bluuebunny/crossref_metadata_2025 huggingface dataset:
Multifunctionality of CD8+ T cells and PD‐L1 expression as a biomarker of anti‐PD‐1 antibody efficacy in advanced melanoma
Authors: Manabe Keiko , Yamasaki Osamu , Nakagawa Yuki , Miyake Tomoko , Udono Heiichiro , Morizane Shin
Published: April 2021

Anti‐programmed cell death protein‐1 (PD‐1) antibodies have become a standard treatment for advanced melanoma. However, a predictive biomarker for assessing the efficacy of anti‐PD‐1 antibodies has not been identified. In cancer, CD8+ T cells specific for tumor antigens undergo repeated T‐cell receptor stimulation due to the persistence of cancer cells and gradually lose their ability to secrete interleukin 2 (IL‐2), tumor necrosis factor‐α (TNF‐α), and interferon‐γ (IFN‐γ). We aimed to evaluate multi‐cytokine production and immune exhaustion of peripheral CD8+ T cells in melanoma patients treated with anti‐PD‐1 antibodies. Twenty‐four melanoma patients treated with nivolumab were included. Effector cytokine production (IL‐2, TNF‐α, and IFN‐γ) and expression of an exhaustion marker (PD‐1) in patients’ CD8+ cells were analyzed with flow cytometry. The relationships between parameters such as the neutrophil‐to‐lymphocyte ratio (NLR) and clinical response to nivolumab were examined. Immunohistochemistry for programmed death‐ligand 1 (PD‐L1) expression in tumor cells and tumor‐infiltrating lymphocytes (TILs) and analysis of their association with clinical response were performed. The clinical response rate to nivolumab was 29%. Regarding TILs, NLR, and several other parameters, no significant difference was found between responders and non‐responders. The responder group showed an increase in the percentage of PD‐1+CD8+/TNF‐α+IFN‐γ+ or PD‐1+CD8+/IFN‐γ+IL‐2+TNF‐α+ T cells compared to non‐responders. Positivity for PD‐L1 expression was significantly higher in the responder group than the non‐responder group. In advanced melanoma, the percentage of multifunctional CD8+PD‐1+ T cells and PD‐L1 expression in the tumors may be a biomarker for a good response to anti‐PD‐1 antibody monotherapy.
A widespread mechanism in ectomycorrhizal fungi to access nitrogen from mineral‐associated proteins
Authors: Wang Tao , Persson Per , Tunlid Anders
Published: April 2021

A large fraction of nitrogen (N) in forest soils is present in mineral‐associated proteinaceous compounds. The strong association between proteins and minerals limits microbial accessibility to this source, which is a relatively stable reservoir of soil N. We have shown that the ectomycorrhizal (ECM) fungus Paxillus involutus can acquire N from iron oxide‐associated proteins. Using tightly controlled isotopic, spectroscopic and chromatographic experiments, we demonstrated that the capacity to access N from iron oxide‐associated bovine serum albumin (BSA) is shared with the ECM fungi Hebeloma cylindrosporum and Piloderma olivaceum. Despite differences in evolutionary history, growth rates, exploration types and the decomposition mechanisms of organic matter, their N acquisition mechanisms were similar to those described for P. involutus. The fungi released N from mineral‐associated BSA by direct action of extracellular aspartic proteases on the mineral‐associated BSA, without initial desorption of the protein. Hydrolysis was suppressed by the adsorption of proteases to minerals, but this adverse effect was counteracted by the secretion of compounds that conditioned the mineral surface. These data suggest that the enzymatic exudate‐driven mechanism to access N from mineral‐associated proteins is found in ECM fungi of multiple lineages and exploration types.
Expanded hemodialysis: Is anticoagulation of the dialysis circuit different from online hemodiafiltration and high‐flux hemodialysis?
Authors: Santos Alba , Macías Nicolás , Vega Almudena , Abad Soraya , Linares Tania , Aragoncillo Inés , Cruzado Leonidas , Pascual Cristina , Goicoechea Marian , López‐Gómez Juan Manuel
Published: April 2021

Expanded hemodialysis (HDx) has a high capacity for removing medium and medium‐large molecules; however, there are no specific recommendations during HDx for anticoagulation of the dialysis circuit. We aimed to evaluate the differences in the efficacy of anticoagulation procedures using the venous port and 40 mg enoxaparin in HDx compared to high‐flux hemodialysis (HF‐HD) and postdilution online hemodiafiltration (HDF). We compared anticoagulant activity in 11 patients in HDx, HF‐HD, and HDF under similar dialysis conditions. In the 33 dialysis sessions, 40 mg enoxaparin was administered through the venous port, and pre‐ and postdialysis antifactor Xa activity (aXa) and activated partial thromboplastin time (APTT), postdialysis clotting time of the vascular access, visual clotting score of the dialyzer, and any complications with the extracorporeal circuit or bleeding were registered. APTT postdialysis in HDx was not significantly different from that in HF‐HD and HDF. Postdialysis aXa in HDx was not significantly different from that in HF‐HD and HDF. We found no significant differences in visual clotting score of the dialyzer. Enoxaparin administered through the venous port was sufficient for anticoagulation within the extracorporeal circuit in HDx, HF‐HD, and HDF. There were no differences in postdialysis aXa or APTT, most likely because when low molecular–weight heparin is applied through venous port, lesser enoxaparin concentration reaches the dialyzer. Thus, we conclude that the dose of enoxaparin administered through the venous port should not be adjusted according to dialysis technique.
Comparison of functional patency rates between paclitaxel‐eluting versus plain balloon angioplasty in hemodialysis patients with central venous stenosis: An intra‐individual comparison study
Authors: Cakir Semih , Guzelbey Tevfik , Mutlu Ilhan N. , Kilickesmez Ozgur
Published: April 2021

Central venous stenosis (CVS) is usually a late‐diagnosed clinical entity that is common in hemodialysis patients. It causes various problems ranging from hemodialysis difficulty to loss of the arterio–venous (A–V) fistula. In the present study, we aimed to determine the effect of drug eluting balloon while excluding the influence of other variable factors by evaluating the same individuals with plain and paclitaxel‐eluting balloons. This research was a prospective study of 18 symptomatic hemodialysis patients (age 50.9 ± 14.0 years, range 32–72 years; 11 male, 7 female) with CVS who underwent treatment by plain balloon angioplasty (PBA) and paclitaxel‐eluting balloon angioplasty (PEBA) in our hospital from January 2016 to June 2017. First, third and sixth month central vein patency rates were compared. The median patency rates of central veins were 109.0 (range: 10–324) days after PBA and 238.5 (range: 157–501) days after PEBA (p < 0.001). There was no statistically significant difference between PBA and PEBA angioplasty in one‐month patency (p ˃ 0.05). By contrast, a statistically significant difference was found between 3‐ and 6‐month patency rates (p = 0.031 and p ˂ 0.001, respectively). Kaplan–Meier analysis revealed that the primary cumulative patency rate of PEBA was significantly longer than that of PBA (p ˂ 0.001). In this prospective study, PEBA patency is superior to PBA patency in the treatment of CVS in dialysis patients.
Lu177‐PSMA therapy for men with advanced prostate cancer: 18 months survival analysis in a single Australian tertiary institution
Authors: Tatkovic Annaleis , McBean Rhiannon , Wong David
Published: April 2021

Introduction

Radioligand therapies, or ‘theranostics’, have an emerging role in patients with metastatic castration‐resistant prostate cancer (mCRPC). Lutetium‐177 (Lu), targeting prostate‐specific membrane antigen (PSMA), has demonstrated promising outcomes including reduced disease progression and improved overall survival. We aim to determine overall survival demonstrated by our LuPSMA patient cohort to date.

Methods

Kaplan–Meier survival analysis and log‐rank test were performed on all LuPSMA therapy patients with at least 12 months of follow‐up data available (n = 68). Comparison across patients was made based on several variables including the baseline characteristics of prostate‐specific antigen (PSA) level, maximum standard uptake value (SUVmax) and metastasis site and by biochemical response.

Results

The 18‐month overall survival estimate for the patient cohort was 63.8%. Patients with baseline serum PSA <20 µg/L had a greater 18‐month survival estimate (79.9%) compared to PSA ≥20 µg/L (53.8%; P < 0.05). Patients with an SUVmax >15 had an 18‐month survival estimate of 56.0%, compared to 38.0% in patients with SUVmax ≤15 (P < 0.05). No significant difference in overall survival was observed by metastasis site. Both a decrease in PSA after two LuPSMA therapy cycles and the maximum response over the treatment course being a decline in PSA were indicative of greater overall survival (P < 0.01 and P < 0.001 respectively).

Conclusion

Our study reported an 18‐month overall survival of 64% in patients with mCRPC who have undergone LuPSMA therapy. Our study identified that baseline serum PSA, SUVmax and biochemical response to treatment are prognostic markers for increased overall survival.
Genetic landscape clustering of a large DNA barcoding data set reveals shared patterns of genetic divergence among freshwater fishes of the Maroni Basin
Authors: Papa Yvan , Le Bail Pierre‐Yves , Covain Raphaël
Published: April 2021

The Maroni is one of the most speciose basins of the Guianas and hosts a megadiverse freshwater fish community. Although taxonomic references based on morphological identification exist for both the Surinamese and Guianese parts of the basin, there are still taxonomic uncertainties concerning the status of several species. We used COI sequences of 1284 fish in conjunction with morphological and biogeographical evidence to assist with species delineation and discovery in order to validate and standardize the current taxonomy. This resulted in a final DNA barcode data set of 199 fish species (125 genera, 36 families and eight orders; 68.86% of strictly freshwater fishes from the basin), among which 25 are new putative candidate species flagged as requiring taxonomic update. DNA barcoding delineation through Barcode Index Numbers (BINs) revealed further cryptic diversity (230 BINs in total). To explore global genetic patterns across the basin, genetic divergence landscapes were computed for 128 species, showing a global trend of high genetic divergence between the Surinamese southwest (Tapanahony and Paloemeu), the Guianese southeast (Marouini, Litany, Tampok, etc.), and the river outlet in the north. This could be explained by lower levels of connectivity between these three main areas and/or the exchange of individuals between these areas and the neighbouring basins. A new method of ordination of genetic landscapes successfully assigned species into cluster groups based on their respective pattern of genetic divergence across the Maroni Basin: genetically homogeneous species were effectively discriminated from species showing high spatial genetic fragmentation and possible lower capacity for dispersal.
Maternal and child genetic liability for smoking and caffeine consumption and child mental health: an intergenerational genetic risk score analysis in the ALSPAC cohort
Authors: Schellhas Laura , Haan Elis , Easey Kayleigh E. , Wootton Robyn E. , Sallis Hannah M. , Sharp Gemma C. , Munafò Marcus R. , Zuccolo Luisa
Published: April 2021

Background and aims

Previous studies suggest an association between maternal tobacco and caffeine consumption during and outside of pregnancy and offspring mental health. We aimed to separate effects of the maternal environment (intrauterine or postnatal) from pleiotropic genetic effects.

Design

Secondary analysis of a longitudinal study. We (i) validated smoking and caffeine genetic risk scores (GRS) derived from published genome‐wide association study (GWAS) for use during pregnancy, (ii) compared estimated effects of maternal and offspring GRS on childhood mental health outcomes and (iii) tested associations between maternal and offspring GRS on their respective outcomes.

Setting

We used data from a longitudinal birth cohort study from England, the Avon Longitudinal Study of Parents and Children (ALSPAC).

Participants

Our sample included 7921 mothers and 7964 offspring.

Measurements

Mental health and non‐mental health phenotypes were derived from questionnaires and clinical assessments: 79 maternal phenotypes assessed during and outside of pregnancy and 71 offspring phenotypes assessed in childhood (<10 years) and adolescence (11–18 years).

Findings

The maternal smoking and caffeine GRS were associated with maternal smoking and caffeine consumption during pregnancy (2nd trimester: Psmoking = 3.0 × 10−7, Pcaffeine = 3.28 × 10−5). Both the maternal and offspring smoking GRS showed evidence of association with reduced childhood anxiety symptoms (βmaternal = −0.033; βoffspring = −0.031) and increased conduct disorder symptoms (βmaternal = 0.024; βoffspring = 0.030), after correcting for multiple testing. Finally, the maternal and offspring smoking GRS were associated with phenotypes related to sensation seeking behaviours in mothers and adolescence (e.g. increased symptoms of externalising disorders, extraversion and monotony avoidance). The caffeine GRS showed weaker evidence for associations with mental health outcomes.

Conclusions

We did not find strong evidence that maternal smoking and caffeine genetic risk scores have a causal effect on offspring mental health outcomes. Our results confirm that the smoking genetic risk scores also captures liability for sensation seeking personality traits.
Oral health status and dental treatment needs of psoriatic patients with different therapy regimes
Authors: Olejnik M , Adamski Z , Osmola‐Mankowska A , Nijakowski K , Dorocka‐Bobkowska B
Published: April 2021

The aim of the study was to investigate the dental treatment requirements and oral health status of psoriatic patients with different severities of the disease, managed by different methods, including biological therapies.

Methods

One hundred and twenty‐seven patients diagnosed with psoriasis were enrolled in this study. All subjects completed a general medical history and a Dermatology Life Quality Index (DLQI) questionnaire. The severity of the disease was assessed using the Psoriasis Area and Severity Index (PASI) scale and a DLQI questionnaire. In order to evaluate the oral health status, the following techniques were used: Approximal Plaque Index (API), the Community Periodontal Index (CPI) and the Decayed, Missing and Filled Teeth (DMFT) index.

Results

Patients treated with biologicals presented a significantly lower mean CPI index and required no surgical interventions. Subjects managed with topical therapy had significantly more decayed teeth and higher treatment needs. Only 11.3% of patients did not require dental intervention.

Conclusions

The study revealed a high need for dental interventions in patients with psoriasis. The type of treatment used may affect the oral health status of patients. However, further investigations are required to explain the significantly lower CPI value in the group treated with biologicals.
Patterns of co‐occurrence and body size in dragonflies and damselflies (Insecta: Odonata) in preserved and altered Amazonian streams
Authors: Oliveira‐Junior José Max B , Teodósio Maria Alexandra , Juen Leandro
Published: April 2021

Interspecific interactions, such as competition, are among the key factors that determine the distribution, abundance and diversity of organisms in natural communities of aquatic ecosystems. However, a marked reduction in the environmental integrity of streams may lead to modifications of the natural dynamics of these communities, including co‐occurrence patterns and body size. In the Amazon, the replacement of forests by production systems is one of the leading causes of alterations to riverine ecosystem. The insects of the order Odonata (dragonflies and damselflies) are predators known to compete for environmental resources but are also sensitive to environmental changes such as those caused by shifts in land use. In this scenario, the present study evaluated species co‐occurrence and body size patterns in adult odonates found at preserved and altered Amazonian streams, to determine whether there are morphological differences among the species that enable their coexistence. During the study, 98 streams in the eastern Amazon region were sampled, and a habitat integrity index (HII) was used to evaluate the integrity of each stream (based on variables such as the condition of the riparian vegetation and channel, and land use). Ten male individuals were selected from each species, and nine morphometric measurements were taken from each individual. A total of 3588 specimens were collected and distributed in nine families, 49 genera and 134 species. We found a non‐random pattern of co‐occurrence in the species of the odonate suborder Zygoptera and a random pattern in the suborder Anisoptera, in both preserved and altered streams. We found morphological divergence between pairs of zygopteran species, in the whole sample and both categories of stream integrity separately. No such morphological divergence was found in the pairs of anisopteran species. The distribution patterns of odonate species are limited by specific environmental processes, especially in preserved environments and in specialists, such as most zygopterans. Zygopteran species have more specific microhabitat requirements, which could explain this pattern, whereas anisopterans prefer open environments, which usually have a greater supply of resources, although there tends to be less microhabitat heterogeneity, which leads to reduced competition. Given this, future studies should use limiting similarity (e.g. morphological attributes) in addition to environmental and spatial factors to better understand the factors structuring these communities. Among these mechanisms, the effects of common ancestry (phylogenetic inertia) and biogeography are important factors that should also be considered in future studies.
CSI Index Reconstitutions: A Quasi‐Natural Experiment in China*
Authors: Li Hongda , Selvam Srinivasan
Published: April 2021

We investigate whether the China Securities Index (CSI) reconstitutions are suitable as a quasi‐natural experiment to investigate the influence of institutional ownership. Using both actual and predicted CSI 300 and 500 index constituents, we document a sharp discontinuity in institutional ownership, especially of domestic mutual funds around index thresholds, overcoming a key concern of the Russell reconstitution approach. Using inclusion in the CSI 500 index as an instrument, we find that higher institutional ownership increases dividend payouts, improves firm performance, and improves the firms’ information environment. These findings inform us of the salience of domestic institutions in emerging markets.
Risky Appearances, Skillful Performances: Female Islamic Preachers and Professional Style in Malaysia
Authors: Kloos David
Published: April 2021

Mass involvement of women in Islamic associations and public religious expressions has led to an unprecedented demand for women Islamic authorities. Yet, paradoxically, the global Islamic revival has also strengthened conservative norms with regard to the exposure of women's bodies and voices. In Malaysia, women Islamic popular preachers navigate, and to some extent obviate, this tension between publicity and modesty by cultivating a professional style. In the context of mass education, mass mediatization, and a public sphere saturated with techno‐political language, these women combine religious guidance with knowledges and performances more commonly associated with nonreligious professions. They perceive their work and careers as an accumulation of professional skills. They work from offices as well as traditional religious institutions. And they provide specialized, often paid services ranging from conventional religious teaching and preaching to professionalized Islamic healing and media performances. The increasing salience of a professional persona in women's preaching requires an analysis that moves beyond pious exemplarity—a central concern of many anthropological studies of women's religious authority—and that recognizes the central role of professional style and associated performances in the shaping of new Muslim femininities. [religious authority, professional style, women preachers, Islam, Malaysia]
Calmodulin is involved in the occurrence of extracellular Ca2+‐dependent full‐type hyperactivation in boar ejaculated spermatozoa incubated with cyclic AMP analogs
Authors: Wada Atsushi , Harayama Hiroshi
Published: April 2021

In mammals, hyperactivation is essential for sperm fertilization with oocytes in vivo. Two types of hyperactivation “full‐type and nonfull‐type patterns” can be observed in the spermatozoa from boars, bulls, and mice. We have a hypothesis that the full‐type hyperactivation is a physiological (in vivo) pattern and are elucidating its molecular bases. The aims of this study were to detect calmodulin in boar sperm flagella by Western blotting and indirect immunofluorescence and to investigate effects of extracellular Ca2+ and calmodulin antagonists “W‐7 and W‐5 (W‐5; a less potent antagonist)” on the occurrence of full‐type hyperactivation in boar spermatozoa. Calmodulin was specifically detected as the 17‐kDa antigen in the flagella and postacrosomal region of the heads. Full‐type hyperactivation could be induced effectively in the samples incubated with 3.42 mM CaCl2 for 120–180 min, and it was significantly reduced in the concentration‐dependent manners of W‐7 and W‐5. Suppressing effects of W‐7 on the full‐type hyperactivation were stronger than those of W‐5. These observations indicate that flagellar calmodulin is involved in the occurrence of extracellular Ca2+‐dependent full‐type hyperactivation in boar spermatozoa. This is the first indication of the intracellular Ca2+‐sensing molecule which can function in the full‐type hyperactivation.
Safety, pharmacokinetics and pharmacodynamics of HTL0009936, a selective muscarinic M1‐acetylcholine receptor agonist: A randomized cross‐over trial
Authors: Bakker Charlotte , Prins Samantha , Liptrot Jan , Hart Ellen P. , Klaassen Erica S. , Brown Giles A. , Brown Alastair , Congreve Miles , Weir Malcolm , Marshall Fiona H. , Stevens Jasper , Cross David M. , Tasker Tim , Nathan Pradeep J. , Groeneveld Geert Jan
Published: April 2021

Aims

HTL0009936 is a selective M1 muscarinic receptor agonist in development for cognitive dysfunction in Alzheimer's disease. Safety, tolerability and pharmacokinetics and exploratory pharmacodynamic effects of HTL0009936 administered by continuous IV infusion at steady state were investigated in elderly subjects with below average cognitive functioning (BACF).

Methods

Part A was a four‐treatment open label sequential study in healthy elderly investigating 10–83 mg HTL0009936 (IV) and a 24 mg HTL0009936 single oral dose. Part B was a five‐treatment randomized, double‐blind, placebo and physostigmine controlled cross‐over study with IV HTL0009936 in elderly subjects with BACF. Pharmacodynamic assessments were performed using neurocognitive and electrophysiological tests.

Results

Pharmacokinetics of HTL0009936 showed dose‐proportional increases in exposure with a mean half‐life of 2.4 hours. HTL0009936 was well‐tolerated with transient dose‐related adverse events (AEs). Small increases in mean systolic blood pressure of 7.12 mmHg (95% CI [3.99–10.24]) and in diastolic of 5.32 mmHg (95% CI [3.18–7.47]) were noted at the highest dose in part B. Overall, there was suggestive, but no definitive, positive or negative pharmacodynamic effects. Statistically significant effects were observed on P300 with HTL0009936 and adaptive tracking with physostigmine.

Conclusions

HTL0009936 showed well‐characterized pharmacokinetics and single doses were safe and generally well‐tolerated in healthy elderly subjects. Due to physostigmine tolerability issues and subject burden, the study design was changed and some pharmacodynamic assessments (neurocognitive) were performed at suboptimal drug exposures. Therefore no clear conclusions can be made on pharmacodynamic effects of HTL0009936, although an effect on P300 is suggestive of central target engagement.
Presuming incapacity in anorexia nervosa is indefensible: A reply to Ip
Authors: Miller Tate Alex James
Published: April 2021

Eric C. Ip has recently argued that seriously anorexic service users ought to be assumed to be legally incapacitous to refuse life‐saving artificial nutrition unless they can demonstrate otherwise, reversing the ordinary legal presumption in place to protect patients’ liberty and values. In this response, I argue against this proposal on two grounds. Firstly, the proposal is wrongfully discriminatory; it would expose service users to serious harm, and wrong them in numerous ways, on the basis of their diagnosis alone, without significantly benefitting them in any way relative to the status quo. Secondly, he is unable to show that a large majority of such service users actually are incapacitous to refuse life‐saving artificial nutrition. This means that his proposal would likely involve declaring a large number of actually capacitous patients to be incapacitous, without even the requirement of a formal assessment, and burdening them with the responsibility of proving their clinical team wrong if they wish to avoid deprivation of liberty and/or compelled treatment. Given this, his proposal is indefensible.
A cascade of rejection and appearance preoccupation: Adolescents’ body dysmorphic symptoms and appearance rejection sensitivity over 4 years
Authors: Zimmer‐Gembeck Melanie J. , Rudolph Julia , Pariz Juliane
Published: April 2021

Adolescence is a high‐risk period for body image disturbance and appearance concerns. In a cascade model, we examined interrelations of body dysmorphic symptoms (BDS) with appearance rejection sensitivity (ARS) and tested gender moderation. Participants were 397 Australian adolescents (T1 Mage = 11.7, SD = 0.91; 56% girls) who completed six surveys over 4 years. In a random‐intercept cross‐lag model, two (of five possible) paths showed ARS predicted higher subsequent BDS, and three (of five possible) paths showed BDS predicted higher subsequent ARS. Girls reported more BDS and ARS than boys, and random intercepts of BDS and ARS were correlated with the correlation stronger in girls than boys. Cross‐lag BDD‐ARS associations over the six waves were not significantly moderated by gender. Overall, girls are at higher risk of appearance concerns than boys, but BDD‐ARS cascade effects do not differ between girls and boys.
A Multiple‐Memory Systems Framework for Examining Attention and Memory Interactions in Infancy
Authors: Amso Dima , Kirkham Natasha
Published: April 2021

Visual attention both guides and is guided by learning and memory systems. In this article, we use a multiple‐memory systems framework to examine the interplay between attention and memory that begins in early postnatal life. We review how attention and memory interact to support infant development with respect to perceptual learning about objects and features, item‐in‐context spatial memory, and reinforcement and reward learning. We argue that the multiple‐memory systems approach offers a useful organizational structure for research on interactions between attention and memory.
Biallelic start loss variant, c.1A > G in GCSH is associated with variant nonketotic hyperglycinemia
Authors: Majethia Purvi , Somashekar Puneeth Hirivate , Hebbar Malavika , Kadavigere Rajagopal , Praveen Balike Krishna , Girisha Katta Mohan , Shukla Anju
Published: April 2021

The glycine cleavage system H protein (GCSH) is an integral part of the glycine cleavage system with its additional involvement in the synthesis and transport of lipoic acid. We hypothesize that pathogenic variants in GCSH can cause variant nonketotic hyperglycinemia (NKH), a heterogeneous group of disorders with findings resembling a combination of severe NKH (elevated levels of glycine in plasma and CSF, progressive lethargy, seizures, severe hypotonia, no developmental progress, early death) and mitochondriopathies (lactic acidosis, leukoencephalopathy and Leigh‐like lesions on MRI). We herein report three individuals from two unrelated Indian families with clinical, biochemical, and radiological findings of variant NKH, harboring a biallelic start loss variant, c.1A > G in GCSH.
Autonomy, Centrality, and Persistence in Place: The Indigenous Movement and the Right to the City in Quito
Authors: Rayner Jeremy
Published: April 2021

This article draws on ethnography with active supporters of the comunas (communes) in Quito to critically engage with the theory and politics of the right to the city. Communal activists—mostly affiliated with the Indigenous movement—forcefully claim rights to the democratic production and appropriation of space advocated by right to the city theorists, as they promote communal self‐management and the authority of communal assemblies over urbanization processes. At the same time, they have had little use for their constitutionally guaranteed right to the city. In carefully laying out the points of convergence between Lefebvrian right to the city theory and communal struggles, I also identify its limits and contradictions, especially: (1) the tension between “the collective power to reshape the process of urbanization” and the fixed forms and meanings of “the city,” and (2) the tension between achieving the “right to centrality” through promoting participation in a concentrated urban center or through the multiplication of centers. A critical theory of urbanization should account for these tensions and for the diversity of political responses to them.
Live wild animal exports to supply the exotic pet trade: A case study from Togo using publicly available social media data
Authors: Harrington Lauren A. , Auliya Mark , Eckman Harry , Harrington Alix P. , Macdonald David W. , D'Cruze Neil
Published: April 2021

Exotic pet supply is a key, predominantly legal, component of global wildlife trade, but few studies have quantified its diversity or global reach. Here, using information extracted from the public (open) Facebook accounts of two wildlife exporters in Togo, West Africa, we identified at least 200 species, predominantly reptiles, but also mammals, birds, amphibians and invertebrates, advertised as available for sale and export, between the years 2016 and 2020. Of the animals identified, several hundred, possibly several thousand, individuals were shipped, at least monthly, to North America, Europe, Asia, and elsewhere in Africa, via a number of major airlines. Among the vertebrates observed, approximately one‐third had not yet been evaluated on the IUCN Red list, and three quarters were not CITES‐listed (i.e., their trade was not regulated under this international treaty). The apparent lack of adequate monitoring of population status, disease, biological invasion, and animal welfare risks associated with this trade, as well as neglected taxa (e.g., invertebrates), has potential implications for environmental, public, and animal health. The findings of this case study suggest that a systematic review of social media activity could efficiently reveal significant insights into the otherwise undocumented global supply of exotic pets, directing legislators to aspects and areas where regulation is insufficient, and informing international and national policy change.
Fine needle aspiration diagnosed a rare case of ovarian clear cell carcinoma metastasis to thyroid gland
Authors: Ji Xiaokun , Zhang Jinyan , Liu Ying , Wu Jianing , Du Yun
Published: April 2021

Metastatic deposits from malignant melanoma, renal clear cell carcinoma, and squamous cell carcinoma involving the thyroid gland have been reported before, but there are no previous reports of ovarian clear cell carcinoma metastatic to the thyroid. Cytological features and immunocytochemistry can help distinguish between primary and metastatic thyroid malignancies.
Structural alteration of the nucleus for the reprogramming of gene expression
Authors: Tomikawa Junko , Miyamoto Kei
Published: April 2021

The regulation of gene expression is a critical process for establishing and maintaining cellular identity. Gene expression is controlled through a chromatin‐based mechanism in the nucleus of eukaryotic cells. Recent studies suggest that chromatin accessibility and the higher‐order structure of chromatin affect transcriptional outcome. This is especially evident when cells change their fate during development and nuclear reprogramming. Furthermore, non‐chromosomal contents of the cell nucleus, namely nucleoskeleton proteins, can also affect chromatin and nuclear structures, resulting in transcriptional alterations. Here, we review our current mechanistic understanding about how chromatin and nuclear structures impact transcription in the course of embryonic development, cellular differentiation and nuclear reprogramming, and also discuss unresolved questions that remain to be addressed in the field.
Predictors of development and persistence of musculoskeletal pain in community‐dwelling older people: A two‐year longitudinal study
Authors: Hirase Tatsuya , Okubo Yoshiro , Delbaere Kim , Menant Jasmine C , Lord Stephen R , Sturnieks Daina L
Published: April 2021

Aim

The aim of this prospective cohort study was to identify the predictors of the development and persistence of musculoskeletal pain (MSKP) in older people.

Methods

Participants comprised 431 community‐dwelling older people aged 70+ years. Demographic, anthropometric, balance, mobility, cognitive function, psychological status and physical activity level measures were obtained at baseline. Participants were asked about the presence of MSKP in the neck/back, hip, knee/leg and/or feet at baseline and two‐year follow‐up. Logistic regression analyses were performed to identify predictors of the development and persistence of MSKP at two‐year follow‐up.

Results

Of 179 participants who reported no MSKP at baseline, 84 (46.9%) reported MSKP at two‐year follow‐up, which was associated with a higher body mass index (odds ratio (OR) 1.10, 95% confidence interval (CI) 1.02–1.18), more reported depressive symptoms (OR 1.30, 95% CI 1.05–1.61) and lower physical activity levels (OR 0.92, 95% CI 0.84–1.00) at baseline. Of 252 participants who reported MSKP at baseline, 202 (80.2%) reported MSKP at follow‐up, which was associated with a slower 6‐m walking time (OR 1.27, 95% CI 1.08–1.49) and more reported depressive symptoms (OR 1.39, 95% CI 1.09–1.78). These associations remained significant after adjusting for age, sex, comorbidities and medication use.

Conclusions

This study suggests that higher body mass index, more depressive symptoms and less physical activity are predictors of developing MSKP, whereas slow gait speed and depressive symptoms are predictors of the persistence of MSKP among older people. The results highlight the importance of weight control, strategies to improve mental wellbeing and an active lifestyle for pain management among older people. Geriatr Gerontol Int 2021; 21: 519–524.
Emicizumab prophylaxis: Prospective longitudinal real‐world follow‐up and monitoring
Authors: Barg Assaf A. , Budnik Ivan , Avishai Einat , Brutman‐Barazani Tami , Bashari Dalia , Misgav Mudi , Lubetsky Aaron , Kuperman Amir A. , Livnat Tami , Kenet Gili
Published: April 2021

Introduction

Real‐world data on prophylaxis of severe haemophilia A (HA) patients treated by emicizumab are scarce.

Aim

To study the efficacy and safety of longitudinal emicizumab prophylaxis and assess laboratory monitoring correlations in a large patient cohort.

Methods

HA patients with and without FVIII inhibitors, initiating emicizumab prophylaxis, were prospectively enrolled. Bleeding, adverse events and surgeries were documented. FVIII inhibitors, emicizumab levels and thrombin generation (TG) were sequentially measured.

Results

A total of 107 patients, including 58 children (whose median (IQR) age was 6 (1–11) years) with severe HA, composed the study cohort. Twenty‐nine per cent (31/107) of our HA patients had FVIII inhibitors. Patients were followed for a median of 67 weeks (up to 144 weeks). Fifty‐three patients, whose median follow‐up was 53 weeks, experienced zero bleeds. Most bleeds (94%) among children were trauma‐related, whereas 61% of adults sustained spontaneous joint bleeds. Four patients experienced major bleeds, with a fatal outcome in one infant, who also presented with central venous line thrombosis. No other serious adverse events were encountered. Seven patients have decided to stop emicizumab treatment for various reasons. Emicizumab plasma levels increased after emicizumab prophylaxis initiation, and values were maintained during follow‐up, in all but one patient, suspected of anti‐drug antibodies. A significant reduction of FVIII inhibitor levels was noted among inhibitor patients. TG was increased and sustained yet could not prognosticate bleeding risk.

Conclusion

Emicizumab prophylaxis was mostly well tolerated, although 50% of patients experienced breakthrough bleeds. Routine TG monitoring is not obligatory, and further studies are warranted in selected patient populations.
Cost‐analysis of opportunistic influenza vaccination in general medical inpatients
Authors: Darmaputra Daniel C. , Zaman Farzana Y. , Khu Yin Li , Nagalingam Vathy , Liew Danny , Aung Ar Kar
Published: April 2021

Influenza vaccination is an important preventative health measure in the elderly and those with medical comorbidities. It has been shown to reduce hospitalisations, cardiovascular and respiratory complications. A significant proportion of patients admitted to general medicine are eligible for opportunistic inpatient influenza vaccination. This study explores the cost‐effectiveness of such a strategy in reducing subsequent healthcare utilisation costs.
Three‐dimensional printing of zirconia scaffolds for load bearing applications: Study of the optimal fabrication conditions
Authors: Gaddam Anuraag , Brazete Daniela S. , Neto Ana S. , Nan Bo , Ferreira José M. F.
Published: April 2021

Yttria‐stabilized zirconia (YSZ) scaffolds with a planned macroporosity fraction of about 70% were fabricated by Robocasting from inks with high solid loadings. The effects of solids loading and the concentrations of processing additives on the flow behavior of the starting suspensions and the viscoelastic properties of the resulting inks were investigated aiming at optimizing the printing process. The shear thinning flow behavior of the starting suspensions containing 45‒48 vol% solids and dispersant concentrations varying within 0.2‒0.8 wt% could be well described by the four‐parameter Cross model. The flow behavior of the suspensions could be correlated with the interaction forces, and the ad‐layer thickness formed around the YSZ particles. Further adding suitable amounts of a binder and a coagulating agent enabled optimizing the viscoelastic properties of inks for 3D printing. Good shape retention was observed for inks with elastic modulus, G′ ≥ 10 MPa. The green scaffolds were dried, sintered at 1350°C, and then used for the assessment of porosity and mechanical properties under compression tests. The porous structures exhibit average compressive strength (σ) of ~70 MPa. Weibull statistics applied to σ data revealed good reliability of the process, which can be used to fabricate YSZ scaffolds for orthopedic applications.
Fermented foods: Availability, cost, ingredients, nutritional content and on‐pack claims
Authors: Whelan Kevin , Jones Nicola
Published: April 2021

Introduction

Fermented foods have been consumed for millennia and commercially‐produced variants are now available in the food supply. The present study aimed to investigate the availability, cost, ingredients, nutritional content and on‐pack claims of commercially‐available fermented foods in the UK.

Methods

All products from seven categories of commercially‐available fermented foods were systematically identified at eight national supermarket chains in the UK. Data were extracted from manufacturer and retailer websites and were compared between categories using a Kruskal–Wallis test and Fisher's exact test.

Results

In total, 143 fermented foods were identified, with kombucha (41, 28.7%), kefir drinks (32, 22.4%), sauerkraut (22, 15.4%) and kefir yoghurts (21, 14.7%) being most common. The number of products sold at each retailer differed between categories (p = 0.016), and was greatest for kefir drink (median = 7.0, interquartile range [IQR] = 9.0), kombucha (median = 5.5, IQR = 11.5) and kefir yoghurts (median = 5.0, IQR = 8.5). Kombucha (£1.99 per serving) and kefir drinks (£1.26 per serving) were the most expensive fermented foods and sauerkraut (£0.66 per serving) and miso (£0.20 per serving) were the least expensive. Energy, fat, saturated fat, sugar, protein and salt content varied between fermented foods (p < 0.001). Nutrition claims were made on 72 (50.3%) products, the total number of cultures was labelled on 29 (20.3%), specific strains were named on 53 (37.1%) and bacteria‐related benefits were promoted on 39 (27.3%) products.

Conclusions

Commercially‐produced fermented foods are widely available in the UK but are diverse in their cost, nutritional content, ingredients and use of on‐pack claims. Consumers should be aware of these variations given the limited evidence of functional benefits from controlled human trials.
The Endurance of Shareholder Value Maximization as the Preferred Corporate Objective
Authors: Inkpen Andrew C. , Sundaram Anant K.
Published: April 2021

Sundaram and Inkpen (2004a, 2004b) proposed shareholder value maximization (SVM) as the preferred corporate objective since it alone impels the firm to implement strategies that enhance outcomes for all stakeholders. Goranova and Ryan (2021) argue that three recent developments – common ownership, decoupling of owners from managers, and greater divergence in shareholder interests – call into question our SVM view. We dispute their arguments: (i) The developments they cite are overplayed in the literature, and may not matter much for SVM; (ii) To the extent they do matter, their concern is less about SVM’s relevance as corporate objective but more whether these developments bias decisions towards the short‐term. We do not disagree since, after all, Sundaram and Inkpen (2004a) is solely about SVM for the long‐term; (iii) If anything, Goranova and Ryan’s (2021) proposed solution of ‘strategic corporate governance’ can be viewed as an endorsement of the relevance and enduring primacy of SVM for the long‐term.
Is peripartum maternal fever alone a reliable predictor of neonatal sepsis? A single‐centre, retrospective cohort study
Authors: Gupta Soumya , Forbes‐Coe Amy , Rudd Donna , Kandasamy Yogavijayan
Published: April 2021

Aim

To determine the incidence rate of early‐onset neonatal sepsis (EONS) among term neonates (gestation greater than 37 weeks) admitted to the neonatal intensive care unit for suspected sepsis and the association of EONS with maternal fever (temperature greater than 38°C).

Methods

A single‐centre retrospective cohort study of all term neonates (gestation >37 weeks) admitted to and treated in the neonatal unit at the Townsville University Hospital between March 2015 and March 2020. Neonatal sepsis was confirmed with positive neonatal blood culture. Data on neonatal birth/stay and maternal pregnancy were collected from the electronic medical records and neonatal database.

Results

Data from 737 neonates who were admitted for treatment of EONS were analysed. Sixty % (426) reported maternal intrapartum fever, with 1.1% (5) of neonates developing blood culture‐proven sepsis. Forty % did not report intrapartum fever (311), with 3% (9) of neonates developing sepsis. As such, the sensitivity and specificity of maternal fever are 1.14% and 97%, respectively. The positive predictive value was 35.7%, and the negative predictive value was 40.1%. Fourteen neonates developed EONS, and all of them were symptomatic. Seventy‐eight % (334/426) of the women in the febrile group received epidural analgesia compared to 5% (16/311) in the afebrile group. Of the 95 neonates born to women with chorioamnionitis, one (1.0%) of the neonates born to women with chorioamnionitis developed sepsis.

Conclusions

Intrapartum maternal fever is an unreliable predictor for EONS and leads to unnecessary antibiotic treatment. Symptoms in the neonate are a more reliable indicator of an ill neonate with blood culture‐proven sepsis.
Variation in desert shrub foliar pH in relation to drought and salinity in Xinjiang, China
Authors: Luo Yan , Yan Zhengbing , Liu Sining , Chen Jiashu , Li Kaihui , Mohammat Anwar , Han Wenxuan
Published: April 2021

Aim

Foliar pH, an emerging plant functional trait, plays a key role in plant eco‐physiological processes. However, it remains unclear how foliar pH varies among plants with different preferences concerning soil salinity, and how it responds to drought stress in desert ecosystems.

Location

Xinjiang, northwestern China (40.24° N to 46.24° N, 80.66° E to 91.33° E).

Methods

We addressed variation in foliar pH in four desert shrub groups (i.e., euhalophytes, secretohalophytes, pseudohalophytes and glycophytes) with differing adaptive strategies to soil salinity in 29 sites in Xinjiang, China, and explored the effects of drought and saline stress on foliar pH variability.

Results

We found that average foliar pH of desert shrubs was 5.54 ± 0.02, higher than that of shrubs from humid areas. At the functional group level, euhalophytes (5.65 ± 0.03) and glycophytes (5.61 ± 0.04) had significantly higher foliar pH than secretohalophytes (5.47 ± 0.03) and pseudohalophytes (5.39 ± 0.05). Coverage‐weighted mean foliar pH of glycophytes‐dominated communities was significantly higher (5.80 ± 0.18) than those of the halophytes‐dominated communities (5.34 ± 0.07 ~ 5.49 ± 0.07). Only in pseudohalophytes there was a significant relationship between foliar pH and both drought stress (i.e., low soil water stress coefficient, aridity index, and mean annual precipitation) and saline stress (shown by high soil electrical conductivity and soil pH). In contrast, secretohalophytes displayed opposite or non‐significant relationships between foliar pH and drought and saline stress. Compared with salinity indicators, drought exerted a much larger impact on foliar pH, particularly in pseudohalophytes and secretohalophytes.

Conclusions

Our work documented a comprehensive analysis of foliar pH across halophyte and glycophyte shrub species, and found contrasting responses of foliar pH to drought and salinity in desert ecosystems, which can provide an alternative perspective for understanding the survival strategies of desert plants, and may also offer new insights into the population dynamics of desert shrub communities under global climate change.