bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and Safety of DW1029M, a Botanical Drug for the Treatment of Diabetic Nephropathy, Following Single Doses in Healthy Subjects
Authors: Kim Yunjeong , Jeon Ji‐Young , Kim Eun‐Young , Lim Cheol‐Hee , Jang Hwan Bong , Kim Min‐Gul 
Published: March 2017

AbstractDW1029M is a botanical extract of Morus albalinne root bark and Puerariae radix that is used for the treatment of diabetic nephropathy. This study evaluated the safety and pharmacokinetics of DW1029M following its administration in healthy Korean subjects. We conducted a randomized, open‐label, single‐dose, crossover phase 1 clinical study. During each period, subjects received 300, 600, or 1200 mg oral doses of DW1029M. Plasma concentrations of puerarin, daidzin, and daidzein were analyzed using a liquid chromatography–tandem mass spectrometry. Six healthy male subjects completed the study. The maximum concentration of the drug in the plasma (Cmax) and area under the plasma drug concentration–time curve to the last measurable concentration (AUClast) for puerarin, daidzin, and daidzein were assessed after oral administration of DW1029M. No serious adverse events or clinically or statistically significant adverse events associated with any of the drug levels were observed. The results of the measurement of vital signs, electrocardiogram, laboratory tests, and physical examinations indicated that no clinically significant changes occurred during this study. The DW1029M tablet was safe and well tolerated over a single dose range of 300–1200 mg. This pharmacokinetic study of a botanical drug may aid in the development of DW1029M.
The Effect of Verapamil, a P‐Glycoprotein Inhibitor, on the Pharmacokinetics of Peficitinib, an Orally Administered, Once‐Daily JAK Inhibitor
Authors: Zhu Tong , Howieson Corrie , Wojtkowski Tomasz , Garg Jay P. , Han David , Fisniku Ogert , Keirns James 
Published: March 2017

AbstractPeficitinib is an orally administered, once‐daily Janus kinase inhibitor currently in development for the treatment of rheumatoid arthritis. It has been shown to be a P‐glycoprotein (P‐gp) substrate in vitro. The effects of verapamil, an inhibitor of the efflux pump P‐gp, on the pharmacokinetic profile of peficitinib were assessed in this open‐label, single‐center, single‐sequence, crossover drug‐interaction study. Twenty‐four healthy volunteers received a single 150‐mg dose of peficitinib on days 1 and 12 of a 14‐day treatment period and received verapamil 80 mg 3 times daily on days 5–14. Repeated‐dose administration of verapamil increased mean peficitinib AUCinf, AUClast, and Cmax by 27%, 27%, and 39%, respectively, and also increased the mean AUC and Cmax of peficitinib metabolites H1, H2, and H4. Coadministration of verapamil with peficitinib 150 mg was generally well tolerated. Overall, the most commonly reported adverse event was headache, which occurred in 5 subjects (21%); all reported adverse events were grade 1 severity, with the exception of 1 grade 2 incident of vomiting.
Central Regulation of Glucose Homeostasis
Authors: Tups Alexander , Benzler Jonas , Sergi Domenico , Ladyman Sharon R. , Williams Lynda M. 
Published: March 2017

ABSTRACTThe ability of the brain to directly control glucose levels in the blood independently of its effects on food intake and body weight has been known ever since 1854 when Claude Bernard, a French physiologist, discovered that lesioning the floor of the fourth ventricle in rabbits led to a rise of sugar in the blood. Despite this outstanding discovery at that time, it took more than 140 years before progress started to be made in identifying the underlying mechanisms of brain‐mediated control of glucose homeostasis. Technological advances including the generation of brain insulin receptor null mice revealed that insulin action specifically in the central nervous system is required for the regulation of glucose metabolism, particularly in the modulation of hepatic glucose production. Furthermore, it was established that the hormone leptin, known for its role in regulating food intake and body weight, actually exerts its most potent effects on glucose metabolism, and that this function of leptin is mediated centrally. Under certain circumstances, high levels of leptin can replicate the actions of insulin, thus challenging the idea that life without insulin is impossible. Disruptions of central insulin signaling and glucose metabolism not only lead to impairments in whole body glucose homeostasis, they also have other serious consequences, including the development of Alzheimer's disease which is sometimes referred to as type 3 diabetes reflecting its common etiology with type 2 diabetes. © 2017 American Physiological Society.Compr Physiol7:471‐764, 2017.
Best Evidence Aside: Why Trump's Executive Order Makes America Less Healthy
Authors: Gostin Lawrence O. 
Published: March 2017

AbstractWhat are the health impacts of President Trump's January 27, 2017, executive order suspending the resettlement of refugees and temporarily banning entry of nationals from Iraq, Syria, Iran, Sudan, Libya, Somalia, and Yemen? Even if the President's constitutional arguments are credible, the order is deeply troubling under international law and humanitarian values. Under the 1967 Refugee Protocol, the United States has assumed a legal obligation to examine the claims of asylum seekers who reach U.S. territory without discrimination based on race, nationality, or religion. Congress has delegated the decision as to how many refugees to accept to the president. Still, the executive order runs contrary to the principle of solidarity—which includes the fair sharing of responsibilities and burdens in accepting endangered individuals. Migrating doctors and nurses fill much of America's health care resources shortfall. The executive order also undermines science and academia, which depend on the free flow of knowledge and the spread of ideas.
Managing Opioid Withdrawal for Hospital Patients in Custody
Authors: Shi Connie R. , Kandola Manjinder S. , Tobey Matthew , Singer Elizabeth 
Published: March 2017

AbstractDr. Brown, a hospitalist, admits Mark, a patient transferred from a local jail for management of cellulitis. The patient, who was taken into custody two days prior to hospital admission, has a history of intravenous heroin use. Mark explains that he had been prescribed buprenorphine‐naloxone maintenance therapy for opioid use disorder for several years prior to being arrested and had not used other opioids during that time. As a policy, the jail where Mark is detained does not prescribe opioid agonists, and his maintenance therapy was stopped upon his arrival there.Dr. Brown discovers that Mark is diaphoretic and appears distressed. Mark's symptoms suggest to Dr. Brown that, in addition to having cellulitis, Mark is actively withdrawing from opioids. Mark tells Dr. Brown that he has felt “horrible” since his buprenorphine‐naloxone therapy was stopped and that he now has intense cravings for opioids. He asks Dr. Brown to help alleviate the withdrawal symptoms. Dr. Brown, who is accustomed to treating opioid withdrawal with opioid replacement therapy, wonders if she should initiate ORT for Mark while he is in the hospital.
Bioethics and Populism:How Should Our Field Respond?
Authors: Solomon Mildred Z. , Jennings Bruce 
Published: March 2017

AbstractAcross the world, an authoritarian and exclusionary form of populism is gaining political traction. Historically, some populist movements have been democratic and based on a sense of inclusive justice and the common good. But the populism on the rise at present speaks and acts otherwise. It is challenging constitutional democracies. The polarization seen in authoritarian populism goes beyond the familiar left‐right political spectrum and generates disturbing forms of extremism, including the so‐called alternative right in the United States and similar ethnic and nationalistic political movements in other countries. The field of bioethics will be profoundly affected if authoritarian populism displaces constitutional democracy. But the field has a significant contribution to make to rebuilding the communal and civic foundations upon which constitutional democracy rests.
Authenticity, Best Interest, and Clinical Nudging
Authors: Holm Søren 
Published: March 2017

AbstractIn this issue of the Hastings Center Report, Moti Gorin, Steven Joffe, Neal Dickert, and Scott Halpern offer a comprehensive defense of the use of nudging techniques in the clinical context, with the aim of promoting the best interests of patients. Their argument is built on three important claims: Nudging is ubiquitous and inescapable in clinical choice situations, and there is no neutral way of informing patients about their treatment choices; many patients do not have authentic (preexisting) preferences concerning their treatment choices, and those that do can easily resist nudging; and, finally, since many people lack authentic preferences and those that do can still act on their preferences, nudging in the patients’ best interest is justified. I agree with the authors that if these three claims stand up to scrutiny, then they will provide a justification for many types of clinical nudging. I am, however, skeptical as to whether the claims can be sustained, despite the valiant efforts of Gorin and colleagues.
Bioethics and “Rightness”
Authors: Frank Arthur W. 
Published: March 2017

AbstractIf bioethics seeks to affect what people do and don't do as they respond to the practical issues that confront them, then it is useful to take seriously people's sense of rightness. Rightness emerges from the fabric of a life—including the economy of its geography, the events of its times, its popular culture—to be what the sociologist Pierre Bourdieu calls a predisposition. It is the product of a way of life and presupposes continuing to live that way. Rightness is local and communal, holding in relationship those who share the same predisposing sense of how to experience. Rightness is an embodied way of evaluating what is known to matter and choosing among possible responses. Bioethics spends considerable time on what people should do and on the arguments that support recommended actions. It might spend more time on what shapes people's sense of the rightness of what they feel called to do.
Evolving application of minimally invasive cancer operations at a tertiary cancer center
Authors: Selby Luke V. , DeMatteo Ronald P. , Tholey Renee M. , Jarnagin William R. , Garcia‐Aguilar Julio , Strombom Paul D. , Allen Peter J. , Kingham T. Peter , Weiser Martin R. , Brennan Murray F. , Strong Vivian E. 
Published: March 2017

BACKGROUNDPatients and providers are increasingly interested in the utilization, safety, and efficacy of minimally invasive surgery (MIS). We reviewed 11 years of MIS resections (laparoscopic and robotic) for intra‐abdominal malignancies.METHODSPatients who underwent gastrectomy, distal pancreatectomy, hepatic resection, and colorectal resection between 2004 and 2014 were identified. Cases were categorized as open, laparoscopic, and robotic based on the initial operation approach. Diagnostic laparoscopies were excluded.RESULTSOf the 10 039 patients who underwent the above procedures, between 2004 and 2014, 2832 (28%) were MIS. In 2004, 12% (100/826) of all resections were performed with MIS approaches, rising to 23% (192/821) of all resections by 2009 and 44% (484/1092) in 2014. The number of open resections has remained largely stable: 726 (88% of all resections) in 2004 and 608 (56% of all resections) in 2014. Initially, laparoscopy experienced incremental adoption. Robotic surgery was implemented in 2009 and is currently the dominant MIS approach, accounting for 76% (368/484) of all MIS resections in 2014. Overall mortality has remained less than 1%.CONCLUSIONSWhile maintaining patient safety, utilization of MIS techniques has increased substantially since 2004, particularly for gastric and colorectal resections. Since 2009 robotic surgery is the predominant MIS approach.
Epidemiology of firearm and other noise exposures in the United States
Authors: Bhatt Jay M. , Lin Harrison W. , Bhattacharyya Neil 
Published: March 2017

ObjectiveIdentify contemporary noise exposures and hearing protection use among adults.Study DesignCross‐sectional analysis of national health survey.MethodsAdult respondents in the 2014 National Health Interview Series hearing survey module were analyzed. Potentially harmful exposures to occupational and recreational noises in the past 12 months were extracted and quantified. Patterns of hearing protection use also were analyzed.ResultsAmong 239.7 million adults, “loud” and “very loud” occupational noise exposures were reported by 5.3% and 21.7%, respectively. Of those exposed to “loud” or “very loud” sounds at work, only 18.7% and 43.6%, respectively, always used hearing protection. A total of 38.2% (1.9 million) of those with “very loud” occupational exposures never used hearing protection. Frequent (> 10/year) “loud” and “very loud” recreational noise exposures were reported by 13.9% and 21.1%, respectively, most commonly to lawn mowers (72.6% and 55.2%, respectively). When exposed to recreational “loud/very loud” noise, only 11.4% always used hearing protection, whereas 62.3% (6.3 million) never used any protection. Lifetime exposure to firearm noise was reported by 36.6% of adults, 11.5% of whom had used firearms in the prior 12 months. Of those, only 58.5% always used hearing protection, whereas 21.4% (7.4 million) never used hearing protection.ConclusionSubstantial noise exposures with potentially serious long‐term hearing health consequences frequently are occurring in occupational and recreational settings, and with the use of firearms. Only a minority of those exposed consistently are using hearing protection. Healthcare providers should actively identify and encourage the use of hearing protection with those patients at risk.Level of Evidence4. Laryngoscope, 127:E340–E346, 2017
Preservation of seawater samples for soluble reactive phosphate, nitrite, and nitrate plus nitrite analyses by the addition of sodium hydroxide
Authors: Wong George T. F. , Li‐Tzu Hou Lisa , Li Kuo‐Yuan 
Published: March 2017

AbstractSeawater storage at ambient temperature is necessary when freezing facilities are unavailable for the preservation of samples collected for the determination of soluble reactive phosphate (SRP), nitrite (
), and nitrate plus nitrite (N + N)—notably, during small boat operations. Here, we report that samples may be preserved at ambient temperature by the addition of NaOH at sampling to induce the precipitation of Mg(OH)2, and then returned to a shore base laboratory for further processing. In the laboratory, SRP, which has been sequestered in the precipitate, is analyzed by the MAGnesium‐induced co‐precipitation method.
and N + N are quantitatively retained in the supernatant liquid and they are analyzed by the standard methods after a pH adjustment. The samples may be stored for up to at least 2 months and they yield concentrations that are indistinguishable from those in frozen samples. Internally added SRP,
, and N + N to seawater samples can be recovered quantitatively after storage. This storage method also offers clear advantages over the preservation of samples at ambient temperature by the addition of HgCl2 as NaOH is a less toxic and less environmentally hazardous chemical and it does not interfere in the determination of N + N. It also allows low level SRP to be determined as part of the analytical routine as a pre‐concentration of SRP has been built into the storage scheme.
Air calibration of an oxygen optode on an underwater glider
Authors: Nicholson David P. , Feen Melanie L. 
Published: March 2017

AbstractAn Aanderaa Data Instruments 4831 oxygen optode was configured on an underwater glider such that the optode extended into the atmosphere during each glider surface interval enabling in situ calibration of the sensor by directly measuring the known oxygen partial pressure of the atmosphere. The approach, which has previously been implemented on profiling floats but not on gliders, was tested during a 15‐d deployment at the New England shelf break in June 2016, a productive period during which surface O2 saturation averaged 110%. Results were validated by shipboard Winkler O2 calibration casts, which were used to determine a sensor gain factor of 1.055 ± 0.004. Consistent with profiling float observations, air measurements contain contamination from splashing water and/or residual seawater on the sensor face. Glider surface measurements were determined to be a linear combination of 36% of surface water and 64% atmospheric air. When correcting air measurements for this effect, a sensor gain correction of 1.055 ± 0.005 was calculated based on comparing glider air measurements to the expected atmospheric pO2 calculated from atmospheric pressure and humidity data from a nearby NOAA buoy. Thus, the two approaches were in agreement and were both demonstrated to be accurate to within ±0.5%. We expect uncertainty in the air‐calibration could be further reduced by increasing the vertical positioning of the optode, lengthening deployment time, or operating in waters with surface O2 saturation closer to equilibrium.
Preparation and characterization of PES/CA microporous membranes via reverse thermally induced phase separation process
Authors: Liu Sheng‐Hui , Xu Zhen‐Liang , Liu Min , Wei Yong‐Ming , Guo Feng 
Published: March 2017

The blend polyethersulfone (PES)/cellulose acetate (CA) flat‐sheet microporous membranes were prepared by reverse thermally induced phase separation (RTIPS) process. The effects of CA content and coagulation bath temperature on membrane structures and properties were investigated in terms of membrane morphology, water contact angle, permeation performance, and mechanical properties. The cloud point results indicated that the cloud point decreased with the increasing content of CA. When the coagulation bath temperature was lower than the cloud point, the membrane formation process underwent nonsolvent induced phase separation (NIPS) process and dense skin layer and finger‐like structure were formed in membranes. These membranes had lower pure water flux and poor mechanical properties. But when the coagulation bath temperature was higher than the cloud point, the membrane formation process underwent RTIPS process. The porous top surface as well as porous cross‐section of the membranes were formed. Therefore, high pure water flux and good mechanical properties were obtained. The contact angles results indicated that the hydrophilicity of the prepared membranes improved obviously with the addition of CA. When the content of CA was 0.5 wt% and the membrane formation temperature was 323K, the PES/CA microporous membrane which was prepared via the RTIPS process displayed a optimal permeability of the pure water flux of 816 L m−2 h−1 and the BSA rejection rate of 49.5%, which showed an increase of 48.9% and 23.6% than that of pure PES membrane, respectively. Moreover, the mechanical strengths of the membranes obtained by RTIPS process were better than those membranes prepared by NIPS process. POLYM. ENG. SCI., 58:180–191, 2018. © 2017 Society of Plastics Engineers
A randomized, open-label, multicenter, phase II study evaluating the efficacy and safety of BTH1677 (1,3–1,6 beta glucan; Imprime PGG) in combination with cetuximab and chemotherapy in patients with advanced non-small cell lung cancer
Authors: Thomas M. , Sadjadian P. , Kollmeier J. , Lowe J. , Mattson P. , Trout J. R. , Gargano M. , Patchen M. L. , Walsh R. , Beliveau M. , Marier J. F. , Bose N. , Gorden K. , Schneller F. 
Published: March 2017

SummaryIntroduction BTH1677, a 1,3–1,6 beta-glucan immunomodulator, stimulates a coordinated anti-cancer immune response in combination with anti-tumor antibody therapies. This phase II study explored the efficacy, pharmacokinetics (PK), and safety of BTH1677 combined with cetuximab/carboplatin/paclitaxel in untreated stage IIIB/IV non-small cell lung cancer (NSCLC) patients. Methods Patients were randomized 2:1 to the BTH1677 arm (N=60; BTH1677, 4 mg/kg, weekly; cetuximab, initial dose 400 mg/m2 and subsequent doses 250 mg/m2, weekly; carboplatin, 6 mg/mL/min AUC (area-under-the-curve) by Calvert formula, once each 3-week cycle [Q3W]); and paclitaxel, 200 mg/m2, Q3W) or Control arm (N=30; cetuximab/carboplatin/paclitaxel as above). Carboplatin/paclitaxel was discontinued after 4–6 cycles; patients who responded or remained stable received maintenance therapy with BTH1677/cetuximab (BTH1677 arm) or cetuximab (Control arm). Investigator and blinded central radiology reviews were conducted. Efficacy assessments included objective response rate (ORR; primary endpoint), disease control rate, duration of objective response, time-to-progression and overall survival (OS); safety was assessed by adverse events (AEs). Potential biomarker analysis for BTH1677 response was also conducted. Results Compared to control treatment, the addition of BTH1677 numerically increased ORR by both investigator (47.8% vs 23.1%; p=0.0468) and central (36.6% vs 23.1%; p=0.2895) reviews. No other endpoints differed between arms. PK was consistent with previous studies. BTH1677 was well tolerated, with AEs expected of the backbone therapy predominating. Biomarker-positive patients displayed better ORR and OS than negative patients. Conclusions BTH1677 combined with cetuximab/carboplatin/paclitaxel was well tolerated and improved ORR as first-line treatment in patients with advanced NSCLC. Future patient selection by biomarker status may further improve efficacy
ClinicalTrials.gov
Identifier: NCT00874848
Vegetation Change in Southwestern Amazonia (Brazil) and Relationship to the Late Pleistocene and Holocene Climate
Authors: Rossetti Dilce F , Cohen Marcelo C L , Pessenda Luiz C R 
Published: March 2017

AbstractThe Late Quaternary climate in Amazonia is an issue still open to debate, with hypotheses varying from alternate dry and wet episodes to stable climate with undisturbed rainforest. We approach this question using δ13C, C/N, and, to a lesser extent, δ15N from deposits derived from four cores, with the results combined with published pollen data from two of these cores. These data were analyzed within the context of radiocarbon dating, which revealed ages ranging from 42.8–41.8 to 2.3–2.2 cal ka BP. Fluvial channel and floodplain deposits with freshwater phytoplankton recorded a trend of wet climate with dry episodes before ~40 cal ka BP, followed by humid and cold climate until the Last Glacial Maximum, with intensified aridity towards the end of the Late Pleistocene. Peaks of increased contributions in C4land plants in the mid- to late Holocene were not synchronous and have no correspondence with Amazonian Holocene dry episodes, being due to sedimentary processes related to fluvial dynamics during the establishment of herbaceous fields on abandoned depositional sites. Thus, the climate remained wet in the Holocene, which would have favored the expansion of the Amazonian rainforest as we see today.