bluuebunny/crossref_metadata_2025 huggingface dataset:
7-Aryl-7-deazapurine 3′-deoxyribonucleoside derivative as a novel lead for Chagas’ disease therapy: in vitro and in vivo pharmacology
Authors: Cardoso-Santos Camila , Ferreira de Almeida Fiuza Ludmila , França da Silva Cristiane , Mazzeti Ana Lia , Donola Girão Roberson , Melo de Oliveira Gabriel , da Gama Jaen Batista Denise , Cruz Moreira Otacilio , Lins da Silva Gomes Natália , Maes Louis , Caljon Guy , Hulpia Fabian , Calenbergh Serge V , Correia Soeiro Maria de Nazaré
Published: November 2021

Background

The protozoan Trypanosoma cruzi is auxotrophic for purines and causes Chagas’ disease (CD), a neglected illness affecting >6 million people. Combining the 3-deoxyribofuranose part of cordycepin with the modified purine ring of a nucleoside ‘hit’ led to the discovery of 4-amino-5-(4-chlorophenyl)-N7-(3′-deoxy-β-d-ribofuranosyl)-pyrrolo[2,3-d]pyrimidine (Cpd1), revealing promising anti-T. cruzi activity.

Objectives

To further evaluate Cpd1 in vitro and in vivo to fully assess its therapeutic potential against CD, covering cell culture sterilization through washout assays, drug combination with benznidazole and long-term administration in T. cruzi-infected mice.

Results

Although less susceptible to Cpd1 than amastigotes, trypomastigotes present an impaired capacity to successfully establish intracellular infection of cardiac cultures. Combination of benznidazole with Cpd1 indicated no interaction (additive effect) (FIC index = 0.72) while administration to mice at one-tenth of the optimal dose (2.5 mg/kg and 10 mg/kg for Cpd1 and benznidazole, respectively) suppressed parasitaemia but failed to avoid mortality. Long-term treatment (60 days) gave a rapid drop of the parasitaemia (>98% decline) and 100% mice survival but only 16% cure. In vitro washout experiments demonstrated that although parasite release into the supernatant of infected cardiac cultures was reduced by >94%, parasite recrudescence did occur after treatment.

Conclusions

Parasite recrudescence did occur after treatment corroborating the hypothesis of therapeutic failure due to subpopulations of dormant forms and/or genetic factors in persister parasites involved in natural drug resistance.
Selecting Processing Robust Markers Using High-Resolution Mass Spectrometry for the Detection of Milk in Food Products
Authors: Van Vlierberghe Kaatje , Gavage Maxime , Dieu Marc , Renard Patsy , Arnould Thierry , Gillard Nathalie , Coudijzer Katleen , de Loose Marc , Gevaert Kris , Van Poucke Christof
Published: November 2021

Background

Cow’s milk allergy is one of the most reported food allergies in Europe. To help patients suffering from food allergies it is important to be able to detect milk in different foods. An analytical method that is gaining interest in the field of allergen detection is ultrahigh performance liquid chromatography-tandem mass spectrometry, where the analyte is a target peptide. When these peptide biomarkers are selected, the effect of food processing should be taken into account to allow a robust detection method.

Objective

This work aims at identifying such processing stable peptide markers for milk for the ultrahigh performance liquid chromatography-tandem mass spectrometry based detection of food allergens in different food products.

Method

Milk-incurred food materials that underwent several processing techniques were produced. This was followed by establishing tryptic peptide profiles from each matrix using ultrahigh performance liquid chromatography-high resolution mass spectrometry.

Results

A careful comparison of peptide profiles/intensities and the use of specific exclusion criteria resulted in the selection of eight peptide biomarkers suitable for application in ultrahigh performance liquid chromatography-tandem mass spectrometry based milk detection methods. One of these markers is an α-lactalbumin specific peptide, which has been determined to be stable in different incurred materials for the first time.

Conclusions

To our knowledge, this is the first systematic and experimentally based approach for the selection of suitable milk peptide biomarkers robust toward multiple, often applied food processing techniques for milk. Ensuring the exact knowledge of the food processing circumstances by starting from well-defined raw material and using fully controlled settings to produce incurred test material allowed the construction of a peptide database with robust markers. These robust markers can be used for the development of a robust detection method for milk in different food matrixes.

Highlights

To facilitate food allergen detection in processed food, processing stable peptide markers for the detection of milk in food products were determined using Ultra-High Performance Liquid Chromatography-High Resolution Mass Spectrometry on well-defined raw materials which were processed in accordance with often used processing techniques.
Impact of Honey Bee Migratory Management on Pathogen Loads and Immune Gene Expression is Affected by Complex Interactions With Environment, Worker Life History, and Season
Authors: Simone-Finstrom Michael , Strand Micheline K , Tarpy David R , Rueppell Olav
Published: November 2021

The effects of honey bee management, such as intensive migratory beekeeping, are part of the ongoing debate concerning causes of colony health problems. Even though comparisons of disease and pathogen loads among differently managed colonies indicate some effects, the direct impact of migratory practices on honey bee pathogens is poorly understood. To test long- and short-term impacts of managed migration on pathogen loads and immunity, experimental honey bee colonies were maintained with or without migratory movement. Individuals that experienced migration as juveniles (e.g., larval and pupal development), as adults, or both were compared to control colonies that remained stationary and therefore did not experience migratory relocation. Samples at different ages and life-history stages (hive bees or foragers), taken at the beginning and end of the active season, were analyzed for pathogen loads and physiological markers of health. Bees exposed to migratory management during adulthood had increased levels of the AKI virus complex (Acute bee paralysis, Kashmir bee, and Israeli acute bee paralysis viruses) and decreased levels of antiviral gene expression (dicer-like). However, those in stationary management as adults had elevated gut parasites (i.e. trypanosomes). Effects of environment during juvenile development were more complex and interacted with life-history stage and season. Age at collection, life-history stage, and season all influenced numerous factors from viral load to immune gene expression. Although the factors that we examined are not independent, the results illuminate potential factors in both migratory and nonmigratory beekeeping that are likely to contribute to colony stress, and also indicate potential mitigation measures.
A stringent upper limit on dark matter self-interaction cross-section from cluster strong lensing
Authors: Andrade Kevin E , Fuson Jackson , Gad-Nasr Sophia , Kong Demao , Minor Quinn , Roberts M Grant , Kaplinghat Manoj
Published: November 2021

We analyse strongly lensed images in eight galaxy clusters to measure their dark matter density profiles in the radial region between 10 kpc and 150 kpc, and use this to constrain the self-interaction cross-section of dark matter (DM) particles. We infer the mass profiles of the central DM haloes, bright central galaxies, key member galaxies, and DM subhaloes for the member galaxies for all eight clusters using the qlens code. The inferred DM halo surface densities are fit to a self-interacting dark matter model, which allows us to constrain the self-interaction cross-section over mass σ/m. When our full method is applied to mock data generated from two clusters in the Illustris-TNG simulation, we find results consistent with no dark matter self-interactions as expected. For the eight observed clusters with average relative velocities of $1458_{-81}^{+80}$ km s−1, we infer $\sigma /m = 0.082_{-0.021}^{+0.027} \rm cm^2\, g^{ -1}$ and $\sigma /m \lt 0.13~ \rm cm^2\, g^{ -1}$ at the 95 per cent confidence level.
The impact of stellar companion UV photons on the chemistry of the circumstellar environments of AGB stars
Authors: Van de Sande M , Millar T J
Published: November 2021

Spherical asymmetries are prevalent within the outflows of AGB stars. Since binary interaction with a stellar or planetary companion is thought to be the underlying mechanism behind large-scale structures, we included the effects of UV radiation originating from a stellar companion in our chemical kinetics model. The one-dimensional model provides a first approximation of its effects on the chemistry throughout the outflow. The presence of a close-by stellar companion can strongly influence the chemistry within the entire outflow. Its impact depends on the intensity of the radiation (set by the stellar radius and blackbody temperature) and on the extinction, the UV radiation experiences (set by the outflow density, density structure, and assumed radius of dust formation). Parent species can be photodissociated by the companion, initiating a rich photon-driven chemistry in the inner parts of the outflow. The outcome depends on the balance between two-body reactions and photoreactions. If two-body reactions dominate, chemical complexity within the outflow increases. This can make the abundance profiles of daughters appear like those of parents, with a larger inner abundance and a Gaussian decline. If photoreactions dominate, the outflow can appear molecule-poor. We model three stellar companions. The impact of a red dwarf companion is limited. Solar-like companions show the largest effect, followed by a white dwarf. A stellar companion can also lead to the formation of unexpected species. The outflow’s molecular content, especially combined with abundance profiles, can indicate a stellar companion’s presence. Our results pave the way for further outflow-specific (three-dimensional) model development.
Electron mirror and cyclotron instabilities for solar wind plasma
Authors: Sarfraz M , López R A , Ahmed Shahzad , Yoon P H
Published: November 2021

The solar wind plasma is characterized by unequal effective kinetic temperatures defined in perpendicular and parallel directions with respect to the ambient magnetic field. For electrons, the excessive perpendicular temperature anisotropy leads to quasi-parallel electromagnetic electron cyclotron (or whistler) instability and aperiodic electron-mirror instability with oblique wave vectors. The present paper carries out a direct side-by-side comparison of quasi-linear (QL) theory and particle-in-cell (PIC) simulation of combined mirror and cyclotron instabilities acting upon the initially anisotropic electron temperatures, and find that the QL theory satisfactorily encapsulates the non-linear aspect of the combined instability effects. However, a discrepancy between the present study and a previous PIC simulation result is also found, which points to the need for further investigation to resolve such an issue.
Mapping the cosmic mass distribution with stacked weak gravitational lensing and Doppler lensing
Authors: Hossen Md Rasel , Ema Sonia Akter , Bolejko Krzysztof , Lewis Geraint F
Published: November 2021

Dark matter haloes represent the highest density peaks in the matter distribution. Conversely, cosmic voids are underdense patches of the universe. Probing the mass distribution of the universe requires various approaches, including weak gravitational lensing that subtly modifies the shape of distant sources, and Doppler lensing that changes the apparent size and magnitude of objects due to peculiar velocities. In this work, we adopt both gravitational and Doppler lensing effects to study the underlying matter distribution in and around cosmic voids or haloes. We use the relativistic N-body code gevolution, to generate the mass perturbations and develop a new ray-tracing code that relies on the design of the ray bundle method. We consider three categories of halo masses and void radii, and extract the cosmological information by stacking weak-lensing and Doppler lensing signals around voids or haloes. The results of this paper show that the most optimal strategy that combines both gravitational and Doppler lensing effects to map the mass distribution should focus on the redshift range z ≈ 0.3−0.4. The recommendation of this paper is that future spectroscopic surveys should focus on these redshifts and utilize the gravitational and Doppler lensing techniques to extract information about underlying matter distribution across the cosmic web, especially inside cosmic voids. This could provide a complimentary cosmological analysis for ongoing or future low-redshift spectroscopic surveys.
Systematic review and meta-analysis of PD-L1 expression discordance between primary tumor and lung cancer brain metastasis
Authors: Tonse Raees , Rubens Muni , Appel Haley , Tom Martin C , Hall Matthew D , Odia Yazmin , McDermott Michael W , Ahluwalia Manmeet S , Mehta Minesh P , Kotecha Rupesh
Published: November 2021

Background

Novel immunotherapeutic strategies targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis are often administered when metastatic tumors show PD-L1 positivity, even in the setting of lung cancer brain metastasis (LCBM). However, biological differences exist between primary tumors and metastatic sites. The objective of this study was to analyze rates of PD-L1 receptor discordance between primary tumors and LCBM.

Methods

A systematic review of studies of biopsied or resected LCBM evaluating PD-L1 discordance published in the Medline database was performed using PRISMA guidelines. Weighted random effects models were used to calculate pooled estimates.

Results

Six full-text articles (n = 230 patients) with a median of 32 patients in each study (range: 24–73) reported PD-L1 receptor expression analyses of both primary lung tumors and brain metastases and met inclusion criteria. The pooled estimate for tumor cell (TC) PD-L1 receptor discordance between primary tumors and LCBM was 19% (95% confidence interval [CI]: 10–27%). For PD-L1 receptor expression in tumor-infiltrating lymphocytes (TIL), the weighted pooled estimate for discordance was 21% (95% CI: 8–44%). For primary versus LCBM, the positive rates by expression levels of <1%, 1–50%, and >50% were 52% (95% CI: 30–73%) versus 56% (95% CI: 34–76%), 30% (95% CI: 22–40%) versus 20% (95% CI: 10–35%), and 15% (95% CI: 6–36%) versus 22% (95% CI: 15–31%) (P = .425), respectively.

Conclusions

PD-L1 discordance occurs in ~20% of LCBM, with the greatest discordance in the 1–50% expression category. Although controversial, confirming discordance might be important for selection of immune checkpoint inhibitor therapy and in the analysis of patterns of failure after treatment.
Reduction of the canonical function of a glycolytic enzyme enolase triggers immune responses that further affect metabolism and growth in Arabidopsis
Authors: Yang Leiyun , Wang Zhixue , Zhang Aiqin , Bhawal Ruchika , Li Chunlong , Zhang Sheng , Cheng Lailiang , Hua Jian
Published: November 2021

Primary metabolism provides energy for growth and development as well as secondary metabolites for diverse environmental responses. Here we describe an unexpected consequence of disruption of a glycolytic enzyme enolase named LOW EXPRESSION OF OSMOTICALLY RESPONSIVE GENE 2 (LOS2) in causing constitutive defense responses or autoimmunity in Arabidopsis thaliana. The autoimmunity in the los2 mutant is accompanied by a higher expression of about one-quarter of intracellular immune receptor nucleotide-binding leucine-rich repeat (NLR) genes in the genome and is partially dependent on one of these NLR genes. The LOS2 gene was hypothesized to produce an alternatively translated protein c-Myc Binding Protein (MBP-1) that functions as a transcriptional repressor. Complementation tests show that LOS2 executes its function in growth and immunity regulation through the canonical enolase activity but not the production of MBP-1. In addition, the autoimmunity in the los2 mutants leads to a higher accumulation of sugars and organic acids and a depletion of glycolytic metabolites. These findings indicate that LOS2 does not exert its function in immune responses through an alternatively translated protein MBP-1. Rather, they show that a perturbation of glycolysis from the reduction of the enolase activity results in activation of NLR-involved immune responses which further influences primary metabolism and plant growth, highlighting the complex interaction between primary metabolism and plant immunity.
Inequality of access to advanced therapies for patients with inflammatory arthritis: a postcode lottery?
Authors: Kaul Arvind , Mistry Jatin , Iagnocco Annamaria , Baraliakos Xenofon , Bosworth Ailsa , McNicol Iain
Published: November 2021

Objectives

Advanced therapies (AT), including biologics, biosimilars and Janus kinase inhibitors, have dramatically improved the quality of life of patients with RA, PsA and axial spondyloarthritis (axSpA). Evidence-based criteria for prescribing these drugs in England and Wales is formulated by the National Institute for Health and Care Excellence (NICE) through health technology appraisals and guidelines, with the aim of providing equitable access to AT for patients with severe or resistant disease. Similar bodies exist in some, but not all European countries, with disparities in AT access between countries for RA. We examined whether this disparity was mirrored in England for RA, PsA and axSpA despite the National Health Service in England and Wales being legally obliged to provide funding for AT recommended by NICE’s Health Technology Appraisal board, through the commissioning bodies, the clinical commissioning groups (CCGs).

Methods

We requested AT pathways from CCGs in England. Where these were not available, individual hospital Trusts were contacted using freedom of information requests.

Results

We found marked variability in the way that CCGs in England interpret NICE guidance. We found 41, 29 and 25 different pathways for RA, PsA and axSpA, respectively. Similar disparities existed with sequential prescribing where one AT did not work, with limits on the numbers of sequential AT in 54%, 59% and 59% of CCGs for RA, PsA and axSpA, respectively, and with these limits being different for the same condition between CCGs.

Conclusion

Although patients at identical stages of their disease course should have access to the same NICE-approved AT, we found this is not the case for large parts of England. Inequality of access was found between regions, mirroring the variability that occurs between countries throughout Europe. Harmonization of access needs to be addressed by policymakers to ensure fairness in the way that clinicians and patients can access AT.
Relationship Match: the neural underpinnings of social feedback in romantic couples
Authors: Ha Thao , Hampton Ryan S
Published: November 2021

Romantic love involves an evaluative process in which couples weigh similarities and differences that facilitates pair bonding. We investigated neural attentive processes (P3) during evaluative relationship feedback within existing romantic couples using the Relationship Match Game. This paradigm included participant-driven expectations about relationship matching and relationship feedback from an expert panel of fictive peers and their romantic partner. In total, 49 couples participated who had dated less than one year. Participants showed significantly larger P3s in anticipation of feedback when they expected a mismatch, especially when supported by panel feedback. P3 amplitudes were also greater when participants received feedback from their partner congruent with their own assessment of compatibility. This was moderated by relational ambiguity, or one’s preference to keep the relationship’s status vague. We discuss how insecurity about the relationship is costly in terms of attentional resources contributing to over-alertness to cues of relationship evaluation.
Synchronizing our clocks as we age: the influence of the brain-gut-immune axis on the sleep-wake cycle across the lifespan
Authors: Sgro Marissa , Kodila Zoe N , Brady Rhys D , Reichelt Amy C , Mychaisuk Richelle , Yamakawa Glenn R
Published: November 2021

The microbes that colonize the small and large intestines, known as the gut microbiome, play an integral role in optimal brain development and function. The gut microbiome is a vital component of the bidirectional communication pathway between the brain, immune system, and gut, also known as the brain-gut-immune axis. To date, there has been minimal investigation into the implications of improper development of the gut microbiome and the brain-gut-immune axis on the sleep-wake cycle, particularly during sensitive periods of physical and neurological development, such as childhood, adolescence, and senescence. Therefore, this review will explore the current literature surrounding the overlapping developmental periods of the gut microbiome, brain, and immune system from birth through to senescence, while highlighting how the brain-gut-immune axis affects the maturation and organization of the sleep-wake cycle. We also examine how a dysfunction to either the microbiome or the sleep-wake cycle negatively affects the bidirectional relationship between the brain and gut, and subsequently the overall health and functionality of this complex system. Additionally, this review integrates therapeutic studies to demonstrate when dietary manipulations, such as supplementation with probiotics and prebiotics, can modulate the gut microbiome to enhance the health of the brain-gut-immune axis and optimize our sleep-wake cycle.
The effect of creep feed composition and form on pre- and post-weaning growth performance of pigs and the utilization of low-complexity nursery diets
Authors: Christensen Brenda , Huber Lee-Anne
Published: November 2021

Fifty-six litters from first-parity sows standardized to 12 piglets were used to determine the effects of creep feed composition and form on pre- and post-weaning pig growth performance and the utilization of low-complexity nursery diets. At 5 days of age, litters (initial body weight [BW] 2.31 ± 0.61 kg) were assigned to one of four creep feeding regimens (n = 14): 1) pelleted commercial creep feed (COM), 2) liquid milk replacer (LMR), 3) pelleted milk replacer (PMR), or 4) no creep feed (NO); creep feeds contained 1.0% brilliant blue as a fecal marker. Individual piglet BW and fecal swabs were collected every 3 ± 1 days during the creep-feeding period. The latter was to identify piglets that regularly consumed creep feed via the visual appearance of blue dye in the feces. At weaning (21 ± 2 days of age), six pigs per litter with median BW that consumed creep feed were placed on either a HIGH− (contained highly digestible animal proteins) or LOW− (contained corn and soybean meal as the main protein sources) complexity nursery diet (n = 7) in a three-phase feeding program over 39 days. On day 8, two pigs per pen were sacrificed to collect organ weights and digesta. The LMR disappeared at the greatest rate (average 37.7 g/pig/d; dry matter-basis) versus COM and PMR (10.6 and 10.3 ± 1.5 g/pig/d, respectively; P < 0.001). Litters that received LMR had the greatest proportion of pigs with blue fecal swabs throughout the creep feeding period (85.0 vs. 54.9 and 63.0% ± 0.4% for COM and PMR, respectively; P < 0.05) and LMR piglets had greater BW at weaning versus all other treatments (6.32 vs. 6.02, 5.92, and 5.67 ± 0.14 kg, for LMR, COM, NO, and PMR, respectively; P < 0.001). Overall, pigs given LOW (vs. HIGH) diets in the nursery period had reduced average daily gain (25.1 vs. 27.7 ± 0.4 g/kg BW; P < 0.001), gain:feed (0.75 vs. 0.81 ± 0.02; P < 0.001), and exit BW (21.2 vs. 24.4 ± 0.6 kg; P < 0.001); no carryover effects of creep feeding program were observed. Creep feed regimen had limited effects on nutrient digestibility of nursery diets but the apparent ileal digestibility of organic matter tended to be less at 28 days of age for pigs that received the LOW nursery diet (64.2 vs. 68.8% ± 2.5%; P = 0.076). Providing supplemental nutrition during the suckling period via LMR improved piglet BW at weaning, which did not correspond to improved post-weaning growth performance, regardless of nursery diet complexity.
Prevalence and Severity of HBV-Associated Acute-on-Chronic Liver Failure Due to Irregular Medication of Nucleos(t)ide Analogs
Authors: Zheng Ying , Chen Shu , Huang Yanxin , Jiang Lisheng , Li Yongguo , Lan Yinghua , Li Shuchen , Xu Yuqin , Li Xiaodong , Zhao Hongwei , Wang Yanbo , Shen Ying , Wei Chao , Zhou Honglin , Fan Rongshan , Zeng Xiqiu , Jiang Mingxia , Song Shupeng , Xu Mingyan
Published: November 2021

Hepatitis B virus (HBV) represents the commonest etiologic agent of acute-on-chronic liver failure (ACLF) in most Asian countries. Nucleos(t)ide analogs (NAs) are effective in the treatment of chronic HBV infections, but may also exacerbate the disease and stimulate its development into HBV-associated ACLF if not used appropriately. The current study aimed to assess the prevalence and severity of HBV-associated ACLF as a result from irregular medication of NAs (IMNA). A total of 1134 individuals with HBV-associated ACLF in nine hospitals in Heilongjiang Province were enrolled in this study between 2005 and 2015. Among these, 777 chronic hepatitis B (CHB) and 357 HBV-associated liver cirrhosis cases were classified based on various predisposing factors, including IMNA, HBV reactivation (HBVR), infections, treatment drugs, alcohol use and others (hepatitis C virus, hepatitis E virus, gastrointestinal bleeding and unknown reasons). The percentage and improvement rate were examined. Among individuals with HBV-associated ACLF and CHB, IMNA was found in 9.01%, HBVR in 46.20%, infections in 9.52%, treatment drugs in 14.67%, alcohol in 11.71%, and others in 24.58% as predisposing factors. Improvement rates in cases with IMNA, HBVR, infections, treatment drugs, alcohol and others were 41.43%, 58.50%, 58.11%, 56.14%, 53.85%, and 65.97%, respectively. Multivariable analysis showed that IMNA, others, infections, hepatic encephalopathy and hepatorenal syndrome were associated with prognosis. Only IMNA independently predicted HBV-associated ACLF prognosis. Overall, our study demonstrated that the percentage of IMNA-induced HBV-associated ACLF was 12.61%, and worse disease conditions resulted from IMNA compared with other factors. Thus, the suitability of treatment with NAs should be thoroughly evaluated.
Pain and Pain Control With Opioid and Nonopioid Medications After Otologic Surgery
Authors: Godse Neal R. , Tarfa Rahilla A. , Perez Philip L. , Hirsch Barry E. , McCall Andrew A.
Published: November 2021

Objective:

To prospectively analyze pain and pain medication use following otologic surgery.

Study Design:

Prospective cohort study with patient reported pain logs and medication use logs.

Setting:

Tertiary academic hospital.

Patients: Sixty adults who underwent outpatient otologic surgeries.

Interventions:

Surveys detailing postoperative pain levels, nonopioid analgesic (NOA) use, and opioid analgesic use.

Main Outcome Measures:

Self-reported pain scores, use of NOA, and use of opioid medications normalized as milligrams morphine equivalents (MME).

Results:

Thirty-two patients had surgery via a transcanal (TC) approach, and 28 patients had surgery via a postauricular (PA) approach. TC surgery had significantly lower reported pain scores than PA surgery on both postoperative day (POD) 1 (median pain score 2.2, IQR 0–5 vs. median pain score 4.8, IQR 3.4–6.3, respectively; p = 0.0013) and at POD5 (median pain score 0, IQR 0–0 vs. median pain score 2.0, IQR 0–3, respectively; p = 0.0002). Patients also used significantly fewer opioid medications with TC approach than patients who underwent PA approach at POD1 (median total MME 0, IQR 0–5 vs. median total MME 5.0, IQR 0–15, respectively; p = 0.03) and at POD5 (median total MME 0, IQR 0–0 vs. median total MME 0, IQR 0–5, respectively; p = 0.0012).

Conclusions:

Surgery with a postauricular approach is associated with higher pain and opioid use following otologic surgery. Patient- and approach-specific opioid prescribing is feasible following otologic surgery.
Modelling migration in birds: competition's role in maintaining individual variation
Authors: Kikuchi D. W. , Reinhold K.
Published: November 2021

Animals exhibit extensive intraspecific variation in behaviour. Causes of such variation are less well understood. Here, we ask when competition leads to the maintenance of multiple behavioural strategies. We model variability using the timing of bird migration as an example. Birds often vary in when they return from non-breeding grounds to establish breeding territories. We assume that early-arriving birds (counting permanent residents as ‘earliest’) select the best territories. But arriving before the optimal (frequency-independent) breeding date incurs a fitness penalty. Using simulations, we find stable sets of return dates. When year-round residency is viable, the greatest between-individual variation occurs when a small proportion of permanent residents is favoured, and the rest of the population varies in their return times. However, when fitness losses due to year-round residency exceed the benefits of breeding in the worst territory, all individuals migrate, although their return dates often vary continuously. In that case, individual variation is inversely related to fitness risks and positively related to territory inequality. This result is applicable across many systems: when there is more to gain through competition, or when its risks are small, a diversity of individual strategies prevails. Additionally, stability can depend upon the distribution of resources.
Individual-based eco-evolutionary models for understanding adaptation in changing seas
Authors: Xuereb Amanda , Rougemont Quentin , Tiffin Peter , Xue Huijie , Phifer-Rixey Megan
Published: November 2021

As climate change threatens species' persistence, predicting the potential for species to adapt to rapidly changing environments is imperative for the development of effective conservation strategies. Eco-evolutionary individual-based models (IBMs) can be useful tools for achieving this objective. We performed a literature review to identify studies that apply these tools in marine systems. Our survey suggested that this is an emerging area of research fuelled in part by developments in modelling frameworks that allow simulation of increasingly complex ecological, genetic and demographic processes. The studies we identified illustrate the promise of this approach and advance our understanding of the capacity for adaptation to outpace climate change. These studies also identify limitations of current models and opportunities for further development. We discuss three main topics that emerged across studies: (i) effects of genetic architecture and non-genetic responses on adaptive potential; (ii) capacity for gene flow to facilitate rapid adaptation; and (iii) impacts of multiple stressors on persistence. Finally, we demonstrate the approach using simple simulations and provide a framework for users to explore eco-evolutionary IBMs as tools for understanding adaptation in changing seas.
Target of Rapamycin drives unequal responses to essential amino acid depletion in egg laying
Authors: Alves André N. , Sgrò Carla M. , Piper Matthew D. , Mirth Christen K.
Published: November 2021

Nutrition shapes a broad range of life history traits, ultimately impacting animal fitness. A key fitness-related trait, female fecundity is well known to change as a function of diet. In particular, the availability of dietary protein is one of the main drivers of egg production, and in the absence of essential amino acids egg laying declines. However, it is unclear whether all essential amino acids have the same impact on phenotypes like fecundity. Using a holidic diet, we fed adult female D. melanogaster diets that contain all necessary nutrients except one of the 10 essential amino acids and assessed the effects on egg production. For most essential amino acids, depleting a single amino acid induced as rapid a decline in egg production as when there were no amino acids in the diet. However, when either methionine or histidine were excluded from the diet, egg production declined more slowly. Next, we tested whether GCN2 and TOR were involved in this difference in response across amino acids. While mutations in GCN2 did not eliminate the differences in the rates of decline in egg laying among amino acid drop-out diets, we found that inhibiting TOR signalling caused egg laying to decline rapidly for all drop-out diets. TOR signalling does this by regulating the yolk-forming stages of egg chamber development. Our results suggest that amino acids differ in their ability to induce signalling via the TOR pathway. This is important because if phenotypes differ in sensitivity to individual amino acids, this generates the potential for mismatches between the output of a pathway and the animal’s true nutritional status.
A new prognostic model for pancreatic cancer based on pyroptosis-related genes
Authors: Ma Liukai , Wang Mengyao , Jia Ruoling , Yan Cheng
Published: November 2021

Pancreatic cancer is one of the most common malignant tumors of the digestive tract. It is known as the “king of cancer” in the field of cancer, and is one of the worst prognosis malignant tumors. Pyroptosis is a kind of programmed cell death, which can promote the inflammatory response of cells. Studies have shown that the effect of pyroptosis-related genes in cancer is significant. However, the role of pyroptosis in pancreatic cancer is not clear. The aim of this study is to establish a prognostic model based on pyroptosis. The gene expression and clinical data of pancreatic cancer patients were obtained from TCGA and verified in GEO. The differential expression of 33 pyroptosis-related genes in pancreatic cancer and normal tissues was analyzed, of which 6 genes were up-regulated and 12 genes were down regulated. Then, it was analyzed that pyroptosis-related genes were mainly enriched in the defense against bacteria and pyroptosis pathways. A concise and reliable model is established by lasso-cox regression analysis. Km curve shows that there are differences between high-risk group and low-risk group. And the nomogram has reliable prediction ability. In conclusion, pyroptosis an important role in pancreatic cancer, which can be used for the prediction of pancreatic cancer and provide a new perspective for the treatment of pancreatic cancer.

AUTHOR APPROVALS

The authors have seen and approved the manuscript, and that it hasn’t been accepted or published elsewhere.

COMPETING INTERESTS

The authors declare no competing interests.
Multifunctional phosphate based nanoparticles as a platform for imaging, targeting and doxorubicin delivery to human breast cancer CD44+ cells
Authors: De Tótaro Priscila Izabel Santos , Alvarenga Betânia Mara , dos Reis Diego Carlos , Martins Thaís Maria da Mata , Santos Anderson Kennedy , Resende Rodrigo Ribeiro , Cassali Geovanni Dantas , Góes Alfredo Miranda , Júnior José Dias Corrêa
Published: November 2021

Functionalized nanostructured systems can be used for imaging and drug delivery for anti-tumor therapy, including breast tumors. This is a more efficient approach that offers reduced systemic side effects compared to conventional diagnostic and chemotherapy methods. Multifunctional nanoparticles are potential tools in the diagnosis, location tracing and kill tumor cells through a less invasive manner. Functionalized phosphate-based nanoparticles are capable of encapsulating, or may be associated, with fluorescent probes. In this study, we synthesize a nanoparticle phosphate-based composite (NPC) and functionalize it with poly-ethylene glycol (PEG), hyaluronic acid (HA), the fluorescent probe rhodamin 6G (R6G) and the antimitotic doxorubicin (DOX). We focused on targeting human breast cancer cells reporting the biological effects of functionalized NPC on them. NPC and NPC formulations containing PEG, HA, and R6G did not cause cell viability reduction on MCF-7 and MDA-MB-231 cell lines. The cellular internalization of NPC was quantified by real-time in vitro observation, and confirmed by electron microscopy techniques. Intracellular NPC distribution is detected in the cytoplasm and nucleus of tumor cells by confocal fluorescent images. The percent association of doxorubicin to NPC matrix was approximately 18% and NPC formulations associated with doxorubicin led to a significant reduction in cell viability in MDA-MB-231 and MCF-7 cells. This data suggest the potential use of NPC as a non-cytotoxic platform for association with functional ligands to selective targeting breast cancer cells. NPC use can be also explored in drug delivery to cancer cells.
Multi-parametric characterization of brain-wide hemodynamic and calcium responses to sensory stimulation in mice
Authors: Chen Zhenyue , Zhou Quanyu , Deán-Ben Xosé Luís , Gezginer Irmak , Ni Ruiqing , Reiss Michael , Shoham Shy , Razansky Daniel
Published: November 2021

Modern optical neuroimaging approaches are expanding our ability to elucidate complex brain function. Diverse imaging contrasts enable direct observation of neural activity with functional sensors along with the induced hemodynamic responses. To date, decoupling the complex interplay of neurovascular coupling and dynamical physiological states has remained challenging when employing single-modality functional neuroimaging tools. We devised a hybrid fluorescence optoacoustic tomography (FLOT) platform combined with a custom data processing pipeline based on statistical parametric mapping, accomplishing the first simultaneous noninvasive observation of both direct and indirect brain-wide activation patterns with optical contrast. Correlated changes in the oxy- and deoxygenated hemoglobin, total hemoglobin, oxygen saturation and rapid GCaMP6f fluorescence signals were observed in response to peripheral sensory stimulation. While the concurrent epifluorescence served to corroborate and complement the functional optoacoustic observations, the latter further aided in decoupling the rapid calcium responses from the slowly varying background in the fluorescence recordings mediated by hemodynamic changes. The hybrid imaging platform expands the capabilities of conventional neuroimaging methods to provide more comprehensive functional readings for studying neurovascular and neurometabolic coupling mechanisms and related diseases.
scDeepHash: An automatic cell type annotation and cell retrieval method for large-scale scRNA-seq datasets using neural network-based hashing
Authors: Ma Shihao , Zhang Yanyi , Wang Bohao , Hu Zian , Zhang Jingwei , Wang Bo
Published: November 2021

Single-cell RNA-sequencing technologies measure transcriptomic expressions, which quantifies cell-to-cell heterogeneity at an unprecedented resolution. As these technologies become more readily available, the number of scRNA-seq datasets increases drastically. Prior works have demonstrated that bias-free, holistic single-cell profiling infrastructures are essential to the emerging automatic cell-type annotation methods. We propose scDeepHash, a scalable scRNA-seq analytic tool that employs content-based deep hashing to index single-cell gene expressions. scDeepHash allows for fast and accurate automated cell-type annotation and similar-cell retrieval. We also demonstrate the performance of scDeepHash by benchmarking it against current state-of-the-art methods across multiple public scRNA-seq datasets.
Influence of transactive memory systems and strategic orientations on the performance of hospitality firms
Authors: Batra Shruti , Dey Ajoy Kumar , Singh Rahul , Chaudhuri Manosi
Published: November 2021

Purpose

Since the hospitality industry is driven by people, effective utilization of knowledge among various organizational units is required to ensure guest satisfaction and in turn superior performance. Research trying to find the implications of transactive memory systems (TMSs), an integrative mechanism for knowledge management in organizations, has yielded ambiguous and mixed results, leading the researchers to believe that the linkages may not be as straightforward as previously imagined. In this study, the authors theoretically build their arguments based on the knowledge-based view of the firm and empirically test these linkages using data collected from the small hotels of India.

Design/methodology/approach

Data were collected from the owner-managers or senior executives of small hotels operating in the Uttarakhand state of India, and analysed using structural equation modelling (SEM) and Hayes process macro.

Findings

It was found that for the hospitality firms, the TMS is an enabler for performance only when the focus of knowledge creation and utilization is on building effective strategic orientations. Further, the technology orientation (TO) and learning orientation (LO) of the hotel mediate the relationship between the TMS and firm performance.

Practical implications

Effective knowledge sharing among employees helps availability of credible and crucial information about customers, which eventually helps in long-term mutually beneficial relationships with the customers, leading to greater economic value creation for the hotel.

Originality/value

By establishing theoretical links between knowledge creation and utilization, and validating these linkages using data collected from the hotel industry in India, this study offers unique and useful insights for the theoretical advancement of the hospitality literature. This study also makes a case that small hotels investing their energy and resources into the creation of a transactive memory systems could reap benefits through appropriate strategic postures.
Stakeholder perceptions on the risk factors, challenges and benefits of business sustainability practices in the Singapore construction industry
Authors: Lau Chee Kwong , Chen Hexin
Published: November 2021

Purpose

This study examines the stakeholder perception of the sustainability risks, challenges and benefits arising from managing these risks in the Singapore construction industry.

Design/methodology/approach

A questionnaire consisting of 89 risk factors, challenges and benefits, was administered, with 216 responses received from various stakeholders. Regression analyses were used to estimate the relationships between sustainability and business risk factors, challenges and benefits associated with business sustainability practices.

Findings

Stakeholders recognise the importance of the emerging sustainability risk factors, and indeed rank these almost on a par with conventional business risk factors. The inherent business risks determine the nature of sustainability risk factors for construction firms, which in turn can affect their business risks and the performance and value creation of firms. However, most stakeholders, while acknowledging that business sustainability practices can provide benefits as well as posing challenges, do not believe that they can derive net benefits from such practices.

Research limitations/implications

Through this perception study, there is an urgent need to turn the existing awareness of the importance of business sustainability (BS) practices into more consistent and solid actions among construction firms in Singapore.

Practical implications

This study’s results imply construction firms to incorporate BS practices more systematically into their business strategies and operations, and to include sustainability risk factors alongside conventional business risks in their risk registers and risk management frameworks.

Originality/value

This study consolidates various variables and constructs of BS matters in the literature and practice into a meaningful framework for the management of BS in the construction industry.
PRDM5 suppresses oesophageal squamous carcinoma cells and modulates 14–3‐3zeta/Akt signalling pathway
Authors: Zhang Chunyang , Liu Ziyang , Sheng Yinliang , Wu Bin , Song Yanan , Ye Guanchao , Qi Yu , Zhao Song
Published: November 2021

Dysregulation of PR (PRDI‐BF1 and RIZ) domain protein 5 (PRDM5) expression has been shown to be associated with the progression of many malignancies. Nevertheless, the role and underlying mechanism of PRDM5 in oesophageal squamous cell carcinoma (ESCC) remain elusive. qRT‐PCR was performed to analyze PRDM5 mRNA expression, and western blot was used to determine protein expression of PRDM5, MMP‐2, MMP‐9, 14–3‐3zeta, pan‐Akt and phosphorylated Akt expression. CCK‐8 staining was employed to evaluate cell proliferation, while wound scratch assay and Transwell assay were carried out to detect cell migration. A tumour xenograft model of ESCC was also established to validate the effect of PRDM5. PRDM5 expression was downregulated in ESCC tissues and positively correlated with the overall survival of ESCC patients. Silencing PRDM5 expression promoted cell proliferation in ESCC cells, while overexpressing PRDM5 inhibited cell proliferation. Moreover, the migratory abilities of ESCC cells were promoted by PRDM5 knockdown but were attenuated by PRDM5 overexpression. Importantly, 14–3‐3zeta expression, along with the phosphorylation of Akt, was suppressed by PRDM5 in ESCC cells. In the established tumour xenograft model, PRDM5 regulated ESCC tumour growth as well as the expression of 14–3‐3zeta and phosphorylation of Akt protein. In conclusion, PRDM5 suppresses ESCC cell proliferation and migration and negatively regulates 14–3‐3zeta/Akt signalling pathway in vitro and in vivo.
The philosophy of the Yijing and Jungian analytical psychology: a comparative study
Authors: Zhang Wenzhi , Shen Heyong
Published: November 2021

The Yijing (Book of Changes) occupied a very significant position in C.G. Jung’s mind, which was closely related to Richard Wilhelm’s active recommendation and introduction of the Yijing wisdom. Inspired by the Yijing, Jung set forth the ‘principle of synchronicity’, by which scholars tend to discuss the relationship between Yijing and Jungian psychology. In fact, Jungian analytical psychology conceives in‐depth onto‐cosmological connotations corresponding to the philosophy of the Yijing. The terms invented or employed by Jung such as ‘archetype’, ‘Self’, ‘individuation’, ‘mandala,’ ‘anima and animus’, ‘persona and shadow’ are interrelated with the connotations of Taiji (Supreme Ultimate) (○) and liang yi (two‐mode) () in the Yijing philosophy. A comparative study of the two disciplines can help us gain a more comprehensive and deeper understanding of both, and further improve the exchanges of Eastern and Western cultures.
Response to ‘Transgender medicalization and the attempt to evade psychological distress’ (Withers 2020) and to Herdzik’s (2021) response to Withers
Authors: Solem David
Published: November 2021

Psyche is non‐binary and multiple and clinical work in the analytic container must be held in the fluidity of multiplicity. Analysts are called to bring Queer energy to analytical attitude. Queer energy is intrinsically non‐conforming and desires to confront a priori concepts in service to the unfolding of the Self. A Queer analytic attitude seeks to blur narrative, deconstruct language and listen deeply for what is emergent in the field. Queer energy is also deeply activating and often results in polarizations of attitude and a failure to hold what is emergent.

This response to Withers (2020) and to (Herdzik 2021) is an invitation for all of us to engage our activated complexes around work with transgender issues and the fluidity of the Queer experience. The multiplicity of the Self seeks to be known through analytic process. Consciously held authentic experience of what is emergent and thus unknown is at the core of this process. An analysis capable of holding Queer energy offers a theatre for the exploration of gender identity and its expression.