bluuebunny/crossref_metadata_2025 huggingface dataset:
Clearing the Fog: A Systematic Review on Cognitive Dysfunction in COVID-19
Authors: Butardo Nicole D. , Coronel Mikaela Frances D. , Dino Alanna Marie O. , Mendoza Tiffany Ritz F. , Sto. Domingo Oliver Kyle DC. , Regencia Zypher Jude G. , Dominguez Jacqueline C. , Baja Emmanuel S. , Ligsay Antonio D.
Published: May 2022

Objective

The systematic review aims to examine the association between COVID-19 and cognitive dysfunction, including the link between the severity of COVID-19 and the occurrence of cognitive impairment and the potential pathophysiological mechanisms related to brain fog among COVID-19 patients.

Methods

PubMed, Oxford University Press, ProQuest Health and Medical Complete, ScienceDirect, Ovid, HERDIN, Google Scholar, and Cochrane Library databases were accessed to retrieve literature using the PRISMA guidelines.

Results

After critical appraisal, thirteen full journal articles were included in the study. The studies showed the most frequent cognitive impairment are attention, memory, and executive function in COVID-19 patients. Compared with healthy controls (HC) in 3 out of 4 studies, cognitive impairment was only evident in COVID-19 patients. Furthermore, two studies showed no correlation between brain fog and depression, and five studies showed a link between the severity of COVID-19 infection and cognitive impairment. Cases ranging from mild to severe illness presented manifestations of brain fog. However, a disparity in the evidence of the pathophysiology of COVID-19 and cognitive dysfunction exists, prompting the need to investigate further. Additionally, recent studies provide insufficient evidence for direct central nervous system invasion, and there are emerging studies that contrast the presumed pathogenesis of neurological complications from neuroinflammation.

Conclusion

There is an association between COVID-19 and cognitive dysfunction. Manifestation of cognitive dysfunction is present regardless of illness severity. Moreover, there are existing pathophysiological mechanisms of the Coronavirus that lead to cognitive dysfunction in COVID-19 patients; however, additional studies are required to substantiate such mechanisms further.

PROSPERO Registration Number

CRD42022325669
Toward more realistic social distancing policies via advanced feedback control
Authors: Join Cédric , d’Onofrio Alberto , Fliess Michel
Published: May 2022

A continuously time-varying transmission rate is suggested by many control-theoretic investigations on non-pharmaceutical interventions for mitigating the COVID-19 pandemic. However, such a continuously varying rate is impossible to implement in any human society. Here, we significantly extend a preliminary work (M. Fliess, C. Join, A. d’Onofrio, Feedback control of social distancing for COVID-19 via elementary formulae, MATHMOD, Vienna, 2022), based on the combination of flatness-based and model-free controls of the classic SIR model. Indeed, to take into account severe uncertainties and perturbations, we propose a feedback control where the transmission rate,i.e., the control variable, is piecewise constant. More precisely, the transmission rate remains constant during an appreciable time interval. Strict extended lockdowns may therefore be avoided. The poor knowledge of fundamental quantities such as the rate of infection hinders a precise calibration of the transmission rate. Thus, the results of our approach ought therefore not to be regarded as rules of action to follow accurately but as a guideline for a wise behavior.
Flexible use of contact calls in a species with high fission-fusion dynamics
Authors: Margarita Briseño-Jaramillo , Roberto Sosa-López José , Gabriel Ramos-Fernández , Alban Lemasson
Published: May 2022

The ‘social complexity hypothesis’ posits that complex social systems (that entail high uncertainty) require complex communicative systems (with high vocal flexibility). In species with fission-fusion dynamics, where the fluid composition of temporary subgroups increases the uncertainty with which group members must manage their social relationships, vocal communication must be particularly flexible. This study assessed whether contact call rates vary with caller and audience characteristics in free-living spider monkeys, as well as with fission and fusion events. Adult females and immature individuals called more when in small audience settings, while audience size did not influence adult males. Adults called more when in the presence of the opposite sex, whereas immatures vocalized more in subgroups composed only by females. Females also called more when with their mature sons. We found higher call rates in periods during which fission and fusion events took place than in periods with more stable compositions and when the composition after a fission or fusion event changed from one sex to two sexes. A flexible use of contact calls allows individuals to identify themselves when they join others, particularly if they are members of the opposite sex. This socio-spatial cohesion function reduces the uncertainty about subgroup composition.
Handedness is associated with less common input to spinal motor neurons innervating different hand muscles
Authors: Maillet Jean , Avrillon Simon , Nordez Antoine , Rossi Jeremy , Hug François
Published: May 2022

Whether the neural control of manual behaviours differs between the dominant and non-dominant hand is poorly understood. This study aimed to determine whether the level of common synaptic input to motor neurons innervating the same or different muscles differs between the dominant and the non-dominant hand. Seventeen participants performed two motor tasks with distinct mechanical requirements: an isometric pinch and an isometric rotation of a pinched dial. Each task was performed at 30% of maximum effort and was repeated with the dominant and non-dominant hand. Motor units were identified from two intrinsic (flexor digitorum interosseous and thenar) and one extrinsic muscle (flexor digitorum superficialis) from high-density surface electromyography recordings. Two complementary approaches were used to estimate common synaptic inputs. First, we calculated the coherence between groups of motor neurons from the same and from different muscles. Then, we estimated the common input for all pairs of motor neurons by correlating the low-frequency oscillations of their discharge rate. Both analyses led to the same conclusion, indicating less common synaptic input between motor neurons innervating different muscles in the dominant hand than in the non-dominant hand, which was only observed during the isometric rotation task. No differences in common input were observed between motor neurons of the same muscle. This lower level of common input could confer higher flexibility in the recruitment of motor units, and therefore, in mechanical outputs. Whether this difference between the dominant and non-dominant arm is the cause or the consequence of handedness remains to be determined.

Key points

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How the neural control of manual behaviours differs between the dominant and non-dominant hand remains poorly understood.

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We decoded the spiking activities of spinal motor neurons innervating one extrinsic and two intrinsic hand muscles during isometric tasks.

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We estimated the common synaptic input to motor neurons innervating the same or different muscles.

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There is less common synaptic input between motor neurons innervating different muscles in the dominant than in the non-dominant hand during isometric rotation tasks.

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No differences in common input were observed between motor neurons of the same muscle.

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Lower level of common input could confer higher flexibility in the recruitment of motor units.
Ubiquitin-like cGAS chain formation by a super enzyme activates anti-phage response
Authors: Yan Yan , Xiao Jun , Huang Fengtao , Yu Bingbing , Cheng Rui , Wu Hui , Lu Xueling , Wang Xionglue , Oyejobi Greater Kayode , Robinson Carol V. , Wu Hao , Wu Di , Wang Longfei , Zhu Bin
Published: May 2022

The cyclic oligonucleotide-based anti-phage signaling system (CBASS) is a family of defense system in prokaryotes1, 2. Composed of a cyclic GMP-AMP synthase (cGAS) and CBASS-associated proteins, CBASS utilizes cyclic oligonucleotides to activate antiviral immunity3–6. One major group of CBASS-associated proteins are homologs of eukaryotic E2 ubiquitin-conjugating enzymes. However, the function of E2 in CBASS remains elusive. Here, we report that a bacterial E2 enzyme regulates cGAS by imitating the entire ubiquitination cascade. This includes the processing of the cGAS C-terminus, conjugation of cGAS to a cysteine residue, ligation of cGAS to a lysine residue, cleavage of the isopeptide bond, and poly-cGASylation. The poly-cGASylation fully activates cGAS to produce cGAMP, which acts as an antiviral signal and leads to cell death. Our findings reveal unique regulatory roles of E2 in CBASS and provide insights into the origin of the ubiquitin system.
Analysis Of Redox Status At The Erythrocyte Level
Authors: Adorbley Bright , Preko Michael Ofosu , Fodil Faiza , Kharoubi Omar
Published: May 2022

Erythrocytes constitute a significant target for oxidative stress because of their principal function as oxygen-carrying cells. Erythrocytes are constantly exposed to reactive oxygen species as they circulate through the bloodstream. As a result, these erythrocytes have developed a complex antioxidant defense system that comprises both enzymatic and non-enzymatic antioxidants, which mitigates and maintains the erythrocytes in a redox state.

This study aimed to explore the in vitro analysis of the redox status by determining the activities of Catalase, Glutathione S transferase, Thiobarbituric Acid reactive species, and total proteins at the erythrocyte level after exposure to aluminum. The experiment was carried out by incubation of erythrocytes.

The erythrocytes were distributed into sterile Petri dishes in four groups (control group, Al intoxicated group, and intoxicated with Al and treated with quercetin groups (2mg/l and 5mg/l). The experiment was observed over three intervals (24H, 48H, and 72H).

Evaluations were made on oxidative stress and biochemical parameters. Results obtained showed that Al treatment significantly increased the activity of thiobarbituric acid reactive substance and decreased the activity of glutathione S-transferase (GST), activities of catalase, and protein in the erythrocyte of rats. Following administration with quercetin significantly decreased the levels of free radicals and increased the activity of GST, Catalase, and protein activities. Quercetin alleviated the toxic effects of aluminum on the studied parameters.

These results indicate that Al-induced oxidative stress in the erythrocytes of rats. Following administration of quercetin, the activities of the oxidative stress parameters tested were improved significantly, indicating the overall good antioxidant properties of the quercetin. In conclusion, quercetin proved to be an effective antioxidant against free radicals produced in the erythrocytes due to aluminum exposure.

HIGHLIGHTS

Erythrocytes are exposed to reactive Oxygen Species as they circulate in the bloodstream.

Aluminum induces oxidative stress in erythrocytes of Wistar rats.

Aluminum increases the activity of TBARS and decreases the activity of GST and CAT in incubated erythrocytes.

Quercetin alleviates the toxic effects of aluminum on biochemical and oxidative stress parameters.
Strategies for improved xylitol production in batch fermentation of sugarcane hydrolysate using Saccharomyces cerevisiae
Authors: Lizarazo Frank Uriel Suarez , Pereira Gonçalo Amarante Guimarães , de Mello Fellipe da Silveira Bezerra
Published: May 2022

A plethora of studies have focused on improvements of xylitol production. The challenges of establishing a biotechnological route for the industrial production of this sugar have been explored using different microorganisms and renewable feedstock. Nevertheless, sugarcane biomass has been neglected as the pentose source for xylitol production using Saccharomyces cerevisiae. Therefore, here we investigate the use of an industrial S. cerevisiae strain for xylitol production in batch fermentation of non-detoxified sugarcane straw hydrolysate, envisioning the diversification of the current infrastructure used for second-generation bioethanol production from the same lignocellulosic material. In order to optimize the xylose conversion in a non-fed cultivation system, guidelines in cell inoculum and medium supplementation are suggested, as well as the first attempt to use electro-fermentation for this purpose. Accordingly, our results show that the increase in initial cell density and hydrolysate supplementation allows a xylitol production of 19.24 ± 0.68 g/L, representing 0,132 g/L.h productivity.
A missense mutation in zinc finger homeobox-3 (ZFHX3) impedes growth and alters metabolism and hypothalamic gene expression in mice
Authors: Nolan Patrick M. , Banks Gareth , Bourbia Nora , Wilcox Ashleigh G. , Bentley Liz , Moir Lee , Kent Lee , Hillier Rosie , Wilson Dana , Barrett Perry , Dumbell Rebecca
Published: May 2022

A protein altering variant in the gene encoding zinc finger homeobox-3 (ZFHX3) has recently been associated with lower BMI in a human genome-wide association study. We investigated metabolic parameters in mice harbouring a missense mutation inZfhx3(Zfhx3Sci/+) and looked for alteredin situexpression of transcripts that are associated with energy balance in the hypothalamus to understand how ZFHX3 may influence growth and metabolic effects. One year old male and femaleZfhx3Sci/+mice weighed less, had shorter body length, reduced fat mass, smaller mesenteric fat depots, and lower circulating insulin, leptin, and insulin-like growth factor-1 (IGF1) concentrations thanZfhx3+/+littermates. In a second cohort of 9 – 20-week-old males and females,Zfhx3Sci/+mice ate less than wildtype controls, in proportion to body weight. In a third cohort of female-onlyZfhx3Sci/+andZfhx3+/+mice that underwent metabolic phenotyping from 6 - 14 weeks old,Zfhx3Sci/+mice weighed less and had lower lean mass and energy expenditure, but fat mass didn’t differ. We detected increased expression of somatostatin, and decreased expression of growth hormone-releasing hormone and growth hormone-receptor mRNAs in the arcuate nucleus (ARC). Similarly, ARC expression of orexigenic neuropeptide Y was decreased and ventricular ependymal expression of orphan G protein-coupled receptorGpr50was decreased. We demonstrate for the first time an energy balance effect of theZfhx3Scimutation, likely by altering expression of key ARC neuropeptides to alter growth, food intake and energy expenditure.
Effect of Puerarin on PI3K-AKT Signaling Pathway in Osteoclast
Authors: Yang Yiqiu , Li Lan , Zhao Na , Kuang Shanshan , Zhang Yaowen , Xie Jisheng
Published: May 2022

objective

This study intends to explore the role of PI3K-AKT signaling pathway in the effect of Puerarin on the proliferation, activity, and function of osteoclasts from the perspective of antioxidation.

Methods

RAW264. 7 cells were divided into control group, induction group treated with 20ng/mL M-CSF and 50ng/mL RANKL, puerarin group treated with 20ng/mL M-CSF, 50ng/mL RANKL, and 50μmol/L puerarin. The staining of osteoclasts before and after puerarin intervention was measured by TRAP staining and cell count. The changes of related molecules before and after puerarin intervention in osteoclasts were detected by real-time fluorescence quantitative PCR and Western Blot, including TRAP, MMP-9, Cathepsin K, NFATc1, PTEN, Catalase, PI3K, AKT, P-AKT(ser473), FoxO1, P-FoxO1.

Results

TRAP staining showed that puerarin inhibited the proliferation and differentiation of RAW264.7 cells into osteoclasts. The results of qRT-PCR and WB showed that compared with the control group, the gene expression of TRAP, MMP-9, cathepsin K and NFATc1 in the induction group was up-regulated, while the gene expression of Catalase was down-regulated. PTEN gene had no significant changes before and after puerarin intervention. The expression of P-AKT (ser473) and NFATc1 protein was up-regulated, while the expression of PI3K and AKT protein had no change. Compared with the induction group, the gene expression of TRAP, MMP-9, Cathepsin K, and NFATc1 in the puerarin group decreased, the gene expression of Catalase increased, the protein expression of PI3K and AKT remained unchanged, the protein expression of P-AKT (ser473), P-FoxO1 and NFATc1 decreased, and the protein expression of FoxO1 and Catalase increased.

Conclusion

Puerarin may promote the transcriptional activity of FoxO1, increase the expression of catalase protein and exert its antioxidant activity by regulating the PI3K-AKT signal pathway, so as to inhibit the proliferation and differentiation of osteoclasts.
MHC class I Ligands of Rhesus Macaque Killer-Cell Immunoglobulin-Like Receptors
Authors: Anderson Jennifer L. , Sandstrom Kjell , Smith Willow R. , Wetzel Molly , Klenchin Vadim A. , Evans David T.
Published: May 2022

Definition of MHC class I ligands of rhesus macaque KIRs is fundamental to NK cell biology in this species as an animal model for infectious diseases, reproductive biology, and transplantation. To provide a more complete foundation for studying NK cell responses, rhesus macaque KIRs representing common allotypes of lineage IIKIRgenes were tested for interactions with MHC class I molecules representing diverseMamu-A, -B, -E, -F, -Iand-AGalleles. KIR-MHC class I interactions were identified by co-incubating reporter cell lines bearing chimeric KIR-CD3ζ receptors with target cells expressing individual MHC class I molecules and were corroborated by staining with KIR IgG-Fc fusion proteins. Ligands for 11 KIRs of previously unknown specificity were identified that fell into two general categories: interactions with multiple Mamu-Bw4 molecules or with Mamu-A-related molecules, including several allotypes of Mamu-AG and the hybrid Mamu-B*045:03 molecule. Although both groups include inhibitory and activating receptors, the majority of KIRs found to interact with Mamu-Bw4 are inhibitory, whereas most of the KIRs that interact with Mamu-AG are activating. We also identified Mamu-A1*012:01 as a ligand for KIR3DLw03*002, which belongs to a phylogenetically distinct group of macaque KIRs with a three amino acid deletion in D0 that is also present in human KIR3DL1/S1 and KIR3DL2. This study more than doubles the number of rhesus macaque KIRs with defined MHC class I ligands and identifies novel interactions with Mamu-AG, -B*045, and -A1*012. These findings support overlapping, but nonredundant, patterns of ligand recognition that reflects extensive functional diversification of these receptors.
An interaction between β’-COP and the ArfGAP, Glo3, maintains post-Golgi cargo recycling
Authors: Xie Boyang , Guillem Clara , Jung Christian , Kendall Amy K. , Date Swapneeta , Best Jordan T. , Graham Todd R. , Jackson Lauren P.
Published: May 2022

The essential COPI vesicular coat mediates retrieval of key transmembrane proteins at the Golgi and endosomes following recruitment by the small GTPase, Arf1. ArfGAP proteins regulate COPI coats, but molecular details for COPI recognition by ArfGAP proteins remain elusive. Biochemical and biophysical data reveal how β’-COP propeller domains directly engage the yeast ArfGAP, Glo3, with a low micromolar binding affinity (KD ~1 µM). Calorimetry data demonstrate both β’-COP propeller domains are required to bind Glo3 using electrostatic interactions. An acidic patch on β’-COP (D437/D450) interacts with Glo3 lysine residues located within the BoCCS (Binding of Coatomer, Cargo, and SNAREs) region. Targeted point mutations in either Glo3 BoCCS or β’-COP abrogate the interaction in vitro, and loss of the β’-COP/Glo3 interaction drives Ste2 mis-sorting to the vacuole and aberrant Golgi morphology in budding yeast. Together, these data suggest cells require the β’-COP/Glo3 interaction for cargo recycling via endosomes and the TGN, where β’-COP may serve as a molecular platform to coordinate binding to multiple protein partners, including Glo3, Arf1, and the COPI F-subcomplex.
Genetic Architecture And Clinical Outcomes Of The Fredrickson-Levy-Lees Dyslipoproteinemias
Authors: Gilliland Thomas , Dron Jaqueline S. , Selvaraj Margaret Sunitha , Trinder Mark , Paruchuri Kaavya , Urbut Sarah M. , Haidermota Sara , Bernardo Rachel , Uddin Md Mesbah , Honigberg Michael C. , Peloso Gina , Natarajan Pradeep
Published: May 2022

Background and Aims

The genetic basis and clinical relevance of the classical Fredrickson-Levy-Lees (FLL) dyslipoproteinemia classifications has not been studied in general population-based cohorts. We aimed to evaluate the phenotypic and genetic characteristics of FLL disorders.

Methods

Among UK Biobank participants free of prevalent coronary artery disease (CAD), we used blood lipids and apolipoprotein B concentrations to infer FLL classes (Types I, IIa, IIb, III, IV, and V). For each FLL class, Cox proportional hazards regression estimated risk of incident CAD. Phenome-wide association testing was performed. GWAS were performed, followed by in silico causal gene prioritization and heritability analyses. Prevalence of disruptive Mendelian lipid variants was assessed from whole exome sequencing.

Results

Of 450,636 individuals, 259,289 (57.5%) met criteria for a FLL dyslipoproteinemia: 63 (0.01%) type I; 40,005 (8.9%) type IIa; 94,785 (21.0%) type IIb; 13,998 (3.1%) type III; 110,389 (24.5%) type IV; and 49 (0.01%) type V. Over median 11.1 years follow-up, compared to normolipidemics the type IIb pattern conferred the highest hazard of incident CAD overall (HR 1.92, 95% CI 1.84-2.01, P<0.001) and in meta-analysis across matched non-HDL-C strata (HR 1.45, 95% CI 1.30-1.60). GWAS revealed 250 loci associated with FLL, of which 13 were shared across all classes; compared to GWAS of isolated lipid traits, 72 additional loci were detected. Mendelian lipid variants were rare (2%), but polygenic heritability was high, ranging from 23% (type III) to 54% (type IIb).

Conclusions

FLL classes have distinct genetic architectures yielding new insights for cardiometabolic disease beyond single lipid analyses.
A Randomised, Multi-centre Phase II Trial of Weekly Paclitaxel and Vistusertib in Platinum-Resistant Ovarian High-Grade Serous Carcinoma: OCTOPUS Arm 1
Authors: Banerjee S. , Giannone G. , Clamp A. , Ennis D. , Glasspool R. , Herbertson R. , Krell J. , Riisnaes R. , Mirza H.B. , Cheng Z. , McDermott J. , Green C. , Kristeleit R.S. , George A. , Gourley C. , Lewsley L-A , Rai D. , Banerji U. , Hinsley S. , McNeish I.A.
Published: May 2022

Background

Preclinical studies support targeting PI3K/AKT/mTOR signalling in platinum-resistant ovarian cancer (PROC). A phase I study of the dual mTORC1/mTORC2 inhibitor vistusertib with weekly paclitaxel (wP) showed activity. We report the results of Arm 1 of OCTOPUS, the first randomised trial of weekly paclitaxel and dual mTORC1/2 inhibition in ovarian cancer.

Methods

Patients with platinum-resistant or refractory high grade serous carcinoma were randomised (1:1) to wP (80mg/m2 D1,8,15 of 28 day cycle) plus oral vistusertib (50mg BD) or placebo (P). The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate (RR) and overall survival (OS).

Results

140 patients (median age 63, range: 36-86; 18% platinum-refractory; 54% ≥3 prior therapies) were randomised. There was no difference in PFS (median 4.5 vs 4.1m (HR 0.84; 80% CI (0.67, 1.07); 1-sided p=0.18), OS (median 9.7 vs 11.1m (HR 1.21; 80% CI (0.91, 1.60); 1-sided p=0.80) or RR (odds ratio 0.86; 80% CI (0.55, 1.36); 1-sided p=0.66). Grade 3/4 adverse events were 41.2% (wP+V) vs 36.7% (wP+P). Low tumour PTEN expression was associated with longer PFS in the wP+V arm (9.4 vs 4.1m p=0.003) but not in the wP arm (4.8 vs 4.2m p=0.60). Tumour genome-wide copy number (CN) analysis suggested that high CN signature 4 was associated with worse outcome in the wP+P arm (2.3 vs 4.6m p=0.018) but not the wP+V arm (5.4 vs 3.3m).

Conclusions

Vistusertib did not improve clinical activity of wP in PROC. However, low tumour cell PTEN expression may be a predictive biomarker for vistusertib activity.

Translational Relevance

Preclinical studies suggest that activation of the PI3K/AKT/mTOR signalling pathway contributes to platinum-resistance in ovarian high grade serous carcinoma (HGSC). Based on activity in a phase I study, we evaluated the clinical efficacy of the dual mTORC1/mTORC2 inhibitor vistusertib in combination with weekly paclitaxel in the OCTOPUS study - a multi-centre, randomised, placebo-controlled, phase II trial in platinum-resistant ovarian (HGSC). In the first randomised trial of weekly paclitaxel and dual mTORC1/2 inhibition in ovarian cancer, vistusertib did not improve clinical activity of weekly paclitaxel. However, translational analyses indicated that low tumour cell PTEN expression may be a predictive biomarker for vistusertib activity. We also showed genome-wide copy number (CN) analysis, in particular high exposure to CN signature 4, may also allow identification of patients with greater chance of benefit from dual mTORC inhibition. Potential predictive biomarkers identified in our study should be evaluated in ongoing/future studies.
iGWAS: image-based genome-wide association of self-supervised deep phenotyping of human medical images
Authors: Xie Ziqian , Zhang Tao , Kim Sangbae , Lu Jiaxiong , Zhang Wanheng , Lin Cheng-Hui , Wu Man-Ru , Davis Alexander , Channa Roomasa , Giancardo Luca , Chen Han , Wang Sui , Chen Rui , Zhi Degui
Published: May 2022

Existing imaging genetics studies have been mostly limited in scope by using imaging-derived phenotypes defined by human experts. Here, leveraging new breakthroughs in self-supervised deep representation learning, we propose a new approach, image-based genome-wide association study (iGWAS), for identifying genetic factors associated with phenotypes discovered from medical images using contrastive learning. Using retinal fundus photos, our model extracts a 128-dimensional vector representing features of the retina as phenotypes. After training the model on 40,000 images from the EyePACS dataset, we generated phenotypes from 130,329 images of 65,629 British White participants in the UK Biobank. We conducted GWAS on three sets of phenotypes: raw image phenotype, phenotypes derived from the original photos; retina color, the average color of the center region of the retinal fundus photos; and vessel-enriched phenotypes, phenotypes derived from vasculature-segmented images. GWAS of raw image phenotypes identified 14 loci with genome-wide significance (p<5×10-8and intersection of hits from left and right eyes), while GWAS of retina colors identified 34 loci, 7 are overlapping with GWAS of raw image phenotype. Finally, a GWAS of vessel-enriched phenotypes identified 34 loci. While 25 are overlapping with the raw image loci and color loci, 9 are unique to vessel-enriched GWAS. We found that vessel-enriched GWAS not only retains most of the loci from raw image GWAS but also discovers new loci related to vessel development. Our results establish the feasibility of this new framework of genomic study based on self-supervised phenotyping of medical images.
How is the COVID-19 pandemic impacting our life, mental health, and well-being? Design and preliminary findings of the pan-Canadian longitudinal COHESION Study
Authors: Gabet Stephan , Thierry Benoit , Wasfi Rania , De Groh Margaret , Simonelli Guido , Hudon Catherine , Lessard Lily , Dubé Ève , Nasri Bouchra , Kestens Yan , Moullec Grégory
Published: May 2022

With the advent of the COVID-19 pandemic, in-person social interactions and opportunities for accessing resources that sustain health and well-being have drastically reduced. We therefore designed the pan-Canadian population-based prospective COVID-19: HEalth and Social Inequities across Neighbourhoods (COHESION) cohort to provide deeper understanding of how the COVID-19 pandemic context affects mental health and well-being, key determinants of health, and health inequities.

This paper presents the design of the two-phase COHESION Study, and descriptive results from the first phase conducted between May 2020 and September 2021. During that period, the COHESION research platform collected monthly data linked to COVID-19 such as infection and vaccination status, perceptions and attitudes regarding pandemic-related measures, and information on participants’ physical and mental health, well-being, sleep, loneliness, resilience, substances use, living conditions, social interactions, activities, and mobility.

The 1,268 people enrolled in the Phase 1 COHESION Study are for the most part from Ontario (47%) and Quebec (33%), aged 48 ± 16 years [mean ± standard deviation (SD)], and mainly women (78%), White (85%), with a university degree (63%), and living in large urban centers (70%). According to the 298 ± 68 (mean ± SD) prospective questionnaires completed each month in average, the first year of follow-up reveals significant temporal variations in standardized indexes of well-being, loneliness, anxiety, depression, and psychological distress.

The COHESION Study will allow identifying trajectories of mental health and well-being while investigating their determinants and how these may vary by subgroup, over time, and across different provinces in Canada, in the unique context of the COVID-19 pandemic.
Spatial-ID: a cell typing method for spatially resolved transcriptomics via transfer learning and spatial embedding
Authors: Shen Rongbo , Liu Lin , Wu Zihan , Zhang Ying , Yuan Zhiyuan , Guo Junfu , Yang Fan , Zhang Chao , Chen Bichao , Liu Chao , Guo Jing , Fan Guozhen , Zhang Yong , Li Yuxiang , Xu Xun , Yao Jianhua
Published: May 2022

Spatially resolved transcriptomics (SRT) provides the opportunity to investigate the gene expression profiles and the spatial context of cells in naive state. Cell type annotation is a crucial task in the spatial transcriptome analysis of cell and tissue biology. In this study, we propose Spatial-ID, a supervision-based cell typing method, for high-throughput cell-level SRT datasets that integrates transfer learning and spatial embedding. Spatial-ID effectively incorporates the existing knowledge of reference scRNA-seq datasets and the spatial information of SRT datasets. A series of quantitative comparison experiments on public available SRT datasets demonstrate the superiority of Spatial-ID compared with other state-of-the-art methods. Besides, the application of Spatial-ID on a SRT dataset with 3D spatial dimension measured by Stereo-seq shows its advancement on the large field tissues with subcellular spatial resolution.
Newly raised anti-c-Kit antibody detects interstitial cells of Cajal in the gut of chicken embryos
Authors: Yagasaki Rei , Shikaya Yuuki , Kawachi Teruaki , Inaba Masafumi , Takase Yuta , Takahashi Yoshiko
Published: May 2022

The gut peristaltic movement, a wave-like propagation of a local contraction, is important for the transportation and digestion of ingested materials. Among three types of cells, the enteric nervous system (ENS), smooth muscle cells, and interstitial cells of Cajal (ICCs), the ICCs have been thought to act as a pacemaker, and therefore it is important to decipher the cellular functions of ICCs for the understanding of gut peristalsis. c-Kit, a tyrosine kinase receptor, has widely been used as a marker for ICCs. Most studies with ICCs have been conducted in mammals using commercially available anti-c-Kit antibody. Recently, the chicken embryonic gut has emerged as a powerful model to study the gut peristalsis. However, since the anti-c-Kit antibody for mammals does not work for chickens, cellular mechanisms by which ICCs are regulated have largely been unexplored. Here, we report a newly raised polyclonal antibody against the chicken c-Kit protein. The specificity of the antibody was validated by both Western blotting analyses and immunocytochemistry. Co-immunostaining with the new antibody and anti-α smooth muscle actin (αSMA) antibody successfully visualized ICCs in the chicken developing hindgut in the circular muscle- and longitudinal muscle layers: as previously shown in mice, common progenitors of ICCs and smooth muscle cells at early stages were double positive for αSMA and c-Kit, and at later stages, differentiated ICCs and smooth muscle cells exhibited only c-Kit and αSMA, respectively. A novel ICC population was also found that radially extended from the submucosal layer to circular muscle layer. Furthermore, the new antibody delineated individual ICCs in a cleared hindgut. The antibody newly developed in this study will facilitate the study of peristaltic movement in chicken embryos.
Inhibition ofArenaviridaenucleoprotein exonuclease by bisphosphonate
Authors: Nguyen Thi Hong Van , Yekwa Elsie , Selisko Barbara , Canard Bruno , Alvarez Karine , Ferron François
Published: May 2022

Arenaviruses are emerging enveloped negative-sense RNA viruses that cause neurological and hemorrhagic diseases in humans. Currently, no FDA-approved vaccine or therapeutic agent is available except for ribavirin, which must be administered early during infection for optimum efficacy. A hallmark of arenavirus infection is rapid and efficient immune suppression mediated by the exonuclease domain encoded by the nucleoprotein. This exonuclease is therefore an attractive target for the design of novel antiviral drugs since exonuclease inhibitors might not only have a direct effect on the enzyme but could also boost viral clearance through stimulation of the innate immune system of the host cell. Here,in silicoscreening and an enzymatic assay were used to identify a novel, specific but weak inhibitor of the arenavirus exonuclease, with IC50values of 65.9 and 68.6 µMfor Mopeia virus and Lymphocytic choriomeningitis virus, respectively. This finding was further characterized using crystallographic and docking approaches. This study serves as a proof of concept and may have assigned a new therapeutic purpose for the bisphosphonate family, therefore paving the way for the development of inhibitors againstArenaviridae.
Antecedents of obesity among Indian youth: from consumer psychological and lifestyle perspective
Authors: Chaudhuri Ranjan , Chatterjee Sheshadri , Thrassou Alkis , Vrontis Demetris
Published: May 2022

Purpose

The purpose of this study is to determine the antecedents of obesity among the younger generation of Indians (Generation Y) from a psychological and lifestyle consumer perspective. The study also investigates the moderating role of demography on the body mass index (BMI) of Indian youths.

Design/methodology/approach

The study initially develops a conceptual model, stemming from an extensive theoretical research, and subsequently validates this using structural equation modeling (SEM) technique with a sample size of 1,242 Indian youths.

Findings

The study concludes that consumers' food habits (FH) and physical activity (PA) positively impact consumers' physical health (PH), which influences their BMI levels (BLs). Anxiety (AX), depression (DE), stress (ST), peer pressure (PP) and work pressure (WP) impact individuals' mental health (MH), which also influences their BLs. Finally, there is a significant moderating impact of demographic factors, such as age (AG), gender (GE) and income levels (ILs) on the relationship between individuals' physical and MH and individuals' BLs.

Research limitations/implications

This study proposes a new model which highlights the issue of youth consumer obesity from the psychological and lifestyle perspectives. The model is effective as it has a high explanative power of 73%. The study investigates consumer obesity from emerging market like India perspective, but the study does not examine consumer food consumption behavior and obesity from developed market perspective.

Practical implications

Youth obesity could be considered a global pandemic, and obesity rates among the Indian youth are also increasing. This study provides valuable inputs and understanding of consumer markets to policy makers, consumer protection institutions, organizations related to the food and beverage industry, healthcare workers and consumers themselves regarding the antecedents of youth obesity (BL) in developing and emerging markets.

Originality/value

The study adds value to the body of literature related to consumer obesity, FH, consumer psychology and lifestyle through findings that are new in terms of findings' specificity, contextual focus and explication. Moreover, the study extends the cognitive theory of DE and the theory of planned behavior (TPB). The research effectively offers significant theoretical and practicable market knowledge to both scholars and marketing practitioners, as well as policy makers and institutions dealing with youth obesity, particularly in emerging markets.
Developing a resilient healthcare supply chain to prevent disruption in the wake of emergency health crisis
Authors: Hossain Md Kamal , Thakur Vikas , Kazancoglu Yigit
Published: May 2022

Purpose

The study aims to identify and analyse the drivers of resilient healthcare supply chain (HCSC) preparedness in emergency health outbreaks to prevent disruption in healthcare services delivery in the context of India.

Design/methodology/approach

The present study has opted for the grey clustering method to identify and analyse the drivers of resilient HCSC preparedness during health outbreaks into high, moderate and low important grey classes based on Grey-Delphi, analytic hierarchy process (AHP) and Shannon's information entropy (IE) theory.

Findings

The drivers of the resilient HCSC are scrutinised using the Grey-Delphi technique. By implementing AHP and Shannon's IE theory and depending upon structure, process and outcome measures of HCSC, eleven drivers of a resilient HCSC preparedness are clustered as highly important, three drivers into moderately important, and two drivers into a low important group.

Originality/value

The analysis and insights developed in the present study would help to plan and execute a viable, resilient emergency HCSC preparedness during the emergence of any health outbreak along with the stakeholders' coordination. The results of the study offer information, rationality, constructiveness, and universality that enable the wider application of AHP-IE/Grey clustering analysis to HCSC resilience in the wake of pandemics.
Effect of crowdsourcing work characteristics on perceived work effort in competitive crowdsourcing markets
Authors: Liu Ying , Liu Yongmei , Xiao Bo Sophia
Published: May 2022

Purpose

This study explored whether crowdsourcing work characteristics are associated with perceived work effort in competitive crowdsourcing markets. The study also investigated the important contextual variables and internal mechanisms related to perceived work effort.

Design/methodology/approach

A questionnaire was posted as a crowdsourcing task on China's Time Fortune website. Data from 231 valid questionnaires were analyzed using SmartPLS 3.

Findings

Crowdsourcing workers' intrinsic and extrinsic motivations were significantly and positively correlated with their perceived work effort. Task autonomy and feedback were significantly and positively correlated with intrinsic motivation. Skill variety, task significance, task identity, and task clarity had no significant correlations with intrinsic motivation. However, task clarity was significantly and positively correlated with perceived work effort. Moreover, the relationship between workers' trust in task requesters and perceived work effort was fully mediated by intrinsic motivation.

Originality/value

This study extended the job characteristic model into the virtual competitive crowdsourcing market. The authors verified the relationship between task clarity/trust in task requesters and workers' motivation and perceived work effort.
Enhancing inter-organisational partnerships in integrated care models for older adults: a multiple case study
Authors: Wankah Paul , Breton Mylaine , Steele Gray Carolyn , Shaw James
Published: May 2022

Purpose

The purpose of this paper was to develop deeper insights into the practices enacted by entrepreneurial healthcare managers to enhance the implementation of a partnership logic in integrated care models for older adults.

Design/methodology/approach

A multiple case study design in two urban centres in two jurisdictions in Canada, Ontario and Quebec. Data collection included 65 semi-structured interviews with policymakers, managers and providers and analysis of key policy documents. The institutional entrepreneur theory provided the theoretical lens and informed a reflexive iterative data analysis.

Findings

While each case faced unique challenges, there were similarities and differences in how managers enhanced a partnership’s institutional logic. In both cases, entrepreneurial healthcare managers created new roles, negotiated mutually beneficial agreements and co-located staff to foster inter-organisational partnerships between public, private and community organisations in the continuum of care for older adults. In addition, managers in Ontario secured additional funding, while managers in Quebec organised biannual meetings and joint training to enhance inter-organisational partnerships.

Originality/value

This study has two main implications. First, efforts to enhance inter-organisational partnerships should strategically include institutional entrepreneurs. Second, successful institutional changes may be supported by investing in integrated implementation strategies that target roles of staff, co-location and inter-organisational agreements.
Understanding flooding events in Ghana: a social marketing and self-determination theory perspective
Authors: Tweneboah-Koduah Ernest Yaw , Adams Matilda , Amoakoh Michael Nana , Braimah Stephen Mahamah
Published: May 2022

Purpose

The purpose of this study is to deepen the understanding of individuals’ flood disaster mitigation behaviour through the theoretical lens of self-determination theory (SDT). Specifically, the paper examines the influence of autonomy, competence and relatedness on individuals’ self-determined motivation for flood disaster mitigation. The study also examines whether self-determined motivation influences individuals’ flood disaster mitigation behaviour adoption.

Design/methodology/approach

Through a cross-sectional survey design, the study used a quantitative research approach for data collection and analyses. Specifically, data was analysed using the structural equation modelling technique.

Findings

The result of this study revealed that competence was the strongest predictor of self-determined motivation, followed by autonomy. The result further shows that self-determined motivation positively influences individual’s adoption of flood mitigation behaviour. However, the results showed that relatedness does not predict self-determined motivation for flood disaster mitigation.

Practical implications

To enhance the effectiveness of flood disaster mitigation social marketing campaigns, the SDT psychological needs constructs (particularly, competence and autonomy) can aid in assessing the motivation of the target population towards adopting mitigation behaviours. An assessment of motivation will help understand perception of flood risk and behavioural evaluation. The consideration of autonomy and competence on motivation will aid in developing effective campaigns to satisfy the needs of the target population.

Originality/value

The paper adds to the limited research that used SDT to understand a social marketing phenomenon.
Foreign and domestic multinationals’ linkages in advanced, small open economies: do foreignness, regional origin and technological capability matter?
Authors: Scott-Kennel Joanna , Giroud Axèle , Saittakari Iiris
Published: May 2022

Purpose

International business theory suggests that multinational enterprises (MNEs) seek to internalise resources embedded in local firms to complement their own through inter-organisational relationships, yet little is known about whether and how these business linkages differ between foreign (F)MNEs and domestic (D)MNEs. This paper aims to explore the linkage differential between DMNEs and FMNEs operating in the same single-country contexts and to examine whether foreignness, regional origin and technological capability make a difference.

Design/methodology/approach

This study is based on a unique firm-level data set of 292 MNEs located in five advanced, small open economies (SMOPECs). This study analyses the benefit received – in the form of technical and organisational resources and knowledge – by DMNEs and FMNEs via backward, forward and collaborative linkages with local business partners.

Findings

Our research finds FMNEs benefit less from linkages than DMNEs; and FMNEs originating from outside the region especially so. However, the results also show technological capability mitigates this difference and is thus a game changer for FMNEs from outside the region.

Originality/value

This paper differentiates between FMNEs and DMNEs in their propensity to benefit from resources received from different local partners and explores the influence of regional origin and technological capability. Despite the advanced and internationally oriented nature of SMOPECs, DMNEs still gain more benefit, suggesting either liabilities of foreignness and outsidership persist, or FMNEs do not desire, need or nurture local linkages.
Case study on simulation analysis of a logistics network with multiple products by applying lateral transshipments algorithms
Authors: Kundu Kaustav , Rossini Matteo
Published: May 2022

Purpose

The purpose of this paper is to develop a simulation model to evaluate inventory and distribution decisions like lateral transshipments in a network with multiple products.

Design/methodology/approach

Data are collected from a company, and a discrete-event simulation in Python is developed to support the decision-making process of managers through different algorithms of lateral transshipments.

Findings

The numerical results show that the periodic delivery-continuous reorder policy is more robust than the others because the reorder process is not affected by the higher saturation that is achieved by periodic reorder–based policies. The new lateral transshipment algorithm will lead to huge savings in logistics costs for any company and increase truck saturation without causing a decrease in the service level.

Research limitations/implications

This paper provides a novel institutional perspective on a complex logistics issue where COVD-19 is believed to complicate the context.

Practical implications

This solution is devised for any company to achieve even greater benefits in terms of customer service improvement and logistics costs reduction.

Originality/value

The main contribution of this paper is the proposal of a new lateral transshipment algorithm that shows performance improvement by simulating distribution network processes according to different configurations.