bluuebunny/crossref_metadata_2025 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 ARTICLES

This 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

Clinical 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

Objective

The 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.

Design

We 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.

Patients

During the study period, 7738 index hospitalizations were identified as patients with AI who met the inclusion criteria. Of these, 7691 were discharged alive.

Measurements

We utilized chi‐squared tests to compare baseline characteristics between readmissions and index hospitalizations. Multivariate Cox regression was used to identify independent predictors of readmission.

Results

The 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).

Conclusions

The 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.
Quantitative magnetic resonance imaging of spinal cord microstructure in adults with cerebral palsy
Authors: Cohen‐Adad Julien
Published: May 2021

This commentary is on the original article by Trevarrow et al. on pages 998‐1003 of this issue
Have you Read This? An Empirical Comparison of the British REF Peer Review and the Italian VQR Bibliometric Algorithm
Authors: Checchi Daniele , Ciolfi Alberto , De Fraja Gianni , Mazzotta Irene , Verzillo Stefano
Published: May 2021

This paper determines the assessment of publications submitted to the UK research evaluation carried out in 2014, the REF, which would have resulted if they had been assessed with the bibliometric algorithm used by the Italian evaluation agency, ANVUR, for its evaluation of the research of Italian universities. We find extremely high correlations between the two assessment approaches.
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

Background

In 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.

Methods

We 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.

Results

Among 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.

Conclusions

We 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

Despite 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

Harvest, 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

The 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

Objective

To 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.

Background

Although 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.

Methods

In 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.

Results

First, 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.

Conclusions

Although 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

Objective

To evaluate the efficacy and safety of lasmiditan in Japanese adults with migraine.

Background

Global clinical studies have demonstrated the efficacy and safety of lasmiditan in the acute treatment of migraine.

Methods

This 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.

Results

Participants (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.

Conclusions

Lasmiditan 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

Aims

Molecular 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.

Methods

Here, 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.

Results

Our analysis revealed high MET amplification. The patient received crizotinib (250 mg, bid) and showed a remarkable response.

Conclusions

Our 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

Background

Patient 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.

Objective

To reach the consensus on an evidence summarization process for PDAs.

Design

A two‐round modified Delphi survey.

Setting and participants

A group of international experts in PDA development invited developers, scientific networks, patient groups and listservs to complete Delphi surveys.

Data collection

We 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.

Analysis

Criteria 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.

Results

Following 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).

Conclusion

A multidisciplinary stakeholder group reached consensus on an evidence summarization process to guide the creation of high‐quality PDAs.

Patient contribution

A 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

Background

As 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.

Methods

We conducted a scoping review through searches in MEDLINE, EMBASE, PsychINFO, AMED.

Results

We 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 conclusion

No 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 Contribution

This review is part of a research project where the hospital youth council has been involved in discussions of focus area and methods.
Do natural ingredients in a dentifrice contribute to prevention of plaque and gingivitis?
Authors: Valkenburg Cees , Rosema N. A. Martijn , Hennequin‐Hoenderdos Nienke L. , Versteeg Paula A. , Slot Dagmar Else , Van der Weijden G. A. (Fridus)
Published: May 2021

Objective

To test the effectiveness of a dentifrice containing the turmeric and licorice extract compared to a control for preventing plaque and gingivitis over a four‐month period.

Material and methods

Ninety (non‐dental) participants with moderate gingival inflammation (≥ 40%) were selected. The triple blind study consisted of two phases, namely at first a 3‐week pre‐experimental phase of using an oxygenating and chlorhexidine (CHX) mouthrinse. Secondly, a 4‐month experimental period in which participants were randomly assigned to a test or control group. All were instructed to brush their teeth twice daily for 2 minutes with their assigned dentifrice. Gingival bleeding (BI), plaque (PI) and gingivitis (GI) were assessed.

Results

Eighty participants completed the protocol. At the first assessment in the pre‐experimental phase, the mean scores of all indices showed no differences for the two groups. At the second session, the values of all three parameters had decreased significantly (p < 0.001). At the last session, the BI values were 0.52(0.25) for the test group and 0.56(0.25) for the control, the mean GI was 0.27(0.17) for the test group and 0.31(0.16) for the control, and for PI the scores were 1.89(0.46) for the test group and 1.98(0.43) for the control group. Statistical comparison of the scores for the two groups at each stage of the study showed no significant difference for any of the parameters.

Conclusion

Within the limits of the current study design, dentifrice formulation and concentration of turmeric/licorice extracts, the results show that the adjuvant effect of the natural ingredients in the test dentifrice was not evident on clinical parameters of gingivitis and plaque.
Clinical characteristics and long‐term outcomes of 97 Korean patients with mycosis fungoides
Authors: Moon Ik Jun , Lee Keon Hee , Choi Jae Won , Lee Woo Jin , Won Chong Hyun , Chang Sungeun , Choi Jee Ho , Lee Mi Woo
Published: May 2021

Background

Mycosis fungoides (MF) shows racial and regional differences in terms of clinical features. The availability of therapeutic options as well as drugs differs from one country to another. There are only limited data on the clinical characteristics and treatment experience of MF from South Korea.

Methods

Medical records of 97 patients with MF were retrospectively analyzed to investigate clinical features, survivals, and prognostic factors. Assessment of prognostic variables was done using univariate Cox proportional hazard models.

Results

Median age at time of diagnosis was 45 years. The median time from onset of skin lesion to diagnosis of MF was 36 months with a median follow‐up period of 96 months. A number of clinical variants of MF were observed. Treatment mainly consisted of narrow‐band UVB, systemic retinoids, methotrexate, chemotherapy, and regional radiotherapy. Complete remission was observed in 78% of patients with records on their clinical course. About 12% experienced disease progression. No clinical prognostic factor apart from TNM staging was identified.

Conclusion

Despite delay in diagnosis, most cases of MF in Korea were diagnosed in early stages. Prognosis of our patients was more favorable than those of other geographic regions as reported in previous studies. Good response to treatment, consisting mainly of phototherapy and radiation therapy, and relatively indolent clinical behavior of disease were observed in this homogeneous cohort of Korean patients with MF.
Retrospective analysis of 578 inpatient dermatology consultations in hematology and hematopoietic stem cell transplant patients
Authors: Hines Alexander , Hazim Antonious , Wetter David A. , Bridges Alina G. , Camilleri Michael J. , McEvoy Marian T. , el‐Azhary Rokea A. , Davis Mark D. P. , Sartori‐Valinotti Julio C.
Published: May 2021

Background

Hospitalized patients with hematologic malignancies are medically complex and commonly affected by dermatologic conditions.

Methods

Retrospective chart review from January 1, 2014, to December 31, 2018, at Rochester Methodist Hospital (Rochester, Minnesota, USA). Patients hospitalized on hematology and BMT services receiving dermatology consultation were included.

Results

In all, 578 consultations (63% male, median age 61 years) were reviewed. Drug reactions (22%), infection (17%), and malignant neoplasm (10%) accounted for nearly half of diagnoses. Exanthematous drug reaction (10%), graft‐versus‐host disease (7%), and lymphoma or leukemia cutis (6%) were the commonest individual diagnoses. There were significantly more drug reactions in severe neutropenia (33.2% vs. 15.0%), neutrophilic dermatoses in myeloid neoplasm (5.2% vs. 0.3%), and viral infection in lymphoid neoplasm (8.3% vs. 1.2%). Consultation frequently altered treatment (68%), diagnostic workup (63%), and the primary service’s initial diagnostic impression (53%). Biopsies were performed in 52% of consultations and helped secure a diagnosis 73% of the time. A total of 16.4% of consultations did not receive a definitive final diagnosis, and 18.5% were resolved in one visit.

Conclusion

This is the largest study to date of hospital dermatology consultation in hematology patients. Biopsies are utilized frequently and are diagnostically useful. The complexity of this patient population is evidenced by the fact that a final diagnosis remains elusive in a number of cases despite the multiple visits required for the vast majority of consultations. Nevertheless, dermatology consultation alters diagnosis and treatment in the majority of patients, highlighting the critical role dermatologists have in the care of these patients.
The stability of ‘add‐on’ coagulation assays in refrigerated citrated plasma stored on a packed cellular fraction
Authors: Quirke William , Toomey Siobhan , Sheikhi Ali
Published: May 2021

Introduction

Haematology laboratories are increasingly faced with requests for add‐on coagulation testing. This study explores extending the specimen storage proposals by examining coagulation parameters on refrigerated citrated plasma retained on a cellular fraction over a 24‐hour period.

Methods

Sodium citrate (Sarstedt® S‐Monovette 3.2%) specimens from 206 patients in University Hospital Limerick, Ireland were refrigerated immediately post‐analysis and re‐analysed in the centrifuged primary container at 4, 8 and 24‐hour intervals using the Diagnostica Stago coagulometer and reagent combination. Coagulation assays examined for statistically and clinically significant differences included PT, APTT, D‐Dimer, fibrinogen and Protein C.

Results

PT, APTT and Protein C values displayed statistical significance from 4 hours. Fibrinogen differences were statistically significant from 8 hours. D‐Dimer differences were not statistically significant at any interval over the 24‐hour period.

The refrigerated storage limit for PT and APTT results was determined to be 4 hours. D‐Dimer was the only test parameter to report a mean percentage variance >10%. However, result changes at the threshold region of 0.5 µg/mL FEU were found to be within assay precision limits and desirable bias up to 8 hours. Maximum mean differences for Protein C (−1.3%) and fibrinogen (2.3%) were within assay precision limits and desirable biases up to 24 hours.

Conclusion

PT and APTT results are stable in refrigerated citrated plasma maintained on a cellular fraction up to 4 hours post‐phlebotomy. D‐Dimers results are reliable up to 8 hours, while fibrinogen and Protein C results are stable for at least 24 hours.
Patients’ experiences of delirium: A systematic review and meta‐summary of qualitative research
Authors: Kuusisto‐Gussmann Eero , Höckelmann Carolin , von der Lühe Verena , Schmädig Roman , Baltes Marion , Stephan Astrid
Published: May 2021

Aims

The purpose of this systematic review and meta‐summary was the aggregation of the empirical qualitative literature on patients’ experiences of delirium in order to support the development and implementation of patient‐oriented delirium management and to guide future research.

Design

We conducted a systematic literature review of qualitative research published between January 1980 and June 2019.

Data sources

In June 2019, we searched in Medline, CINAHL, SSCI and PsycInfo to identify relevant reports. In addition, we conducted searches in three dissertation databases (BASE, DART and ProQuest) and Google Scholar.

Review methods

We used methods developed by Sandelowski and Barroso to construct a meta‐summary of the findings by extracting them from the reports, abstracting them into meta‐ findings and calculating their manifest interstudy frequency effect sizes.

Results

Out of the 742 identified records, 24 reports based on delirium experience accounts of 483 patients met our criteria and were included. One thousand ninety‐seven findings were extracted from these reports and abstracted into 92 meta‐findings. These were grouped to the five emerging themes ‘perception’, ‘emotions’, ‘interaction with others’, ‘dealing with delirium’ and ‘influence on further life’.

Conclusion

Delirium is commonly perceived as an overall distressing condition, which can accompany and influence patients even after hospital discharge.

Impact

This systematic review and meta‐summary is the most comprehensive aggregation of qualitative research of the patient delirium experience to date. It allows us to better understand, extract meaning from, and weigh the qualitative findings in their context by calculating their manifest frequency effect sizes. This can be used to support the development and implementation of delirium management concepts.
PP1, PKA and DARPP‐32 in breast cancer: A retrospective assessment of protein and mRNA expression
Authors: Saidy Behnaz , Kotecha Shreeya , Butler Anna , Rakha Emad A. , Ellis Ian O. , Green Andrew R. , Martin Stewart G. , Storr Sarah J.
Published: May 2021

Cyclic AMP–dependent protein kinase A (PKA) and protein phosphatase 1 (PP1) are proteins involved in numerous essential signalling pathways that modulate physiological and pathological functions. Both PP1 and PKA can be inhibited by dopamine‐ and cAMP‐regulated phosphoprotein 32 kD (DARPP‐32). Using immunohistochemistry, PKA and PP1 expression was determined in a large primary breast tumour cohort to evaluate associations between clinical outcome and clinicopathological criteria (n > 1100). In addition, mRNA expression of PKA and PP1 subunits was assessed in the METABRIC data set (n = 1980). Low protein expression of PKA was significantly associated with adverse survival of breast cancer patients; interestingly, this relationship was stronger in ER‐positive breast cancer patients. PP1 protein expression was not associated with patient survival. PKA and PP1 subunit mRNA was also assessed; PPP1CA, PRKACG and PRKAR1B were associated with breast cancer–specific survival. In patients with high expression of DARPP‐32, low expression of PP1 was associated with adverse survival when compared to high expression in the same group. PKA expression and PP1 expression are of significant interest in cancer as they are involved in a wide array of cellular processes, and these data indicate PKA and PP1 may play an important role in patient outcome.
MicroRNA‐181a/b‐1‐encapsulated PEG/PLGA nanofibrous scaffold promotes osteogenesis of human mesenchymal stem cells
Authors: Qi Peiyi , Niu Yali , Wang Bin
Published: May 2021

Bioactive nanofibres play a useful role in increasing the efficiency of tissue engineering scaffolds. MicroRNAs (miRs) alone, and in combination with tissue engineering scaffolds, can be effective in treating bone fractures and osteoporosis by regulating many post‐transcriptional cellular pathways. Herein, miR‐181a/b‐1 was incorporated in the electrospun poly (lactic‐co‐glycolic acid) (PLGA) nanofibres (PLGA‐miR). After characterization scaffolds, the osteoinductive capacity of the nanofibres was investigated when adipose‐derived mesenchymal stem cells (AT‐MSCs) were cultured on the PLGA and PLGA‐miR nanofibres. miR incorporating in the nanofibres has not any significant effect on the size and morphology of the nanofibres, but its biocompatibility was increased significantly compared to the empty nanofibres. Alkaline phosphatase (ALP) activity and calcium measures were evaluated as two important osteogenic markers, and the results revealed that the highest measures were observed in the AT‐MSCs cultured on PLGA‐miR nanofibres. Detected ALP activity and calcium measures in miR‐transduced AT‐MSCs cultured on TCPS were also significantly higher than AT‐MSCs cultured on PLGA and TCPS groups. The highest expression levels of bone‐related genes were observed in the AT‐MSCs cultured on PLGA‐miR nanofibres. This improvement in the osteogenic differentiation potential of the AT‐MSCs was also confirmed by evaluating osteopontin protein in the cells cultured on PLGA‐miR. It can be concluded that miR‐181a/b‐1 has a significant impact on the AT‐MSC osteogenic differentiation, and this impact synergistically increased when incorporated in the PLGA nanofibres.
Diabetes coexistent with Charcot–Marie–Tooth disease presenting as a recurrent foot ulcer misdiagnosed as diabetic foot: A case report
Authors: Yan Zhe , Chen Dawei , Yao Li , Wang Chun , Ran Xing‐Wu
Published: May 2021

Both diabetes mellitus and Charcot–Marie–Tooth disease (CMT) can lead to severe peripheral neuropathy. The differential diagnosis of peripheral neuropathy is difficult due to the similar clinical features. There are still some clues, such as unusual muscle atrophy, unmatched severity of peripheral neurogenic damage with nephropathy or retinopathy, which could alert clinicians to make differential diagnosis. Although diabetes mellitus is rarely concurrent with CMT, it will exacerbate clinical disorders in patients with CMT. To date, there is no specific medicine for CMT treatment. Offloading devices and desirable comprehensive management of diabetes mellitus might be beneficial to avoid plantar ulcer recurrence and anti‐progression of CMT.
High variability in anatomic patterns of cutaneous photodamage: a population‐based study
Authors: Betz‐Stablein B. , Llewellyn S. , Bearzi P. , Grochulska K. , Rutjes C. , Aitken J.F. , Janda M. , O’Rouke P. , Soyer H.P. , Green A.C.
Published: May 2021

Background

Skin cancer is strongly associated with photodamaged skin, but body sites are often referred to as ‘exposed’ or ‘unexposed’ to sun without recognizing extent of site‐specific variation.

Objectives

To assess whole‐body patterns of photodamage in an Australian population.

Methods

A random sample of adult residents of Queensland underwent imaging across 10 body sites. Photodamage was graded from images using an ordinal photonumeric scale. We used cluster analysis to identify whole‐body photodamage patterns and prevalence proportion ratios (PPRs) to assess associated factors.

Results

Of 190 adults (median age 52; 58% males), 58% showed severe or moderate‐to‐severe photodamage on most body sites. A higher proportion of woman had severe photodamage on the arms (upper: P = 0.002, lower: P = 0.034). A higher proportion of men had moderate or severe photodamage on the lower back (P = 0.004). We identified four photodamage patterns: ‘severe general’ (n = 24, 13%), ‘moderate‐severe general’ (n = 86, 45%), ‘moderate‐severe v‐neck’ (n = 40, 21%) and ‘mild‐moderate upper body’ (n = 12, 6%). All participants with ‘severe‐general’ photodamage were >50 years and more likely to have past skin cancer (PPR: 2.54, 95% CI: 1.44–4.49) than those with 'moderate‐severe v‐neck' photodamage. Those with ‘moderate‐severe general’ photodamage showed similar associations and were more likely female (PPR: 1.33, 95% CI: 1.04–1.69). Past or current smoking was associated with having higher levels of photodamage, with no smokers in those with ‘mild‐moderate upper body’ photodamage.

Conclusions

Moderate‐to‐severe photodamage across much of the body is common in Queensland adults and associated with age, sex, past skin cancer and smoking. Assuming a universal pattern of site‐specific sun exposure could lead to spurious correlations, while accurate and objective assessment of site‐specific photodamage can add to understanding of the development of sun‐associated skin cancers, in particular site‐specific skin carcinogenesis. Additionally, degree of site‐specific photodamage has the potential to assist skin cancer screening.
Clinical and trichoscopic features in various forms of scalp psoriasis
Authors: Bruni F. , Alessandrini A. , Starace M. , Orlando G. , Piraccini B.M.
Published: May 2021

Background

Scalp psoriasis is often undiagnosed or inadequately treated. The patient himself underestimates the seriousness of this hair disease and consults too late to a dermatologist.

Objectives

The aim of our study was to create a correlation between the clinical patterns and trichoscopy of scalp psoriasis such in a way to help the clinician to make the diagnosis and select the appropriate therapy.

Material and methods

We gathered all patients affected of scalp psoriasis afferent to Outpatient's hair consultation of the Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, from January 2012 to December 2018. All patients were evaluated through clinical, trichoscopic examination and a skin biopsy only in doubtful cases. We quantified the severity of the disease with several objective and subjective parameters every 4 months, up to 1 year. We recorded therapies, outcome data and quality of life.

Results

We collected 156 patients affected by scalp psoriasis, identifying seven clinical patterns with specific trichoscopical correlation. In the order of frequency, the clinical patterns were as follows: plaque psoriasis (with a prevalence of erythema, silver‐white scales and twisted red loops vessels and red dots); thin scales (with silvery‐white scales, simple red lines and signet red ring vessels); sebopsoriasis (with greasy scales, erythema with red dots, globules and twisted and bushy red loops at high magnification); psoriatic cap (with silver‐white scales, erythema and polymorphic vascular pattern); pityriasis amiantacea (with yellowish adherent scales, erythema and simple red loops capillaries); cicatricial psoriatic alopecia (with erythema associated with yellowish, silver‐white scales with twisted and bushy red loops capillaries) and pustular psoriasis (with ‘flower shape’ pustular lesions, erythema simple red loops capillaries).

Conclusions

The description of different clinical patterns of scalp psoriasis and its trichoscopical correlations may help the clinician to make the diagnosis also in atypical presentations and to prescribe an adequate therapeutic regimen.
Biology and ecology of the Northern walkingstick, Diapheromera femorata (Say) (Phasmatodea: Diapheromerinae): A review
Authors: Liu Houping
Published: May 2021

The northern walkingstick, Diapheromera femorata (Say), is the only stick insect of economic importance native to the United States. Young nymphs feed on various understory shrubs and trees whereas older nymphs and adults prefer oaks and cherries. Occasionally, field populations reach outbreak levels and cause complete tree defoliation. Widespread damage rarely occurs except those reported from Michigan (1930–1960), Wisconsin (1950–1960) and Arkansas and Oklahoma (1960–1975) where thousands to tens of thousands of hectares of trees were affected. The most recent infestations were detected in Arkansas, Maryland, and Pennsylvania with severe damage observed in localized areas. The morphology, life stages, host species, damage, biology, life history, natural enemies and management of this insect were reviewed. Host preference and insect predation were confirmed in Pennsylvania. Other notable stick insects in the United States and economically important species around the world are discussed to raise awareness about the ecological impacts of this understudied group of mostly nocturnal herbivores.
Surface treatments on CAD/CAM glass–ceramics: Influence on roughness, topography, and bond strength
Authors: Azevedo Veber Luiz Bomfim , de Castro Eduardo Fernandes , Bonvent Jean‐Jacques , de Andrade Oswaldo Scopin , Nascimento Fábio Dupart , Giannini Marcelo , Cavalli Vanessa
Published: May 2021

Objective

To evaluate the influence of surface treatment on roughness (SA), topography, and shear bond strength (SBS) of computer‐aided designer and manufacture (CAD/CAM) zirconia‐reinforced lithium silicate (ZLS) and feldspathic (FEL) glass–ceramics.

Materials and methods

FEL and ZLS specimens were submitted to 5% or 10% hydrofluoric acid (HF) or self‐etching ceramic primer (MEP) and different application times (20, 40, and 60 s), or to sandblasting (Control, 20 s). Resin cement cylinders were bonded to the specimens and tested in shear (n = 10) after 24 h and 16‐months of water storage. SA and topography were evaluated by atomic force (AFM, n = 10) and scanning electron microscopy. Data were analyzed by ANOVA and Bonferroni test (α = 0.05).

Results

Sandblasting promoted the highest SA for ZLS, but 10% HF (40, 60 s) promoted higher SBS at 16 months. 10% HF produced the highest SA for FEL, but sandblasting and 5% HF (20 s) maintained SBS after 16 months, without differences from 10% HF (20 s) (p > 0.05). Overall, MEP produced lower SA and SBS among groups (p < 0.05). HF displayed greater morphological changes on FEL.

Conclusion

10% HF (40 s) provided better results for ZLS, while 5% or 10% HF (20 s) was suitable for FEL.

Clinical significance

Surface treatments influenced SA, topography, and SBS of materials. HF etching is the surface treatment of choice for both CAD/CAM glass–ceramics.
Molecular systematics of the Awaous banana complex (River gobies; Teleostei: Oxudercidae)
Authors: McMahan Caleb D. , Elías Diego J. , Li Yue , Domínguez‐Domínguez Omár , Rodriguez‐Machado Sheila , Morales‐Cabrera Alejandra , Velásquez‐Ramírez Diana , Piller Kyle R. , Chakrabarty Prosanta , Matamoros Wilfredo A.
Published: May 2021

Diadromous fishes can exhibit interesting evolutionary and population‐level patterns given their use of freshwater and marine environments as part of their life histories. The River goby genus Awaous are prominent members of riverine ichthyofaunas and occur throughout Atlantic and Pacific slopes of the Americas from the southern United States to Ecuador and Brazil. Here we study the widespread and polymorphic Awaous banana complex to assess phylogeographic patterns and test previous hypotheses that all populations of this species in the Americas belong to the same species. Analysis of sequence data based on the mitochondrial cytochrome oxidase I gene shows multiple clades within the Atlantic and Pacific basins, which correspond to previously described species. Additionally, haplotype analysis demonstrates unique and unconnected networks between these species. Within these clades we document biogeographic patterns that are congruent with results of other co‐occurring diadromous species, as well as a novel biogeographic pattern for the region. Our results support the recognition of distinct species of Awaous in the Atlantic (A. banana and A. tajasica) and Pacific (A. transandeanus) basins. These results are concordant with previously established morphological characters permitting the separation of these species.