised trial nested within the CRASH-3 trial to examine the effect of TXA versus placebo on intracranial bleeding and infarction. Methods: Patients eligible for the CRASH-3 trial, with a GCS of 12 or less or intracranial bleeding on a pre-randomisation CT scan are eligible for the IBMS. The occurrence of intracranial bleeding, infarction, haemorrhagic oedematous lesions, mass effect and haemorrhage evacuation is examined within 28 days of randomisation using routinely collected brain scans. The primary outcome is the volume of intra-parenchymal bleeding in patients randomised within three hours of injury (adjusted for prognostic covariates). Secondary outcomes include a composite “poor” outcome, progressive and new intracranial bleeding, intracranial bleeding after neurosurgery and cerebral infarcts seen up to 28 days post-randomisation. All outcomes will be compared between treatment groups. Statistical analyses: The primary outcome will be analysed using a covariate adjusted linear mixed model. The same analysis will be done separately for patients who undergo haemorrhage evacuation post-randomisation. We will express the effect of TXA on the composite outcome, new and progressive bleeding using relative risks and 95% CIs, and on cerebral infarcts using hazard ratios and 95% CIs. We will conduct sensitivity analyses assuming missing data are MCAR or MNAR. Conclusion: The IBMS will provide information on the mechanism of action of TXA in TBI. This pre-specified statistical analysis plan is a technical extension of the published protocol. Trial registration: The CRASH-3 trial was prospectively registered at the International Standard Randomised Controlled Trials registry (19 July 2011) and ClinicalTrials.gov (25 July 2011). The registries were updated with details for the IBMS on 20 December 2016.
Terapia de células madre mononucleares concentradas asociada a nanofarmacología en paciente con Envejecimiento Precoz (Progeria no clásica)
Authors: Torres Obando Andrés Felipe , Velasco Quijano Juan Manuel , Paez Ospina Juan Manuel 
Published: November 2019

Introducción: el Envejecimiento Precoz (EP) es una enfermedad poco común. Se han descrito varios cuadros clínicos denominados Síndromes Progeroides (SP), entre los que se incluye la Progeria (P) y el EP, los cuales afectan diferentes órganos y sistemas, confiriendo aspectos sindromáticos característicos en estos pacientes. Hasta la fecha no existe una terapia definitiva que permita curar o tratar adecuadamente dicha enfermedad. Es una patología clasificada en las enfermedades huérfanas y raras, con pobre pronóstico; es relevante, entonces, exponer el caso de un paciente tratado con una respuesta favorable al tratamiento.
Caso clínico: paciente masculino natural y procedente de Bogotá (Colombia), con diagnóstico de SP (progeria no clásica) desde los nueve años, sometido a varios tratamientos sin presentar cambios significativos en el curso de su enfermedad. Consulta al Instituto Dr. Felipe Torres por pérdida progresiva de la fuerza muscular, caída permanente del cabello, osteoporosis y falla cardíaca. Se realiza tratamiento con factor neurotrófico derivado de cerebro (BDNF), interleukina 10 (IL-10) , anti interleukina 1 (Ant-IL1), β-endorfina, terapia de células madre, DNA, RNA recombinante y neurotrofina 4. Esto logró una disminución significativa de su sintomatología inicial y detención del proceso degenerativo, sin la presencia de eventos adversos.
Conclusiones: El presente caso clínico sugiere que la terapia con células madre mononucleares concentradas asociadas a tratamiento nanofarmacológico, pueden ser una alternativa segura, novedosa y efectiva, para los pacientes con síndromes progeroides, que en la actualidad no disponen de ningún tratamiento realmente eficaz.
Law, Gender, and Development: Potent Hauntings
Authors: Bedford Kate 
Published: November 2019

AbstractThis article excavates and analyses an early, feminist conversation about law that emerged from foundational texts on Gender and Development (GAD). Rather than starting from current, law-heavy GAD practices, it goes backwards to see what, if anything, some canonical texts published between 1970 and 1989 said about law. My aim is to offer an account of legally-relevant GAD theorising written before the current consensus about law reform as a tool had solidified, and – in so doing – to unsettle that consensus and identify some intellectual inheritances that might offer us an alternative way forward.
Going Beyond the Bench - The Paper Conservator Today
Authors: Ellis Margaret Holben 
Published: November 2019

Abstract
Paper conservators today face a growing preservation mandate that demands a comprehensive education.

These remarks refer to the education of North American paper conservators.
The path required to attain the necessary knowledge and skills to preserve works on paper has changed drastically over the past two generations starting with the establishment of graduate degree-granting programs and their dynamic and responsive curricula.
Kohelet in Distanz zu Eschatologie und Apokalyptik
Authors: Bauer Uwe F. W. 
Published: November 2019

Zusammenfassung
Im Beitrag wird die These vertreten, dass Koh eschatologische und apokalyptische Vorstellungen kritisiert. Der Frage, wie das genau geschieht, wird dann in diesem Beitrag nachgegangen. Wichtige Aspekte sind der Kreislauf der Natur, die sich wiederholende Geschichte, die ungewisse Zukunft, die Warnung vor Träumen, der unabänderliche Tod und die Entmythologisierung des Gerichts Jhwhs.
Orthodox-evangelische Ökumene und religiöse Bildung. Rahmenbedingungen, Themen, Perspektiven
Authors: Illert Martin 
Published: November 2019

Zusammenfassung
Der Beitrag beschreibt die orthodoxe Migration nach Deutschland und bedenkt den sozialen Rahmen der Präsenz Orthodoxer in Deutschland. Auf die Beschreibung dieser Voraussetzungen und die Auflistung der unterschiedlichen Formate ökumenischer Zusammenarbeit im nationalen und internationalen Zusammenhang werden die Hauptthemen des orthodox-protestantischen Dialoges erwähnt. In diesen Zusammenhang werden die Perspektiven auf dem Feld der Bildung gestellt.
Rod Photoreceptors Signal Fast Changes in Daylight Levels Using a Cx36-Independent Retinal Pathway in Mouse
Authors: Pasquale Rose , Umino Yumiko , Solessio Eduardo 
Published: November 2019

Temporal contrast detected by rod photoreceptors is channeled into multiple retinal rod pathways that ultimately connect to cone photoreceptor pathways via Cx36 gap junctions or via chemical synapses. However, we do not yet understand how the different rod pathways contribute to the perception of temporal contrast (changes in luminance with time) at mesopic light levels, where both rods and cones actively respond to light. Here, we use a forced-choice, operant behavior assay to investigate rod-driven, temporal contrast sensitivity (TCS) in mice of either sex. Transgenic mice with desensitized cones (GNAT2cpfl3line) were used to identify rod contributions to TCS in mesopic lights. We found that at low mesopic lights (400 photons/s/μm2at the retina), control and GNAT2cpfl3mice had similar TCS. Surprisingly, at upper mesopic lights (8000 photons/s/μm2), GNAT2cpfl3mice exhibited a relative reduction in TCS to low (<12 Hz) while maintaining normal TCS to high (12–36 Hz) temporal frequencies. The rod-driven responses to high temporal frequencies developed gradually over time (>30 min). Furthermore, the TCS of GNAT2cpfl3and GNAT2cpfl3::Cx36−/−mice matched closely, indicating that transmission of high-frequency signals (1) does not require the rod-cone Cx36 gap junctions as has been proposed in the past; and (2) a Cx36-independent rod pathway(s) (e.g., direct rod to OFF cone bipolar cell synapses and/or glycinergic synapses from AII amacrine cells to OFF ganglion cells) is sufficient for fast, mesopic rod-driven vision. These findings extend our understanding of the link between visual circuits and perception in mouse.SIGNIFICANCE STATEMENTThe contributions of specific retinal pathways to visual perception are not well understood. We found that the temporal processing properties of rod-driven vision in mice change significantly with light level. In dim lights, rods relay relatively slow temporal variations. However, in daylight conditions, rod pathways exhibit high sensitivity to fast but not to slow temporal variations, whereas cone-driven responses supplement the loss in rod-driven sensitivity to slow temporal variations. Our findings highlight the dynamic interplay of rod- and cone-driven vision as light levels rise from night to daytime levels. Furthermore, the fast, rod-driven signals do not require the rod-to-cone Cx36 gap junctions as proposed in the past, but rather, can be relayed by alternative Cx36-independent rod pathways.
Level of Consciousness Is Dissociable from Electroencephalographic Measures of Cortical Connectivity, Slow Oscillations, and Complexity
Authors: Pal Dinesh , Li Duan , Dean Jon G. , Brito Michael A. , Liu Tiecheng , Fryzel Anna M. , Hudetz Anthony G. , Mashour George A. 
Published: November 2019

Leading neuroscientific theories posit a central role for the functional integration of cortical areas in conscious states. Considerable evidence supporting this hypothesis is based on network changes during anesthesia, but it is unclear whether these changes represent state-related (conscious vs unconscious) or drug-related (anesthetic vs no anesthetic) effects. We recently demonstrated that carbachol delivery to prefrontal cortex (PFC) restored wakefulness despite continuous administration of the general anesthetic sevoflurane. By contrast, carbachol delivery to parietal cortex, or noradrenaline delivery to either prefrontal or parietal cortices, failed to restore wakefulness. Thus, carbachol-induced reversal of sevoflurane anesthesia represents a unique state that combines wakefulness with clinically relevant anesthetic concentrations in the brain. To differentiate the state-related and drug-related associations of cortical connectivity and dynamics, we analyzed the electroencephalographic data gathered from adult male Sprague Dawley rats during the aforementioned experiments for changes in functional cortical gamma connectivity (25–155 Hz), slow oscillations (0.5–1 Hz), and complexity (<175 Hz). We show that higher gamma (85–155 Hz) connectivity is decreased (p≤ 0.02) during sevoflurane anesthesia, an expected finding, but was not restored during wakefulness induced by carbachol delivery to PFC. Conversely, for rats in which wakefulness was not restored, the functional gamma connectivity remained reduced, but there was a significant decrease (p< 0.001) in the power of slow oscillations and increase (p< 0.001) in cortical complexity, which was similar to that observed during wakefulness induced after carbachol delivery to PFC. We conclude that the level of consciousness can be dissociated from cortical connectivity, oscillations, and dynamics.SIGNIFICANCE STATEMENTNumerous theories of consciousness suggest that functional connectivity across the cortex is characteristic of the conscious state and is reduced during anesthesia. However, it is unknown whether the observed changes are state-related (conscious vs unconscious) or drug-related (drug vs no drug). We used a novel rat model in which cholinergic stimulation of PFC produced wakefulness despite continuous exposure to a general anesthetic. We demonstrate that, as expected, general anesthesia reduces connectivity. Surprisingly, the connectivity remains suppressed despite pharmacologically induced wakefulness in the presence of anesthetic, with restoration occurring only after the anesthetic is discontinued. Thus, whether an animal exhibits wakefulness or not can be dissociated from cortical connectivity, prompting a reevaluation of the role of connectivity in level of consciousness.
Antioxidant Effect of Chlorella vulgaris on Physiological Response of Rat Induced by Carbon Tetrachloride
Authors: Hernayanti Hernayanti , Simanjuntak Sorta Basar Ida 
Published: November 2019

Chlorella vulgaris is an algae with high nutrition content. Carbon tetrachloride (CCl4) is a hepatotoxic chemical.The aims of this study were to determine the effect of C. vulgaris extract on the physiological response of liver such as MDA, SOD and GPx activity on rat after induced by CCl4 exposure as well as to determine the effective dose of C. vulgaris extract as antioxidant that can neutralize CCl4 exposure. This research was conducted experimentally with Completely Randomized Design that consists of 6 treatment and 5 times repetition. The doses of C. vulgaris extract used were 3, 4, and 5 mg per /100 g of rat’sbody weight (BW).The administration of C. vulgaris extract was performed within 30 days, while the CCl4 (0.25 ml/100 g BW) was administered orally on the day 9, 12, 16, 19, 23, and 26. Parameters measured were levels of MDA, SOD and GPx of rat blood serum.The results showed that the administration of C. vulgaris extract can inhibit lipid peroxidation indicated by decrease in MDA activities and oxidative stress by increasing SOD and GPx activity. In conclusion, 5 mg/100 g BW of C.vulgaris extract is an effective dose to be uses as endogenous antioxidant to protect the liver cell from damage caused by CCl4exposure. The benefit of C. vulgaris as a supplement for antihepatotoxin in humans.
The Potential Endophytic Bacteria Isolated from Rice (Oryza sativa) as Biofertilizer
Authors: Putriani Putriani , Fitri Lenni , Ismail Yulia Sari 
Published: November 2019

Endophytic bacteria are beneficial microorganisms that interact with host plants without causing any interference or damage to plants. This research aimed to obtain endophytic bacteria isolated from the root tissue of rice plants (Oryza sativa L.) which have potential to produce IAA hormones,, identify the endophytic bacteria in morphologically and physiologically, and analysis of the selected isolate 16S rRNA genes. Based on the results of this research, there were six endophytic bacteria isolates obtained. They have high morphological diversity and differen ability producing IAA hormones. The highest concentration of IAA (425 ppm) was obtained isolates from EAP3. Isolate EAP3 also produce inhibit the growth of Xanthomonas oryzae with a 5.2 mm inhibition zone. Based on the biochemical test, EAP3 had 60% similarity with Enterobacter asburiae. Analysis of the 16S rRNA gene showed that EAP3 had the highest similarity with Enterobacter asburiae strain U4 by 99%. This research data is considered as new information about the potential of endophytic bacteria from the roots of rice plants (Oryza sativa L.) which is capable of producing IAA hormones and is able to inhibit pathogenic bacteria. This research provides information that can be used as a basis for developing endophytic bacteria as biological fertilizers.
Potency of Brown Sugar as a Nectar Substitute for Trichoglossus haematodus in Captivity
Authors: Prijono Siti Nuramaliati , Rachmatika Rini 
Published: November 2019

Trichoglossus haematodus (Linnaeus, 1771) is nectarivorous bird that feed on nectar as a source of carbohydrate. In captivity, it is not practical to provide a continued diet of nectar from the flowers. Therefore, this study aimed to find other carbohydrate sources such as brown sugar as substitute nectar for T. haematodus. Twelve wild T. haematodus in four cages offered five types different brown sugar solution with different concentrations. Since brown sugar has low protein content, therefore the birds also offered commercial baby biscuit to meet the protein requirement. The results showed that the birds like to consume all types of brown sugar solution with sugar concentration up to 40% . However, the siwalan brown sugar solution was the most favored by the bird. over the other type of brown sugar solutions (aren, coconut, sugar cane and regular commercial “palm” brown sugar). Furthermore, the result showed that the birds prefer commercial baby biscuit was soaked in the brown sugar solution with concentration 20%. This study provides the information that the brown sugar solution based diet has potency as an alternative carbohydrate source to substitute nectar for T. haematodus in captivity which is more practical and can increase the survival rate in birds.