bluuebunny/crossref_metadata_2025_split huggingface dataset:
The diverse effects of brain glucagon‐like peptide 1 receptors on ingestive behaviour
Authors: Williams Diana L. 
Published: May 2021

Glucagon‐like peptide 1 (GLP‐1) is well known as a gut hormone and also acts as a neuropeptide, produced in a discrete population of caudal brainstem neurons that project widely throughout the brain. GLP‐1 receptors are expressed in many brain areas of relevance to energy balance, and stimulation of these receptors at many of these sites potently suppresses food intake. This review surveys the current evidence for effects mediated by GLP‐1 receptors on feeding behaviour at a wide array of brain sites and discusses behavioural and neurophysiological mechanisms for the effects identified thus far. Taken together, it is clear that GLP‐1 receptor activity in the brain can influence feeding by diverse means, including mediation of gastrointestinal satiation and/or satiety signalling, suppression of motivation for food reward, induction of nausea and mediation of restraint stress‐induced hypophagia, but many questions about the organization of this system remain.LINKED ARTICLESThis article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc
Guidelines for clinical evaluation of anti‐cancer drugs
Authors: Minami Hironobu , Kiyota Naomi , Kimbara Shiro , Ando Yuichi , Shimokata Tomoya , Ohtsu Atsushi , Fuse Nozomu , Kuboki Yasutoshi , Shimizu Toshio , Yamamoto Noboru , Nishio Kazuto , Kawakami Yutaka , Nihira Shin‐ichi , Sase Kazuhiro , Nonaka Takahiro , Takahashi Hideaki , Komori Yukiko , Kiyohara Koshin 
Published: May 2021

AbstractClinical studies intended for regulatory approval must demonstrate the clinical benefits of the drug in a target population. Clinical development of a drug proceeds by stepwise clinical studies; after safety and pharmacokinetics are evaluated and the recommended dosage and administration are determined, efficacy and safety are evaluated in an exploratory manner, and finally clinical benefits are compared with conventional standard therapies. Guidelines for the clinical evaluation of anti‐cancer drugs in Japan were established in 1991 and amended in 2006 after molecular‐targeted drugs were introduced. Recent progress in the development of drugs acting on the immune system and cancer genomic medicine targeting rare but important molecular subtypes have altered the strategy for development of anti‐cancer drugs. It is often difficult to conduct a confirmatory randomized controlled study using overall survival as the primary endpoint in rare molecular subtypes, and the primary evaluation of the efficacy of some drugs and subsequent approval is based on the tumor response. As conducting clinical studies for rare subtypes solely within Japan is difficult, drug development needs to be conducted within a global study. However, this requires robust monitoring to detect possible ethnic differences in pharmacokinetics and drug efficacy. Development using the conditional approval system for drugs enforced in 2020 may be considered, when clinical utility is evaluated based on surrogate endpoints. Because of these changes, we have revised the guidelines for the clinical evaluation of anti‐cancer drugs in Japan. To promote global development of anti‐cancer drugs involving Japan, the guidelines have been translated into English.
Predictors of 30‐day readmissions for adrenal insufficiency: A retrospective national database study
Authors: Kichloo Asim , El‐amir Zain , Shaka Hafeez , Wani Farah , Syed Sofia Junaid 
Published: May 2021

AbstractObjectiveThe aim of this study was to describe rates and characteristics of non‐elective 30‐day readmission among patients hospitalized for adrenal insufficiency and to assess predictors of readmission.DesignWe analysed the 2018 National Readmission Database. Adrenal insufficiency hospitalizations were identified using the International Classification of Diseases, Tenth Revisions, Clinical Modification diagnosis codes for principal diagnostic codes of primary adrenal insufficiency, Addisonian crisis, drug‐induced adrenocortical insufficiency, and other and unspecified adrenocortical insufficiency.PatientsDuring the study period, 7738 index hospitalizations were identified as patients with AI who met the inclusion criteria. Of these, 7691 were discharged alive.MeasurementsWe utilized chi‐squared tests to compare baseline characteristics between readmissions and index hospitalizations. Multivariate Cox regression was used to identify independent predictors of readmission.ResultsThe 30‐day all‐cause readmission rate for AI was 17.3%. About 1 in 5 readmissions was for AI. Other reasons for readmission included sepsis (10.8%), unspecified pneumonia (3.1%) and acute renal failure unspecified (1.6%). Readmission was associated with significantly higher odds of inpatient mortality. Independent predictors of 30‐day all‐cause readmissions included index hospitalizations with the Charlson Comorbidity Index (CCI) ≥3 (adjusted hazards ratio (aHR): 2.53, 95% CI: 1.85–3.46,p < .001), protein‐energy malnutrition (aHR: 1.28, 95% CI: 1.02–1.60,p = .035) and obesity (aHR: 1.26, 95% CI: 1.02–1.56,p = .035).ConclusionsThe 30‐day all‐cause readmission rate was 17.3%. AI was the most common reason for readmission among other causes. Readmissions were associated with increased mortality. CCIs of 3 or more, protein‐energy malnutrition and obesity were significant predictors of readmission.
Ethnic similarities in genetic polymorphisms associated with atrial fibrillation: Far East Asian vs European populations
Authors: Hong Myunghee , Ebana Yusuke , Shim Jaemin , Choi Eue‐Keun , Lim Hong Euy , Hwang Inseok , Yu Hee Tae , Kim Tae‐Hoon , Uhm Jae‐Sun , Joung Boyoung , Oh Seil , Lee Moon‐Hyoung , Kim Young‐Hoon , Jee Sun Ha , Pak Hui‐Nam 
Published: May 2021

AbstractBackgroundIn European ancestry, 111 genetic loci were identified as associated with atrial fibrillation (AF). We explored the reproducibility of those single nucleotide polymorphisms (SNPs) in a genome‐wide association study (GWAS) meta‐analysis of Far East Asian populations.MethodsWe performed a meta‐analysis of the Korean AF network and Japanese AF data sets (9118 cases and 33 467 controls) by an inverse‐variance fixed‐effects model. We compared the results with 111 previously reported SNPs proven in Europeans after excluding 36 missing loci and a locus with a minor allelic frequency (MAF) < 0.01 in the European population.ResultsAmong remaining 74 loci, 29 loci were replicated at a P < .05, and 17 of those loci were newly found in the Far East Asian population: 3 loci with a P < 5×10−8 (METTL11B at 1q24, KCNN2 at 5q22 and LRMDA at 10q22), 4 loci at the threshold of the Bonferroni correction of P = 4.5 × 10−4 ~ 5×10−8 (KIF3C at 2p23, REEP3, NRBF2 at 10q21, SIRT1, MYPN at 10q21 and CFL2 at 14q13) and 10 SNPs with a P = .05 ~ 4.5 × 10−4. Among 18 AF loci with a MAF< 0.01 in the Far East Asian populations, 2 loci (GATA4 at 8q23 and SGCG at 13q12) were replicated after a fine mapping. Twenty‐seven AF loci, including a locus, which had a sufficient sample size to get a power of over 80% (with a type 1 error α = 4.5 × 10−4), were not replicated in the Far East Asian populations.ConclusionsWe newly replicated 19 AF‐associated genetic loci in the European descent among the Far East Asian populations. It highlights the extensive sharing of AF genetic risks across Far East Asian populations.
The core/penumbra model: implications for acute stroke treatment and patient selection in 2021
Authors: Baron Jean‐Claude 
Published: May 2021

AbstractDespite major advances in prevention, ischaemic stroke remains one of the leading causes of death and disability worldwide. After centuries of nihilism and decades of failed neuroprotection trials, the discovery, initially in non‐human primates and subsequently in man, that ischaemic brain tissue termed the ischaemic penumbra can be salvaged from infarction up to and perhaps beyond 24 h after stroke onset has underpinned the development of highly efficient reperfusion therapies, namely intravenous thrombolysis and endovascular thrombectomy, which have revolutionized the management of the acute stroke patient. Animal experiments have documented that how long the penumbra can survive depends not only on time elapsed since arterial occlusion (‘time is brain’), but also on how severely perfusion is reduced. Novel imaging techniques allowing the penumbra and the already irreversibly damaged core in the individual subject to be mapped have documented that the time course of core growth at the expense of the penumbra widely differs from patient to patient, and hence that individual physiology should be considered in addition to time since stroke onset for decision‐making. This concept has been implemented to optimize patient selection in pivotal trials of reperfusion therapies beyond 3 h after stroke onset and is now routinely applied in clinical practice, using computed tomography or magnetic resonance imaging. The notion that, in order to be both efficient and harmless, treatment should be tailored to each patient's physiological characteristics represents a radical move towards precision medicine.
The interplay between hunting rate, hunting selectivity, and reproductive strategies shapes population dynamics of a large carnivore
Authors: Van de Walle Joanie , Pelletier Fanie , Zedrosser Andreas , Swenson Jon E. , Jenouvrier Stéphanie , Bischof Richard 
Published: May 2021

AbstractHarvest, through its intensity and regulation, often results in selection on female reproductive traits. Changes in female traits can have demographic consequences, as they are fundamental in shaping population dynamics. It is thus imperative to understand and quantify the demographic consequences of changes in female reproductive traits to better understand and anticipate population trajectories under different harvest intensities and regulations. Here, using a dynamic, frequency‐dependent, population model of the intensively hunted brown bear (Ursus arctos) population in Sweden, we quantify and compare population responses to changes in four reproductive traits susceptible to harvest‐induced selection: litter size, weaning age, age at first reproduction, and annual probability to reproduce. We did so for different hunting quotas and under four possible hunting regulations: (i) no individuals are protected, (ii) mothers but not dependent offspring are protected, (iii) mothers and dependent offspring of the year (cubs) are protected, and (iv) entire family groups are protected (i.e., mothers and dependent offspring of any age). We found that population growth rate declines sharply with increasing hunting quotas. Increases in litter size and the probability to reproduce have the greatest potential to affect population growth rate. Population growth rate increases the most when mothers are protected. Adding protection on offspring (of any age), however, reduces the availability of bears for hunting, which feeds back to increase hunting pressure on the nonprotected categories of individuals, leading to reduced population growth. Finally, we found that changes in reproductive traits can dampen population declines at very high hunting quotas, but only when protecting mothers. Our results illustrate that changes in female reproductive traits may have context‐dependent consequences for demography. Thus, to predict population consequences of harvest‐induced selection in wild populations, it is critical to integrate both hunting intensity and regulation, especially if hunting selectivity targets female reproductive strategies.
Converting lignin into long‐chain fatty acids with the electro‐Fenton reaction
Authors: Zhang Shuai , Zhang Zhaokun , Ge Mingyue , Liu Bowen , Chen Shulin , Zhang Dongyuan , Gao Le 
Published: May 2021

AbstractThe lack of effective lignin valorization technology remains a major barrier to utilize lignocellulose for producing biofuels and biochemicals. In this work, a new technology via the three‐phase three‐dimensional electro‐Fenton reaction was employed for the first time to convert lignin or its derived aromatics. The operating parameters were optimized by central composite design, which was controlled to prompt the synthesis of long‐chain fatty acids from lignin instead of degrading lignin to CO2. Under the optimized condition, the yields of palmitic acid and octadecanoic acid from lignin reached 138.41 and 112.31 mg/g, respectively. Key intermediators were identified during the electrolysis of lignin model compound using gas chromatography–quantitative time of flight mass spectrometry. The mechanism for the production of long‐chain fatty acids from lignin was proposed. Lignin successively underwent degradation, opening ring, and couple reactions and produced free radicals. This study is the first to report the conversion of lignin into the precursor of biodiesel or advanced biofuels through electro‐Fenton electrolysis at room temperature and atmosphere pressure. This study provides an environment‐friendly route for direct conversion of lignin into high‐value added products as a new strategy to valorize this undervalued component in lignocellulosic biomass.
Grand rounds education in neurology, with a focus on headache medicine
Authors: Burish Mark J. , Ahmed Zubair A. , Rosen Noah L. , Halker Singh Rashmi B. 
Published: May 2021

AbstractObjectiveTo quantify the proportion of headache‐related grand rounds in academic neurology programs and to compare this with adult neurology residency director views on the need for an increase in headache‐related grand rounds.BackgroundAlthough headache are among the most prevalent and most burdensome neurologic conditions, headache medicine is often considered underrepresented in neurology departments. Additionally, prior studies have shown that many neurology residency directors feel that training programs do not include an adequate amount of exposure to headache clinics or headache‐related didactics. One important aspect of didactic education in neurology departments is adult neurology grand rounds. Previous publications have evaluated neither the proportion of headache‐related grand rounds in academic neurology departments nor the residency program directors’ views on appropriate amount of headache‐related grand rounds. Our study has attempted to quantify this information to elucidate opportunities to improve practice educational gaps.MethodsIn this cross‐sectional study, we surveyed adult neurology residency directors (from the Accreditation Council for Graduate Medical Education [ACGME] listing of academic adult neurology residency programs) between October 2018 and September 2019. In addition, we used two methods to obtain the proportion of headache‐related grand rounds in neurology: (1) emailing residency directors a questionnaire asking for a list of prior grand rounds topics and (2) an online search for each academic neurology program.ResultsFirst, for our grand rounds analysis, headache medicine consisted of 3.7% of the lectures in 2017–2018 and 6.3% of the lectures in 2018–2019 (average of each institution; 17 institutions and 411 total lectures in 2017–2018, 21 institutions and 463 total lectures in 2018–2019). The most common number of lectures on headache medicine for each grand rounds series was zero (for 7 of 17 grand rounds series in 2017–2018 and 7 of 21 in 2018–2019), followed closely by one lecture (for 6 of 17 grand rounds series in 2017–2018 and 6 of 21 in 2018–2019). Second, for our survey, the response rate was 19.3% (29/150). No residency director thought their institution had too many grand rounds dedicated to headache medicine, and 62.1% (18/29) thought they had an adequate amount of headache grand rounds. Within the survey responders, 75.9% (22/29) of adult neurology residency programs have a board‐certified headache specialist at their institution.ConclusionsAlthough most adult neurology residency directors believe that headache is adequately represented in adult neurology grand rounds, headache medicine makes up 4%–6% of all neurology grand rounds. Compared with other neurology subspecialties and the other core ACGME milestones, headache makes up the fewest grand rounds lectures that were assessed in this study.
Phase 2 randomized placebo‐controlled study of lasmiditan for the acute treatment of migraine in Japanese patients
Authors: Sakai Fumihiko , Takeshima Takao , Homma Gosuke , Tanji Yuka , Katagiri Hideaki , Komori Mika 
Published: May 2021

AbstractObjectiveTo evaluate the efficacy and safety of lasmiditan in Japanese adults with migraine.BackgroundGlobal clinical studies have demonstrated the efficacy and safety of lasmiditan in the acute treatment of migraine.MethodsThis was a multicenter, randomized, double‐blind, placebo‐controlled, phase 2 study in Japan (NCT03962738), which enrolled adults with migraine with or without aura. Participants were randomized 7:3:7:6 to placebo, lasmiditan 50 mg, 100 mg, or 200 mg to be self‐administered orally within 4 h of onset of a single moderate‐to‐severe migraine attack. Participants recorded their response to treatment prior to dosing and for 48 h postdose. The primary endpoint was headache pain freedom at 2 h postdose.ResultsParticipants (N = 846) were randomized and treated (N = 691, safety; N = 682, modified intent‐to‐treat). At 2 h postdose, a significantly higher proportion of participants were headache pain‐free in the lasmiditan 200 mg (40.8%, 73/179; odds ratio 3.46 [95% confidence interval 2.17 to 5.54]; p < 0.001; primary objective) and 100 mg groups (32.4%, 67/207; odds ratio 2.41 [1.51 to 3.83]; p < 0.001) compared with the placebo group (16.6%, 35/211), whereas the lasmiditan 50 mg group had a numerically higher proportion of participants headache pain‐free (23.5%, 20/85; odds ratio 1.55 [0.83 to 2.87]; p = 0.167) compared with placebo. A statistically significant linear dose–response relationship for pain freedom was achieved at 2 h by a Cochran–Armitage trend test (p < 0.001). Lasmiditan treatment was also associated with headache pain relief, most bothersome symptom freedom, and improvement on disability and Patient Global Impression of Change outcomes. The majority of treatment‐emergent adverse events were mild and of short duration, the most common of which were dizziness (39.4%; 188/477), somnolence (19.3%; 92/477), and malaise (10.5%; 50/477) in all lasmiditan groups, with no serious adverse events reported.ConclusionsLasmiditan was well tolerated and effective for the acute treatment of Japanese patients with migraine, consistent with global phase 3 studies.
Response to crizotinib in a patient with MET‐amplified hepatocellular carcinoma
Authors: Chen Qinglian , Xie Chunfeng , Feng Kunliang , Huang Haijun , Xiong Chengming , Lin Tengjiao , Wang Wenjing , Xu Mian , Yang Xianwei , Zhong Chong 
Published: May 2021

AbstractAimsMolecular profiling of hepatocellular carcinoma (HCC) has helped identify actionable genomic alterations that could guide therapeutic decision‐making and clinical trial enrollment. However, in clinical practice, next‐generation sequencing (NGS) is not extensively used in routine clinical care to identify patients with HCC who are likely to benefit from genome‐directed targeted therapies.MethodsHere, we describe the case of a 66‐year‐old man with advanced HCC. After rapid progression on transarterial chemoembolization, the tissue sample obtained from biopsy was subjected to NGS to verify whether precision therapy was an option.ResultsOur analysis revealed high MET amplification. The patient received crizotinib (250 mg, bid) and showed a remarkable response.ConclusionsOur case report suggests NGS could help identify patients with high MET amplification in HCC who were likely to benefit from MET inhibitors; moreover, this requires further investigation in clinical trials.
Processes for evidence summarization for patient decision aids: A Delphi consensus study
Authors: Scalia Peter , Saunders Catherine H , Dannenberg Michelle , MC Giguere Anik , Alper Brian S , Hoffmann Tammy , Perestelo‐Perez Lilisbeth , Durand Marie‐Anne , Elwyn Glyn 
Published: May 2021

AbstractBackgroundPatient decision aids (PDAs) should provide evidence‐based information so patients can make informed decisions. Yet, PDA developers do not have an agreed‐upon process to select, synthesize and present evidence in PDAs.ObjectiveTo reach the consensus on an evidence summarization process for PDAs.DesignA two‐round modified Delphi survey.Setting and participantsA group of international experts in PDA development invited developers, scientific networks, patient groups and listservs to complete Delphi surveys.Data collectionWe emailed participants the study description and a link to the online survey. Participants were asked to rate each potential criterion (omit, possible, desirable, essential) and provide qualitative feedback.AnalysisCriteria in each round were retained if rated by >80% of participants as desirable or essential. If two or more participants suggested rewording, reordering or merging, the steering group considered the suggestion.ResultsFollowing two Delphi survey rounds, the evidence summarization process included defining the decision, reporting the processes and policies of the evidence summarization process, assembling the editorial team and managing (collect, manage, report) their conflicts of interest, conducting a systematic search, selecting and appraising the evidence, presenting the harms and benefits in plain language, and describing the method of seeking external review and the plan for updating the evidence (search, selection and appraisal of new evidence).ConclusionA multidisciplinary stakeholder group reached consensus on an evidence summarization process to guide the creation of high‐quality PDAs.Patient contributionA patient partner was part of the steering group and involved in the development of the Delphi survey.
Adolescent and young adult patients as co‐researchers: A scoping review
Authors: Fløtten Kjersti J. Ø. , Guerreiro Ana Isabel Fernandes , Simonelli Ilaria , Solevåg Anne Lee , Aujoulat Isabelle 
Published: May 2021

AbstractBackgroundAs part of a research project aimed at evaluating a hospital‐based adolescent transition programme, we asked ourselves what is known about the ethical and methodological challenges of research involving adolescent patients as co‐researchers. The aim of our review was to summarize empirical evidence and identify knowledge gaps about the involvement of young patients as co‐researchers.MethodsWe conducted a scoping review through searches in MEDLINE, EMBASE, PsychINFO, AMED.ResultsWe found reports of young patients being actively engaged as co‐researchers in any stage of a research project, although commonly they were not involved in every stage. Including young patients as co‐researchers is resource demanding and time‐consuming. Involving young patients as co‐researchers contributes to the fulfilment of their right to participation and may improve the relevance of research. Benefits for the young co‐researcher include empowerment, skills building and raised self‐esteem. Few authors go into detail about ethical considerations when involving young co‐researchers. None of the included articles discuss legal considerations.Discussion and conclusionNo lists of recommendations are given, but recommendations can be deduced from the articles. There is need for time, funding and flexibility when including young patients as co‐researchers. Knowledge gaps concern legal and ethical dilemmas of including a vulnerable group as co‐researchers. More reflection is needed about what meaningful participation is and what it entails in this context.Patient or Public ContributionThis review is part of a research project where the hospital youth council has been involved in discussions of focus area and methods.