bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating metabolites and physical performance are predictors of overall survival in metastatic lung cancer patients
Authors: Neves Willian das , Alves Christiano R. R. , Santos Gabriela dos , Alves Maria J. N. , Deik Amy , Pierce Kerry , Dennis Courtney , Buckley Lily , Clish Clary B. , Swoboda Kathryn J. , Brum Patricia C. , de Castro Gilberto
Published: August 2023

Background:Skeletal muscle atrophy and low physical performance are associated with disease progression and higher mortality rates in multiple pathological conditions. Here, we determined whether body composition and physical performance would predict mortality in metastatic non-small cell lung cancer (NSCLC) patients. In addition, we defined whether plasma samples from NSCLC patients would directly affect the homeostasis of skeletal muscle cells.Methods:The prospective cohort included 55 metastatic NSCLC patients and seven age-matched control subjects. We assessed clinical characteristics, body composition, cancer cachexia, and quality of life (QoL). We determined physical performance with a series of functional tests. We analyzed skeletal muscle and adipose tissue areas. Finally, we evaluated the overall survival rate, and additional blood samples were collected from a subcohort of eighteen patients for further studies in cell culture and metabolomic analysis.Results:We found that physical performance, not body composition, was associated with overall survival in this cohort. Moreover, incubation with plasma derived from NSCLC patients with low physical performance impaired the metabolism and proliferation of primary human myotubes. Unbiased metabolomics revealed several metabolites differentially expressed in the plasma of NSCLC patients with low physical performance compared to healthy control subjects, with serine and N2,N2-dimethylguanosine (M22G) being the most reduced and increased metabolites, respectively.Conclusion:These novel findings confirm physical performance as a significant predictor of overall survival in metastatic NSCLC patients and provide insights into cancer-induced circulating factors that can directly affect skeletal muscle homeostasis and prognosis.
Re-emergent Tremor during stable posture in Parkinson’s Disease: Evidence of Pathological Beta and Prokinetic Gamma Activity
Authors: Ding Hao , Nasseroleslami Bahman , Mirzac Daniela , Volkmann Jens , Deuschl Gunter , Groppa Sergiu , Muthuraman Muthuraman
Published: August 2023

Re-emergent tremor (RET) during stable posture in Parkinson’s disease (PD) is characterized as a continuation of resting tremor (RT) and is often highly therapy refractory. The pathophysiology of both RT and RET is linked to deficits in cerebello-cortical circuits and dopaminergic depletion. However, it remains unclear how these two types of tremors differ functionally. The aim of this study is to examine the differences in brain activity between RT and RET in PD, as well as to investigate the relationship between neuronal oscillatory activity, in PD tremor phenotype patients.

Forty PD patients (25 males, mean age 66.78 ± 5.03 years) and 40 age- and sex-matched healthy controls were assessed. 256 channel HD-EEG and EMG signals were recorded while the participants extended their hands against gravity. Tremor was recorded in both L-dopa ON and OFF for PD patients and mimicked by healthy controls. Coherent sources of EEG-EMG were located using beamforming technique, and information flow between different sources was estimated using time-resolved partial-directed coherence. Cross-frequency coupling (CFC) was then used to analyze the association between tremor frequency and neuronal oscillatory activity.

Under L-dopa administration, coherent sources referenced to the tremor frequency revealed differences in brain activity between RT and RET in the premotor cortex and cerebellum of PD patients, which were similar to those observed in healthy controls. However, PD patients exhibited an additional source location in the primary sensorimotor cortex. Withdrawal of L-dopa led to coherent sources being observed in the supplementary motor area and subthalamic nucleus. Furthermore, L-dopa was found to suppress the strength of connections between these coherent sources and modulate the tremor-associated beta and gamma frequency, leading to a decrease in beta power and an increase in gamma power.

The findings of this study reveal discernible neural activity patterns during resting and re-emergent tremors. In patients with PD, the primary sensorimotor cortex plays a primordial role as the exclusive source of activity involved in the generation of RET. It shows a significant amount of co-activation within the network involving the premotor areas and cerebellum, and its activation accounts for the discrepancy in tremor phenotypes. Moreover, the oscillatory neuronal responses involve pathological beta and prokinetic gamma activity alterations that are highly specific to tremor phenotypes. These peculiarities play an essential role in our understanding of tremor phenomena and its therapeutic modulation by dopamine medication or deep brain stimulation, which could specifically target the tremor- and motor-control-related pathological beta and prokinetic gamma oscillations.
Factors Associated with Physical Function among People with Systemic Sclerosis: A Scleroderma Patient-centered Intervention Network (SPIN) Cohort Cross-sectional Study
Authors: Santo Tiffany Dal , Rice Danielle B. , Carrier Marie-Eve , Virgili-Gervais Gabrielle , Levis Brooke , Kwakkenbos Linda , Bartlett Susan J. , Gietzen Amy , Gottesman Karen , Guillot Geneviève , Hudson Marie , Hummers Laura K. , Malcarne Vanessa L. , Mayes Maureen D. , Mouthon Luc , Richard Michelle , Sauvé Maureen , Wojeck Robyn K. , Geoffroy Marie-Claude , Benedetti Andrea , Thombs Brett D.
Published: August 2023

Objectives

To compare physical function in systemic sclerosis (SSc, scleroderma) to general population normative data and identify associated factors.

Methods

Scleroderma Patient-centered Intervention Network Cohort participants completed the Physical Function domain of the Patient-Reported Outcomes Measurement Information System Version 2 upon enrollment. Multivariable linear regression was used to assess associations of sociodemographic, lifestyle, and disease-related variables.

Results

Among 2,385 participants, mean physical function T-score (43.7, SD = 8.9) was approximately 2/3 of a standard deviation (SD) below the US general population (mean = 50, SD = 10). Factors associated in multivariable analysis included older age (-0.74 points per SD years, 95% CI -0.78 to -1.08), female sex (-1.35, -2.37 to -0.34), fewer years of education (-0.41 points per SD in years, -0.75 to -0.07), being single, divorced, or widowed (-0.76, -1.48 to -0.03), smoking (-3.14, -4.42 to -1.85), alcohol consumption (0.79 points per SD drinks per week, 0.45 to 1.14), BMI (-1.41 points per SD, -1.75 to -1.07), diffuse subtype (-1.43, -2.23 to -0.62), gastrointestinal involvement (-2.58, -3.53 to -1.62), digital ulcers (-1.96, -2.94 to -0.98), moderate (-1.94, -2.94 to -0.93) and severe (-1.76, -3.24 to -0.28) small joint contractures, moderate (-2.10, -3.44 to -0.76) and severe (-2.54, -4.64 to -0.44) large joint contractures, interstitial lung disease (-1.52, -2.27 to -0.77); pulmonary arterial hypertension (-3.72, -4.91 to -2.52); rheumatoid arthritis (-2.10, -3.64 to -0.56) and idiopathic inflammatory myositis (-2.10, -3.63 to -0.56).

Conclusion

Physical function is impaired for many individuals with SSc and associated with multiple disease factors.

KEY MESSAGES

Individuals with systemic sclerosis (SSc) face many challenges that can impact their physical function

Levels of physical function in individuals with SSc are impaired compared to the general population

Multiple disease factors are significantly associated with worse physical function in SSc
Understanding and Mitigating Health Disparities Arising from the Social Determinants of Health
Authors: Cho Aaron
Published: August 2023

Over the pandemic, health has become increasingly important, and our idea of what it means to be healthy has changed. Previously we viewed health disparities as an issue that affected those who were less fortunate, but the pandemic has shown us that the health of all of us is interconnected. Reducing health disparities is important for everyone, as it would improve health not just for those who are directly impacted, but for society as a whole. This study contributes towards reducing health disparities by analyzing what factors have the largest impact on health disparities, and discussing policy changes that are relevant to these factors. This study uses a random forest algorithm to identify important predictors of health from a large variety of factors in Chicagoland and the Bay Area. The analysis finds that race is an important factor in both Chicagoland and the Bay Area, and that lack of internet access and computing devices is an especially important predictor of neighborhoods with poor health.
Assessing the potential population-level impacts of HIV self-testing distribution among key populations in Côte d’Ivoire, Mali, and Senegal: a mathematical modelling analysis
Authors: Silhol Romain , Maheu-Giroux Mathieu , Soni Nirali , Fotso Arlette Simo , Rouveau Nicolas , Vautier Anthony , Doumenc-Aïdara Clémence , Geoffroy Olivier , N’Guessan Kouassi Noel , Sidibé Younoussa , Kabemba Odé Kanku , Gueye Papa Alioune , Mukandavire Christinah , Vickerman Peter , Keita Abdelaye , Ndour Cheikh Tidiane , Ehui Eboi , Larmarange Joseph , Boily Marie-Claude ,   ATLAS Team
Published: August 2023

Background

A third of people living with HIV (PLHIV) in Western Africa had an undiagnosed infection in 2020. In 2019-2021, the ATLAS programme has distributed a total of 380 000 HIV self-testing (HIVST) kits to key populations (KP) including female sex workers (FSW) and men who have sex with men (MSM), and their partners in Côte d’Ivoire, Mali and Senegal. We predicted the potential impact of ATLAS and of national HIVST scale-up strategies among KP.

Methods

A deterministic model of HIV transmission was calibrated to country-specific empirical HIV and intervention data over time. We simulated scenarios reflecting 1) the actual ATLAS HIVST distribution only over 2019-2021 (∼2% of all tests done in countries), and 2) ATLAS followed by a scale-up of HIVST distribution to KP (total of ∼570 000 kits distributed each year). Impacts on HIV diagnosis, new HIV infections and deaths were derived using counterfactual scenarios without HIVST.

Findings

ATLAS was predicted to substantially increase HIV diagnosis among KP by the end of 2021, especially among MSM in Mali (9·3 percentage point [pp] increase), and a 1·0pp increase overall. ATLAS might have averted a median of 706 new HIV infections among KP over 2019-2028 in the 3 countries combined, especially among MSM, and 1794 new HIV infections (0·4-3·3% of all new HIV infections across countries) and 591 HIV-related deaths overall. HIVST scale-up increased HIV diagnosis at the end of 2028 by around 8pp among FSW and 33pp among MSM in every country. Overall increases ranged from 1·0pp (Côte d’Ivoire) to 11·0pp (Senegal). HIVST scale-up may avert 3-5% of new HIV infections among FSW, 3-10% among FSW clients, and 20-28% among MSM across countries (and 2-16% overall), and avert 13-18% of HIV-related deaths among MSM over 2019-2028.

Interpretation

Scaling-up HIVST distribution among KP in Western Africa may substantially attenuate disparities in access to HIV testing and help reduce HIV infections and deaths among KP and their partners.

Funding

Unitaid MRC
CRISPR-based Genome Editing of a Diurnal Rodent, Nile Grass Rat (Arvicanthis niloticus)
Authors: Xie Huirong , Linning-Duffy Katrina , Demireva Elena Y. , Toh Huishi , Abolibdeh Bana , Shi Jiaming , Zhou Bo , Iwase Shigeki , Yan Lily
Published: August 2023

Diurnal and nocturnal mammals have evolved distinct pathways to optimize survival for their chronotype-specific lifestyles. Conventional rodent models, being nocturnal, may not sufficiently recapitulate the biology of diurnal humans in health and disease. Although diurnal rodents are potentially advantageous for translational research, until recently, they have not been genetically tractable. Here, we address this major limitation by demonstrating the first successful CRISPR genome editing of the Nile grass rat (Arvicanthis niloticus), a valuable diurnal rodent. We establish methods for superovulation; embryo development, manipulation, and culture; and pregnancy maintenance to guide future genome editing of this and other diurnal rodent species.
The functional small RNA interactome reveals targets for the vancomycin-responsive sRNA RsaOI in vancomycin tolerantStaphylococcus aureus
Authors: Wu Winton , Pang Chi Nam Ignatius , Mediati Daniel , Tree Jai Justin
Published: August 2023

RNA-RNA interactome profiling techniques have expanded our understanding of sRNA-mRNA interactions in bacteria. However, determining the function of these interactions for hundreds of sRNA-mRNA pairs is a major challenge. At steady-state, protein and mRNA abundances are often highly correlated and lower than expected protein abundance may indicate translational repression of an mRNA. To specifically identify sRNA-mRNA interactions that regulate mRNA translation, we examined the correlation between gene transcript abundance, ribosome occupancy, and protein levels. We used SOMS to cluster genes with similar transcription and translation patterns and identified a cluster of mRNAs that appeared to be post-transcriptionally repressed. By integrating this clustering analysis with sRNA-mRNA interactome data generated in vancomycin tolerantS. aureusby RNase III-CLASH, we identified sRNAs that may be mediating this translational repression. We have confirmed sRNA-dependant post-transcriptional repression of several mRNAs in this cluster. Two of these interactions are mediated by RsaOI, a sRNA that is highly upregulated by vancomycin treatment. While RsaOI is not essential for vancomycin tolerance, we demonstrate regulation of the phosphocarrier protein HPr and the cell-wall autolysin Atl. These findings suggest that RsaOI may serve as a regulator of carbon metabolism and cell wall turnover during cell wall stress exerted by vancomycin.
Hearing loss in juvenile rats leads to excessive play fighting and hyperactivity, mild cognitive deficits and altered neuronal activity in the prefrontal cortex
Authors: Jelinek Jonas , Johne Marie , Alam Mesbah , Krauss Joachim K. , Kral Andrej , Schwabe Kerstin
Published: August 2023

Background

In children, hearing loss has been associated with hyperactivity, disturbed social interaction, and risk of cognitive disturbances. Mechanistic explanations of these relations sometimes involve language. To investigate the effect of hearing loss on behavioral deficits in the absence of language, we tested the impact of hearing loss in juvenile rats on motor, social, and cognitive behavior and on physiology of prefrontal cortex.

Methods

Hearing loss was induced in juvenile (postnatal day 14) male Sprague-Dawley rats by intracochlear injection of neomycin under general anaesthesia. Sham-operated and non-operated hearing rats served as controls. One week after surgery auditory brainstem response (ABR) measurements verified hearing loss or intact hearing in sham-operated and non-operated controls. All rats were then tested for locomotor activity (open field), coordination (Rotarod), and for social interaction during development in weeks 1, 2, 4, 8, 16, and 24 after surgery. From week 8 on, rats were trained and tested for spatial learning and memory (4-arm baited 8-arm radial maze test). In a final setting, neuronal activity was recorded in the medial prefrontal cortex (mPFC).

Results

In the open field deafened rats moved faster and covered more distance than sham-operated and non-operated controls from week 8 on (both p<0.05). Deafened rats showed significantly more play fighting during development (p<0.05), whereas other aspects of social interaction, such as following, were not affected. Learning of the radial maze test was not impaired in deafened rats (p>0.05), but rats used less next-arm entries than other groups indicating impaired concept learning (p<0.05). In the mPFC neuronal firing rate was reduced and enhanced irregular firing was observed. Moreover, oscillatory activity was altered, both within the mPFC and in coherence of mPFC with the somatosensory cortex (p<0.05).

Conclusions

Hearing loss in juvenile rats leads to hyperactive behavior and pronounced play-fighting during development, suggesting a causal relationship between hearing loss and cognitive development. Altered neuronal activities in the mPFC after hearing loss support such effects on neuronal networks outside the central auditory system. This animal model provides evidence of developmental consequences of juvenile hearing loss on prefrontal cortex in absence of language as potential confounding factor.
The molecular basis of macrochaete diversification highlighted by a single-cell atlas ofBicyclus anynanabutterfly pupal forewings
Authors: Prakash Anupama , Dion Emilie , Monteiro Antónia
Published: August 2023

Butterfly wings display a large diversity of cell types, including scale cells of different colors, shapes, and sizes, yet the molecular basis of such diversity is poorly understood. Scales are single-cellular projections homologous to sensory bristles in other arthropods, and different scale types are often found intermingled on the wing, alongside other sensory and epidermal cell types, making the analysis of the complete transcriptomes of each scale type difficult to achieve. To explore scale cell diversity at a transcriptomic level we employed single-cell RNA sequencing of ∼5200 large cells (>6 µm) from 22.5-25-hour male pupal forewings of the butterflyBicyclus anynana. Using single-cell unsupervised, transcriptome clustering, based on shared and differentially expressed genes, followed byin situhybridization, immunofluorescence, and CRISPR/Cas9 editing of candidate cell type specific genes, we annotate various cell types on the wing. We identify the molecular identities of non-innervated scale cells at various stages of differentiation, innervated sensory cell types, and pheromone producing glandular cells. We further show thatsenseless, a zinc finger transcription factor, andHR38, a hormone receptor, determine the identity, size, and color of different scale cell types and are important regulators of scale cell differentiation.

Graphical abstract
Neurodevelopmental defects in a mouse model of O-GlcNAc transferase intellectual disability
Authors: Authier Florence , Ondruskova Nina , Ferenbach Andrew T. , McNeilly Alison , van Aalten Daan M. F.
Published: August 2023

O-GlcNAcylation is a protein modification that is critical for vertebrate development, catalysed by O-GlcNAc transferase (OGT) and reversed by O-GlcNAcase (OGA). Missense mutations inOGThave recently been shown to segregate with a syndromic form of intellectual disability, OGT-linked Congenital Disorder of Glycosylation (OGT-CDG). Although OGT-CDG suggests a critical role of O-GlcNAcylation in neurodevelopment and/or cognitive function, the underlying pathophysiologic mechanisms remain unknown. Here we report three mouse lines that carry three different catalytically impaired OGT-CDG variants. These mice show altered O-GlcNAc homeostasis with decreased global O-GlcNAcylation and OGT/OGA levels in the brain. Phenotypic characterization of the mice revealed microcephaly and cognitive deficits including hyperactivity, anxiety and altered spatial working memory. These mouse models will serve as an important tool to study genotype-phenotype correlation in OGT-CDGin vivoand for the development of possible treatment avenues for this disorder.

Significant statement

Mutations in O-GlcNAc transferase (OGT), the sole enzyme that installs O-GlcNAc sugar on proteins, lead to intellectual disability through unknown mechanisms. We have generated mouse models carrying OGT mutations that show reduction in brain size, hyperactivity and defects in memory. These mouse models will serve as a valuable tool to further investigate disease mechanism and propose future treatment avenues.
Metabolic state modulates neural processing of odors in the human olfactory bulb
Authors: Iravani Behzad , Frasnelli Johannes , Arshamian Artin , Lundström Johan N.
Published: August 2023

The olfactory and endocrine systems have recently been shown to reciprocally shape the homeostatic processes of energy intake. As demonstrated in animal models, the individual’s metabolic state dynamically modulates how the olfactory bulb process odor stimuli using a range of endocrine signals. Here we aimed to determine whether the neural processing of odors in human olfactory bulb is modulated by metabolic state. Participants were exposed to food-associated odors, in separate sessions being hungry and sated, while neural responses from the olfactory bulb was obtained using electrobulbogram. We found significantly higher gamma power activity (51-100Hz) in the OB’s response to odors during the Hunger compared to Sated condition. Specifically, EBG gamma power were elevated while hungry already at 100ms after odor onset, thereby suggesting intra-bulbar modulation according to metabolic state. These results demonstrate that, akin to other animal models, hunger state affects OB activity in humans. Moreover, we show that the EBG method has the potential to measure internal metabolic states and, as such, could be used to study specificities in olfactory processing of individuals suffering from pathologies such as obesity or anorexia.
Thermal Contrast Enhancement Predicts Paradoxical Heat Sensation
Authors: Mitchell Alexandra G. , Fischer Ehmsen Jesper , Basińska Małgorzata , Courtin Arthur S. , Böhme Rebecca A. , Sardeto Deolindo Camila , Allen Micah G. , Sandberg Kristian , Fardo Francesca
Published: August 2023

Paradoxical Heat Sensation (PHS) is the remarkable feeling of warmth or heat pain while the skin is cooling. Despite its initial documentation over 100 years ago, a unified explanation for this perplexing experience remains elusive. Here we apply contrast enhancement principles, known for their instrumental role in understanding visual illusions, to the domain of thermosensation. Contrast enhancement describes the amplification of two contrasting visual features, such as the enhanced perception of an edge between a light and dark bar. In thermosensation, this encompasses an enhancement of the difference between sequential warming and cooling of the skin, and is defined as the normalised difference between successive temporal warm and cold temperatures. Remarkably, thermal contrast predicts the occurrence of PHS. Our findings reveal compelling evidence supporting the role of thermal contrast in the generation of PHS, shedding light on its underlying mechanism and offering a framework for broader encoding principles in thermosensation and pain.
Separating cognitive and motor processes in the behaving mouse
Authors: Hasnain Munib A , Birnbaum Jaclyn E , Nunez Juan Luis Ugarte , Hartman Emma , Chandrasekaran Chandramouli , Economo Michael N
Published: August 2023

The cognitive processes supporting complex animal behavior are closely associated with ubiquitous movements responsible for our posture, facial expressions, ability to actively sample our sensory environments, and other critical processes. These movements are strongly related to neural activity across much of the brain and are often highly correlated with ongoing cognitive processes, making it challenging to dissociate the neural dynamics that support cognitive processes from those supporting related movements. In such cases, a critical issue is whether cognitive processes are separable from related movements, or if they are driven by common neural mechanisms. Here, we demonstrate how the separability of cognitive and motor processes can be assessed, and, when separable, how the neural dynamics associated with each component can be isolated. We establish a novel two-context behavioral task in mice that involves multiple cognitive processes and show that commonly observed dynamics taken to support cognitive processes are strongly contaminated by movements. When cognitive and motor components are isolated using a novel approach for subspace decomposition, we find that they exhibit distinct dynamical trajectories. Further, properly accounting for movement revealed that largely separate populations of cells encode cognitive and motor variables, in contrast to the "mixed selectivity" often reported. Accurately isolating the dynamics associated with particular cognitive and motor processes will be essential for developing conceptual and computational models of neural circuit function and evaluating the function of the cell types of which neural circuits are composed.
Functional Diversity of Dopamine Axons in Prefrontal Cortex During Classical Conditioning
Authors: Abe Kenta , Kambe Yuki , Majima Kei , Hu Zijing , Ohtake Makoto , Momennezhad Ali , Izumi Hideki , Tanaka Takuma , Matunis Ashley , Stacy Emma , Itokazu Takahide , Sato Takashi R. , Sato Tatsuo K.
Published: August 2023

Midbrain dopamine neurons impact neural processing in the prefrontal cortex (PFC) through mesocortical projections. However, the signals conveyed by dopamine projections to the PFC remain unclear, particularly at the single-axon level. Here, we investigated dopaminergic axonal activity in the medial PFC (mPFC) during reward and aversive processing. By optimizing microprism-mediated two-photon calcium imaging of dopamine axon terminals, we found diverse activity in dopamine axons responsive to both reward and aversive stimuli. Some axons exhibited a preference for reward, while others favored aversive stimuli, and there was a strong bias for the latter at the population level. Long-term longitudinal imaging revealed that the preference was maintained in reward- and aversive-preferring axons throughout classical conditioning in which rewarding and aversive stimuli were paired with preceding auditory cues. However, as mice learned to discriminate reward or aversive cues, a cue activity preference gradually developed only in aversive-preferring axons. We inferred the trial-by-trial cue discrimination based on machine learning using anticipatory licking or facial expressions, and found that successful discrimination was accompanied by sharper selectivity for the aversive cue in aversive-preferring axons. Our findings indicate that a group of mesocortical dopamine axons encodes aversive-related signals, which are modulated by both classical conditioning across days and trial-by-trial discrimination within a day.

Impact statement

Two-photon calcium imaging revealed that many mesocortical dopamine axons show enhanced selectivity for aversive cue processing during classical conditioning.
Innate immune control of influenza virus interspecies adaptation
Authors: Denz Parker J. , Speaks Samuel , Kenney Adam D. , Eddy Adrian C. , Papa Jonathan L. , Roettger Jack , Scace Sydney C. , Hemann Emily A. , Forero Adriana , Webby Richard J. , Bowman Andrew S. , Yount Jacob S.
Published: August 2023

Influenza virus pandemics are caused by viruses from animal reservoirs that adapt to efficiently infect and replicate in human hosts. Here, we investigated whether Interferon-Induced Transmembrane Protein 3 (IFITM3), a host antiviral factor with known human deficiencies, plays a role in interspecies virus infection and adaptation. We found that IFITM3-deficient mice and human cells could be infected with low doses of avian influenza viruses that failed to infect WT counterparts, identifying a new role for IFITM3 in controlling the minimum infectious viral dose threshold. Remarkably, influenza viruses passaged throughIfitm3-/-mice exhibited enhanced host adaptation, a result that was distinct from passaging in mice deficient for interferon signaling, which caused virus attenuation. Our data demonstrate that IFITM3 deficiency uniquely facilitates zoonotic influenza virus infections and subsequent adaptation, implicating IFITM3 deficiencies in the human population as a vulnerability for emergence of new pandemic viruses.
An experimental approach in analyzing the cell cycle dynamics of food-entrapping cells of sponges
Authors: Melnikov Nikolai P. , Lavrov Andrey I.
Published: August 2023

Sponges (phylum Porifera) exhibit surprisingly complex tissue dynamics, maintaining constant cell turnover and migration, rearranging internal structures, and regenerating after severe injuries. Such tissue plasticity relies on the activity of proliferating cells represented primarily by the food-entrapping cells, choanocytes. While there is plenty of studies regarding the dynamics of regeneration and tissue rearrangement in sponges, cell cycle kinetics of choanocytes in intact tissues remains a controversial issue.

This study is devoted to the comparative description of choanocyte cell cycle dynamics in intact tissues of two sponges,Halisarca dujardinii(class Demospongiae) andLeucosolenia corallorrhiza(class Calcarea). We have identified populations of proliferating cells and synchronized them in the S-phase to estimate the growth fraction of cycling cells. Using continuous exposure to labeled thymidine analog EdU, we calculated choanocyte cell cycle duration and the length of the S-phase. We also applied double labeling with EdU and antibodies against phosphorylated histone 3 to estimate the lengths of choanocyte M- and G2-phases. Finally, flow cytometry-based quantitative analysis of DNA content provided us with the lengths of G2- and G1-phases.

We found that tissue growth and renewal in studied sponges are generally maintained by a relatively large population of slowly cycling choanocytes with a total cell cycle duration of 40 hours inH. dujardiniiand 60 hours inL. corallorrhiza. In both species, choanocytes are characterized by an extremely short M-phase and heterogeneity in the duration of the G2-phase.
ATG8 delipidation is not universally critical for autophagy in plants
Authors: Zou Yong , Ohlsson Jonas A , Holla Sanjana , Sabljić Igor , Leong Jia Xuan , Ballhaus Florentine , Krebs Melanie , Schumacher Karin , Moschou Panagiotis N , Stael Simon , Üstün Suayb , Dagdas Yasin , Bozhkov Peter V , Minina Elena A
Published: August 2023

Intracellular recycling via autophagy is governed by post-translational modifications of the autophagy-related (ATG) proteins. One notable example is ATG4-dependent delipidation of ATG8, a process that plays critical but distinct roles in autophagosome formation in yeast and mammals. Here, we aimed to elucidate the specific contribution of this process to autophagosome formation in species representative of evolutionary distant green plant lineages: unicellular green algaChlamydomonas reinhardtii, with a relatively simple set ofATGgenes, and a vascular plantArabidopsis thaliana, harboring expandedATGgene families.

Remarkably, the more complex autophagy machinery ofArabidopsisrendered ATG8 delipidation entirely dispensable for the maturation of autophagosomes, autophagic flux and related stress tolerance; whereas autophagy inChlamydomonasstrictly depended on the ATG4-mediated delipidation of ATG8. Importantly, we uncovered the distinct impact of different Arabidopsis ATG8 orthologs on autophagosome formation, especially prevalent under nitrogen depletion, providing a new insight into potential drivers behind the expansion of the ATG8 family in higher plants.

Our findings underscore the evolutionary diversification of the molecular mechanism governing the maturation of autophagosomes in eukaryotic lineages and highlight how this conserved pathway is tailored to diverse organisms.
Monitoring Lake Okeechobee Harmful Algal Bloom populations and dynamics with a long-duration Autonomous Surface Vehicle
Authors: Xomchuk Veronica Ruiz , Duncan Scott , McFarland Malcolm N. , Beckler Jordon S.
Published: August 2023

This article describes the main findings of a full year of continuous operation of a 2-meter Autonomous Sail and Solar Surface Drone, the Nav2 (Navocean Inc.), as part of a Harmful Algal Bloom (HAB) monitoring program in Lake Okeechobee. The Nav2 was equipped with a set of water quality and atmospheric sensors, that recorded high frequency measurements (¡ 1 min) and transmitted near real-time information to allow reporting through a web portal for assessment and operation responses. Major findings include detection of HABs early in the year through chlorophyll (chl-a) and phycocyanin (phyco) fluorometric measurements, as well as different spatial scales of variability in the algal patches. The 24/7 high resolution monitoring allowed detection of patch motion and discrimination between growth and motion along a transect. Furthermore, the platform can potentially fingerprint specific HAB species based on the relatively fine-scale spatial expression of the phyco to chl-a ratio, which essentially captures the bloom macrostructure (e.g. surface scums versus more uniform sub-surface waves over 0.1 - 1 km scale). Sensor outputs, when converted to concentrations based on calibrated with pure laboratory standards, did not accurately yield true chl-a or phyco values when compared to validation samples, likely due to the high turbidity of the lake. However, routine solid-state validations of fluorometric measurements proved useful for assessing consistency in optical sensors to check for sensor drift (e.g. to due biofouling), which was not significant. Overall this demonstration shows that the Nav2 can uniquely and reliably provide in situ HAB and environmental monitoring capabilities in a large, turbid, shallow lake. We envision that platform as an innovative technology for water resource managers by providing turn-key long-duration baseline environmental data (hands-off waypoint navigation), early warnings of HABs for protecting human health, and for HAB mitigation monitoring.
The fast multipole method–accelerated line integration boundary element method for 3D heat conduction analysis with heat source
Authors: Liu Biao , Wang Qiao , Feng Y.T. , Zhang Zongliang , Huang Quanshui , Tian Wenxiang , Zhou Wei
Published: August 2023

Purpose

3D steady heat conduction analysis considering heat source is conducted on the fundamental of the fast multipole method (FMM)-accelerated line integration boundary element method (LIBEM).

Design/methodology/approach

Due to considering the heat source, domain integral is generated in the traditional heat conduction boundary integral equation (BIE), which will counteract the well-known merit of the BEM, namely, boundary-only discretization. To avoid volume discretization, the enhanced BEM, the LIBEM with dimension reduction property is introduced to transfer the domain integral into line integrals. Besides, owing to the unsatisfactory performance of the LIBEM when it comes to large-scale structures requiring massive computation, the FMM-accelerated LIBEM (FM-LIBEM) is proposed to improve the computation efficiency further.

Findings

Assuming N and M are the numbers of nodes and integral lines, respectively, the FM-LIBEM can reduce the time complexity from O(NM) to about O(N+ M), and a full discussion and verification of the advantage are done based on numerical examples under heat conduction.

Originality/value

(1) The LIBEM is applied to 3D heat conduction analysis with heat source. (2) The domain integrals can be transformed into boundary integrals with straight line integrals by the LIM. (3) A FM-LIBEM is proposed and can reduce the time complexity from O(NM) to O(N+ M). (4) The FM-LIBEM with high computational efficiency is exerted to solve 3D heat conduction analysis with heat source in massive computation successfully.
Work-life balance policies and organizational financial performance: a scoping review
Authors: Opatrná Zuzana , Prochazka Jakub
Published: August 2023

Purpose

Work-life balance (WLB) policies have become a popular topic in both academic literature and organizations. However, previous studies in this area have provided mixed results, and the impact of WLB policies on various indicators of organizational financial performance remains unclear. There has been no comprehensive review that synthesizes the current state of knowledge and indicates future research directions. This review addresses this gap and provides a systematic review of published papers investigating the relationship between WLB policies and organizational financial performance.

Design/methodology/approach

The review follows the PRISMA-ScR guidelines for scoping reviews. An analysis of 421 relevant records in Web of Science and Scopus databases identified 22 original empirical studies that focused on the relationship between WLB policies and financial performance at the level of the organization.

Findings

Most reviewed studies indicated a weak positive relationship between WLB policies and financial performance. There was the strongest support for the effectiveness of flexible working hours and job sharing, while there was mixed support for the policy of working from home. There were a higher proportion of positive results in studies conducted in Western countries compared to Asian countries, which indicates a potential moderating effect of culture. This review also describes the primary limitations of previous studies, namely, low test power and insufficient evidence about causality.

Originality/value

This review summarizes the growing body of quantitative research on the relationship between WLB policies and organizational financial performance. It presents a model that includes moderators and mediators of this relationship and indicates potentially fruitful areas for future research.
Examining women leaders’ identity conflict in a low gender egalitarian culture: a study of female corporate sector leaders in Pakistan
Authors: Bano Ayesha , Nadeem Sadia
Published: August 2023

Purpose

This study aims to explore the factors that build positive leadership identities in women and reduce woman-leader identity conflict in societies with low gender equality. In doing so, it responds to calls to examine the role of “context” for women aspiring to leadership roles.

Design/methodology/approach

The required data were collected through semistructured interviews with 30 senior-level female leaders in the corporate sector of Pakistan and analyzed using NVivo.

Findings

Successful professional women are often facilitated by various social and organizational factors that boost their confidence and ability to view themselves positively as leaders, reducing woman-leader identity conflict. The main facilitators observed were egalitarian values practiced at home, male sponsorship in organizations and individual leadership experiences. Furthermore, the age and socio-economic status of women have also emerged as important factors contributing to the success of women leaders in Pakistani society, which is characterized by gender inequality and high power distance.

Practical implications

Organizations committed to developing women for leadership roles and attaining their gender diversity goals need to address the structural and psychological barriers that hinder women’s progress in the workplace. Moreover, men need to be engaged as allies to enable women’s advancement as organizational leaders.

Originality/value

This study highlights how culture, gender norms and significant experiences of women moderate equality lows in patriarchal societies. It aims to demonstrate that women can progress as leaders within a low gender-egalitarian culture in the presence of factors that facilitate the establishment of their identities as leaders, thus reducing identity conflict. In addition, the role that men can play in creating a supportive environment for establishing women’s leadership identities is particularly highlighted in this study.
Energy management in small and medium manufacturing firms: examining the enhancing role of top management commitment in a developing country context
Authors: Arinaitwe Alice , Bagire Vincent , Tukamuhabwa Benjamin , Sulait Tumwine
Published: August 2023

Purpose

The purpose of this paper is to examine the relationship between top management commitment and energy management in small and medium manufacturing firms in a developing country context.

Design/methodology/approach

This study was executed through a survey of 66 manufacturing firms in Kampala, Uganda. The data collected were analysed using SPSS v.26.

Findings

The results show that top management commitment influences energy management. A further probe of its three dimensions of top management participation, top management support and top management beliefs reveals that all of them positively and significantly predict energy management in manufacturing firms.

Research limitations/implications

The current study results were obtained from manufacturing small and medium firms in Kampala, Uganda. Therefore, caution should be taken prior to generalization. Furthermore, this study only focuses on top management participation, top management support and top management beliefs as the dimensions of top management commitment. This study thus provides the foundation for future studies to test other dimensions of top management commitment, particularly in other sectors.

Originality/value

To the best of the authors’ knowledge, this is the first study to examine the contribution of top management commitment dimensions top management participation, top management support and top management beliefs to energy management in a developing country context. Although all dimensions are significant, top management beliefs contribute more to energy management.
Customer experience in pharmaceutical B2B markets: perspectives of buyers and sellers
Authors: Abraham Balaji , Sarkar Soumya , DasGupta Krishna
Published: August 2023

Purpose

The purpose of this study is to understand customer experience (CX) in business-to-business (B2B) markets through the perspectives of buyer–seller dyads. This study aims to evaluate how customer journey, touchpoints and digital and social media (DSM) influence CX and offer avenues for sellers to align their efforts with buyers’ requirements to create and manage CX.

Design/methodology/approach

Integrating insights of practicing buyers and sellers in the pharmaceutical B2B industry, this study follows the phenomenological approach to understand their experience through their perspectives on the customer journey, touchpoints and DSM.

Findings

The findings of this study include convergence in the perspectives in journey stages, journey enablers, stakeholder involvement, touchpoint preference and DSM’s use. The study findings also include divergence in perspectives in the senior management engagement, journey enablers, selling center involvement, DSM purpose and usage of DSM platforms. These offer opportunities for sellers to align with buyer journey, touchpoints and DSM to create and manage CX.

Practical implications

Sellers in pharmaceutical B2B markets have been dependent on traditional knowledge to influence customer journey and touchpoints and the advent of DSM has enhanced the challenge. To avoid this confusion, sellers need to have clarity of customers’ expectations on the journey, touchpoints and DSM. This enables sellers to allocate their resources better to achieve the desired outcome in CX.

Originality/value

This first-of-its-kind study captured the convergence and divergence perspectives of pharmaceutical B2B buyer–seller dyads from the lens of the uncertainty reduction theory and social penetration theory. The study suggests opportunities for pharmaceutical sellers to create and manage CX.
Is internal migration a way to cope with weather extremes? Evidence from Egypt
Authors: Arouri Mohamed , Ben-Youssef Adel , Nguyen Cuong Viet
Published: August 2023

Purpose

In this study, the authors examine the push and pull effects of extreme weather events on migration among governorates in Egypt.

Design/methodology/approach

To estimate the effect of extreme weather events on internal migration, the authors use migration gravity models and data from the 1996 and 2006 Population and Housing Censuses. The authors measure weather extremes by the number of months in the past 36 months with temperatures or precipitation of a governorate below the 5th percentile and above the 95th percentile of the distribution of monthly temperatures or precipitation of the corresponding governorate during the period 1900–2006.

Findings

This study’s results suggest that high temperatures in the origin area act as a push factor. High-temperature extremes have a positive effect on out-migration. A 1% increase in the number of months with high-temperature extremes in the original governorate results in a 0.1% increase in the number of out-migrants.

Practical implications

The study suggests that people may respond to weather extremes through migration. However, climate migrants in Egypt may encounter several significant risks that authorities must address.

Originality/value

This study is one of the first attempts to measure the push and pull effect of weather extremes on migration in Egypt.
Real‐world retention rates and effectiveness of secukinumab in psoriasis: Results from a multicenter cohort study (RAILWAY)
Authors: Tada Yayoi , Morita Akimichi , Yamanaka Keiichi , Kono Michihiro , Imafuku Shinichi , Okubo Yukari , Yamazaki Fumikazu , Kawamura Taisuke , Itakura Asako , Ohtsuki Mamitaro
Published: August 2023

Psoriasis is a chronic, immune‐mediated inflammatory skin disease with a high negative impact on patient's quality of life. Secukinumab, the first interleukin 17A inhibitor, has been used for the systemic treatment of psoriasis, but its long‐term, real‐world retention rates in Japan have not been fully investigated. In this multicenter, noninterventional, retrospective chart review study, the retention rate of secukinumab and its effectiveness among patients with psoriasis in Japan was evaluated up to 5 years. Data of patients who received secukinumab after December 26, 2014, were collected from medical charts obtained from seven sites, all certified for biologics use by the Japanese Dermatological Association. Patient characteristics, secukinumab retention, factors affecting secukinumab retention, reason for drug discontinuation, and effectiveness data were collected. The primary end point was secukinumab retention rate at week 52. A total of 123 patients were included in the analysis. Of these, 27 patients discontinued secukinumab by week 52, yielding a 78.0% (95% confidence interval, 69.6–84.4) retention rate at week 52. For patients whose Psoriasis Area and Severity Index (PASI) score was available, mean ± standard deviation PASI at baseline and at week 52 were 9.21 ± 7.37 and 1.4 ± 2.6, respectively. During the entire study period, “insufficient response” was the most common reason for discontinuation, and “history of biologics use” was a factor significantly associated with secukinumab discontinuation (hazard ratio, 1.72; p = 0.018). This study demonstrates the real‐world retention rate and effectiveness of secukinumab in patients with psoriasis in Japan for up to 5 years and provides clinical insights into psoriasis treatment strategies.