bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with low‐intake dehydration among older inpatients: A pilot study
Authors: Wham Carol , Smithers Allie , Kruger Rozanne , Mazahery Hajar , Richter Marilize
Published: December 2020

Objectives

To assess fluid intake among older inpatients and factors associated with low‐intake dehydration.

Methods

Daily fluid intake and access were assessed within the 24‐hour period, and blood was drawn to measure serum osmolality.

Results

Of 89 patients, 16% and 27% had serum osmolality ≥ 300 (dehydrated) and 295‐299 mOsm/kg (impending dehydration), respectively. Median (IQR) total fluid intake was 1.7 (1.6, 1.9) L/day. Fluid intake from beverages (P = .06) and water (P = .02) was higher in hydrated than impending/dehydrated patients. Of all fluid sources, only water intake was associated with hydration status (P = .02). The adjusted odds of serum osmolality ≥ 295 were increased for patients in the first (<0.3 L, P = .007) and second (0.3‐0.8 L, P = .04) tertiles of water intake than those in the third tertile (≥0.8 L). Bladder control difficulty was associated with lower water intake (P = .03).

Conclusion

Monitoring water intake and assisting patients with bladder control difficulty may be key strategies to maintain hydration.
Post‐fire changes in plant growth form composition and diversity in Andean páramo grassland
Authors: Zomer Maya A. , Ramsay Paul M
Published: December 2020

Questions

Fire suppression policies have been widely adopted in the páramo grasslands of the northern Andes to protect their biodiversity and ecosystem services. Páramos have been regularly burned for many years, and it is not clear how páramo vegetation will respond to significant changes in their fire regimes. This study investigates differences in plant growth form composition, light levels and soil temperatures in páramo plots representing a range of recovery times since the last fire.

Location

Reserva Ecológica El Ángel and La Bretaña Nature Reserve, Carchi, Northern Ecuador.

Methods

We assessed the frequency of ten páramo growth forms, vegetation height, soil temperature, and light intensity in fifteen fire sites with historical records of fire (<1–15 years since fire), and one recently unburned site (at least 40 years since fire). A chronosequence of sites was used to assess potential changes in plant community composition in post‐fire succession of páramo.

Results

The recovery of páramo vegetation after fire comprised three phases: initial recruitment with high growth form diversity, followed by reduced diversity, light and soil temperatures in dense tussock vegetation, and ultimately canopy height stratification with a return of diversity. All but one of the plant growth forms were represented in each of the three phases, and the changes reflected differences in relative abundance.

Conclusions

Post‐fire páramo succession is characterised by clear shifts in the relative abundance of plant growth forms, ending with (co‐)dominance of upright shrubs. The long‐term consequences of such shifts for biodiversity and ecosystem function, given the widespread adoption of fire suppression policies in the páramo, need careful, evidence‐based consideration.
Effect of capmatinib on the pharmacokinetics of digoxin and rosuvastatin administered as a 2‐drug cocktail in patients with MET‐dysregulated advanced solid tumours: A phase I, multicentre, open‐label, single‐sequence drug–drug interaction study
Authors: Grande Enrique , Giovannini Monica , Marriere Eddie , Pultar Philippe , Quinlan Michelle , Chen Xinhui , Rahmanzadeh Gholamreza , Curigliano Giuseppe , Cui Xiaoming
Published: December 2020

Aims

Capmatinib, an orally bioavailable, highly potent and selective MET inhibitor, was recently approved to treat adult patients with metastatic nonsmall cell lung cancer with METex14 skipping mutations. The study investigated the effect of capmatinib on the pharmacokinetics of a single oral dose of digoxin and rosuvastatin in patients with MET‐dysregulated advanced solid tumours.

Methods

This was a multicentre, open‐label, single‐sequence study. An oral drug cocktail containing 0.25 mg digoxin and 10 mg rosuvastatin was administered to adult patients with MET‐dysregulated advanced solid tumours on Day 1, and then on Day 22 with capmatinib. Between Days 11 and 32, capmatinib 400 mg was administered twice daily to ensure the attainment of steady state for drug–drug interaction assessment. Pharmacokinetics of cocktail drugs and safety of capmatinib were evaluated.

Results

Thirty‐two patients were enrolled. Compared to digoxin alone, the geometric mean ratios (90% confidence interval) of area under the concentration–time curve from time zero to infinity and maximum concentration for digoxin plus capmatinib were 1.47 (1.28, 1.68) and 1.74 (1.43, 2.13), respectively. Compared to rosuvastatin alone, the geometric mean ratios (90% confidence interval) of area under the curve to infinity and maximum concentration for rosuvastatin plus capmatinib were 2.08 (1.56, 2.76) and 3.04 (2.36, 3.92), respectively. Most frequent adverse events (≥25% for all grades) were nausea, asthenia, constipation, vomiting, peripheral oedema and pyrexia. Most frequent Grade 3/4 adverse events (≥5%) were anaemia, pulmonary embolism, asthenia, dyspnoea, nausea and vomiting.

Conclusion

This study demonstrated that capmatinib is an inhibitor of P‐gp and BCRP transporters, with clinically relevant drug–drug interaction potential. Capmatinib was well‐tolerated and no unexpected safety concerns were observed.
Establishing dose bands for commonly prescribed oral medications for children in the UK: Results of a Delphi study
Authors: Rashed Asia N. , Tomlin Stephen
Published: December 2020

Objective

To establish weight‐based dose bands for commonly used oral medicines, given in liquid forms, for children in the UK that could be used for prescribing and administering accurate and safe drug doses.

Methods

A list of commonly prescribed, oral liquid medications was established from the medication dispensing database of four UK hospitals and a primary care database. The evidence base of currently used dose regimens for each drug was identified from paediatric reference books, summary of product characteristics and the literature. Then, weight‐based dose bands were developed and a modified Delphi process was used to achieve healthcare professional consensus about the suggested dose bands for each drug.

Results

Forty‐six experts in paediatric medicines participated in the Delphi process (mean years of experience 17.3 ± 9.4 [standard deviation]) and assessed 45 oral liquid drugs in total.

Four categories of weight‐based dose bands were established: drugs with two dose bands (17.8%, 8/45), drugs with three dose bands (64.4%, 29/45), drugs with four dose bands (15.6%, 7/45) and drugs with five dose bands (2.2%, 1/45). The 46 participants reached consensus on all the suggested dose bands for 53.3% (24/45) of the drugs. Consensus was reached in the first round of the Delphi process for 91.7% (22/24) of the drugs and after two rounds for two drugs.

No agreement was achieved on any of the suggested dose bands for 26.7% (12/45) of the drugs.

Conclusion

This study provides healthcare professionals with a set of recommended weight‐based dose bands for commonly prescribed oral liquid drugs for children. These bands could establish the basis for change in clinical practice to reduce dosing errors and improve healthcare for children.
Hair as a matrix in monitoring drug epilepsy therapy
Authors: Zakrzewska Alicja , Dermanowski Michał , Mierzejewski Paweł , Kuczyńska Julita
Published: December 2020

Hair is considered an efficient tool to investigate drug‐related histories; thus, the selection of the method of sample preparation is important to obtain a reliable result. The aim of this study was to compare two methods of hair preparation (cutting and pulverizing) to analyse levetiracetam concentration in hair. An additional aim was to evaluate the potential usefulness of the levetiracetam concentration measured as an index of a dosing schedule. Four groups of 12 rats were included in the experiment. Depending on the group, the rats received 10 mg/kg of levetiracetam intraperitoneally every 24, 48 and 72 hours for 30 days. The control group was not treated. At the end of the drug administration, the rats’ hair was shaved, cut or pulverized and analysed by the LC/MS‐MS method to determine the concentration of levetiracetam. A stronger correlation between the mean hair levetiracetam concentration in hair and the number of drug doses was found in pulverized hair than in cut hair. A smaller standard deviation between the results was obtained in the case of pulverized hair. The results indicate that pulverization gives a more reliable result of drug concentration in hair than cutting and that drug concentration in hair can reflect the scheme of levetiracetam administration.
From rifting to hyperextension: Upper Jurassic–Lower Cretaceous tectono‐stratigraphy of the Porcupine Basin, Irish Atlantic Margin
Authors: Whiting Lewis , Haughton Peter D. W. , Shannon Patrick M.
Published: December 2020

Hyperextended basins are increasingly recognized along the outboard parts of continental margins as aborted basins created during continental break‐up. Many of the concepts for understanding and modelling basin evolution and fill were developed for regions that have undergone modest crustal stretching (β < 2) and may not be valid in basins where the crust and upper mantle are heavily modified by extreme stretching. The present study uses extensive 2D and 3D seismic and well data to analyse the Late Jurassic–Cretaceous tectono‐stratigraphic evolution of the Porcupine Basin, bracketing the timing of hyperextension. It is an instructive basin, offshore west of Ireland, preserving low‐magnitude strain in the north, with increasing degrees of hyperextension in the south. Detailed mapping of strain domains (proximal, necking and hyperextended) across the Porcupine Basin reveals five main rift segments, each with a distinctive geometry and strain history. During early low‐strain rifting, inherited crustal structures strongly influenced the rift architecture by controlling the location and geometry of fault‐controlled marine depocentres. The transition from hyperextension to post‐rift subsidence was marked by locally developed, unconformity‐bounded, marine sequences that draped the underlying rift topography. Whilst these ‘transition sequences’ are dated as Tithonian above the necking domain, similar but younger Early Cretaceous transition packages developed in the hyperextended domain, suggesting extension migrated towards the rift axis during hyperextension. Early post‐rift sequences were broadly distributed across the rift centre and basin flanks before strong, thermally‐controlled subsidence of the hyperextended crust, along with hinging of the necking domain, locally to the point of slope failure, gave rise to axially‐focused marine deposition. Hyperextension may have left the basin susceptible to intra‐plate stress changes accounting for several unconformities within the post‐rift fill. This study provides an improved basin‐wide understanding of the tectono‐stratigraphic evolution of hyperextended basins.
Children’s Knowledge of Symbolic Number in Grades 1 and 2: Integration of Associations
Authors: Xu Chang , LeFevre Jo‐Anne
Published: December 2020

How do children develop associations among number symbols? For Grade 1 children (n = 66, M = 78 months), sequence knowledge (i.e., identify missing numbers) and number comparison (i.e., choose larger number) predicted addition, both concurrently and indirectly at the end of Grade 1. Number ordering (i.e., touch numbers in order) did not predict addition but was predicted by number comparison, suggesting that magnitude associations underlie ordering performance. In contrast, for Grade 2 children (n = 80, M = 90 months), number ordering predicted addition concurrently and at the end of Grade 2; number ordering was predicted by number comparison, sequencing, and inhibitory processing. Development of symbolic number competence involves the hierarchical integration of sequence, magnitude, order, and arithmetic associations.
PET detectives: Molecular imaging for phaeochromocytomas and paragangliomas in the genomics era
Authors: Ryder Simon J. , Love Amanda J. , Duncan Emma L. , Pattison David A.
Published: December 2020

Phaeochromocytomas and paragangliomas (PPGLs) are rare tumours that arise from the adrenal medulla or extra‐adrenal sympathetic or parasympathetic paraganglia. Recent advances in genetics have greatly enhanced understanding of the pathogenesis and molecular physiology of PPGL. Concomitantly, advances in molecular imaging mean four techniques are now available for use in PPGLs: [123I]‐MIBG coupled with SPECT/CT; [18F]‐ FDG, [68Ga]‐DOTATATE and [18F]‐FDOPA coupled with PET/CT. Each modality relies on unique cellular uptake mechanisms that are contingent upon the tumour's molecular behaviour—which, in turn, is determined by the tumour's genetic profile. This genotype‐phenotype correlation means the appropriate choice of radiotracer may depend on the known (or suspected) underlying genetic mutation, in addition to the clinical indication for the scan—whether confirming diagnosis, staging disease, surveillance or determining eligibility for radionuclide therapy. Given these rapid recent changes in genetic understanding and molecular imaging options, many clinicians find it challenging to choose the most appropriate scan for an individual with PPGL. To this end, recent guidelines published by the European Association of Nuclear Medicine and the Society of Nuclear Medicine and Molecular Imaging (EANM/SNMMI) have detailed the preferred radiotracer choices for individuals with PPGL based on their genotype and/or clinical presentation, providing timely clarity in this rapidly moving field. The current review summarizes the implications of the genotype‐phenotype relationship of PPGL, specifically relating this to the performance of molecular imaging modalities, to inform and enable practising endocrinologists to provide tailored, personalized care for individuals with PPGL.
Supporting habitat conservation with automated change detection in Google Earth Engine
Authors: Evans Michael J. , Malcom Jacob W.
Published: December 2020

A significant limitation in biodiversity conservation has been the effective implementation of laws and regulations that protect species’ habitats from degradation. Flexible, efficient, and effective monitoring and enforcement methods are needed to help conservation policies realize their full benefit. As remote sensing data become more numerous and accessible, they can be used to identify and quantify land‐cover changes and habitat loss. However, these data remain underused for systematic conservation monitoring in part because of a lack of simple tools. We adapted 2 algorithms that automatically identify differences between pairs of images. We used free, publicly available satellite data to evaluate their ability to rapidly detect land‐cover changes in a variety of land‐cover types. We compared algorithm predictions with ground‐truthed results at 100 sites of known change in the United States. We also compared algorithm predictions to manually created polygons delineating anthropogenic change in 4 case studies involving imperiled species’ habitat: oil and gas development in the range of the Greater Sage Grouse (Centrocercus urophasianus); sand mining operations in the range of the dunes sagebrush lizard (Sceloporus arenicolus); loss of Piping Plover (Charadrius melodus) coastal habitat after Hurricane Michael (2018); and residential development in St. Andrew beach mouse (Peromyscus polionotus peninsularis) habitat. Both algorithms effectively discriminated between pixels corresponding to land‐cover change and unchanged pixels as indicated by area under a receiver operating characteristic curve >0.90. The algorithm that was most effective differed among the case‐study habitat types, and both effectively delineated habitat loss as indicated by low omission (min. = 0.0) and commission (min. = 0.0) rates, and moderate polygon overlap (max. = 47%). Our results showed how these algorithms can be used to help close the implementation gap of monitoring and enforcement in biodiversity conservation. We provide a free online tool that can be used to run these analyses (https://conservationist.io/habitatpatrol).
Activation of nuclear factor‐κB in the angiogenesis of glioma: Insights into the associated molecular mechanisms and targeted therapies
Authors: Tu Jiajie , Fang Yilong , Han Dafei , Tan Xuewen , Jiang Haifeng , Gong Xun , Wang Xinming , Hong Wenming , Wei Wei
Published: December 2020

Glioma is the most commonly observed primary intracranial tumour and is associated with massive angiogenesis. Glioma neovascularization provides nutrients for the growth and metabolism of tumour tissues, promotes tumour cell division and proliferation, and provides conditions ideal for the infiltration and migration of tumour cells to distant places. Growing evidence suggests that there is a correlation between the activation of nuclear factor (NF)‐κB and the angiogenesis of glioma. In this review article, we highlighted the functions of NF‐κB in the angiogenesis of glioma, showing that NF‐κB activation plays a pivotal role in the growth and progression of glioma angiogenesis and is a rational therapeutic target for antiangiogenic strategies aimed at glioma.
Effect of group cognitive behavioural therapy on psychological stress and blood glucose in people with type 2 diabetes mellitus: A community‐based cluster randomized controlled trial in China
Authors: Xu Chunrong , Dong Zongmei , Zhang Pan , Chang Guiqiu , Xiang Quanyong , Zhang Ming , Zhou Jinyi , Qiao Cheng , Yang Qing , Qin Yu , Lou Peian
Published: December 2020

Objective

To assess whether group cognitive behavioural therapy (GCBT) delivered by general practitioners reduces anxiety and depression and improves glycaemic levels in adults with type 2 diabetes mellitus.

Methods

We conducted a community‐based cluster randomized controlled trial in adults with type 2 diabetes mellitus from 48 communities in China. Participants received either GCBT plus usual care (UC) or UC only. General practitioners were trained in GCBT before intervention in the intervention group. The primary outcome was glycated haemoglobin (HbA1c) concentration. Outcome data were collected from all participants at baseline, 2 months, 6 months and 1 year. The secondary outcomes were depression (Patient Health Questionnaire‐9; PHQ‐9) and anxiety (General Anxiety Disorder questionnaire; GAD‐7).

Results

The GCBT group showed greater improvement in GAD‐7 and PHQ‐9 scores, respectively, than the UC group after 2 months post‐baseline (T = −6.46, p < 0.0001; T = −5.29, p < 0.001), 6 months (T = −4.58, p < 0.001; T = −4.37, p < 0.001) and 1 year post‐intervention (T = −3.91, p < 0.001; T = −3.57, p < 0.001). There was no difference in HbA1c values between the GCBT and UC groups at 2 months while the values were lower in the GCBT group at 6 months and 1 year (T = −6.83, p < 0.001; T = −4.93, p < 0.001, respectively). Subgroup analysis indicated a long‐term effect of GCBT only for mild and moderate anxiety and mild depression groups. Similarly, HbA1c values reduced only in the mild and moderate anxiety and the mild depression groups.

Conclusions

General practitioners can deliver GCBT interventions. GCBT plus UC is superior to UC for reducing mild/moderate anxiety and depression, and improving glycaemic levels.

Trial registration

Chinese clinical trials registration (ChiCTR‐IOP‐16008045).
Invasive paper wasps have strong cascading effects on the host plant of monarch butterflies
Authors: McGruddy Rose A. , Howse Matthew W. F. , Haywood John , Ward Chrissie J. I. , Staufer Tony B. , Hayek‐Williams Mary , Toft Richard J. , Lester Philip J.
Published: December 2020

The direct and indirect impacts that invasive predators have on communities within their invaded range are poorly understood, particularly in the early stages of invasion. Through top‐down control of their prey, predators have the capacity to trigger cascading effects on lower trophic levels.

We found the recent arrival of the invasive paper wasp Polistes dominula Christ has been associated with substantial declines in local butterfly abundance in New Zealand. One of the butterfly species we observed to be affected is the monarch, Danaus plexippus Linnaeus with densities reduced by 66% at the study site. Field experiments were conducted to examine the strength of the predation pressure exerted by P. dominula on monarch caterpillars and the cascading effects on milkweed (Gomphocarpus physocarpus E. Mey.) fitness.

A survival study of monarch caterpillars was conducted across three habitat types (coastal, forest, and suburban). Caterpillar survival in suburban areas was lowest, with only 45% of caterpillars remaining after just 6 h of exposure to wasp foraging. Predation by P. dominula explained 85% of caterpillar deaths within the trial period.

The cascading effects of P. dominula presence were quantified through changes in the height, foliage, and reproductive output of milkweed plants. Monarch caterpillar predation by P. dominula was found to have a positive effect on milkweed fitness.

This study demonstrates a strong trophic cascade initiated by an invasive predator. These findings highlight the impacts an invasive species can have on local communities beyond their direct predatory effects.
Plasticity in bilateral hippocampi after a 3‐month physical activity programme in lung cancer patients
Authors: Vaquero Lucía , Rodríguez‐Fornells Antoni , Pera‐Jambrina María Ángeles , Bruna Jordi , Simó Marta
Published: December 2020

Background and purpose

Cancer treatments have deleterious effects on both brain structure and the cognition of lung cancer patients. Physical activity (PA) has beneficial effects on the cognition of healthy adults by eliciting brain plasticity, especially on the medial temporal lobe (hippocampus). Therefore, the aim was to study the neuroprotective effects of a 3‐month PA programme (PAP) on the brain structure and cognitive performance of lung cancer patients.

Methods

Twelve patients (seven non‐small‐cell lung cancer [NSCLC] patients following chemotherapy, five small‐cell lung cancer [SCLC] patients following chemotherapy and prophylactic cranial irradiation) agreed to complete the PAP and underwent baseline and 3‐month (post‐PAP) brain magnetic resonance imaging and neuropsychological evaluations (PAP group). Twelve lung cancer patients (seven NSCLC, five SCLC; non‐PAP group) and 12 healthy sex‐, age‐ and education‐matched controls were recruited and completed two evaluations separated by the same amount of time. A region of interest voxel‐based morphometry analysis focused on bilateral hippocampi was performed.

Results

Physical activity programme patients presented greater grey matter volume (GMV) across time in both hippocampi. Moreover, it was observed that SCLC patients in both the PAP and non‐PAP groups presented a time‐dependent GMV loss in bilateral hippocampi that was not significant in NSCLC patients. Importantly, the PA intervention decreased the magnitude of that GMV loss, becoming thus especially beneficial at the brain structural level for SCLC patients.

Conclusions

Our study demonstrates, using a neuroimaging approach for the first time, that PA is able to stop the deleterious effects of systemic chemotherapy and brain radiation on brain structures of the lung cancer population, especially in SCLC patients.
Functional reciprocity of proteins involved in mitosis and endocytosis
Authors: Yu Haibin , Li Yinshuang , Li Li , Huang Juanxin , Wang Xujuan , Tang Ruijun , Jiang Zhenghui , Lv Lu , Chen Fang , Yu Chunhong , Yuan Kai
Published: December 2020

Mitosis and endocytosis are two fundamental cellular processes essential for maintaining a eukaryotic life. Mitosis partitions duplicated chromatin enveloped in the nuclear membrane into two new cells, whereas endocytosis takes in extracellular substances through membrane invagination. These two processes are spatiotemporally separated and seemingly unrelated. However, recent studies have uncovered that endocytic proteins have moonlighting functions in mitosis, and mitotic complexes manifest additional roles in endocytosis. In this review, we summarize important proteins or protein complexes that participate in both processes, compare their mechanism of action, and discuss the rationale behind this multifunctionality. We also speculate on the possible origin of the functional reciprocity from an evolutionary perspective.
An approach to sustainable agriculture by untangling the fate of contrasting nitrogen sources in double‐season rice grown with and without biochar
Authors: Ullah Saif , Ali Izhar , Liang He , Zhao Quan , Wei Shanqing , Muhammad Ihsan , Huang Min , Amanullah  , Ali Nawab , Jiang Ligeng
Published: December 2020

Excessive use of inorganic nitrogen (N) fertilizers is the primary anthropogenic cause of low N use efficiency and environmental damage in wetland rice agriculture. However, little is known about the performance of traditional inorganic N sources used in paddy rice production. Biochar (BC) is considered to be a climate change mitigation tool that can enhance N uptake and utilization in N‐fertilized crops. To test this hypothesis, we performed a pot experiment to study the fate of15N‐labeled urea, ammonium nitrate, and ammonium sulfate with and without BC at tillering, heading, and maturity stages of rice in the early and late seasons of 2019. Fertilizer N leaching was significantly reduced by 75.69% and 110.32% in BC vs. non‐BC treatments across growth stages in the early and late seasons. The rate of leaching was lower for urea than for ammonium nitrate and ammonium sulfate. Furthermore, the addition of BC resulted in 55.58% and 41.33% higher soil15N concentrations in the early and late season, respectively, indicating that BC increased N adsorption.15N uptake by roots, stems, leaves, panicles, and grains averaged 52.39%, 37.14%, 40.86%, 36.37%, and 29.94% higher in BC‐amended pots than in BC‐free pots in both seasons. There were significant differences (p < 0.05) among N sources in terms of fertilizer N loss, residual N, and N uptake, and performance was ranked in the order urea > ammonium sulfate > ammonium nitrate. Overall, our results indicate that urea with BC is a preferable N source for double rice cropping systems compared with ammonium nitrate and ammonium sulfate.
Apocalyptic Arithmetic: Numbers and Worldview in the Book of Revelation
Authors: Newton Jon K.
Published: December 2020

One of the most noticeable features of the book of Revelation is the ubiquity of arithmetic in the text. In this article, I survey the arithmetical functions found in the text (not only numbers but functions such as multiplication and applied mathematics, such as measurements), and note some patterns in John’s use of numbers. Then the article explores precedents in the Hebrew Scriptures, Hellenistic culture (including astrology) and Jewish apocalyptic literature. I argue rhetorical criticism helps us identify what John is trying to do with his apocalyptic arithmetic. I draw on theological analysis, literary analysis (particularly the “writerly” nature of the text with its missing pieces for the audience to fill in) and especially intertextuality to understand his rhetorical strategy. I discuss various numbers but focus especially on ten and two passages (Rev 14:20 and 12:1‐6) as examples of John’s use of numbers and arithmetical functions. I conclude that John uses arithmetic to support his Christocentric narrative and worldview in addressing his Jewish and Greek audience.
The human melanocyte and melanoblast populations per unit area of epidermis in the rete ridge are greater than in the inter‐rete ridge
Authors: Hirobe Tomohisa , Enami Hisao , Nakayama Ai
Published: December 2020

Objective

In human skin, melanocytes and melanoblasts are mostly located in the epidermis in addition to hair follicles. In hairy skin such as mouse skin, the inter‐follicular epidermis is generally flat. In contrast, in human skin, the epidermis is wavy and possesses well‐developed rete ridges. It is not well understood what difference exists in cell function between melanocytes present in the inter‐rete ridge and those in the rete ridge. To clarify this problem, we first tried to determine the melanocyte and melanoblast populations per unit area of epidermis both in the rete ridge and inter‐rete ridge epidermis.

Methods

Thirty‐eight samples from normal skin sites of 28 patients (14 males and 14 females) aged from 5 to 76 years were fixed and processed to dopa and combined dopa‐premelanin reactions. The numbers of cells positive to the dopa (melanocytes) and combined dopa‐premelanin (melanoblasts and melanocytes) reactions were scored.

Results

The average melanocyte population/0.1 mm2 of the inter‐rete ridge was 74 cells, whereas that of the rete ridge was 147 cells. Moreover, the average melanoblast population/0.1 mm2 in the inter‐rete ridge was 43 cells, whereas that of the rete ridge was 131 cells. The melanoblast population in the rete ridge differed between female and male, but the melanocyte populations in the rete ridge and inter‐rete ridge and the melanoblast population in the inter‐rete ridge did not differ between female and male. However, no age difference in the melanocyte and melanoblast populations was observed between the rete ridge and inter‐rete ridge.

Conclusion

Human epidermal melanocytes and melanoblasts in the rete ridge exist more numerously than in the inter‐rete ridge.
IgG4‐positive plasma cells are more often detected in chronic periapical lesions arising from permanent rather than primary teeth
Authors: Polanco X. B. J. , Bertasso A. S. , Silveira H. A. , Yamamoto de Almeida L. , Almeida L. K. Y. , da Silva R. A. B. , da Silva L. A. B. , de Rossi A. , Nelson‐Filho P. , León J. E.
Published: December 2020

Aim

To characterize plasma cell subsets in chronic periapical lesions affecting permanent and primary teeth.

Methodology

Only chronic periapical lesions without root canal treatment were selected. Twenty‐one radicular cysts and 7 periapical granulomas affecting permanent teeth and 19 radicular cysts and 4 periapical granulomas affecting primary teeth were assessed for immunoglobulin (Ig) light chain (kappa and lambda), Ig heavy chain (IgG, IgG4, IgA, IgM and IgD) and plasma cell immunohistochemical markers (MUM1/IRF4, EMA and CD138). The data acquired were analysed by Student’s t test, Mann–Whitney U, Friedman test followed by Dunn's multiple comparison test and Spearman’s rank correlation.

Results

All cases were polyclonal (having similar kappa/lambda light chain ratios). IgG was most abundant compared to other Ig heavy chains (all, P < 0.001); like Ig light chains, but unlike IgA, there was greater expression of IgG in the primary compared to the permanent dentition, for both radicular cysts (P < 0.001) and periapical granulomas (P = 0.53). Notably, IgG4 expression was greater in the permanent than the primary dentition, for both radicular cyst (P < 0.05) and periapical granuloma (P = 0.65). IgM and IgD expression was scarce and variable, whereas plasma cell populations were detected efficiently through EMA, CD138 and MUM1/IRF4 markers, the latter being more sensitive in both dentitions.

Conclusions

There were slight variations in the Ig light and heavy chain profiles in chronic periapical lesions when comparing the permanent and primary dentitions. The ability of IgG4+ plasma cell infiltration to modulate inflammatory responses in chronic periapical lesions arising from permanent as opposed to primary teeth should be considered in future studies.
Response rate and diagnostic accuracy of early PET‐CT during neo‐adjuvant therapies in oesophageal adenocarcinoma: A systematic review and meta‐analysis
Authors: Foley Kieran G. , Jeffries Jacqueline , Hannon Clare , Coles Bernadette , Bradley Kevin M. , Smyth Elizabeth
Published: December 2020

Purpose

Only 25% of oesophageal adenocarcinoma (OAC) patients have a pathological response to neo‐adjuvant therapy (NAT) before oesophagectomy. Early response assessment using PET imaging may help guide management of these patients. We performed a systematic review and meta‐analysis to synthesise the evidence detailing response rate and diagnostic accuracy of early PET‐CT assessment.

Methods

We systematically searched several databases including MEDLINE and Embase. Studies with mixed cohorts of histology, tumour location and a repeat PET‐CT assessment after more than one cycle of NAT were excluded. Reference standard was pathological response defined by Becker or Mandard classifications. Primary outcome was metabolic response rate after one cycle of NAT defined by a reduction in maximum standardised uptake value (SUVmax) of 35%. Secondary outcome was diagnostic accuracy of treatment response prediction, defined as the sensitivity and specificity of early PET‐CT using this threshold. Quality of evidence was also assessed. Random‐effects meta‐analysis pooled response rates and diagnostic accuracy. This study was registered with PROSPERO (CRD42019147034).

Results

Overall, 1341 articles were screened, and 6 studies were eligible for analysis. These studies reported data for 518 patients (aged 27‐78 years; 452 [87.3%] were men) between 2005 and 2020. Pooled sensitivity of early metabolic response to predict pathological response was 77.2% (95% CI 53.2%‐100%). Significant heterogeneity existed between studies (I2 = 80.6% (95% CI 38.9%‐93.8%), P = .006). Pooled specificity was 75.0% (95% CI 68.2%‐82.5%), however, no significant heterogeneity between studies existed (I2 = 0.0% (95% CI 0.0%‐67.4%), P = .73).

Conclusion

High‐quality evidence is lacking, and few studies met the inclusion criteria of this systematic review. The sensitivity of PET using a SUVmax reduction threshold of 35% was suboptimal and varied widely. However, specificity was consistent across studies with a pooled value of 75.0%, suggesting early PET assessment is a better predictor of treatment resistance than of pathological response. Further research is required to define optimal PET‐guided treatment decisions in OAC.
Differences in pulmonary group 2 innate lymphoid cells are dependent on mouse age, sex and strain
Authors: Loering Svenja , Cameron Guy JM , Bhatt Nirmal P , Belz Gabrielle T , Foster Paul S , Hansbro Philip M , Starkey Malcolm R
Published: December 2020

Innate lymphoid cells (ILCs) are resident in the lung and are involved in both the maintenance of homeostasis and the pathogenesis of respiratory diseases. In this study, murine lung ILCs were characterized using flow cytometry and the impact of mouse age, sex and strain were assessed. Lung ILCs were found as early as postnatal day 4 and numbers peaked at 2 weeks, and then decreased as the lung matured. During postnatal lung development, ILC expressed differential amounts of group 2 ILC (ILC2)‐associated cell surface antigens including ST2, CD90.2 and ICOS. Using Il5venusIl13td‐tomato dual reporter mice, neonates were found to have increased constitutive interleukin (IL)‐13 expression compared with adult mice. Neonates and adults had similar ratios of IL‐5+CD45+ leukocytes; however, these cells were mostly composed of ILCs in neonates and T cells in adults. Sex‐specific differences in ILC numbers were also observed, with females having greater numbers of lung ILCs than males in both neonatal and adult mice. Female lung ILCs also expressed higher levels of ICOS and decreased KLRG1. Mouse strain also impacted on lung ILCs with BALB/c mice having more ILCs in the lung and increased expression of ST2 and ICOS compared with C57BL/6J mice. Collectively, these data show that lung ILC numbers, cell surface antigen expression, IL‐5 and IL‐13 levels differed between neonatal and adult lung ILCs. In addition, cell surface antigens commonly used for ILC2 quantification, such as ST2, CD90.2 and ICOS, differ depending on age, sex and strain and these are important considerations for consistent universal identification of lung ILC2s.
Tabu search with strategic oscillation for improving collection assignment plans of waste electric and electronic equipment
Authors: Ríos‐Mercado Roger Z. , González‐Velarde José Luis , Maldonado‐Flores Jabneel R.
Published: December 2020

This paper studies a districting problem arising in the collection of waste of electrical and electronic equipment. Given a set of collection bins, where users return end‐of‐life electronic goods, located across a region or country, the design problem involves assigning these bins to the companies responsible for the collection at a later stage. This assignment must meet specific planning and legal requirements such as a fair household distribution according to each company's market share and a fair assignment based on the bin infrastructure quality. According to the current law, this assignment must be done in such a way to avoid, to the best possible extent, regional monopolies. This anti‐monopoly requirement is achieved by maximizing a dispersion function. A tabu search metaheuristic with an advanced feature of strategic oscillation is proposed for this ‐hard combinatorial optimization problem. The particular components are designed to exploit the mathematical structure of the problem entirely. Besides, a few upper bounding schemes are developed and tested. The empirical work shows the tabu search's effectiveness and its components over a broad set of instances from the literature. In particular, the strategic oscillation idea turned out to have a very positive impact. Overall, the proposed metaheuristic outperformed the best existing method for this problem.
Rethinking Macro Measurement
Authors: Sweeney James
Published: December 2020

Economists have long recognized that widely reported and followed economic indicators such as GDP, productivity, and real wage growth often fail to do a good job of capturing the concepts they purport to measure. And as the chief economist of Credit Suisse begins by noting in this article, this mismeasurement problem has been viewed as significant in the cases of inflation and inflation‐adjusted (or real) measures, and even more troubling in the case of productivity.

Even before the onset of the COVID‐19 pandemic, the U.S. economy, as viewed through the lens of conventional macro statistics, was almost universally agreed to be struggling with pronounced demographic and productivity slowdowns. But if the slowdowns in nominal GDP and wage growth are indisputable, the author suggests that systematic overstatement of U.S. inflation may well have not only exaggerated the extent of such slowdowns, but obscured the possibility of actual increases in productivity and real wages during the past three or four decades.

Along with the possible mismeasurement of some macroeconomic data, the author also discusses the ways in which macro measures tend to be misused. Though the limitations of macro data have long been understood by experts, the widespread use and uncritical acceptance of such numbers as representing concepts such as living standards, the cost of living, worker efficiency, technology growth, and welfare have very significant implications for today's policy debates and public assessment of the health of the economy. After discussing some of these measurement challenges and calling for greater acknowledgment of the limitations of conventional macro statistics by economists when citing them, the author suggests that “the prestige of national accounts data has likely peaked,” and better approaches appear to be emerging. Notable among such approaches are alternative measures, some spawned by the pandemic, that are improving how economists track the economy in real time and, in so doing, making possible “a deeper, more accurate, and more realistic view of economic activity.”
Using ESG to Enhance Fixed‐Income Returns: The Case of Inherent Group
Authors: Mirchandani Nikhil , Rossetti Chelsea
Published: December 2020

The authors discuss how their investment firm uses environmental and social as well as financial considerations to produce superior fixed‐income returns for its limited partners. The firm is committed to the idea that, by making ESG analysis part of its deal sourcing, underwriting, monitoring, issuer engagement, and portfolio management decisions, such labor‐intensive practices end up providing valuable investment insights that help drive long‐term value creation.

Using three of its investments as case studies—two involving short credit positions and one long position—the authors show how the incorporation of ESG in leveraged credit analysis has not only differentiated its approach, but proved effective in identifying undervalued (and distressed) debt as well as overvalued credits ripe for a fall. Conviction about the firm's two credit shorts rested on fundamental analysis reinforced by social and governance considerations—one involving opioids and price gouging, the other a conflicted governance structure. The third case involved investment in the distressed credit of a California utility premised on both environmental tailwinds from investments in renewables and a view of the bankruptcy process, triggered by California wildfire liabilities, as a social and economic forum for accomplishing an overall welfare‐increasing reassignment of risks and rewards—one likely to benefit society as a whole as well as (some) investors.
The Economic (Not Literary) Offenses of Michael Lewis: The Case of The Big Short and the Global Financial Crisis
Authors: Chew Don
Published: December 2020

In a shameless abuse of editorial prerogative, the editor of this journal uses Lewis's bestseller as a pretext and occasion for presenting his own theory of the cause of the global financial crisis of 2008. After thanking Lewis for his entertaining and informative account of aspects of the mortgage backed securities markets, the author goes on to cite Peter Wallison's “Dissent” to the 900‐page report compiled by the Financial Crisis Inquiry Commission as “the only plausible explanation of the crisis he has encountered.” Wallison's main focus is the debasement of U.S. mortgage underwriting standards in the name of expanded home ownership that was initiated by U.S. law and policy makers, starting with President Clinton in 1992 and carried on by the Bush Administration.

Along with the 31 million U.S. mortgages (or 56% of the 55 million total) that in June 2008 were classified “sub‐prime” or “Alt‐A”—with typical down payments ranging from anywhere from 0‐3%—the author identifies as the second main contributor to the crisis the “absurdly” low bank capital ratios (roughly 3% of total assets during the height of the crisis) that encouraged excessive risk‐taking throughout the system. Indeed, in what some observers have identified as a “game of bank bargains,” the low capital ratios were widely understood to be concessions by Congress and regulators to banks in return for their relaxation of lending standards—again, all in the name of expanded home ownerships. But this combination of policies, as we now know, did not end well.
The moving learner: Object manipulation in virtual reality improves vocabulary learning
Authors: Fuhrman Orly , Eckerling Anabel , Friedmann Naama , Tarrasch Ricardo , Raz Gal
Published: December 2020

A challenging aspect of foreign language acquisition is learning new vocabulary. Research has demonstrated the benefits of motor action to vocabulary learning, though these findings are rarely translated into teaching and learning practices. In this work, we present a novel paradigm for vocabulary learning in a virtual reality environment, capitalizing on the prominent advantages of this technology as an ‘embodied learning’ tool. Hebrew‐speaking adults explored a virtual room and learned the Finnish names of 40 daily objects. Every participant learned the new object names under three conditions: (1) Watch‐only: watching the object without performing any movement (2) performing an irrelevant movement or (3) performing a manipulation movement that implied its habitual use. Participants completed a word–picture matching test after each training block, as well as additional word–picture matching and recall tests a week after the initial training session. The overall results demonstrate improved comprehension rates for items that were learned in the manipulation movement condition compared to the irrelevant movement condition, both in the initial learning session and 1 week following it. These initial findings suggest that VR technology may indeed hold the potential to offer a more authentic, multisensory and motor context to efficient foreign language learning.
Loureirin B activates GLP‐1R and promotes insulin secretion in Ins‐1 cells
Authors: Ding Yanting , Xia Sijing , Zhang Han , Chen Qin , Niu Bing
Published: December 2020

Loureirin B (LB) is a natural product derived from Sanguis draconis, which has hypoglycaemic effects. In order to research the possible target of LB in the treatment of diabetes, molecular docking was used to simulate the interaction between LB and potential targets, and among them, glucagon‐like peptide‐1 receptor (GLP‐1R) had the optimal results. Further, spectroscopy and surface plasmon resonance (SPR) experiments were applied to detect the interaction between LB and GLP‐1R. Ultimately, after GLP‐1R siRNA interfering the expression of GLP‐1R in Ins‐1 cell, the promoting insulin secretion of LB was weaken, which directly proved that GLP‐1R plays an important role. These results show that LB promotes insulin secretion of Ins‐1 cells through GLP‐1R. Hence, the strategy of LB as a prodrug will provide a potential approach for non‐peptide GLP‐1R agonist.
MBNL1 regulates isoproterenol‐induced myocardial remodelling in vitro and in vivo
Authors: Xu Yao , Liang Chen , Luo Ying , Zhang Tongcun
Published: December 2020

Myocardial remodelling is a common phenomenon in cardiovascular diseases, which threaten human health and the quality of life. Due to the lack of effective early diagnosis and treatment methods, the molecular mechanism of myocardial remodelling should be explored in depth. In this study, we observed the high expression of MBNL1 in cardiac tissue and peripheral blood of an isoproterenol (ISO)‐induced cardiac hypertrophy mouse model. MBNL1 promoted ISO‐induced cardiac hypertrophy and fibrosis by stabilizing Myocardin mRNA in vivo and in vitro. Meanwhile, an increase in MBNL1 may induce the apoptosis of cardiomyocytes treated with ISO via TNF‐α signalling. Interestingly, MBNL1 can be activated by p300 in cardiomyocytes treated with ISO. At last, Myocardin can reverse activate the expression of MBNL1. These results suggest that MBNL1 may be a potential target for the early diagnosis and clinical treatment of myocardial remodelling.
Potential of pulsed electric field to control Aspergillus parasiticus, aflatoxin and mutagenicity levels: Sesame seed quality
Authors: Bulut Nurullah , Atmaca Bahar , Akdemir Evrendilek Gülsün , Uzuner Sibel
Published: December 2020

Seed processing technologies are essential for seed safety and functionality through protection of physicochemical quality, pathogen inactivation, aflatoxin detoxification and alleviation of mutagenicity. Design of a pilot‐scale unit of pulsed electric fields (PEF) to treat sesame seeds with respect to quality parameters, Aspergillus parasiticus inactivation and aflatoxin reduction as well as alleviation of aflatoxin mutagenicity were prompted in this study. PEF energy ranged from 0.97 to 17.28 J achieved maximum reductions of peroxide value and acidity number of 67.4 and 85.7%, respectively, and did not change color L*, a*, b* and hue values. A 60% reduction of A. parasiticus counts occurred at the maximum PEF energy. Aflatoxins G1, G2, B1, and B2 contents decreased by 94.7, 92.7, 86.9, and 98.7%, respectively. Except for the samples treated by 2.16 J with 100 μg/plate and by 6.80 J with 10 μg/plate, PEF treatment provided elimination of aflatoxin mutagenity. It is concluded that PEF treatment can be used to treat sesame seeds with preservation of physicochemical properties, inactivation of A. parasiticus and decomposition of aflatoxins with reduced mutagenicity.