bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma Carboxylesterase 1 Predicts Methylphenidate Exposure: A Proof‐of‐Concept Study Using Plasma Protein Biomarker for Hepatic Drug Metabolism
Authors: Shi Jian , Xiao Jingcheng , Wang Xinwen , Jung Sun Min , Bleske Barry E. , Markowitz John S. , Patrick Kennerly S. , Zhu Hao‐Jie 
Published: November 2021

Hepatic drug‐metabolizing enzymes (DMEs) play critical roles in determining the pharmacokinetics and pharmacodynamics of numerous therapeutic agents. As such, noninvasive biomarkers capable of predicting DME expression in the liver have the potential to be used to personalize pharmacotherapy and improve drug treatment outcomes. In the present study, we quantified carboxylesterase 1 (CES1) protein concentrations in plasma samples collected during a methylphenidate pharmacokinetics study. CES1 is a prominent hepatic enzyme responsible for the metabolism of many medications containing small ester moieties, including methylphenidate. The results revealed a significant inverse correlation between plasma CES1 protein concentrations and the area under the concentration‐time curves (AUCs) of plasma d‐methylphenidate (P = 0.014, r = −0.617). In addition, when plasma CES1 protein levels were normalized to the plasma concentrations of 24 liver‐enriched proteins to account for potential interindividual differences in hepatic protein release rate, the correlation was further improved (P = 0.003, r = −0.703), suggesting that plasma CES1 protein could explain ~ 50% of the variability in d‐methylphenidate AUCs in the study participants. A physiologically‐based pharmacokinetic modeling simulation revealed that the CES1‐based individualized dosing strategy might significantly reduce d‐methylphenidate exposure variability in pediatric patients relative to conventional trial and error fixed dosing regimens. This proof‐of‐concept study indicates that the plasma protein of a hepatic DME may serve as a biomarker for predicting its metabolic function and the pharmacokinetics of its substrate drugs.
Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double‐Blind, Placebo‐Controlled, Crossover Study in Healthy Subjects
Authors: Becker Anna M. , Holze Friederike , Grandinetti Tanja , Klaiber Aaron , Toedtli Vanja E. , Kolaczynska Karolina E. , Duthaler Urs , Varghese Nimmy , Eckert Anne , Grünblatt Edna , Liechti Matthias E. 
Published: November 2021

The psychedelic psilocybin is being investigated for the treatment of depression and anxiety. Unclear is whether antidepressant treatments interact with psilocybin. The present study used a double‐blind, placebo‐controlled, crossover design with two experimental test sessions to investigate the response to psilocybin (25 mg) in healthy subjects after pretreatment with escitalopram or placebo. The treatment order was random and counterbalanced. Pretreatment consisted of 10 mg escitalopram daily for 7 days, followed by 20 mg daily for 7 days, including the day of psilocybin administration, or 14 days of placebo pretreatment before psilocybin administration. Psilocybin treatments were separated by at least 16 days. The outcome measures included self‐rating scales that evaluated subjective effects, autonomic effects, adverse effects, plasma brain‐derived neurotrophic factor (BDNF) levels, electrocardiogram QTc time, whole‐blood HTR2A and SCL6A4 gene expression, and pharmacokinetics. Escitalopram pretreatment had no relevant effect on positive mood effects of psilocybin but significantly reduced bad drug effects, anxiety, adverse cardiovascular effects, and other adverse effects of psilocybin compared with placebo pretreatment. Escitalopram did not alter the pharmacokinetics of psilocin. The half‐life of psychoactive free (unconjugated) psilocin was 1.8 hours (range 1.1–2.2 hours), consistent with the short duration of action of psilocybin. Escitalopram did not alter HTR2A or SCL6A4 gene expression before psilocybin administration, QTc intervals, or circulating BDNF levels before or after psilocybin administration. Further studies are needed with a longer antidepressant pretreatment time and patients with psychiatric disorders to further define interactions between antidepressants and psilocybin.
A Low‐Temperature Dehydration Carbon‐Fixation Strategy for Lignocellulose‐Based Hierarchical Porous Carbon for Supercapacitors
Authors: Chen Zhimin , Wang Xiaofeng , Li Wei , Yang Xiaomin , Qiu Jieshan , Wang Zichen 
Published: November 2021

AbstractLignocellulose‐based hierarchical porous carbon is a very promising electrode material for supercapacitors, but lower volumetric energy density and yield have hindered its practical applications. Herein, a low‐temperature dehydration carbon‐fixation method using NH4Cl as modification reagent was developed to prepare rice husk‐based hierarchical porous carbon (RHPC) with high volumetric performance and yield. The RHPC‐N electrode exhibited a higher volumetric specific capacitance of 134.4 F cm−3 than that of the RHPC electrode (98.4 F cm−3) in 1 m Et4NBF4/propylene carbonate electrolyte. The volumetric energy density (28.8 Wh L−1) of the RHPC‐N electrode was 37.1 % higher than that of the RHPC electrode (21.0 Wh L−1), which greatly enhanced the practical application potential of RHPC in supercapacitors. Moreover, the yield of RHPC increased 1.2 times by this method, which greatly improved the production capacity and reduced the cost. This research establishes a simple and highly efficient method to improve the volumetric energy density and the yield of lignocellulose‐based hierarchical porous carbon.
A multidimensional stability framework enhances interpretation and comparison of carbon cycling response to disturbance
Authors: Mathes Kayla C. , Ju Yang , Kleinke Callie , Oldfield Callie , Bohrer Gil , Bond‐Lamberty Ben , Vogel Christoph S. , Dorheim Kalyn , Gough Christopher M. 
Published: November 2021

AbstractThe concept of stability is central to the study and sustainability of vital ecosystem goods and services as disturbances increase globally. While ecosystem ecologists, including carbon (C) cycling scientists, have long‐considered multiple dimensions of disturbance response, our discipline lacks an agreed‐upon analytical framework for characterizing multidimensional stability. Here, we advocate for the broader adoption of a standardized and normalized multidimensional stability framework for analyzing disturbance response. This framework includes four dimensions of stability: the degree of initial change in C fluxes (i.e.,resistance); rate (i.e.,resilience) and variability (i.e.,temporal stability) of return to pre‐disturbance C fluxes; and the extent of return to pre‐disturbance C fluxes (i.e.,recovery). Using this framework, we highlight findings not readily seen from analysis of absolute fluxes, including trade‐offs between initial and long‐term C flux responses to disturbance; different overall stability profiles among fluxes; and, using a pilot dataset, similar relative stability of net primary production following fire and insect disturbances. We conclude that ecosystem ecologists’ embrace of a unifying multidimensional stability framework as a complement to approaches focused on absolute C fluxes could advance global change research by aiding in the novel interpretation, comprehensive synthesis, and improved forecasting of ecosystems’ response to an increasing array of disturbances.
The characterization and sodium borohydride electrooxidation of novel carbon nanotube supported copromoted Pd as anode catalyst for fuel cell
Authors: Caglar Aykut , Hansu Tulin A. , Sahin Omer , Kivrak Hilal 
Published: November 2021

AbstractIn the present study, the effect of Co addition on Pd is investigated. Pd/CNT and PdCo/CNT catalysts are prepared via the sodium borohydride (SBH, NaBH4) reduction method. The X‐ray diffraction, transmission electron microscope, and inductively coupled plasma‐mass spectrometry analyses are performed to characterize the PdCo(70‐30)/CNT catalyst. These characterization results reveal that Pd/CNT and PdCo/CNT catalysts are prepared successfully. NaBH4 electrooxidation activities of PdCo/CNT catalysts are examined with electrochemical methods such as cyclic voltammetry, chronoamperometry, and electrochemical impedance spectroscopy. PdCo(70‐30)/CNT catalyst has 11.52 mA/cm2 specific activity, 477.18 m2/g electrochemical active surface area, and the best electrochemical stability. Pd is a promising catalyst for NaBH4 electrooxidation reaction.
Lithic arrowheads: Siliceous raw material sources and technology in Southern Portugal
Authors: Costa Mafalda , Dias Luís , Rocha Leonor , Oliveira Jorge , Barrulas Pedro , Mirão José 
Published: November 2021

AbstractThis analysis focused on one hundred and fifteen lithic arrowheads recovered from the Zambujeiro and Mitra 2 dolmens, funerary monuments in Évora, Portugal. These were analyzed by noninvasive and minimally invasive analytical techniques, including handheld X‐ray fluorescence (hXRF), variable pressure scanning electron microscope coupled with energy dispersive X‐ray spectrometry (VP‐SEM‐EDS), and laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) to establish the sources of the raw materials used to manufacture these arrowheads and to compare and cluster different artefacts. The raw materials used in the manufacture of the arrowheads were found to be from different sources suggesting that long‐distance trade routes extending south, east and possibly west were in place in Southern Iberia during the Neolithic and Chalcolithic periods. Whether this difference is related to the availability of raw materials throughout time, different procurement strategies, or simply by choice, remains unknown. The trade routes associated with the Mitra 2 Dolmen also seem to have a greater range than those connected to the Zambujeiro Dolmen.
Characterization of whole‐brain task‐modulated functional connectivity in response to nociceptive pain: A multisensory comparison study
Authors: Li Linling , Di Xin , Zhang Huijuan , Huang Gan , Zhang Li , Liang Zhen , Zhang Zhiguo 
Published: November 2021

AbstractPrevious functional magnetic resonance imaging (fMRI) studies have shown that brain responses to nociceptive pain, non‐nociceptive somatosensory, visual, and auditory stimuli are extremely similar. Actually, perception of external sensory stimulation requires complex interactions among distributed cortical and subcortical brain regions. However, the interactions among these regions elicited by nociceptive pain remain unclear, which limits our understanding of mechanisms of pain from a brain network perspective. Task fMRI data were collected with a random sequence of intermixed stimuli of four sensory modalities in 80 healthy subjects. Whole‐brain psychophysiological interaction analysis was performed to identify task‐modulated functional connectivity (FC) patterns for each modality. Task‐modulated FC strength and graph‐theoretical‐based network properties were compared among the four modalities. Lastly, we performed across‐sensory‐modality prediction analysis based on the whole‐brain task‐modulated FC patterns to confirm the specific relationship between brain patterns and sensory modalities. For each sensory modality, task‐modulated FC patterns were distributed over widespread brain regions beyond those typically activated or deactivated during the stimulation. As compared with the other three sensory modalities, nociceptive stimulation exhibited significantly different patterns (more widespread and stronger FC within the cingulo‐opercular network, between cingulo‐opercular and sensorimotor networks, between cingulo‐opercular and emotional networks, and between default mode and emotional networks) and global property (smaller modularity). Further, a cross‐sensory‐modality prediction analysis found that task‐modulated FC patterns could predict sensory modality at the subject level successfully. Collectively, these results demonstrated that the whole‐brain task‐modulated FC is preferentially modulated by pain, thus providing new insights into the neural mechanisms of pain processing.
Incidence and prediction of HBsAg seroclearance in a prospective multi‐ethnic HBeAg‐negative chronic hepatitis B cohort
Authors: Terrault Norah A. , Wahed Abdus S. , Feld Jordan J. , Cooper Stewart L. , Ghany Mark G. , Lisker‐Melman Mauricio , Perrillo Robert , Sterling Richard K. , Khalili Mandana , Chung Raymond T. , Rosenthal Philip , Fontana Robert J. , Sarowar Arif , Lau Daryl T. Y. , Wang Junyao , Lok Anna S. , Janssen Harry L. A. 
Published: November 2021

Abstract

Background and Aims
Achieving HBsAg loss is an important landmark in the natural history of chronic hepatitis B (CHB). A more personalized approach to prediction of HBsAg loss is relevant in counseling patients. This study sought to develop and validate a prediction model for HBsAg loss based on quantitative HBsAg levels (qHBsAg) and other baseline characteristics.

Methods
The Hepatitis B Research Network (HBRN) is a prospective cohort including 1240 untreated HBeAg‐negative patients (1150 adults, 90 children) with median follow‐up of 5.5 years. Incidence rates of HBsAg loss and hepatitis B surface antibody (anti‐HBs) acquisition were determined, and a predictor score of HBsAg loss using readily available variables was developed and externally validated.

Results
Crude incidence rates of HBsAg loss and anti‐HBs acquisition were 1.6 and 1.1 per 100 person‐years (PY); 67 achieved sustained HBsAg loss for an incidence rate of 1.2 per 100 PY. Increased HBsAg loss was significantly associated with older age, non‐Asian race, HBV phenotype (inactive CHB vs. others), HBV genotype A, lower HBV‐DNA levels, and lower and greater change in qHBsAg. The HBRN‐SQuARe (sex,∆quantHBsAg, age, race) score predicted HBsAg loss over time with area under the receiver operating characteristic curve (AUROC) (95% CIs) at 1 and 3 years of 0.99 (95% CI: 0.987–1.00) and 0.95 (95% CI 0.91–1.00), respectively. In validation in another cohort of 1253 HBeAg‐negative patients with median follow‐up of 3.1 years, HBRN SQuARe predicted HBsAg loss at 1 and 3 years with AUROC values of 0.99 (0.98–1.00) and 0.88 (0.77–0.99), respectively.

Conclusion
HBsAg loss in predominantly untreated patients with HBeAg‐negative CHB can be accurately predicted over a 3‐year horizon using a simple validated score (HBRN SQuARe). This prognostication tool can be used to support patient care and counseling.
Melatonin receptor 1A, but not 1B, knockout decreases biliary damage and liver fibrosis during cholestatic liver injury
Authors: Wu Nan , Carpino Guido , Ceci Ludovica , Baiocchi Leonardo , Francis Heather , Kennedy Lindsey , Zhou Tianhao , Chen Lixian , Sato Keisaku , Kyritsi Konstantina , Meadows Vik , Ekser Burcin , Franchitto Antonio , Mancinelli Romina , Onori Paolo , Gaudio Eugenio , Glaser Shannon , Alpini Gianfranco 
Published: November 2021

Abstract

Background and Aims
Melatonin reduces biliary damage and liver fibrosis in cholestatic models by interaction with melatonin receptors 1A (MT1) and 1B (MT2). MT1 and MT2 can form heterodimers and homodimers, but MT1 and MT2 can heterodimerize with the orphan receptor G protein–coupled receptor 50 (GPR50). MT1/GPR50 dimerization blocks melatonin binding, but MT2/GPR50 dimerization does not affect melatonin binding. GPR50 can dimerize with TGFβ receptor type I (TGFβRI) to activate this receptor. We aimed to determine the differential roles of MT1 and MT2 during cholestasis.

Approach and Results
Wild‐type (WT), MT1 knockout (KO), MT2KO, and MT1/MT2 double KO (DKO) mice underwent sham or bile duct ligation (BDL); these mice were also treated with melatonin. BDL WT and multidrug resistance 2 KO (Mdr2−/−) mice received mismatch, MT1, or MT2 Vivo‐Morpholino. Biliary expression of MT1 and GPR50 increases in cholestatic rodents and human primary sclerosing cholangitis (PSC) samples. Loss of MT1 in BDL and Mdr2−/− mice ameliorated biliary and liver damage, whereas these parameters were enhanced following loss of MT2 and in DKO mice. Interestingly, melatonin treatment alleviated BDL‐induced biliary and liver injury in BDL WT and BDL MT2KO mice but not in BDL MT1KO or BDL DKO mice, demonstrating melatonin’s interaction with MT1. Loss of MT2 or DKO mice exhibited enhanced GPR50/TGFβR1 signaling, which was reduced by loss of MT1.

Conclusions
Melatonin ameliorates liver phenotypes through MT1, whereas down‐regulation of MT2 promotes liver damage through GPR50/TGFβR1 activation. Blocking GPR50/TGFβR1 binding through modulation of melatonin signaling may be a therapeutic approach for PSC.
Post‐relapse survival in Waldenstrom macroglobulinemia patients experiencing therapy failure following autologous transplantation
Authors: Ahmed Sairah , Zhao Qiuhong , Hanel Walter , Qazilbash Muzaffar H. , Patel Krina , Narra Ravi , Kansagra Ankit , Iqbal Madiha , Awan Farrukh T. , Christian Beth , Jaglowski Samantha M. , Kharfan‐Dabaja Mohamed A. , Hamadani Mehdi , Epperla Narendranath 
Published: November 2021

AbstractWaldenström macroglobulinemia (WM) is a rare B‐cell lymphoproliferative malignancy. Autologous hematopoietic cell transplantation (auto‐HCT) is considered in a subset of WM patients with relapsed disease. While registry data has shown a benefit for auto‐HCT in relapsed WM, there is a paucity of data on outcomes of patients relapsing after auto‐HCT. Eligibility criteria included adult patients with relapsed/refractory WM who underwent auto‐HCT between 2007 and 2017. The primary endpoint was post‐relapse overall survival (PR‐OS). Secondary endpoints were to identify factors prognostic of PR‐OS. Of the 48 patients with WM who underwent auto‐HCT, 22 (46%) experienced relapse following auto‐HCT. Median PR‐OS of relapsed WM patients after auto‐HCT (n = 22) was not reached (NR) (95% confidence interval [CI]: 17.5 months‐NR). Among patients who relapsed <1 year versus ≥1 year from auto‐HCT, the median PR‐OS was 18.4 months (95%CI: 0.8‐NR) months and NR (95%CI: 17.5‐NR), respectively (p = 0.06). Of note, disease status at the time of transplant, CR/VGPR versus partial remission did not appear to impact PR‐OS. The median PR‐OS was significantly longer in patients who received ibrutinib in the post‐transplant setting compared to those who did not (NR vs. 18.4 months, 95%CI: 9.1‐NR, p = 0.02). On univariable analysis, the presence of complex karyotype (RR = 4.87, 95% CI = 1.22–19.53) and a higher number of prior lines of therapy (RR = 1.81, 95% CI = 1.23–2.67) were associated with a significantly higher risk of relapse. This is the only study to date that evaluated outcomes of WM patients who relapsed following auto‐HCT and provides a benchmark for future trials evaluating survival following auto‐HCT relapse.
Tuberculosis care designed with barramarrany (family): Participatory action research that prioritised partnership, healthy housing and nutrition
Authors: Devlin Sue , Ross Wayne , Widders Richard , McAvoy Gregory , Browne Kirsty , Lawrence Kerryn , MacLaren David , Massey Peter D , Judd Jenni A 
Published: November 2021

AbstractIssue addressed.Ongoing tuberculosis (TB) transmission in Aboriginal communities in Australia is unfair and unacceptable. Redressing the inequity in TB affecting Aboriginal peoples is a priority in Australia's Strategic Plan for Tuberculosis Control. Improving TB care needs not to just identify barriers but do something about them. Privileging the voices of Aboriginal people affected by TB is essential to identify effective and enabling strategies.MethodsA barramarrany (Aboriginal family) affected by recurring TB partnered with TB and Environmental Health teams using a participatory action research (PAR) methodology to improve housing health hardware and nutrition alongside biomedical TB prevention and care. A combination of the Ottawa Charter for Health Promotion; the International “End TB” Strategy; and Aboriginal barramarrany leadership, worldviews and traditional values guided actions to reduce TB transmission.ResultsTogether the partners improved housing hardware and access to nutritious food, so the barramarrany could create a setting for good health and wellbeing. These actions supported the barramarrany to regain the physical, social and emotional wellbeing to deal with day‐to‐day challenges and stresses. The barramarrany were able to better sustain supportive relationships; grow, prepare and eat healthy food; and participate in health care activities. The barramarrany could better engage with medical approaches for TB and four barramarrany members completed TB treatment. The PAR action‐project enabled and supported early TB diagnosis, treatment and prevention.ConclusionAmplifying the voices of Aboriginal people and shared ownership of TB diagnosis, treatment and prevention by the barramarrany, was underpinned with principles of self‐determination, capacity building and social justice. This PAR action‐project provides further evidence that improving housing and nutrition can assist in Ending TB while improving wellbeing.So what?Our action‐research project undertaken within a PAR framework demonstrates the implementation of End TB Strategies by utilising the Ottawa Charter's five actions to promote health, by understanding and centralising the social determinants of health.
Wellbeing and nature connectedness for emerging adult undergraduates after a short expedition: A small pilot study
Authors: Down Michael J. A. , Chivers Paola , Kirsch Prudence , Picknoll Duncan 
Published: November 2021

AbstractIssue addressedEmerging adult university undergraduates are a vulnerable population due to various life stressors. Previous studies have reported a range of positive outcomes from outdoor expeditions for this population. This small pilot study aimed to investigate the impacts of an outdoor expedition on wellbeing and connectedness to nature and possible confounding by gender and living environment.MethodsA sample of 54 Health and Physical Education emerging adult undergraduates in the second year of their four‐year degree completed a 3‐day/2‐night immersion expedition. Pre–post differences and a repeated‐measures analysis with confounders examined the expedition's impact on scores from the Warwick‐Edinburgh Mental Well‐being Scale and Connectedness to Nature Scale.ResultsInvolvement in a short expedition resulted in improvements to wellbeing and connectedness to nature. Females reported a stronger connectedness to nature than males, while living environments may affect well‐being.Conclusions/So what?Incorporating regular contact with nature into the structure of undergraduate programs may improve wellbeing and protect this population's mental and emotional health. In a world adjusting to the effects of a global pandemic, opportunities for teaching in non‐traditional classrooms (such as outdoors) may also protect physical health.
Understanding the costs and benefits of politics among adolescents within a sociocultural context
Authors: Oosterhoff Benjamin , Poppler Ashleigh , Hill Ryan M. , Fitzgerald Holly , Shook Natalie J. 
Published: November 2021

AbstractPolitics entails personal costs and benefits, which may differ for youth from different sociocultural backgrounds. Theat‐stakehypothesis proposes that politically marginalized youth experience greater costs (e.g., stress, conflict) and benefits (e.g., empowerment) related to politics, whereas theat‐riskhypothesis proposes that politically marginalized youth experience greater costs but lower benefits. In Study 1, we examined the factor structure of a new political costs and benefits measure among youth (N = 1,056,Mage = 15.91 years) and tested mental health and demographic correlates. Consistent with the at‐stake hypothesis, marginalized youth experienced greater political costs and benefits than non‐marginalized youth, although findings were nuanced. In Study 2, a sub‐sample of participants (N = 191,Mage = 16.05 years) were recontacted from Study 1 to provide written explanations for why specific findings emerged. Adolescents' reasons indicated that laws and policies disproportionately affect youth from marginalized populations, thus producing both negative and positive political experiences