bluuebunny/crossref_metadata_2025 huggingface dataset:
The formation of microcrystalline defects on the surface of silica glass arising from mechanochemical processing
Authors: Lunin Boris S. , Tokmakov Kirill V.
Published: February 2022

The aim of this article is to study the nature of the defects arising on the surface of silica glass during mechanical processing followed by chemical cleaning and etching. Such defects manifest themselves as a narrow Raman peak near 85 cm–1. It is shown that chemical etching of the ground surface of silica glass leads to the formation of microcrystalline defects embedded at the depth of the near‐surface layer. Defects of this kind create heterogeneities in the structure of the atomic network and increase internal friction in silica glass mechanical resonators. This phenomenon should be taken into account when developing the technology for fabrication of high‐Q resonators.
Itaconate and fumarate derivatives inhibit priming and activation of the canonical NLRP3 inflammasome in macrophages
Authors: Hoyle Christopher , Green Jack P. , Allan Stuart M. , Brough David , Lemarchand Eloise
Published: February 2022

The NLRP3 inflammasome is a multiprotein complex that regulates caspase‐1 activation and subsequent interleukin (IL)‐1β and IL‐18 release from innate immune cells in response to infection or injury. Derivatives of the metabolites itaconate and fumarate, dimethyl itaconate (DMI), 4‐octyl itaconate (4OI) and dimethyl fumarate (DMF) limit both expression and release of IL‐1β following NLRP3 inflammasome activation. However, the direct effects of these metabolite derivatives on NLRP3 inflammasome responses require further investigation. Using murine bone marrow‐derived macrophages, mixed glia and organotypic hippocampal slice cultures (OHSCs), we demonstrate that DMI, 4OI and DMF pretreatments inhibit pro‐inflammatory cytokine production in response to lipopolysaccharide (LPS), as well as inhibit subsequent NLRP3 inflammasome activation induced by nigericin. DMI, 4OI, DMF and monomethyl fumarate (MMF), another fumarate derivative, also directly inhibited biochemical markers of NLRP3 activation in LPS‐primed macrophages, mixed glia, OHSCs and human macrophages in response to nigericin and imiquimod, including ASC speck formation, caspase‐1 activation, gasdermin D cleavage and IL‐1β release. DMF, an approved treatment of multiple sclerosis, as well as DMI, 4OI and MMF, inhibited NLRP3 activation in macrophages in response to lysophosphatidylcholine, which is used to induce demyelination, suggesting a possible mechanism for DMF in multiple sclerosis through NLRP3 inhibition. The derivatives also reduced pro‐IL‐1α cleavage in response to the calcium ionophore ionomycin. Together, these findings reveal the immunometabolic regulation of both the priming and activation steps of NLRP3 activation in macrophages. Furthermore, we highlight itaconate and fumarate derivatives as potential therapeutic options in NLRP3‐ and IL‐1α‐driven diseases, including in the brain.
Physico‐chemical properties of international simple glass (ISG) nuclear waste simulants: Luminescence baseline study
Authors: Jiménez José A. , Crawford Charles L. , Lascola Robert J.
Published: February 2022

Borosilicate glass has been adopted internationally for the treatment of nuclear waste with the object of long‐term stabilization through vitrification. Aiming to facilitate experimental comparisons across laboratories, the six‐component international simple glass (ISG) was developed as benchmark. The original ISG produced by Mo‐SCI Corporation (Rolla, MO) was distributed and characterized for different physical properties thus serving as reference for further studies. Still, photoluminescence (PL) properties, which may be useful for scrutinizing radiation‐induced damage, have not been reported. Further, the original ISG contained significant iron impurities, which may present interference in various studies (e.g., optical). Consequently, two new ISG analogs lacking iron impurities (labeled ISG‐1 [closest composition to original ISG] and ISG‐2 [some MgO added at expense of CaO]) were synthesized by Corning Inc. (Corning, NY) (also doped with lanthanum for subsequent corrosion tests involving atom probe tomography), which remain to be fully characterized. Accordingly, this work was undertaken to perform a comprehensive study comparing the three ISG specimens. Various characterizations were then performed on the pristine glasses: X‐ray diffraction and vibrational spectroscopy (structural properties); static‐leach product consistency test (PCT, dissolution behavior); dilatometry and calorimetry measurements (thermal properties); and optical absorption with Tauc and Urbach plots analysis, followed by PL spectroscopy with decay kinetics assessment (optical properties). While the general structural features appeared similar among the glasses, the deconvolution of Raman spectra suggested a lower degree of connectivity in the silica network for ISG‐2. In addition, some differences were indicated from the PCT results and thermal properties assessed, which were discussed based on compositional variations. Further on, the optical properties were shown to be the most distinct. The optical absorption of the original ISG was characterized by Fe2+/Fe3+ impurities not detected for ISG‐1 and ISG‐2. The glasses all exhibited two main PL features (∼1.8 and 2.5 eV) with multiexponential decay behavior apparently of intrinsic origin. In addition, ISG‐1 and ISG‐2 showed a third high‐energy (∼3.4 eV) fast‐decaying contribution tentatively credited to tin impurities, which appeared most significantly for ISG‐1. The results are expected to serve as baseline for future studies simulating the effects of radioactive element decay.
Role of yeasts in the qualitative structuring of extra virgin olive oil
Authors: Zullo Biagi Angelo , Ciafardini Gino
Published: February 2022

This review sought to describe the role played by some components of the microbiota of extra virgin olive oil (EVOO), particularly yeasts, in structuring the physicochemical and sensorial quality of freshly produced olive oil. Yeasts can survive during the entire storage period of the product. To date, approximately 25 yeast species isolated from oil produced in more than six countries have been identified, eight of which are classified as new species. Some yeast species improve the health qualities of oil, whereas many others improve the chemical composition and sensory characteristics based on β-glucosidase and esterase enzymes, which are involved in the hydrolysis of the bitter glucoside known as oleuropein. However, some species, which are typically favoured by the high water content in the oily matrix, such as lipase-producing yeasts, can worsen the initial chemical characteristics of EVOO oil during storage. Some physical treatments that are compatible with the EVOO production specification affect the biotic component of the oil by reducing the concentration of yeasts. The possibility of minimizing the invasive action on the biotic component of the oil by appropriately selecting the physical treatment for each oil is discussed.
Melanoma and intellectual disability: do prognostic factors at diagnosis differ from general population?
Authors: Lesage C. , Habib‐Hadef S. , Trétarre B. , Lesage F.‐X. , Bessaoud F. , Varey E. , Guillot B. , Satgé D.
Published: February 2022

Background

Few melanoma cases are reported in individuals with intellectual disability (ID), and prognostic factors at diagnosis are unknown in this population. This work was designed to investigate whether prognostic factors at diagnostic are different in patients with ID compared with a general population.

Methods

Melanoma cases retrieved from Hérault's Tumour Registry (HTR) from 1995 to 2015 were cross‐referenced against a list of adult patients with ID, living in Hérault. Major prognostic factors were compared with those in non‐ID melanoma patients included in HTR and in patients followed by Montpellier University Hospital and included in the Réseau pour la Recherche et l'Investigation Clinique sur le Mélanome (RIC‐Mel) database.

Results

Ten melanoma cases in individuals with ID were identified and compared with 3804 non‐ID melanoma cases in HTR and 1024 non‐ID melanoma cases included in RIC‐Mel. Mean Breslow thickness at diagnosis was 4.6 mm in melanoma cases among those with ID versus 1.89 mm in HTR (P = 0.109) and 2.36 mm in RIC‐Mel (P = 0.156). Stage at diagnosis was superior to stage IIB in 42.9% of ID cases versus 11.4% of non‐ID cases in HTR (P < 0.05) and 8.5% in RIC‐Mel (P < 0.05).

Conclusions

Melanomas in patients with ID had less favourable prognostic factors at diagnosis, including higher Breslow thickness and more advanced stage, than melanomas in non‐ID patients. These adverse prognostic factors indicate a later diagnosis in this population, leading to a poorer prognosis. This work underlines the need to improve melanoma screening among individuals with ID.
Variations within Toll‐like receptor (TLR) and TLR signaling pathway‐related genes and their synergistic effects on the risk of Guillain‐Barré syndrome
Authors: Dutta Debprasad , Nagappa Madhu , Sreekumaran Nair Binu V. , Das Sumit Kumar , Wahatule Rahul , Sinha Sanjib , Vasanthapuram Ravi , Taly Arun B. , Debnath Monojit
Published: February 2022

Guillain‐Barré syndrome (GBS) is the commonest post‐infectious polyradiculopathy. Although genetic background of the host seems to play an important role in the susceptibility to GBS, genes conferring major risk are not yet known. Dysregulation of Toll‐like receptor (TLR) molecules exacerbates immune‐inflammatory responses and the genetic variations within TLR pathway‐related genes contribute to differential risk to infection. The aim of this study was to delineate the impact of genetic variations within TLR2, TLR3, and TLR4 genes as well as TLR signaling pathway‐related genes such as MyD88, TRIF, TRAF3, TRAF6, IRF3, NFκβ1, and IκBα on risk of developing GBS. Fourteen polymorphisms located within TLR2 (rs3804099, rs111200466), TLR3 (rs3775290, rs3775291), TLR4 (rs1927911, rs11536891), MyD88 (rs7744, rs4988453), TRIF (rs8120), TRAF3 (rs12147254), TRAF6 (rs4755453), IRF3 (rs2304204), NFκβ1 (rs28362491), and IκBα (rs696) genes were genotyped in 150 GBS patients and 150 healthy subjects either by PCR‐RFLP or TaqMan Allelic Discrimination Assay. Genotypes of two polymorphic variants, Del/Del of rs111200466 insertion and deletion (INDEL) polymorphism of TLR2 gene and TT of rs3775290 single nucleotide polymorphism (SNP) of TLR3 gene had significantly higher frequencies among GBS patients, while the frequencies of TT genotype of rs3804099 SNP of TLR2 gene and TT genotype of rs11536891 SNP of TLR4 gene were significantly higher in controls. Gene‐gene interaction study by Multifactor Dimensionality Reduction analysis also suggested a significant combined effect of TLR2, and NFκβ1 genes on the risk of GBS. The SNPs in the IκBα and IRF3 genes correlated with severity of GBS. The genes encoding TLRs and TLR signaling pathway‐related molecules could serve as crucial genetic markers of susceptibility and severity of GBS.
Ambient air pollution and cardiovascular diseases: An umbrella review of systematic reviews and meta‐analyses
Authors: de Bont Jeroen , Jaganathan Suganthi , Dahlquist Marcus , Persson Åsa , Stafoggia Massimo , Ljungman Petter
Published: February 2022

The available evidence on the effects of ambient air pollution on cardiovascular diseases (CVDs) has increased substantially. In this umbrella review, we summarized the current epidemiological evidence from systematic reviews and meta‐analyses linking ambient air pollution and CVDs, with a focus on geographical differences and vulnerable subpopulations. We performed a search strategy through multiple databases including articles between 2010 and 31 January 2021. We performed a quality assessment and evaluated the strength of evidence. Of the 56 included reviews, the most studied outcomes were stroke (22 reviews), all‐cause CVD mortality, and morbidity (19). The strongest evidence was found between higher short‐ and long‐term ambient air pollution exposure and all‐cause CVD mortality and morbidity, stroke, blood pressure, and ischemic heart diseases (IHD). Short‐term exposures to particulate matter <2.5 μm (PM2.5), <10 μm (PM10), and nitrogen oxides (NOx) were consistently associated with increased risks of hypertension and triggering of myocardial infarction (MI), and stroke (fatal and nonfatal). Long‐term exposures of PM2.5 were largely associated with increased risk of atherosclerosis, incident MI, hypertension, and incident stroke and stroke mortality. Few reviews evaluated other CVD outcomes including arrhythmias, atrial fibrillation, or heart failure but they generally reported positive statistical associations. Stronger associations were found in Asian countries and vulnerable subpopulations, especially among the elderly, cardiac patients, and people with higher weight status. Consistent with experimental data, this comprehensive umbrella review found strong evidence that higher levels of ambient air pollution increase the risk of CVDs, especially all‐cause CVD mortality, stroke, and IHD. These results emphasize the importance of reducing the alarming levels of air pollution across the globe, especially in Asia, and among vulnerable subpopulations.
Epicondylar plate fixation of humeral condylar fractures in immature French bulldogs: 45 cases (2014‐2020)
Authors: Kvale E. , Kalmukov I. , Grassato L. , Kalff S. , Solano M.
Published: February 2022

Objectives

The objective of this study was to report outcome and postoperative complications following stabilisation of humeral condylar fractures in skeletally immature French bulldogs with a transcondylar screw combined with locking or hybrid locking plates.

Materials and Methods

Medical records from one referral hospital were reviewed to identify skeletally immature French bulldogs with humeral condylar fractures treated with a transcondylar screw and epicondylar locking or hybrid locking plates crossing the distal humeral physis.

Results

Forty‐five fractures in 41 different dogs with a mean age of 4 months (range 3.5 to 5) were identified. Six cases had complications: two (4.4%) minor and four (8.9%) major. Short‐term clinical outcome was excellent in 35 (77.8%), good in nine (20%) and poor in one (2.2%) case. Forty‐one of 45 fractures reached radiographic union without further surgical intervention; the remaining four cases reached union following revision surgery. Long‐term owner assessed outcome by telephone interview was graded as excellent in all available cases (26 of 41 dogs).

Clinical Significance

This study suggests that the stabilisation of humeral condylar fractures in skeletally immature French bulldogs with combinations of a transcondylar screw and epicondylar locking or hybrid locking plates crossing the distal humeral physis was safe and led comparable outcomes and complication rates to previous reports.
The effect of commercial and artisanal fishing practices on the behavioral budget of bottlenose dolphins off the coast of Montenegro, South Adriatic Sea
Authors: Rudd Laura E. , Awbery Tim , Waller Romina , Crowe Molly , Bauer Julianna , Jacquemart Anna , Nikpaljevic Natasa , Akkaya Aylin
Published: February 2022

The spatial–temporal distribution of cetacean species often overlaps with fishing practices in the Mediterranean, having direct and indirect consequences. This is the first long‐term study focusing on the effects of fisheries on the behavior of T. truncatus in Montenegro. Focal group scan sampling was used during surveys between September 2016 and August 2020 to create transition probability matrices using first‐order Markov chains for behavioral states in both control (absence of fishery practices) and impact chains (presence of fishery practices). Despite the low number of dolphin‐fishery interactions in Montenegro, results revealed that the behavioral budgets of T. truncatus were significantly altered both for commercial and artisanal fisheries. However, the magnitude of the threat differed between practices, with commercial fisheries altering three out of the four behaviors in the behavioral budget while artisanal fisheries altered just one. Significant behavioral changes due to disturbance can have negative consequences on the energy budget of individuals and while the Montenegrin fishing fleet is currently limited to 224 vessels, the significant effects already witnessed are concerning for Montenegrin bottlenose dolphins. To develop in‐situ mitigation strategies, there is a clear need to better understand the impact that fisheries interactions have on these individuals.
Knowledge, Freedom and the Meaning of Life according to Herbert McCabe
Authors: Manni Franco
Published: February 2022

Herbert McCabe was not an academic, he was a teacher and a preacher. He was a scholar also, but aiming to the truth for its own sake and, subsequently, for his own life improvement. Not in order to be ‘up-to-date’ with the intellectual fashions of the moment or to flatter his peers. Therefore he focused on the classics, most of all on Aquinas. The result of McCabe's peculiar intellectual attitude was the vast amount of original and impressive ideas he conceived and conveyed despite having written little, in terms of the number of texts and the length of them. The right tribute of praise to a thinker is the presentation of his/her ideas, the test of truth, coherence, originality and power they have in explaining the reality in which we live. This is one of the things that strikes a reader of McCabe's writings. While it is hard to name a single original idea of many authors in vogue, and of most of them only one, it is easy to name many ideas from McCabe. This paper focuses on two of them: 1) freedom as based on knowledge; 2) the meaning of life.
Cerebellar ataxia following antitubercular therapy
Authors: Chittilappilly Jomal Mathew , Kalampadan Jerry Jose , Kaitharath Sholy Vareed
Published: February 2022

Cerebellar ataxia following antitubercular therapy is extremely rare and occurs in certain susceptible individuals. MRI Brain showed characteristic Dentate nucleus T2/FLAIR hyperintensity. Prompt recognition of this uncommon adverse event is crucial as it is reversible with Pyridoxine supplementation and withdrawal of the culprit drugs.
Rice increases phosphorus uptake in strongly sorbing soils by intra‐root facilitation
Authors: Kuppe Christian W. , Kirk Guy J. D. , Wissuwa Matthias , Postma Johannes A.
Published: February 2022

Upland rice (Oryza sativa) is adapted to strongly phosphorus (P) sorbing soils. The mechanisms underlying P acquisition, however, are not well understood, and models typically underestimate uptake. This complicates root ideotype development and trait‐based selection for further improvement. We present a novel model, which correctly simulates the P uptake by a P‐efficient rice genotype measured over 48 days of growth. The model represents root morphology at the local rhizosphere scale, including root hairs and fine S‐type laterals. It simulates fast‐ and slowly reacting soil P and the P‐solubilizing effect of root‐induced pH changes in the soil. Simulations predict that the zone of pH changes and P solubilization around a root spreads further into the soil than the zone of P depletion. A root needs to place laterals outside its depletion‐ but inside its solubilization zone to maximize P uptake. S‐type laterals, which are short but hairy, appear to be the key root structures to achieve that. Thus, thicker roots facilitate the P uptake by fine lateral roots. Uptake can be enhanced through longer root hairs and greater root length density but was less sensitive to total root length and root class proportions.
Reproductive biology of wild and domesticated Ensete ventricosum: Further evidence for maintenance of sexual reproductive capacity in a vegetatively propagated perennial crop
Authors: Tamrat S. , Borrell J. S. , Shiferaw E. , Wondimu T. , Kallow S. , Davies R. M. , Dickie J. B. , Nuraga G. W. , White O. , Woldeyes F. , Demissew S. , Wilkin P.
Published: February 2022

Loss of sexual reproductive capacity has been proposed as a syndrome of domestication in vegetatively propagated crops, but there are relatively few examples from agricultural systems. In this study, we compare sexual reproductive capacity in wild (sexual) and domesticated (vegetative) populations of enset (Ensete ventricosum (Welw.) Cheesman), a tropical banana relative and Ethiopian food security crop.

We examined floral and seed morphology and germination ecology across 35 wild and domesticated enset. We surveyed variation in floral and seed traits, including seed weight, viability and internal morphology, and germinated seeds across a range of constant and alternating temperature regimes to characterize optimum germination requirements.

We report highly consistent floral allometry, seed viability, internal morphology and days to germination in wild and domesticated enset. However, seeds from domesticated plants responded to cooler temperatures with greater diurnal range. Shifts in germination behaviour appear concordant with a climatic envelope shift in the domesticated distribution.

Our findings provide evidence that sexual reproductive capacity has been maintained despite long‐term near‐exclusive vegetative propagation in domesticated enset. Furthermore, certain traits such as germination behaviour and floral morphology may be under continued selection, presumably through rare sexually reproductive events. Compared to sexually propagated crops banked as seeds, vegetative crop diversity is typically conserved in living collections that are more costly and insecure. Improved understanding of sexual propagation in vegetative crops may have applications in germplasm conservation and plant breeding.
Two Readings of Bentham's Theory of Meaning as Applied to Moral and Political Discourse
Authors: Palmer Simon
Published: February 2022

In this paper, I sketch out and assess two readings of Bentham's theory of meaning, one reductive (Section 2), the other quasi‐pragmatist (Section 3)—both implicating Bentham's ontological and epistemological views. I focus on the way these readings would understand Bentham's analyses of claims in moral and political discourse that rely on putatively normative notions such as obligations and rights, good and bad, and what ought to be the case. I conclude the paper by suggesting tentatively that the independent merits of both readings could signal an irreconcilable tension at the heart of Bentham's thought (Section 4).
Relationship between neuromuscular fatigue, muscle activation and the work done above the critical power during severe‐intensity exercise
Authors: Ducrocq Guillaume P. , Blain Grégory M.
Published: February 2022

New Findings

What is the central question of this study?

Does the work done above critical power (W′) or muscle activation determine the degree of peripheral fatigue induced by cycling time trials performed in the severe‐intensity domain?

What is the main finding and its importance?

Peripheral fatigue increased when power output and muscle activation increased, whereas W′ did not change between the time trials. Therefore, no relationship was found between W′ and exercise‐induced peripheral fatigue such as previously postulated in the literature. In contrast, we found a significant association between EMG amplitude during exercise and exercise‐induced reduction in the potentiated quadriceps twitch, suggesting that muscle activation plays a key role in determining peripheral fatigue during severe‐intensity exercise.

In order to determine the relationship between peripheral fatigue, muscle activation and the total work done above critical power (W′), 10 men and four women performed, on separated days, self‐paced cycling time trials of 3, 6, 10 and 15 min. Exercise‐induced quadriceps fatigue was quantified using pre‐ to postexercise (15 s to 15 min recovery) changes in maximal voluntary contraction (MVC) peak force, voluntary activation and potentiated twitch force (QT). Voluntary activation was measured using the interpolated twitch technique, and QT was evoked by electrical stimulations of the femoral nerve. Quadriceps muscle activation was determined using the root mean square of surface EMG of vastus lateralis (VLRMS), vastus medialis (VMRMS) and rectus femoris (RFRMS). Critical power and W′ were calculated from the power–duration relationship from the four time trials. Mean power output and mean VLRMS, VMRMS and RFRMS were greater during shorter compared with longer exercise periods (P < 0.05), whereas no significant between‐trial change in W′ was found. The magnitude of exercise‐induced reductions in QT increased with the increase in power output (P < 0.001) and was associated with mean VLRMS, VMRMS and RFRMS (P < 0.001, r2 > 0.369) but not W′ (P > 0.150, r2 < 0.044). Reduction in voluntary activation tended (P = 0.067) to be more pronounced with the lengthening in time trial duration, whereas no significant between‐trial changes in MVC peak force were found. Our data suggest that peripheral fatigue is not related to the amount of work done above the critical power but rather to the level of muscle activation during exercise in the severe‐intensity domain.
Shape morphing mechanical metamaterials through reversible plasticity
Authors: Hwang Dohgyu , Barron Edward J. , Haque A. B. M. Tahidul , Bartlett Michael D.
Published: February 2022

Biological organisms such as the octopus can reconfigure their shape and properties to perform diverse tasks. However, soft machines struggle to achieve complex configurations, morph into shape to support loads, and go between multiple states reversibly. Here, we introduce a multifunctional shape-morphing material with reversible and rapid polymorphic reconfigurability. We couple elastomeric kirigami with an unconventional reversible plasticity mechanism in metal alloys to rapidly (
<
0.1 seconds) morph flat sheets into complex, load-bearing shapes, with reversibility and self-healing through phase change. This kirigami composite overcomes trade-offs in deformability and load-bearing capacity and eliminates power requirements to sustain reconfigured shapes. We demonstrate this material through integration with onboard control, motors, and power to create a soft robotic morphing drone, which autonomously transforms from a ground to air vehicle and an underwater morphing machine, which can be reversibly deployed to collect cargo.
Activation of the sigma-1 receptor chaperone alleviates symptoms of Wolfram syndrome in preclinical models
Authors: Crouzier Lucie , Danese Alberto , Yasui Yuko , Richard Elodie M. , Liévens Jean-Charles , Patergnani Simone , Couly Simon , Diez Camille , Denus Morgane , Cubedo Nicolas , Rossel Mireille , Thiry Marc , Su Tsung-Ping , Pinton Paolo , Maurice Tangui , Delprat Benjamin
Published: February 2022

The Wolfram syndrome is a rare autosomal recessive disease affecting many organs with life-threatening consequences; currently, no treatment is available. The disease is caused by mutations in the
WSF1
gene, coding for the protein wolframin, an endoplasmic reticulum (ER) transmembrane protein involved in contacts between ER and mitochondria termed as mitochondria-associated ER membranes (MAMs). Inherited mutations usually reduce the protein’s stability, altering its homeostasis and ultimately reducing ER to mitochondria calcium ion transfer, leading to mitochondrial dysfunction and cell death. In this study, we found that activation of the sigma-1 receptor (S1R), an ER-resident protein involved in calcium ion transfer, could counteract the functional alterations of MAMs due to wolframin deficiency. The S1R agonist PRE-084 restored calcium ion transfer and mitochondrial respiration in vitro, corrected the associated increased autophagy and mitophagy, and was able to alleviate the behavioral symptoms observed in zebrafish and mouse models of the disease. Our findings provide a potential therapeutic strategy for treating Wolfram syndrome by efficiently boosting MAM function using the ligand-operated S1R chaperone. Moreover, such strategy might also be relevant for other degenerative and mitochondrial diseases involving MAM dysfunction.
Escape from recognition of SARS-CoV-2 variant spike epitopes but overall preservation of T cell immunity
Authors: Riou Catherine , Keeton Roanne , Moyo-Gwete Thandeka , Hermanus Tandile , Kgagudi Prudence , Baguma Richard , Valley-Omar Ziyaad , Smith Mikhail , Tegally Houriiyah , Doolabh Deelan , Iranzadeh Arash , Tyers Lynn , Mutavhatsindi Hygon , Tincho Marius B. , Benede Ntombi , Marais Gert , Chinhoyi Lionel R. , Mennen Mathilda , Skelem Sango , du Bruyn Elsa , Stek Cari ,   South African cellular immunity network, de Oliveira Tulio , Williamson Carolyn , Moore Penny L. , Wilkinson Robert J. , Ntusi Ntobeko A. B. , Burgers Wendy A.
Published: February 2022

SARS-CoV-2 variants that escape neutralization and potentially affect vaccine efficacy have emerged. T cell responses play a role in protection from reinfection and severe disease, but the potential for spike mutations to affect T cell immunity is incompletely understood. We assessed neutralizing antibody and T cell responses in 44 South African COVID-19 patients either infected with the Beta variant (dominant from November 2020 to May 2021) or infected before its emergence (first wave, Wuhan strain) to provide an overall measure of immune evasion. We show that robust spike-specific CD4 and CD8 T cell responses were detectable in Beta-infected patients, similar to first-wave patients. Using peptides spanning the Beta-mutated regions, we identified CD4 T cell responses targeting the wild-type peptides in 12 of 22 first-wave patients, all of whom failed to recognize corresponding Beta-mutated peptides. However, responses to mutated regions formed only a small proportion (15.7%) of the overall CD4 response, and few patients (3 of 44) mounted CD8 responses that targeted the mutated regions. Among the spike epitopes tested, we identified three epitopes containing the D215, L18, or D80 residues that were specifically recognized by CD4 T cells, and their mutated versions were associated with a loss of response. This study shows that despite loss of recognition of immunogenic CD4 epitopes, CD4 and CD8 T cell responses to Beta are preserved overall. These observations may explain why several vaccines have retained the ability to protect against severe COVID-19 even with substantial loss of neutralizing antibody activity against Beta.
Predicting Parallelism and Quantifying Divergence in Microbial Evolution Experiments
Authors: Shoemaker William R. , Lennon Jay T.
Published: February 2022

There is currently no framework for identifying genes that contribute to molecular divergence between microbial populations in different environments. To address this absence, we developed a null modeling approach to describe the distribution of mutation counts among genes.
In Vitro
Activity of KBP-7072 against 536 Acinetobacter baumannii Complex Isolates Collected in China
Authors: Han Renru , Ding Li , Yang Yang , Guo Yan , Yin Dandan , Wu Shi , Zhi Peiyuan , Zhu Demei , Liu Qingmei , Tan Xiaojuan , Zhu Yuanju , Zhang Jay , Li Li , Hu Fupin
Published: February 2022

It is reported that
A. baumannii
has emerged as an intractable nosocomial pathogen in hospitals especially when it develops resistance to carbapenems and other antibiotics, which limits treatment options and leads to high mortality. In February 2017, the WHO published a list of ESKAPE pathogens designated “priority status” for which new antibiotics are urgently needed.
Intrathecal Synthesis Index of Specific Anti-
Treponema
IgG: a New Tool for the Diagnosis of Neurosyphilis
Authors: Alberto Chloé , Deffert Christine , Lambeng Nathalie , Breville Gautier , Gayet-Ageron Angèle , Lalive Patrice , Toutous Trellu Laurence , Fontao Lionel
Published: February 2022

In the context of a lack of a gold standard for the diagnosis of neurosyphilis due to either nonspecific or nonsensitive tests, we present in this article a new promising tool highly specific for NS diagnosis. This new test involves measuring an intrathecal synthesis index of specific anti-
Treponema
IgG by ELISA.
Axillary Microbiota Is Associated with Cognitive Impairment in Parkinson’s Disease Patients
Authors: Arikan Muzaffer , Yildiz Zeynep , Kahraman Demir Tugce , Yilmaz Nesrin H. , Sen Aysu , Hanoglu Lutfu , Yildirim Suleyman
Published: February 2022

Parkinson's disease (PD) is the second most common neurodegenerative disease. Cognitive impairment (CI) in PD has significant negative impacts on life quality of patients.
Receptor conversion and vocal cord paralysis in a patient with breast cancer
Authors: Tan Harold Nathan , Catedral Lance Isidore Garcenila , Velasco Rogelio Jr , San Juan Michael
Published: February 2022

Receptor conversion in breast cancer occurs in up to 32% of patients, resulting in ineffective therapy in the absence of corresponding biomarkers. We report a case of a middle-aged woman who presented with a 2-month history of hoarseness. Laryngoscopy demonstrated right vocal cord paralysis. Whole body positron emission tomography-CT (PET-CT) scan showed a hypermetabolic cervical lymph node, worrisome for metastasis. Biopsy of the cervical lymph node was consistent with metastatic carcinoma of the breast (GATA3 and mammaglobin positive, oestrogen receptor (OR)-positive, progesterone receptor-negative and human epidermal growth factor receptor 2 (HER2)-positive). She underwent targeted therapy with ado-trastuzumab emtansine every 3 weeks. Repeat PET-CT scan after 6 months showed stable disease. Reassessment of receptor status in metastatic breast cancer is encouraged to rule out receptor conversion. There is significant cross-talk between OR and HER2 signalling pathways, leading to treatment resistance. Close collaboration and teamwork among various subspecialties facilitate prompt management of patients with suspected metastatic breast cancer.
Spontaneous regression of metastatic hepatocellular carcinoma following 3 weeks of lenvatinib
Authors: Curry Lauren , Limaye Warda , Ramjeesingh Ravi
Published: February 2022

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality and is associated with a poor prognosis. Rarely, there is spontaneous regression of the tumour. We present a case of a middle-aged male with presumed metastatic HCC who experienced enduring regression following 3 weeks of lenvatinib, which was discontinued due to side effects. While this could represent an unusually successful response to therapy, spontaneous tumour regression or an alternative diagnosis should be considered. We discuss possible mechanisms that might explain this unusual case and advocate for tissue confirmation in select cases, where there is diagnostic doubt or when the disease pattern does not clearly follow the recognised natural history. Therefore, if regression occurs—whether spontaneous or in response to treatment—it can be better understood and subsequent therapies recommended.
Feasibility of an automated interview grounded in multiple mini interview (MMI) methodology for selection into the health professions: an international multimethod evaluation
Authors: Callwood Alison , Gillam Lee , Christidis Angelos , Doulton Jia , Harris Jenny , Piano Marianne , Kubacki Angela , Tiffin Paul A , Roberts Karen , Tarmey Drew , Dalton Doris , Valentin Virginia L
Published: February 2022

Objectives

Global, COVID-driven restrictions around face-to-face interviews for healthcare student selection have forced admission staff to rapidly adopt adapted online systems before supporting evidence is available. We have developed, what we believe is, the first automated interview grounded in multiple mini-interview (MMI) methodology. This study aimed to explore test–retest reliability, acceptability and usability of the system.

Design, setting and participants

Multimethod feasibility study in Physician Associate programmes from two UK and one US university during 2019–2020.

Primary, secondary outcomes

Feasibility measures (test–retest reliability, acceptability and usability) were assessed using intraclass correlation (ICC), descriptive statistics, thematic and content analysis.

Methods

Volunteers took (T1), then repeated (T2), the automated MMI, with a 7-day interval (±2) then completed an evaluation questionnaire. Admission staff participated in focus group discussions.

Results

Sixty-two students and seven admission staff participated; 34 students and 4 staff from UK and 28 students and 3 staff from US universities. Good-excellent test–retest reliability was observed at two sites (US and UK2) with T1 and T2 ICC between 0.65 and 0.81 (p<0.001) when assessed by individual total scores (range 80.6–119), station total scores 0.6–0.91, p<0.005 and individual site (≥0.79 p<0.001). Mean test re-test ICC across all three sites was 0.82 p<0.001 (95% CI 0.7 to 0.9). Admission staff reported potential to reduce resource costs and bias through a more objective screening tool for preselection or to replace some MMI stations in a ‘hybrid model’. Maintaining human interaction through ‘touch points’ was considered essential. Users positively evaluated the system, stating it was intuitive with an accessible interface. Concepts chosen for dynamic probing needed to be appropriately tailored.

Conclusion

These preliminary findings suggest that the system is reliable, generating consistent scores for candidates and is acceptable to end users provided human touchpoints are maintained. Thus, there is evidence for the potential of such an automated system to augment healthcare student selection.
‘You’re just there, alone in your room with your thoughts’: a qualitative study about the psychosocial impact of the COVID-19 pandemic among young people living in the UK
Authors: McKinlay Alison R , May Tom , Dawes Jo , Fancourt Daisy , Burton Alexandra
Published: February 2022

Objectives

Adolescents and young adults have been greatly affected by quarantine measures during the COVID-19 pandemic, but little is understood about how restrictions have affected their well-being, mental health, and social life. We therefore aimed to learn more about how UK quarantine measures affected the social lives, mental health and well-being of adolescents and young adults.

Design

Qualitative interview study. The data were analysed using reflexive thematic analysis, with particular attention paid to contextual factors (such as age, gender, ethnicity and health status) when analysing each individual transcript.

Setting

Data collection took place remotely across the UK via audio or video call, between June 2020 and January 2021.

Participants

We conducted semi-structured interviews with 37 participants (aged 13–24 years) to elicit their views.

Results

Authors generated four themes during the qualitative analysis: (a) concerns about disruption to education, (b) missing social contact during lockdown, (c) changes to social relationships and (d) improved well-being during lockdown. Many participants said they struggled with a decline in mental health during the pandemic, lack of support and concern about socialising after the pandemic. However, some participants described experiences and changes brought on by the pandemic as helpful, including an increased awareness of mental health and feeling more at ease when talking about it, as well as stronger relationship ties with family members.

Conclusions

Findings suggest that young people may have felt more comfortable when talking about their mental health compared with prepandemic, in part facilitated by initiatives through schools, universities and employers. However, many were worried about how the pandemic has affected their education and social connections, and support for young people should be tailored accordingly around some of these concerns.
Individual and contextual predictors of emergency department visits among community-living older adults: a register-based prospective cohort study
Authors: Naseer Mahwish , J McKee Kevin , Ehrenberg Anna , Schön Pär , Dahlberg Lena
Published: February 2022

Objectives

To examine the extent to which contextual factors explain emergency department (ED) visits and ED revisits, additional to that explained by individual factors.

Design

A register-based prospective cohort study.

Setting

Swedish region of Dalarna.

Participants

Participants were 16 543 community-living adults aged 80 or older who were residents of the Dalarna region of Sweden, excluding older adults who moved out of Dalarna or into residential care during the study period.

Outcome measures

Dependent variables were initial ED visit, and at least one ED revisit within 30 days of an initial ED visit.

Results

Approximately 36% of the participants visited the ED during the study period with 18.9% returning to the ED within 30 days. For both initial ED visits and ED revisits, the addition of contextual factors to models containing individual factors significantly improved model fit (p<0.001; p<0.022) and the amount of variance explained in the outcome. In the final models, initial ED visit was significantly associated with older age, number of chronic diseases, receipt of home help, number of primary care visits, proportion of 80+ in the population and shorter distance to the ED; while an ED revisit was significantly associated with greater use of social care, number of hospital admissions and disposition (discharged; admitted to hospital) at initial ED visit.

Conclusion

Contextual factors explain variance in initial ED visit, additional to that explained by individual factors alone, which indicates inequitable access to ED care. These findings suggest considering local variations in contextual factors in order to improve health-related outcomes among older adults.
Changes in mental health problems and suicidal behaviour in students and their associations with COVID-19-related restrictions in Norway: a national repeated cross-sectional analysis
Authors: Sivertsen Børge , Knapstad Marit , Petrie Keith , O’Connor Rory , Lønning Kari Jussie , Hysing Mari
Published: February 2022

Objective

The COVID-19 pandemic has had a devastating impact on higher education, with the closure of student campuses. The aim of this study was to examine changes and prevalence of mental health problems, suicidal ideation and suicidal behaviour, and their associations with COVID-19-related restrictions.

Design, setting and participants

As part of the SHoT-study in Norway, 62 498 students completed an online questionnaire (65.6% women; response rate of 34.4%) in March 2021. Data were compared with previous waves, conducted in 2018, 2014 and 2010.

Primary and secondary outcome measures

Mental health problems were assessed using the Hopkins Symptoms Checklist. Suicidal ideation, suicide attempts and non-suicidal self-harm (NSSH) were assessed with three items drawn from the Adult Psychiatric Morbidity Survey, and thoughts of NSSH were assessed with one item from the Child and Adolescent Self-Harm in Europe study.

Results

There was a significant increase in mental health problems from 2010 to 2021, and especially from 2018 (men: 27%/women: 45%) to 2021 (men: 41%/women: 62%, p <0.001). A similar pattern was also observed for suicidal thoughts. Unlike previous waves, there were large geographical differences in mental health problems in 2021, which mapped onto the different levels of COVID-19 cases and regional COVID-19-related restrictions. There was a significant negative dose–response association between days spent physically on campus and both mental health problems and indicators of suicide risk. We found the fewer days spent on campus in the last 2 weeks, the higher levels of mental health problems during the same time period. There was also an association between days on campus and a higher prevalence of suicidal thoughts, NSSH and suicide attempts in the last year.

Conclusion

This study demonstrates a sharp increase and disturbing levels of mental health problems and suicide risk among students during the COVID-19 pandemic. Although causal conclusions cannot be drawn, the associations between closure of campuses and mental problems emphasise the importance of having access to campuses for student well-being.
Are professors of human nutrition faculty at Canadian universities representative with respect to common social constructs of gender and race?
Authors: McBurney Michael I.
Published: February 2022

Attributes such as sex and race/ethnicity are associated with inequities in representation. The objective of this study was to assess representation of 2 social constructs, gender and race, of professors of human nutrition in Canada. Using information publicly available October 2021, individuals with the title of assistant, associate, or full professor were identified on websites of 20 Canadian universities offering undergraduate and/or graduate degrees in human nutrition. Individuals were subjectively stratified to social constructs, i.e., white, racialized, or Indigenous, based on photographs, ethnic origin of a surname, and regional and ethnic origin disclosures on university websites, LinkedIn, social media, etc. Gender was assigned based on publicly available photographs and self-disclosed pronouns (when available). Of the 190 individuals, 80% were white, 16.4% were racialized, and 2.6% were Indigenous peoples. The majority (65.3%) were women. In a subset with established doctoral thesis dates and dates of hire at their current institution (n = 153), racialized and Indigenous professors, especially assistant and associate, had earned their doctorate and been hired more recently than their white peers. This study is limited because only individuals with professorial titles were included and the assignment of social constructs for race and gender was subjective. Nevertheless, it establishes an understanding of the proportions of professors of human nutrition who are white, racialized, Indigenous, women, and men.

Novelty: Canadian universities strive to be equitable, diverse, and inclusive. One hundred and ninety professors of human nutrition were stratified using social constructs for race and gender. Findings: 65% Women, 80% white, 16.4% racialized, and 2.6% Indigenous
Threatened skates exhibit abiotic niche stability despite climate change in the southwestern Atlantic Ocean
Authors: Coelho Jéssica Fernanda Ramos , Lima Sergio Maia Queiroz , Petean Flávia de Figueiredo
Published: February 2022

Climatic changes are disrupting distribution patterns of populations through shifts in species abiotic niches and habitat loss. The abiotic niche of marine benthic taxa such as skates, however, may be more climatically stable compared with the upper layers of the water column, which are more exposed to immediate impacts of warming. Here, we estimate climate change impacts in Riorajini, a tribe of four skates, as a proxy to evaluate the vulnerability of a temperate coastal zone in the Southwest Atlantic, and study niche dynamics in a scenario of environmental changes on this group of threatened species. We modelled the abiotic niche of each species under present climatic conditions (2000–2014), projected them to the future (2100), then measured distributional stability, expansion, and unfilling. Our results revealed abiotic stability between the scenarios modelled despite the advancement of climate change, suggesting that the benthic layers where these skates occur may be a refuge from the increasing thermal stress. However, the exposure of shallow waters to climate change may be detrimental to nursery habitats. Thus, although their abiotic niche may remain stable in the future, the loss of extension of occurrence might be a peril for them with climate change.