bluuebunny/crossref_metadata_2025 huggingface dataset:
The molecular structure, morphology, and physicochemical property and digestibility of potato starch after repeated and continuous heat–moisture treatment
Authors: Zhang Bo , Saleh Ahmed S. M. , Su Chunyan , Gong Bing , Zhao Kun , Zhang Guoquan , Li Wenhao , Yan Wenjie
Published: November 2020

The multiscale structural, physicochemical, and digestible properties of potato starch before and after heat–moisture treatment were investigated, and further compared between repeated heat–moisture treatment (RHMT) and continuous heat–moisture treatment (CHMT). After heat–moisture treatment, there appeared partial disruption and pits on the starch granules, and the birefringence edges of HMT starch particles became blurred. Besides, the molecular weight of samples conspicuously decreased after two kinds of treatments. The crystal type of HMT starches transformed from B‐type to C‐type according to X‐ray analysis. A decrease in the solubility and swelling power in high temperatures were identified. The pasting temperature, the gelatinization transition temperature (To, Tp, Tc), and the slowly digestible starch (SDS) content of HMT starches were significantly higher than native potato starch, while the peak viscosity, the trough viscosity, the final viscosity, the breakdown, and the gelatinization enthalpy (ΔH) of RHMT and CHMT potato starches decreased compared to the native. RHMT potato starches displayed significantly higher relative crystallinity degree and gelatinization transition temperatures. The cooling process of RHMT in which the linkage between the recombinant amylose/amylopectin was enhanced compared with CHMT, which contributed to that RHMT potato starches exhibited greater advantages in practical applications.

Practical Application

The described RHMT and CHMT starches provide new ideas for the study of modified starch. Furthermore, this study revealed the mechanism of heat–moisture processing provided some instructions to the application of RHMT potato starch.
Detection of amoxicillin residues in egg extract with a molecularly imprinted polymer on gold microchip using surface plasmon resonance and quartz crystal microbalance methods
Authors: Bereli Nilay , Çimen Duygu , Hüseynli Sabina , Denizli Adil
Published: November 2020

In this study, surface plasmon resonance (SPR) and quartz crystal microbalance (QCM) sensors were prepared for the detection of amoxicillin from the commercial and local chicken eggs by using molecular imprinting technique. Amoxicillin imprinted poly(hydroxyethyl methacrylate‐methacrylic acid) polymeric film was synthesized onto the surface of the SPR and QCM chips by ultra violet polymerization to determine lower concentrations of amoxicillin. Ellipsometry, contact angle analysis, and atomic force microscopy measurements were used for the surface morphology of the polymeric film layer. The ellipsometric thickness of AMOX imprinted and nonimprinted SPR and QCM chip surfaces were measured as 35 ± 0.9 nm, 32.89 ± 1.9 nm, 30 ± 0.6 nm, and 28 ± 0.22 nm, respectively. Contact angles of bare gold surfaces, AMOX imprinted SPR and QCM chip surfaces were measured to be as 82.3° ± 0.15, 79.2° ± 0.14, 75.01° ± 1.07, and 69.11° ± 0.89, respectively. The range of linearity was measured as 0.1 to 10 ng/mL for amoxicillin imprinted SPR and QCM sensors. The maximum residue limit of AMOX in eggs is at 10 µg/kg in accordance with the “Positive List System for Agricultural Chemical Residues in Foods.” The response time for the test, including adsorption, desorption, and regeneration, was approximately 45 min. The limit of detections for SPR and QCM sensors were found to be 0.0005 and 0.0023 ng/mL, respectively. The reusabilities of amoxicillin imprinted SPR and QCM sensors were observed by the equilibration‐binding‐regeneration. Validation studies of the AMOX imprinted SPR and QCM sensors were performed by liquid chromatography‐tandem mass spectrometry.
Application of colorimetric indicators to predict the fermentation stage of kimchi
Authors: Moon Eun Woo , Yang Ji‐Su , Yoon So‐Ra , Ha Ji‐Hyoung
Published: November 2020

Cabbage kimchi, a popular side dish in Korean cuisine, produces several fermentation by‐products (FBPs). Kimchi is praised for its flavor, taste, and texture when suitably fermented at 0.7% to 0.9% total acidity, or a pH of approximately 4.1. Beyond this acidity level, the quality of the product decreases, negatively impacting consumers’ purchase preferences. Therefore, the current study seeks to develop an optimally fermented (OptF) kimchi indicator that can be inserted into product packaging to evaluate its utility at 4 and 10 °C. A gradual change in the total color difference (ΔE) was observed during the kimchi fermentation stage, and the highest ΔE values were observed at 4 (34.87) and 10 °C (37.99), after 9 weeks. Moreover, the color‐change response function value F(Xc) was more linear at 4 and 10 °C (0.981 and 0.984, respectively) compared to the ΔE over time, during kimchi fermentation. Coefficients of determination for F(Xc)‐carbon dioxide (0.983), F(Xc)‐pH (0.979), and F(Xc)‐titratable acidity (0.974) were sufficient to meet the optimal polynomial regression model, while that for F(Xc)‐lactic acid bacteria (0.881) was not. Standardized residuals of predicted data indicated that 95% of the residuals were in the range of −2.0 to 2.0. The regression analysis further suggested that the OptF kimchi indicator could be used as a kimchi fermentation indicator.

Practical Application

Cabbage kimchi, a traditional Korean fermented food, produces several fermentation by‐products. After the optimal fermenting stage, the sensory evaluation of cabbage kimchi and consumers’ purchase preference decreases. This study describes an optimally fermented kimchi indicator and its utility at 4 and 10 °C. Our results demonstrate the ability of this indicator to predict the freshness and fermentation stage of kimchi without the need for sensory evaluation. This method could help increase the purchase preference for commercial kimchi.
Basic flavor types and component characteristics of Chinese traditional liquors: A review
Authors: Wei Yang , Zou Wei , Shen Cai‐Hong , Yang Jian‐Gang
Published: November 2020

Chinese traditional liquor, a major type of global distilled spirits, offers a unique flavor system acquired across thousands of years of development. Owing to the various raw brewing materials, types of koji, fermentation vessels, and processes used during liquor production, significant differences can occur in the content of flavor chemical components, such as esters, alcohols, aromatics, ketones, nitrogen compounds, acids, and aldehydes in the resulting liquor. Therefore, the liquor can be characterized on the basis of four basic flavors: sauce‐, strong‐, light‐, and rice‐aroma, and eight derivative flavors: feng‐, sesame‐, chi‐, te‐, mixed‐, laobaigan‐, herbal‐, and fuyu‐aroma. In this review, we describe the production and development process of Chinese traditional liquor in detail; summarize the flavor types, flavor chemical composition characteristics, and research progress related to this liquor; and discuss the influence of trace chemical components on liquor flavor, with the aim of laying a theoretical foundation for stabilizing the quality and increasing the yield of traditional liquor.
Dabrafenib and trametinib therapy in an elderly patient with non‐small cell lung cancer harboring the BRAF V600E mutation
Authors: Dotsu Yosuke , Fukuda Minoru , Honda Noritaka , Gyotoku Hiroshi , Kohno Yoshihisa , Suyama Takayuki , Umeyama Yasuhiro , Taniguchi Hirokazu , Takemoto Shinnosuke , Yamaguchi Hiroyuki , Miyazaki Taiga , Sakamoto Noriho , Obase Yasushi , Ikeda Hiroaki , Ashizawa Kazuto , Mukae Hiroshi
Published: November 2020

Dabrafenib and trametinib therapy for BRAF V600E‐mutant non‐small cell lung cancer (NSCLC) has demonstrated strong antitumor effects in clinical trials and has been approved for use in clinical practice. However, the efficacy and safety of this combination therapy in elderly patients remain unclear. An 86‐year‐old male patient, who had been diagnosed with lung adenocarcinoma with the BRAF V600E mutation, received dabrafenib and trametinib combination chemotherapy. The tumor shrunk rapidly; however, therapy was discontinued after 40 days because adverse events (hypoalbuminemia, peripheral edema, and pneumonia) developed. Although this targeted combination therapy seemed to cause relatively severe adverse events compared with single‐agent targeted therapy in this “oldest old” elderly patient, the marked tumor shrinkage prolonged the patient's life and helped him to maintain a good general condition. Active targeted therapy may therefore be considered with appropriate drug dose reduction instead of conservative treatment, even if a patient is extremely old.
Linguistic Formality and Audience Engagement: Investors' Reactions to Characteristics of Social Media Disclosures*
Authors: Rennekamp Kristina M. , Witz Patrick D.
Published: November 2020

As firms increasingly use social media to provide disclosures to investors, it is important to understand whether the characteristics that are associated with these disclosures lead to different reactions from investors than disclosures provided via more traditional channels. In this paper, we use an experiment to examine whether linguistic formality in positive news disclosures, and engagement of social media users surrounding the disclosures (e.g., “likes” and “retweets”), affect investors' judgments about a firm and its management. Results suggest that, as predicted, investors are more sensitive to signals of audience engagement when disclosures use informal rather than formal language. Specifically, when associated with signals of high audience engagement, the use of informal language leads to greater willingness to invest than the use of formal language in a disclosure. However, also as predicted, the use of informal language hurts willingness to invest when associated with signals of low audience engagement. In two follow‐up experiments, we investigate how news valence and linguistic formality are expected to affect the level of audience engagement in the first place, and we investigate whether managers strategically vary their use of linguistic formality based on characteristics of the setting. Overall, our results provide evidence on how firms might use social media disclosures to better connect with investors. This study contributes to the growing literature on linguistic attributes of disclosures, and the emerging literature investigating the consequences of issuing financial disclosures through social media.
lefko3: Analysing individual history through size‐classified matrix population models
Authors: Shefferson Richard P. , Kurokawa Shun , Ehrlén Johan
Published: November 2020

The histories of individuals impact the dynamics of their populations. Matrix projection models (MPMs) are used to analyse population dynamics, but are not structured to incorporate these influences. Historical MPMs (hMPM) were developed to incorporate these impacts, but their complexity has left them little used. We developed r package lefko3 to provide simple, quick methods to estimate and analyse hMPMs, as well as ahistorical MPMs.

Package lefko3 handles the entire workflow from dataset organization to the construction and analysis of hMPMs. Dataset management functions reorganize most demographic data formats, and matrix creation functions estimate both raw and function‐based matrices. Vital rates may be modelled as mixed or generalized linear models, with model selection protocols involving current best practices.

The core kernels are binaries allowing even matrices with over 10,000 rows and columns to be estimated quickly without parallelization. We also include functions to conduct basic deterministic projection analyses.

Package lefko3, available on CRAN, dramatically reduces the difficulties in testing the impacts of individual history on population dynamics. We provide three vignettes to showcase how hMPMs can be developed and analysed.
Alcohol Use Disorder is Associated with Upregulation of MicroRNA‐34a and MicroRNA‐34c in Hippocampal Postmortem Tissue
Authors: Santos‐Bezerra Daniele P. , Cavaleiro Ana Mercedes , Santos Aritania Sousa , Suemoto Claudia Kimie , Pasqualucci Carlos Augusto , Jacob‐Filho Wilson , Leite Renata Elaine Paraizo , Passarelli Marisa , Marie Suely Kazue Nagahashi , Machado Ubiratan Fabres , Correa‐Giannella Maria Lucia
Published: November 2020

Background

To investigate epigenetic mechanisms potentially involved in the cognitive decline associated with chronic alcohol intake, we evaluated the expressions of three micro‐RNAs (miR‐34a, ‐34b, and ‐34c) highly expressed in the hippocampus and involved in neuronal physiology and pathology. MiR‐34a participates in functioning and survival of mature neurons; miR‐34b is associated with Alzheimer‐like disorders; and miR‐34c is implicated in the memory impairment of Alzheimer disease in rodents and humans.

Methods

A total of 69 cases were selected from the Biobank for Aging Studies and categorized according to the absence (n = 50) or presence (n = 19) of alcohol use disorder (AUD). Cases presenting with neuropathological diagnoses of dementias were excluded. Total RNA was extracted from hippocampal paraffinized slices, complementary DNA was synthesized from miRs, and RT‐qPCR was performed with TaqMan® assays.

Results

Higher expressions of miR‐34a and miR‐34c, but not of miR‐34b, were found in the group with AUD in comparison with the group without AUD after adjustment for potential confounders (age, sex, body mass index, presence of hypertension, diabetes mellitus, smoking, and physical inactivity).

Conclusions

Hippocampal upregulation of miR‐34a and miR‐34c may be involved in the cognitive decline associated with chronic alcohol consumption.
Cross‐Sectional Analysis of Spatial Working Memory Development in Children with Histories of Heavy Prenatal Alcohol Exposure
Authors: Moore Eileen M. , Glass Leila , Infante M. Alejandra , Coles Claire D. , Kable Julie A. , Jones Kenneth L. , Riley Edward P. , Mattson Sarah N. ,   the CIFASD
Published: November 2020

Background

In children with prenatal alcohol exposure, spatial working memory is affected and brain regions important for spatial working memory performance exhibit atypical neurodevelopment. We therefore hypothesized that children with prenatal alcohol exposure may also have atypical development of spatial working memory ability.

Methods

We examined the relation between spatial working memory and age using a cross‐sectional developmental trajectory approach in youth with and without histories of heavy prenatal alcohol exposure. The Cambridge Neuropsychological Test Automated Battery Spatial Working Memory subtest was administered to children 5.0 to 16.9 years old.

Results

While the controls and children with prenatal alcohol exposure showed similar performance at younger ages, larger group differences were observed in older children. This effect was replicated in a separate sample.

Conclusions

The atypical brain development that has previously been reported in children with heavy prenatal alcohol exposure may have clinically relevant implications for cognitive development; however, longitudinal cognitive analyses are needed.
A Critical Review of Alcohol Administration Guidelines in Laboratory Medication Screening Research: Is It Time to Include Treatment Seekers?
Authors: Roberts Walter , Verplaetse Terril L. , Ramchandani Vijay A. , McKee Sherry A.
Published: November 2020

Human laboratory studies play an important role in alcohol use disorder (AUD) medication development. Medications that are found to be safe and effective during human laboratory screening will then move to more expensive clinical trials in patient populations. Given the gatekeeping role of human laboratory studies in the medication development pipeline, it is critical that these studies accurately forecast how pharmacotherapies will perform under true‐to‐life clinical conditions. On the other hand, the design of these studies also must adhere to ethical guidelines: certain aspects of clinical reality cannot be incorporated into screening studies because doing so might place the participant at risk for harm or breach other ethical guidelines. Conventions exist that guide the resolution of these conflicting ideals. This article considers the practice of recruiting non–treatment‐seeking heavy drinkers to participate in laboratory screening studies. By convention, volunteers are excluded from laboratory screening studies that involve alcohol administration if they are deemed “treatment seeking,” meaning that they recently stopped drinking or are motivated to do so. Although this common practice may reduce risk to participants, findings may not accurately predict medication effects on treatment seekers. Indeed, there is empirical evidence that treatment seekers differ from nontreatment seekers in their responses to medications (Neuropsychopharmacology 2017a; 42: 1776; Am J Drug Alcohol Abuse 2017b; 43: 703; J Psychiatr Res 2006; 40: 383). Here, we argue for the importance of recruiting treatment seekers for this research due to their qualitative difference from nontreatment seekers. We argue that these individuals should be the default population in human laboratory medication screening studies. We conclude by discussing 2 case examples of medication experiments led by our research groups that involved administering medications to treatment seekers.
Heterogeneity of Executive Function Abilities in Recently Detoxified Patients with Alcohol Use Disorder: Evidence from a Cluster Analysis
Authors: Schmid Franca , Benzerouk Farid , Barrière Sarah , Henry Audrey , Limosin Frédéric , Kaladjian Arthur , Gierski Fabien
Published: November 2020

Background

Impairments of executive functions (EF) have been consistently reported in patients with alcohol use disorder (AUD), mostly in studies which were based on comparisons of means between groups. However, given the high heterogeneity in AUD patients, this approach could actually cover a wide range of EF patterns. In the present study, we addressed the paucity of the literature about cognitive heterogeneity in AUD by applying a cluster analytical approach on EF measures.

Methods

Seventy‐eight withdrawn AUD patients and 77 healthy Control participants completed measures targeting a variety of EF components. We then used cluster analysis to identify subgroups of AUD patients. Furthermore, the AUD subgroups were compared to the Control group to establish their specific EF patterns.

Results

Findings showed that AUD patients could be divided into 3 clusters based on their EF performances. A first cluster accounting for half of the AUD sample was characterized by unimpaired EF (Cluster 1). The 2 other clusters displayed major EF deficits but differed regarding the deficient EF component. While Cluster 2 was mainly impaired on measures of rule deduction and mental flexibility, Cluster 3 was mainly characterized by a lower processing speed and impaired inhibition of an ongoing motor response. Differences in EF performances of AUD patients could be related to differences in premorbid cognitive reserve, impulsiveness patterns, and withdrawal complications.

Conclusions

This study highlights the importance of the cognitive heterogeneity in AUD by showing that AUD patients display substantially different EF patterns. Future studies should try to go beyond mere group comparisons to further deepen our understanding about cognitive differences between AUD patients. In the long run, this could lead to more personalized prevention and treatment programs specifically tailored to the patient’s impairments.
Utilization of extracorporeal life support for diffuse alveolar damage and diffuse alveolar hemorrhage: A systematic review
Authors: Reddy Haritha G. , Maynes Elizabeth J. , Saxena Abhiraj , Austin Melissa A. , O’Malley Thomas J. , Gadda Marc N. , Al‐Rawas Nawar N. , Baram Michael , Awsare Bharat K. , Massey H. Todd , Tchantchaleishvili Vakhtang
Published: November 2020

Modern extracorporeal life‐support (ECLS) technology has been successfully utilized to treat patients with diffuse alveolar damage (DAD) and diffuse alveolar hemorrhage (DAH); however, reports in the literature remain scarce. We sought to pool existing evidence to better characterize ECLS use in these patients. An electronic search was conducted to identify all studies in the English literature reporting the use of ECLS for DAD/DAH. Thirty‐two articles consisting of 38 patients were selected, and patient‐level data were extracted and pooled for analysis. Median patient age was 36 [IQR: 27, 48] years, and the majority (63.2%) were female. Most common etiological factors included granulomatosis with polyangiitis (8/38, 21.1%), systemic lupus erythematosus (8/38, 21.1%), Goodpasture's syndrome (4/38, 10.5%), and microscopic polyangiitis (4/38, 10.5%). Immunologic markers included anti‐neutrophil cytoplasmic antibody (ANCA) in 15/38 (39.5%), anti‐nuclear antibody (ANA) in 6/38 (15.8%), and anti‐glomerular basement membrane (anti‐GBM) antibodies in 4/38 (10.5%). DAH was present in 32/38 (84.2%) of cases and DAD without evidence of DAH was present in 6/38 (15.8%) of cases. ECLS strategies included extracorporeal membrane oxygenation of veno‐venous type (VV‐ECMO) in 28/38 (73.7%), veno‐arterial type (VA‐ECMO) in 5/38 (13.2%), and one case of right ventricular assist device with oxygenator (RVAD‐ECMO). Heparin was utilized in 18/38 (47.4%) of cases with no difference in use between DAH versus no DAH (P = .46) or VA‐ versus VV‐ECLS (P = 1). Median duration of ECLS was 10 [5, 14] days. Pre‐ versus post‐ECLS comparison of blood gases showed improvement in median PaO2 (49 [45, 59] mm Hg vs. 80 [70, 99] mm Hg, P < .001), PaO2:FiO2 ratio (48.2 [41.4, 54.8] vs. 182.0 [149.4, 212.2], P < .01), and pulse oximetry values (76% [72, 80] vs. 96% [94, 97], P = .086). Overall, 94.7% (36/38) of patients survived to decannulation while 30‐day mortality was 10.5% (4/38) with no differences between VA‐ and VV‐ECMO (P = 1 and P = .94, respectively). DAD/DAH occurs in a younger, predominantly female population, and tends to be associated with systemic autoimmune processes. ECLS, independent of its type, appears to result in favorable short‐term survival.
Dynamic extracorporeal life support: A novel management modality in temporary cardio‐circulatory assistance
Authors: Lo Coco Valeria , Swol Justyna , De Piero Maria Elena , Massimi Giulio , Chiarini Giovanni , Broman Lars Mikael , Lorusso Roberto
Published: November 2020

Extracorporeal life support (ECLS) is a temporary mechanical assistance method employed in acute respiratory, cardiocirculatory, and cardio‐respiratory failure, refractory to conventional treatments. Patient's hemodynamic, respiratory and metabolic condition, or situations related to ECLS support or performance, may change during ECLS treatment. Provision of an additional drainage or perfusion cannula, or even of an additional associated device, for example, transaortic suction device or intra‐aortic balloon pump (IABP), may be required to improve the ECLS/patient interaction and effects. Besides such a modified ECLS mode, however, a potential asset is represented by the “dynamic ECLS,” which is the change of the flow direction (drainage or perfusion) in the already implanted cannula during the ECLS run. This particular management may be achieved in venous femoral or jugular cannulation, but it finds an even more appealing potential with the pulmonary artery (PA) cannulation. The PA allows the institution of a multitasking ECLS circuit, ranging from enhanced left ventricle (LV) unloading (drainage from the PA) to a right ventricular support or “central” veno‐venous ECLS (perfusing the PA), tailored according to the patient hemodynamic, gas exchange, metabolic state, underlying cardiac involvement, and ECLS performance. Dynamic ECLS may, therefore, represent an additional option in ECLS management, particularly including the PA cannulation. Based on this new dynamic management of ECLS mode, we propose the Extracorporeal Life Support Organization nomenclature update.
Multisystem inflammatory syndrome in children rose and fell with the first wave of the COVID‐19 pandemic in France
Authors: Carbajal Ricardo , Lorrot Mathie , Levy Yael , Grimprel Emmanuel , Lecarpentier Thibault , Heritier Sebastien , Faivre Judith , Schnuriger Aurélie , Parisot Pauline , Blondiaux Eléonore , Loschi Solene , Rivière Simon , Guilbert Julia , Romain Anne‐Sophie , Leger Pierre‐Louis , Guedj Romain
Published: November 2020

Aim

This study determined the influence of the COVID‐19 pandemic on the occurrence of multisystem inflammatory syndrome in children (MIS‐C) and compared the main characteristics of MIS‐C and Kawasaki disease (KD).

Methods

We included patients aged up to 18 years of age who were diagnosed with MIS‐C or KD in a paediatric university hospital in Paris from 1 January 2018 to 15 July 2020. Clinical, laboratory and imaging characteristics were compared, and new French COVID‐19 cases were correlated with MIS‐C cases in our hospital.

Results

There were seven children with MIS‐C, from 6 months to 12 years of age, who were all positive for the virus that causes COVID‐19, and 40 virus‐negative children with KD. Their respective characteristics were as follows: under 5 years of age (14.3% vs. 85.0%), paediatric intensive care unit admission (100% vs. 10.0%), abdominal pain (71.4% vs. 12.5%), myocardial dysfunction (85.7% vs. 5.0%), shock syndrome (85.7% vs. 2.5%) and mean and standard deviation C‐reactive protein (339 ± 131 vs. 153 ± 87). There was a strong lagged correlation between the rise and fall in MIS‐C patients and COVID‐19 cases.

Conclusion

The rise and fall of COVID‐19 first wave mirrored the MIS‐C cases. There were important differences between MIS‐C and KD.
Influence of single nucleotide polymorphism of LAT1 on therapeutic response to gabapentinoids in Pakistani patients with neuropathic pain
Authors: Shaheen Abida , Alam Syed Mahboob , Azam Fahad , Khan Moosa , Ahmad Saleem Salman , Liaquat Afrose , Mumtaz Sana
Published: November 2020

Gabapentinoids are substrate of L‐type amino acid transporter 1 (LAT1) for distribution across the blood‐brain barrier. The present study aimed to evaluate the effect of LAT1 rs4240803 genetic polymorphism on the clinical efficacy and tolerability of gabapentinoids in Pakistani patients with neuropathic pain. Three‐hundred and ninety‐two patients were recruited, genotyped for SNP rs4240803, and followed up for eight weeks to evaluate the clinical response to gabapentinoids in terms of pain relief, inadequate response, and the emergence of adverse events. LAT1 rs4240803 GG, GA, and AA genotype frequency were 33.42%, 47.96% and 18.62%, respectively. Out of 392 patients, 323 responded to the treatment and 17.6% discontinued either due to insufficient response or intolerable adverse events (AEs). GA genotype was more frequent in non‐responder group (P ˂ 0.001). Maximum pain responders (≥50%) in combination with the lowest incidence of AEs were observed in the GG group, whereas partial responders belonged to GA genotype and with the highest frequency of somnolence (83.6%) and dizziness (69.9%). Overall, 72.5% patients with GA genotype experienced AEs (P ˂ 0.001). In conclusion, clinical outcomes of gabapentinoids are influenced by LAT1 rs4240803 polymorphism and population pharmacogenetics should be considered to evaluate the maximum potential of gabapentinoids in the management of neuropathic pain.
Assessment of adherence to corticosteroids in asthma by drug monitoring or fractional exhaled nitric oxide: A literature review
Authors: Alahmadi Fahad , Peel Adam , Keevil Brian , Niven Rob , Fowler Stephen J.
Published: November 2020

Background

Although the efficacy of corticosteroid treatment in controlling asthma is widely accepted, its effectiveness is undermined by poor adherence. However, the optimal method for measuring adherence to asthma therapy remains unclear.

Objective

To perform a review of the literature reporting biological, objective methods for assessing adherence to inhaled or oral corticosteroids in asthma; we included studies reporting direct measurement of exogenous corticosteroids in blood, or the effect of adherence on exhaled nitric oxide.

Design

We searched three databases MEDLINE (using both PubMed and Ovid), the Cumulative Index of Nursing and Allied Health Literature (CINAHL) and Web of Science for articles published between January 1975 and July 2020. Quality of the studies was assessed using the National Institute of Health checklist.

Results

From 2850 screened articles, 26 fulfilled the inclusion criteria. Measurement of blood prednisolone with or without cortisol was used in eight studies as a measure of oral corticosteroid adherence, and fractional exhaled nitric oxide (FeNO) in 17 studies for inhaled corticosteroid adherence. Inhaled corticosteroids were measured directly in the blood in one study. By direct measurement of drug levels in the blood, adherence rates to oral corticosteroids ranged from 47% to 92%, although the performance and timing of the test were often not known, making interpretation of findings and serum prednisolone concentrations difficult. FeNO is generally lower in adherent than non‐adherent patients, but no absolute cut‐off can be proposed based on the available data. However, a fall in FeNO following supervised inhaled corticosteroid dosing could indicate previous poor adherence.

Conclusions and Clinical Relevance

Despite prednisolone and cortisol levels commonly being used as adherence markers in clinical practice, further work is required to assess the influence of the dose and timing on blood levels. The promising findings of FeNO suppression testing should be explored in further prospective studies.
Null variants in DYSF result in earlier symptom onset
Authors: Park Hyung Jun , Hong Young Bin , Hong Ji‐Man , Yun UnKyu , Kim Seung Woo , Shin Ha Young , Kim Seung Min , Choi Young‐Chul
Published: November 2020

We investigated the clinical, laboratory, and genetic spectra in Korean patients with dysferlinopathy to clarify its genotype–phenotype correlation. We retrospectively reviewed 101 patients from 96 unrelated families with pathogenic variants of DYSF. The most common initial phenotype was Miyoshi myopathy in 50 patients. Median ages at examination and symptom onset were 23 [interquartile range (IQR): 18–30] and 36 years [IQR: 27–48], respectively. We observed 38 variants, including nine novel variants. Four variants (c.2494C > T, c.1284 + 2 T > C, c.663 + 1G > C, and c.2997G > T) in DYSF accounted for 62% of total allele frequencies of pathogenic variants. To analyze the genotype–phenotype correlation, we compared the clinical phenotype between patients with null/null (N/N; n = 55) and null/missense variants (N/M; n = 35). The N/N group had an earlier symptom onset age (median: 20 years [IQR: 17–25]) than the N/M group (median: 29 years [IQR: 23–35], p < .001). Total manual muscle testing scores in lower extremities were lower in the N/N group (median: 80 [IQR: 56–92]) than in the N/M group (median: 89 [IQR: 78–98], p = .013). Our study is the first to report that null variants in DYSF result in an earlier symptom onset than missense variants.
Survival and treatment outcome of head and neck cancer patients with pulmonary oligometastases
Authors: Lardinois Ines , Dequanter Didier , Lechien Jérôme R. , Bouland Cyril , Javadian Rokneddine , Rodriguez Alexandra , Loeb Isabelle , Journe Fabrice , Saussez Sven
Published: November 2020

Objectives

The purpose of this study was to determine the outcome of head and neck squamous cell carcinoma (HNSCC) patients developing lung metastasis.

Design

Retrospective study.

Participants

HNSCC patients with lung metastasis treated between 2001 and 2018 were included.

Mean outcomes measures

Statistical analyses described the relationship between patient survival, treatment efficacy and pulmonary metastasis occurrence.

Results

One hundred HNSCC patients were included in the study. The median overall survival (OS) was 21 months. The median recurrence‐free survival (RFS) was seven months. Patient survival with only lung metastases was significantly longer compared to patients with lung metastases and lymph nodes involvement or other metastases. Moreover, patients with a single metastasis had longer post‐RFS and OS than patients with multiple metastases. The local control of metastasis was better when patients presented only lung metastases, and it was more effective in single metastasis. The surgery allowed better metastases local control than supportive care or radio and/or chemotherapy. In case of specific therapy, pulmonary resection was associated with a longer post‐RFS and a longer OS compared to supportive care or radio and/or chemotherapy.

Conclusions

We confirmed, in the current study, the significant survival benefit for HNSCC patients treated by surgery for their pulmonary metastasis. While treatment of multiple metastases required palliative chemotherapy or best supportive care in most of the cases, specific surgical treatment in selected HNSCC patients should be considered.
Liver transplant recipients have an increased risk of developing colorectal adenomas: Results from a retrospective study
Authors: Herrero José Ignacio , Quiñones Marta , Pérez Xabier , Mora Lorena , Bojórquez Alejandro , Toledo Estefanía , Betés Maite
Published: November 2020

Background

Liver transplant recipients have an increased incidence of malignancies, but it is unclear whether they have a higher risk of colorectal cancer.

Aim

To investigate whether liver transplant recipients have an increased risk of developing colorectal adenomas (a surrogate marker of colorectal cancer risk).

Patients and methods

One hundred thirty‐nine liver transplant recipients (excluding primary sclerosing cholangitis) who underwent a colonoscopy and polypectomy before and after transplantation, and 367 nontransplanted patients who underwent a colonoscopy for colorectal cancer screening and a second colonoscopy later were retrospectively studied. The risks of incident colorectal adenomas and high‐risk adenomas (advanced or multiple adenomas or carcinomas) were compared between both cohorts.

Results

Incident colorectal adenomas were found in 40.3% of the transplanted patients and 30.0% of the nontransplanted patients (15.1% and 5.5%, respectively, had high‐risk adenomas). After adjusting for age, sex, presence of adenomas in the baseline endoscopy, and interval between colonoscopies, transplant recipients showed a higher risk of developing colorectal adenomas (OR: 1.61; 95% CI: 1.05‐2.47; p = .03) and high‐risk adenomas (OR: 2.87; 95% CI: 1.46‐5.65; p = .002).

Conclusions

Our results suggest that liver transplant recipients have an increased risk of developing colorectal adenomas and lesions with high risk of colorectal cancer.
Study drug use among university students in Western Australia: Results of a web survey and their policy and practice implications
Authors: Nelson Marina , Jensen Charmaine , Lenton Simon
Published: November 2020

Introduction and Aims

Recent research and anecdotal reports suggest increased use of ‘study drugs’ or cognitive enhancers (CE) by university students. Evidence suggests students who use CEs tend to perceive them as effective, but whether CEs improve cognition in healthy individuals is unclear and any drug use carries a risk of harm. Two previous studies have investigated the prevalence of use in Australian university student samples and neither assessed university system factors which may contribute to use.

Design and Methods

During 2016, a convenience sample of 2133 18–29‐year‐old students across all five Western Australian universities completed a quantitative anonymous web survey targeting both users and non‐users of CE.

Results

Of the final sample, 7.9% reported use of a prescription drug for CE purposes in the last 12 months. Prescription CE use was predicted by greater frequency of illicit drug use and among students who reported they had not had a take‐home exam in the last 12 months. Rates of use and predictors of over the counter (28.6%) and illicit drugs (2.4%) were predicted by different individual and contextual factors. There were high rates of reporting positive effects from CE use, but although negative effects were reported less commonly, they were not trivial.

Discussion and Conclusions

These findings have implications for university policy and university health services raising the issue with students and potentially providing clinical interventions addressing CE use. Further research should include representative samples and address both system and individual variables in understanding patterns of CE use among students.
Similar outcomes for antenatally or postnatally acquired haemorrhages
Authors: de Vries Linda S , de Vries Johanna I P
Published: November 2020

This commentary is on the systematic review by Dunbar et al. on pages 144–155 of this issue.
Towards more intimacy: moderate elevation of temperature drives increases in foraging and mutualistic interactions between Lasius niger and Aphis fabae
Authors: Blanchard Solène , Van Offelen Julie , Verheggen François , Detrain Claire
Published: November 2020

1. Climate change will likely affect the association between species interacting at different trophic levels. However, studies focusing on the impact of an elevation of temperature on ant‐hemipteran mutualism remain scarce.

2. In the present study we investigated, in laboratory conditions, the foraging behaviour of the ant Lasius niger and its mutualistic interaction with the aphid Aphis fabae under three conditions of temperatures (i.e. 20°C, 23°C, and 26°C), as predicted by climatic scenarios.

3. Aphids were more mobile but as likely to release honeydew droplets at higher temperatures. As regards the ants, a moderate 3°C increase of temperature positively impacted their mutualistic interaction with aphids. Such reinforcement was achieved through an increase in the walking speed of ant foragers, in the number of mobilised ants as well as in the total amount of honeydew harvested by the colony.

4. A further elevation of temperature to 26°C reduced the benefits gained by the aphid‐tending ants, in terms of lower amount of collected honeydew.

5. Based on our results, we hypothesise that, in temperate regions, a moderate increase of ambient atmospheric temperature by 3°C will benefit to the L. niger ‐ A. fabae mutualistic interaction. A more marked elevation of 6°C may represent a threshold thermal value above which a switch of partners or a disruption of the interaction may occur under the temperatures predicted for the end of the century. These results demonstrate the fragility of mutualistic interactions, and more particularly their sensitivity to temperature increases predicted by realistic forecast models.
Reflection before and after clinical practice—Enhancing and broadening experience through self‐, peer‐ and teacher‐guided learning
Authors: Botelho Michael , Bhuyan Sangeeta Y.
Published: November 2020

Introduction

This paper explores a novel pedagogy surrounding students’ clinical practice sessions. Before each clinical session, student clinical groups meet and each student presents their treatment planned for that session. The teachers question their understanding and explore “what‐if” and other management scenarios. Peers in the clinical group observe the presentation and learning dialogue. After the clinical session, students gather on the clinic to debrief their performance with the tutor. Peers observe this dialogue, the shared clinical experience. This paper explores students’ perceptions of reflection before action and reflection on action surrounding their clinical practice.

Methods

Focus groups were conducted to explore this phenomenon and to create a questionnaire, which was administered to the whole class. Transcriptions of the focus groups and open‐ended response in the questionnaire were subjected to a thematic analysis to identify emerging themes and supported by closed‐ended question responses.

Results

Briefing sessions before clinical sessions helped students identify problems and clear doubts before entering clinics. Students were able to recall and rehearse the clinical procedural knowledge and felt well prepared and confident for patient care. Student sharing of knowledge with peers provided a broader learning experience and helped gain confidence. Students also reported to learn from the teacher facilitating their preparation for the session. Debriefing sessions after the clinical session allowed reflection and learning including error correction on their own and peer experiences. Students learnt personally, from peers and from the teacher, and emphasised the importance of the student‐teacher relation.

Conclusions

Briefing and debriefing sessions were highly valued by students for preparation and learning on clinics and in learning from peers. Briefing sessions cleared misunderstanding, prevented errors, broadened procedural knowledge and improved both confidence and clinical experience. Debriefing sessions facilitated reflective practice, error correction and prevention, and helped gain insights from teachers’ own experience and perspectives.
Locus coeruleus in memory formation and Alzheimer's disease
Authors: James Tony , Kula Bartosz , Choi Seowon , Khan Shahzad S. , Bekar Lane K. , Smith Nathan A.
Published: November 2020

Catecholamine neurons of the locus coeruleus (LC) in the dorsal pontine tegmentum innervate the entire neuroaxis, with signaling actions implicated in the regulation of attention, arousal, sleep–wake cycle, learning, memory, anxiety, pain, mood, and brain metabolism. The co‐release of norepinephrine (NE) and dopamine (DA) from LC terminals in the hippocampus plays a role in all stages of hippocampal‐memory processing. This catecholaminergic regulation modulates the encoding, consolidation, retrieval, and reversal of hippocampus‐based memory. LC neurons in awake animals have two distinct firing modes: tonic firing (explorative) and phasic firing (exploitative). These two firing modes exert different modulatory effects on post‐synaptic dendritic spines. In the hippocampus, the firing modes regulate long‐term potentiation (LTP) and long‐term depression, which differentially regulate the mRNA expression and transcription of plasticity‐related proteins (PRPs). These proteins aid in structural alterations of dendritic spines, that is, structural long‐term potentiation (sLTP), via expansion and structural long‐term depression (sLTD) via contraction of post‐synaptic dendritic spines. Given the LC's role in all phases of memory processing, the degeneration of 50% of the LC neuron population occurring in Alzheimer's disease (AD) is a clinically relevant aspect of disease pathology. The loss of catecholaminergic regulation contributes to dysfunction in memory processes along with impaired functions associated with attention and task completion. The multifaceted role of the LC in memory and general task performance and the close correlation of LC degeneration with neurodegenerative disease progression together implicate it as a target for new clinical assessment tools.
Hypomyelinating leukodystrophies in adults: Clinical and genetic features
Authors: Di Bella Daniela , Magri Stefania , Benzoni Chiara , Farina Laura , Maccagnano Carmelo , Sarto Elisa , Moscatelli Marco , Baratta Silvia , Ciano Claudia , Piacentini Sylvie H. M. J. , Draghi Lara , Mauro Elena , Pareyson Davide , Gellera Cinzia , Taroni Franco , Salsano Ettore
Published: November 2020

Background and purpose

Little is known about hypomyelinating leukodystrophies (HLDs) in adults. The aim of this study was to investigate HLD occurrence, clinical features, and etiology among undefined leukoencephalopathies in adulthood.

Methods

We recruited the patients with cerebral hypomyelinating magnetic resonance imaging pattern (mild T2 hyperintensity with normal or near‐normal T1 signal) from our cohort of 62 adult index cases with undefined leukoencephalopathies, reviewed their clinical features, and used a leukoencephalopathy‐targeted next generation sequencing panel.

Results

We identified 25/62 patients (~40%) with hypomyelination. Cardinal manifestations were spastic gait and varying degree of cognitive impairment. Etiology was determined in 44% (definite, 10/25; likely, 1/25). Specifically, we found pathogenic variants in the POLR3A (n = 2), POLR1C (n = 1), RARS1 (n = 1), and TUBB4A (n = 1) genes, which are typically associated with severe early‐onset HLDs, and in the GJA1 gene (n = 1), which is associated with oculodentodigital dysplasia. Duplication of a large chromosome X region encompassing PLP1 and a pathogenic GJC2 variant were found in two patients, both females, with early‐onset HLDs persisting into adulthood. Finally, we found likely pathogenic variants in PEX3 (n = 1) and PEX13 (n = 1) and potentially relevant variants of unknown significance in TBCD (n = 1), which are genes associated with severe, early‐onset diseases with central hypomyelination/dysmyelination.

Conclusions

A hypomyelinating pattern characterizes a relevant number of undefined leukoencephalopathies in adulthood. A comprehensive genetic screening allows definite diagnosis in about half of patients, and demonstrates the involvement of many disease‐causing genes, including genes associated with severe early‐onset HLDs, and genes causing peroxisome biogenesis disorders.
Why women have more autoimmune diseases than men: An evolutionary perspective
Authors: Kronzer Vanessa L. , Bridges Stanley Louis , Davis John M.
Published: November 2020

Women have up to a fourfold increase in risk for autoimmune disease compared to men. Many explanations have been proposed, including sex hormones, the X chromosome, microchimerism, environmental factors, and the microbiome. However, the mechanism for this autoimmune sex bias remains obscure. In this manuscript, we evaluate the hypothesis that qualitative or quantitative differences in circulating antibodies may explain, at least in part, the pathogenesis of autoimmune disease and its sex bias—especially when considering an evolutionary perspective. Indeed, women have higher absolute levels of antibodies than men, and (auto)antibodies are also associated with most autoimmune diseases. Several facts suggest differences in antibodies may cause increased prevalence of autoimmune disease in women. First, the association between increased quantities of serum antibodies and increased prevalence of autoimmunity is found not only in women, but also in men with Klinefelter syndrome. Second, both serum antibody levels and autoimmunity spike in the postpartum period. Third, a dose–response effect exists between parity and both serum antibodies and prevalence of autoimmune disease. Fourth, many biologically plausible mechanisms explain the association, such as T cell‐dependent activation of B cells and/or VGLL3. The evolutionary underpinning of increased antibodies in women is likely to be protection of offspring from infections. Overall, this evolutionary paradigm can help explain why the phenomenon of autoimmunity occurs preferentially in women and raises the possibility of new treatment options.