bluuebunny/crossref_metadata_2025 huggingface dataset:
Citizenship, Nationality, and the Treatment of Aliens
Authors: Low Choo Chin
Published: November 2023

This chapter identifies several similarities in the ways that constitutional systems of East and Southeast Asia treat resident aliens. First, citizenship, rather than permanent residency, is required for political rights such as the rights to vote and hold public office. Political rights do not attach to residency except in Hong Kong, Macau, and South Korea. Second, Asian states maintain selective naturalization regimes with no access to citizenship for temporary migrant workers and with arbitrary access for marriage migrants. Third, most Asian countries prohibit dual citizenship for naturalized citizens, marriage migrants, and bi-national children. This chapter shows that in East and Southeast Asian jurisdictions, there is a substantial gap between territorial membership (living in a jurisdiction) and state membership (being a citizen of that jurisdiction). Asia thus differs from Western Europe, where countries have done more to close the gap between territorial membership and state membership.
Allele-dependent expression and functionality of lipid enzyme phospholipid:diacylglycerol acyltransferase affect diatom carbon storage and growth
Authors: Pan Yufang , Zhang Wanting , Wang Xiaofei , Jouhet Juliette , Maréchal Eric , Liu Jin , Xia Xiao-Qin , Hu Hanhua
Published: November 2023

In the acyl-CoA-independent pathway of triacylglycerol (TAG) synthesis unique to plants, fungi, and algae, TAG formation is catalyzed by the enzyme phospholipid:diacylglycerol acyltransferase (PDAT). The unique PDAT gene of the model diatom Phaeodactylum tricornutum strain CCMP2561 boasts 47 single nucleotide variants within protein coding regions of the alleles. To deepen our understanding of TAG synthesis, we observed the allele-specific expression of PDAT by the analysis of 87 published RNA-sequencing (RNA-seq) data and experimental validation. The transcription of one of the two PDAT alleles, Allele 2, could be specifically induced by decreasing nitrogen concentrations. Overexpression of Allele 2 in P. tricornutum substantially enhanced the accumulation of TAG by 44% to 74% under nutrient stress; however, overexpression of Allele 1 resulted in little increase of TAG accumulation. Interestingly, a more serious growth inhibition was observed in the PDAT Allele 1 overexpression strains compared with Allele 2 counterparts. Heterologous expression in yeast (Saccharomyces cerevisiae) showed that enzymes encoded by PDAT Allele 2 but not Allele 1 had TAG biosynthetic activity, and 7 N-terminal and 3 C-terminal amino acid variants between the 2 allele-encoded proteins substantially affected enzymatic activity. P. tricornutum PDAT, localized in the innermost chloroplast membrane, used monogalactosyldiacylglycerol and phosphatidylcholine as acyl donors as demonstrated by the increase of the 2 lipids in PDAT knockout lines, which indicated a common origin in evolution with green algal PDATs. Our study reveals unequal roles among allele-encoded PDATs in mediating carbon storage and growth in response to nitrogen stress and suggests an unsuspected strategy toward lipid and biomass improvement for biotechnological purposes.
Association between de novo variants of nuclear-encoded mitochondrial-related genes and undiagnosed developmental disorder and autism
Authors: Luo T , Pan J , Zhu Y , Wang X , Li K , Zhao G , Li B , Hu Z , Xia K , Li J
Published: November 2023

Background

Evidence suggests that mitochondrial abnormalities increase the risk of two neurodevelopmental disorders: undiagnosed developmental disorder (UDD) and autism spectrum disorder (ASD). However, which nuclear-encoded mitochondrial-related genes (NEMGs) were associated with UDD–ASD is unclear.

Aim

To explore the association between de novo variants (DNVs) of NEMGs and UDD–ASD.

Design

Comprehensive analysis based on DNVs of NEMGs identified in patients (31 058 UDD probands and 10 318 ASD probands) and 4262 controls.

Methods

By curating NEMGs and cataloging publicly published DNVs in NEMGs, we compared the frequency of DNVs in cases and controls. We also applied a TADA-denovo model to highlight disease-associated NEMGs and characterized them based on gene intolerance, functional networks and expression patterns.

Results

Compared with levels in 4262 controls, an excess of protein-truncating variants and deleterious missense variants in 1421 cataloged NEMGs from 41 376 patients (31 058 UDD and 10 318 ASD probands) was observed. Overall, 3.23% of de novo deleterious missense variants and 3.20% of de novo protein-truncating variants contributed to 1.1% and 0.39% of UDD–ASD cases, respectively. We prioritized 130 disease-associated NEMGs and showed distinct expression patterns in the developing human brain. Disease-associated NEMGs expression was enriched in both excitatory and inhibitory neuronal lineages from the developing human cortex.

Conclusions

Rare genetic alterations of disease-associated NEMGs may play a role in UDD–ASD development and lay the groundwork for a better understanding of the biology of UDD–ASD.
Micro-RNA content of circulating extracellular vesicles in early rheumatoid arthritis as biomarkers and mediators of methotrexate efficacy
Authors: Maunder Daniel , Brown Philip M , Barron-Millar Ben , Lendrem Dennis W , Naamane Najib , Macdonald Jamie , Wang Xiao N , Isaacs John D , Anderson Amy E , Morgan Ann W , Crossland Rachel E , Mackie Sarah L , Pratt Arthur G
Published: November 2023

Objectives

Extracellular vesicles (EVs) are abundant in body fluids, contributing to intercellular signalling by transferring cargo that includes microRNAs (miRs)—themselves implicated in pathobiology. For the first time we evaluated the potential of EV miRs to contribute diagnostic information in early RA, predict methotrexate (MTX) efficacy or shed light on the drug’s mechanism of action.

Methods

Seven hundred and ninety-eight miRs isolated from serum-derived EVs of 46 patients with untreated RA, 23 with untreated polymyalgia rheumatica (PMR; inflammatory disease control group) and 12 in whom significant inflammatory disease had been excluded (non-inflammatory controls; NICs) were profiled (NanoString); the same measurements were made for RA patients after 6 months’ MTX treatment. Analyses took multiple testing into account.

Results

Twenty-eight EV miRs were robustly differentially expressed between early RA (but not PMR) patients and NICs after correction for age and sex, suggesting discriminatory value. Cross-validated partial least squares-discriminant analysis also indicated the predictive potential of a distinct baseline EV miR signature with respect to MTX-induced remission at 6 months. The change in expression of 13 miRs over the course of MTX treatment differed significantly between responders and non-responders, and four of those exhibiting increased relative abundance amongst responders have known roles in regulating the pathogenic potential of synovial fibroblasts, namely miR-212-3p, miR-338-5p, miR-410-3p and miR-537.

Conclusion

Our data highlight the potential of serum EV miRs as diagnostic and therapeutic biomarkers, highlighting a novel potential mechanism by which MTX may exert its therapeutic effect in early RA that warrants further investigation.
Implementing treat-to-target urate-lowering therapy during hospitalizations for gout flares
Authors: Russell Mark D , Ameyaw-Kyeremeh Louise , Dell’Accio Flora , Lapham Heather , Head Natalie , Stovin Christopher , Patel Vishit , Clarke Benjamin D , Nagra Deepak , Alveyn Edward , Adas Maryam A , Bechman Katie , de la Puente María A , Ellis Benjamin , Byrne Corrine , Patel Rina , Rutherford Andrew I , Cantle Fleur , Norton Sam , Roddy Edward , Hudson Joanna , Cope Andrew P , Galloway James B
Published: November 2023

Objectives

To evaluate a strategy designed to optimize care and increase uptake of urate-lowering therapy (ULT) during hospitalizations for gout flares.

Methods

We conducted a prospective cohort study to evaluate a strategy that combined optimal in-hospital gout management with a nurse-led, follow-up appointment, followed by handover to primary care. Outcomes, including ULT initiation, urate target attainment and re-hospitalization rates, were compared between patients hospitalized for flares in the 12 months post-implementation and a retrospective cohort of hospitalized patients from 12 months pre-implementation.

Results

One hundred and nineteen and 108 patients, respectively, were hospitalized for gout flares in the 12 months pre- and post-implementation. For patients with 6-month follow-up data available (n = 94 and n = 97, respectively), the proportion newly initiated on ULT increased from 49.2% pre-implementation to 92.3% post-implementation (age/sex-adjusted odds ratio [aOR] 11.5; 95% CI 4.36, 30.5; P < 0.001). After implementation, more patients achieved a serum urate ≤360 μmol/l within 6 months of discharge (10.6% pre-implementation vs 26.8% post-implementation; aOR 3.04; 95% CI 1.36, 6.78; P = 0.007). The proportion of patients re-hospitalized for flares was 14.9% pre-implementation vs 9.3% post-implementation (aOR 0.53; 95% CI 0.22, 1.32; P = 0.18).

Conclusion

Over 90% of patients were initiated on ULT after implementing a strategy to optimize hospital gout care. Despite increased initiation of ULT during flares, recurrent hospitalizations were not more frequent following implementation. Significant relative improvements in urate target attainment were observed post-implementation; however, for the majority of hospitalized gout patients to achieve urate targets, closer primary–secondary care integration is still needed.
Effect of antimalarials on clinical outcomes in lupus nephritis
Authors: Peña-Vizcarra Óscar R , Zavala-Miranda María Fernanda , Juárez-Cuevas Bernardo , Márquez-Macedo Sofía E , Hernández-Andrade Adriana , Nordmann-Gomes Alberto , Pérez-Arias Abril A , Morales-Buenrostro Luis E , Mejía-Vilet Juan M
Published: November 2023

Objectives

To evaluate the effect of antimalarial drugs in response to therapy, incidence of LN flares, and progression of kidney disease in a large LN cohort.

Methods

We retrospectively studied 424 biopsy-proven LN patients followed for >3 years. We obtained demographic, clinical, laboratory, histopathological and treatment variables. Antimalarial use was approached as (i) users vs no users, (ii) according to prevalent vs incident use regarding the LN flare and (iii) according to the type of antimalarial. All outcomes were evaluated by time-to-event analyses. Adjusted hazard ratios were obtained by Cox regression.

Results

The cohort included 424 patients, median age of 29 years (IQR 23–37), 96% female, with a median eGFR of 81 ml/min/1.73 m2 (IQR 48–118) and proteinuria of 3.4 g/g (IQR 1.9–5.5). Antimalarial use was associated with higher complete response (aHR 1.57, 1.08–2.27), lower incidence of kidney flares (aHR 0.63, 0.43–0.92) and lower progression to kidney failure (aHR 0.37, 0.23–0.53). The effect of antimalarials on these outcomes was modified by the presentation eGFR, histological class and/or concomitant initial immunosuppressor. These protective effects were observed in patients with prevalent or incident use regarding the LN flare and patients using hydroxychloroquine. The incidence of toxic retinopathy was 1.7%, 5.7% and 8.8% by 3, 5 and 7 years of continued antimalarial use, respectively.

Conclusion

The use of antimalarial drugs is associated with increased response to therapy, lower incidence of kidney flares, and lower progression to kidney failure in LN patients. Conversely, this population is at high risk of toxic maculopathy, and yearly ophthalmologic examination is recommended.
Patient’s knowledge regarding radiation exposure from various imaging modalities: a pilot study
Authors: Matković Andro , Ferenc Thomas , Dimjašević Lucija , Drinković Martin , Lovreković Bruno , Popić Jelena , Mužar Rhea M , Vidjak Vinko
Published: November 2023

To determine patients’ knowledge about ionising radiation used in diagnostic imaging and whether they were adequately informed about the procedure they were referred to. A cross-sectional study was conducted at the University Hospital Merkur, Zagreb, Croatia during 2019–20. A questionnaire with 14 questions was given to patients in waiting rooms for imaging examinations. Statistical analysis was conducted using the standard software package. Chi-square with Yates correction was used to determine differences in patients’ answers between those who received the explanation about the procedure and those who did not. The differences depending on the educational level were also evaluated. The survey was completed by 374 participants (200 women, 174 men) with a mean age of 55.45 ± 15.92 y. Of all patients, 8.63% had no formal education or only finished elementary school, 52.83% had finished high school and 38.55% had a college or a higher degree. The referring physicians informed 63.66% of participants about the radiological exam they were being referred to, and 226 thought that the given explanation was sufficient. Most patients knew that some radiological procedures use ionising radiation. Only 47.37% of respondents correctly identified MRI as a non-ionising method, whereas 37.40% of participants recognised chest X-ray as the modality with the lowest radiation dose. Higher-educated patients had better knowledge of radiological procedures and the potential risks. The study demonstrated suboptimal patients’ knowledge about ionising radiation, and additional efforts in their education are needed.
Causal roles of prefrontal and temporo-parietal theta oscillations for inequity aversion
Authors: Christian Patricia , Kapetaniou Georgia E , Soutschek Alexander
Published: November 2023

The right temporo-parietal junction (rTPJ) and the right lateral prefrontal cortex (rLPFC) are known to play prominent roles in human social behaviour. However, it remains unknown which brain rhythms in these regions contribute to trading-off fairness norms against selfish interests as well as whether the influence of these oscillations depends on whether fairness violations are advantageous or disadvantageous for a decision maker. To answer these questions, we used non-invasive transcranial alternating current stimulation (tACS) to determine which brain rhythms in rTPJ and rLPFC are causally involved in moderating aversion to advantageous and disadvantageous inequity. Our results show that theta oscillations in rTPJ strengthen the aversion to unequal splits, which is statistically mediated by the rTPJ’s role for perspective taking. In contrast, theta tACS over rLPFC enhanced the preference for outcome-maximizing unequal choices more strongly for disadvantageous compared to advantageous outcome distributions. Taken together, we provide evidence that neural oscillations in rTPJ and rLPFC have distinct causal roles in implementing inequity aversion, which can be explained by their involvement in distinct psychological processes.
The Importance of Mitochondrial Disease Testing in Young Adults With New Onset Sensorineural Hearing Loss
Authors: Koleilat Alaa , Poling Gayla L. , Schimmenti Lisa A. , Hasadsri Linda
Published: November 2023

Objectives:

Sensorineural hearing loss (SNHL) occurs commonly as part of mitochondriopathies and varies in severity and onset. In this study, we characterized hearing with specific consideration for hearing loss as a potential early indicator of mitochondrial disease (MD). We hypothesize that genetic testing at the earliest detection of SNHL may lead to an earlier MD diagnosis.

Design:

We reviewed the clinical and audiometric data of 49 patients undergoing genetic testing for MD.

Results:

One-third of individuals with molecularly confirmed MD presented with SNHL. On average, patients had hearing loss at least 10 years before genetic testing. The collective audiometric profile includes mild to moderate SNHL at lower frequencies and moderate SNHL at 2 kHz and higher frequencies.

Conclusions:

This study suggests that screening for SNHL could be an early indicator of MD. We propose that the audiometric profile for those with a MD diagnosis may have clinical triage utility.
Vision related quality of life among Nepalese patients with keratoconus
Authors: Koirala Bipin , Sapkota Arjun , Chaudhary Meenu , Sitaula Sanjeeta , Mishra Sanjeeb , Mahat Manoj , Chandan Aayush
Published: November 2023

Introduction:

Keratoconus (KC) is a bilateral progressive noninflammatory disorder characterized by irregular astigmatism and corneal thinning. KC results in a disproportionate impact on major aspects of quality of life (QoL) of a person due to its early onset and chronic nature. This study aims to evaluate vision-related QoL in Nepalese patients with KC.

Method:

A cross-sectional hospital-based study was carried out for 1 year. A sample of 35 KC subjects and 38 control subjects who met the eligibility criteria were enrolled. All subjects underwent corneal topography and abberometry along with a comprehensive eye examination. Both cases and controls completed the NEI VFQ 25 questionnaire. Visual acuity (high contrast visual acuity and LCVA), CS, color vision, refraction, and scores of all subscales of QoL were measured. The QoL scores were correlated with each of the visual function parameters in KC subjects.

Result:

The mean scores of all of the subscales of QoL were found significantly less in the KC group than in age and sex matched control group with P<0.001 The mean composite score was found to reduce significantly as the grade of KC increased. The mean composite score for grade 1 KC was 70.79±7.96, grade 2 KC was 60.56±6.49 and for grade 3 KC was 55.99±0.67 with P=0.001 about better eye. There was a highly significant difference in the mean composite score of QoL between these contact lens wearers and spectacle wearers. The mean composite score for spectacle wearer was 67.86±07.99 and that of contact lens wearer was 58.63±04.26 with P=0.004.

Conclusion:

This study concluded that the QoL of keratoconic individuals was found to reduce gradually as the severity of the disease increased. QoL score in contact lens-wearing Nepalese KC patients is worse than spectacle wearers. By stopping the progression of disease we can maintain functional vision as well as a vision-related QoL. Our study findings suggested that vision and visual function parameters in the better eye is the most important parameter affecting VR-QOL of patients with KC. KC patients should maintain the best vision that they can have.
Diagnostic journey and multimodal management of a rare urogenital rhabdomyosarcoma with rectovaginal fistula in an adolescent: a case report
Authors: Katwal Shailendra , Ghimire Aastha , Shrestha Kriti , Amatya Suban
Published: November 2023

Introduction and importance:

Rhabdomyosarcoma is a malignant tumour that originates from immature muscle cells and belongs to the category of soft-tissue sarcomas. It is predominantly diagnosed in children under the age of 6. This condition can manifest within the genitourinary tract and may exhibit non-specific symptoms such as changes in bowel habits and fever. Early detection and a comprehensive, multidisciplinary approach are essential to achieving more favourable outcomes. This report highlights an uncommon case of urogenital rhabdomyosarcoma in a 15-year-old girl, in addition to the presence of a rectovaginal fistula.

Case presentation:

A 15-year-old girl with presented with fever, altered bowel habits, and a lump in her lower abdomen, abdominal discomfort, and incomplete bowel evacuation. She also had faecal discharge from the vagina. Diagnostic imaging and biopsy confirmed urogenital rhabdomyosarcoma with a rectovaginal fistula. The patient is currently undergoing induction chemotherapy and is scheduled for radiation therapy and surgery.

Clinical discussion:

Rhabdomyosarcoma is a rare paediatric oncologic concern due to its aggressive nature and potential metastasis. The presentation varies based on age, tumour location, and metastasis presence. This patient presented with altered bowel habits, a pelvic mass and unusual feculent discharge, suggesting a rectovaginal fistula. Diagnostic imaging confirmed the diagnosis, and induction chemotherapy led to a positive response and reduced tumour size.

Conclusion:

Urogenital rhabdomyosarcoma is an aggressive malignancy with non-specific symptoms, making early diagnosis challenging. An accurate diagnosis requires high suspicion, imaging, and a biopsy. Multidisciplinary management, including surgery, chemotherapy, and radiation therapy, improves outcomes and improves paediatric patients’ prognosis and quality of life
Rising meningitis in USA and Mexico: insights from the fatal outbreak
Authors: Anis Heeba , Shaik Akbar Basha , Berjaoui Christin , Karabulut Ece , Tiwari Angad , Nazir Abubakar , Hamitoglu Ali Emir , Uwishema Olivier
Published: November 2023

Meningitis, an inflammatory disease affecting the meningeal layers of the brain and the spinal cord, poses a significant public health concern globally. Most meningitis cases are caused by viral infections, bacterial infections being the second most common cause, while fungal or parasitic infections are deemed rare. Despite the decrease in bacterial meningitis because of vaccination and treatment, a recent meningitis outbreak in the United States and Mexico highlighted ongoing challenges. The current meningitis outbreak is caused by a pathogenic fungus and is associated with surgical procedures performed under spinal anaesthesia as reported by the Centers for Disease Control and Prevention (CDC) on the 11 May of 2023. Around 20 cases with clinical suspicion of meningitis, including two fatalities, have been attributed to this rampant outbreak. Timely diagnosis, utilising diagnostic modalities such as lumbar puncture and pathogen detection methods, is crucial for appropriate management. Iatrogenic meningitis must be avoided by enhancing surveillance, infection control procedures, and adherence to aseptic practices. To lessen the effects of meningitis and enhance patient outcomes, the WHO’s roadmap and preventive interventions, such as targeted immunisations, are essential.
Risk factors for sepsis and mortality in patients with emphysematous pyelonephritis : a series of 68 cases (case series)
Authors: Bedoui Mohamed A. , Saadi Ahmed , Zaghbib Selim , Mokadem Seif , Boussaffa Hamza , Hermi Amine , Ayed Haroun , Bouzouita Abderrazek , Chakroun Marouene , Ben Slama Riadh
Published: November 2023

Background:

Emphysematous pyelonephritis (EPN) is a rare and severe necrotizing infection of the kidney with a high rate of complications and mortality. Our aim was to investigate risk factors of urosepsis and mortality in case of EPN.

Materials and methods:

Between January 2010 and December 2022 the charts of patients diagnosed with EPN were retrospectively reviewed. Patients medical records were collected and data including demographics, BMI, EPN type, the organism causing the infection and biochemical variables were registered. The authors performed an univariate and multivariate logistic regression analysis for sepsis, septic shock, and mortality. Statistical significance was defined as a P-value of <0.05.

Results:

Our study included 68 patients (63% females, mean age 58.6 years old). Forty-eight patients (70.6%) had diabetes. Half of the patients (50%) presented with sepsis and 11 patients (16.2%) developed a septic shock. The following factors were associated with sepsis by univariate analysis: diabetes (P=0.01), higher blood sugar on admission (P=0.01), higher leukocytic count (P<0.001), higher lymphocytic count (P<0.001), and lower platelet to leukocytes ratio (P<0.001). Multivariate regression analysis revealed that the main risk factors of urosepsis were the leukocytic (OR: 85.7; 95% CI: 9.177–800.486; P<0.001) and lymphocytic count (OR: 6.65; 95% CI: 1.228–36.050; P=0.028). Neither of the variables was significantly associated with a higher risk of mortality.

Conclusion:

Leukocytic and lymphocytic count on admission are independent simple predictors for sepsis in patients with EPN.
Curvature-dependent Eulerian interfaces in elastic solids
Authors: Brazda Katharina , Kružík Martin , Rupp Fabian , Stefanelli Ulisse
Published: November 2023

We propose a sharp-interface model for a hyperelastic material consisting of two phases. In this model, phase interfaces are treated in the deformed configuration, resulting in a fully Eulerian interfacial energy. In order to penalize large curvature of the interface, we include a geometric term featuring a curvature varifold. Equilibrium solutions are proved to exist via minimization. We then use this model in an Eulerian topology optimization problem that incorporates a curvature penalization.

This article is part of the theme issue ‘Foundational issues, analysis and geometry in continuum mechanics’.
Weak elastic energy of irregular curves
Authors: Mucci D. , Saracco A.
Published: November 2023

A weak notion of elastic energy for (not necessarily regular) rectifiable curves in any space dimension is proposed. Ourp-energy is defined through a relaxation process, where a suitablep-rotation of inscribed polygons is adopted. The discretep-rotation we choose has a geometric flavour: a polygon is viewed as an approximation to a smooth curve, and hence its discrete curvature is spread out into a smooth density. For any exponentpgreater than 1, thep-energy is finite if and only if the arc-length parametrization of the curve has a second-order summability with the same growth exponent. In that case, moreover, the energy agrees with the natural extension of the integral of thepth power of the scalar curvature. Finally, a comparison with other definitions of discrete curvature is provided.

This article is part of the theme issue ‘Foundational issues, analysis and geometry in continuum mechanics’.
Eckart equations, Maxwellian iteration and relativistic causal theories of divergence type
Authors: Ruggeri Tommaso
Published: November 2023

We consider a general causal relativistic theory of divergence type in the framework of rational extended thermodynamics (RET) for a compressible, possibly dense, gas. We require that the system converges in the Maxwellian iteration’s first step to the parabolic Eckart equations. This requirement implies a constraint between the two coefficients present in the triple tensor evaluated at equilibrium. Moreover, the production tensor is determined for prescript thermal and caloric state equations and given heat conductivity, shear and bulk viscosities. In the second part, we prove that if the original hyperbolic system satisfies the universal principles of RET, as can be put in the symmetric form using the
main field
, it always satisfies the previous compatibility condition. Therefore, any causal system of divergence type that satisfies the entropy principle with a convex entropy converges to the Eckart system in the Maxwellian iteration also when we have no information at the mesoscopic scale from the kinetic theory. The obtained results are tested on the RET theories of rarefied monatomic and polyatomic gases.

This article is part of the theme issue ‘Foundational issues, analysis and geometry in continuum mechanics’.
High-resolution vasomotion analysis reveals novel arteriole physiological features and progressive modulation of cerebral vascular networks by stroke
Authors: Zhang Yi-Yi , Li Jin-Ze , Xie Hui-Qi , Jin Yu-Xiao , Wang Wen-Tao , Zhao Bing-Rui , Jia Jie-Min
Published: November 2023

Spontaneous cerebral vasomotion, characterized by ∼0.1 Hz rhythmic contractility, is crucial for brain homeostasis. However, our understanding of vasomotion is limited due to a lack of high-precision analytical methods to determine single vasomotion events at basal levels. Here, we developed a novel strategy that integrates a baseline smoothing algorithm, allowing precise measurements of vasodynamics and concomitant Ca2+ dynamics in mouse cerebrovasculature imaged by two-photon microscopy. We identified several previously unrecognized vasomotion properties under different physiological and pathological conditions, especially in ischemic stroke, which is a highly harmful brain disease that results from vessel occlusion. First, the dynamic characteristics between SMCs Ca2+and corresponding arteriolar vasomotion are interplayed. Second, compared to previous diameter-based estimations, our radius-based measurements reveal nonisotropic vascular movements, enabling a more precise determination of the latency between smooth muscle cell (SMC) Ca2+activity and vasocontraction. Third, we characterized single vasomotion event kinetics at scales of less than 4 seconds. Finally, following pathological vasoconstrictions induced by ischemic stroke, vasoactive arterioles transitioned to an inert state and persisted despite recanalization. In summary, we developed a highly accurate technique for analyzing spontaneous vasomotion, and we suggest a potential strategy to reduce stroke damage by promoting vasomotion recovery.
Proteolytic degradation of atrial sarcomere proteins underlies contractile defects in atrial fibrillation
Authors: Cizauskas Hannah E , Burnham Hope V , Panni Azaria , Pena Alexandra , Alvarez-Arce Alejandro , Davis M Therese , Araujo Kelly N , Delligatti Christine , Edassery Seby , Kirk Jonathan A , Arora Rishi , Barefield David Y
Published: November 2023

(ii) ABSTRACT

Aims

Atrial fibrillation (AFib) is the most common cardiac rhythm disturbance. Treatment of AFib involves restoration of the atrial electrical rhythm. Following rhythm restoration, a period of depressed mechanical function known as atrial stunning occurs that involves decreased blood flow velocity and reduced atrial contractility. This suggests that defects in contractility occur in AFib and are revealed upon restoration of rhythm. The aim of this project is to define the contractile remodeling that occurs in AFib

Methods and Results

To assess contractile function, we used a canine atrial tachypacing model of induced AFib. Mass spectrometry analysis showed dysregulation of contractile proteins in samples from AFib compared to sinus rhythm atria. Atrial cardiomyocytes showed reduced force of contraction in skinned single cardiomyocyte calcium-force studies. There were no significant differences in myosin heavy chain isoform expression. Resting tension is decreased in the AFib samples correlating with reduced full-length titin in the sarcomere. We measured degradation of other myofilament proteins including cMyBP-C, actinin, and cTnI, showing significant degradation in the AFib samples compared to sinus rhythm atria. Many of the protein degradation products appeared as discrete cleavage products that are generated by calpain proteolysis. We assessed calpain activity and found it to be significantly increased. Skinned cardiomyocytes from AFib atria showed decreased troponin I phosphorylation, consistent with the increased calcium sensitivity that was found within these cardiomyocytes.

Conclusions

With these results it can be concluded that AFib causes alterations in contraction that can be explained by both molecular changes occurring in myofilament proteins and overall myofilament protein degradation. These results provide an understanding of the contractile remodeling that occurs in AFib and provides insight into the molecular explanation for atrial stunning and the increased risk of atrial thrombus and stroke in AFib.
Sex- and age-dependent effects of locus coeruleus-originated tau dysfunction on olfaction and neurophysiology in rats
Authors: Dutton Olivia D. E. , Wasef Marie A. , Burke Alexander T. , Chirinos Ella A. , Jones Amelia T. , Vey Rachel , Skinner Darlene M. , Harley Carolyn W. , Walling Susan G.
Published: November 2023

Braak and colleagues (2011) described human pretangle stages of abnormal tau protein originating in the locus coeruleus (LC) of young adults (Braak’s Stages a-c, 1a-b), decades prior to the neurofibrillary tangle stages observed in Alzheimer’s disease. To capture the features of LC-originated pretangle tau stages, we used a rat model where male and female TH-Cre+/-rats received bilateral LC infusions of a hyperphosphorylated human tau (htauE14) gene via a viral vector. To assess the effects of age and sex on pretangle stage tau, we assayed physiological and behavioural changes 1-3mo (young) and 12+mo (aged) post LC-infusion (p.i.).

Open field measures revealed age and sex-dependent differences in anxiety in LC-htauE14 infused rats and overall sex- and age-dependent differences in activity. Odour discrimination tests showed little impairment in LC-htauE14 infused rats at 1-3mo after LC infusion. At 12+mo p.i. however, LC-htauE14 male rats failed a difficult odour discrimination test and a further olfactory detection test (habituation-dishabituation), but male LC-Control rats and female rats were not impaired.

LC neuronal firing rates were assessed in urethane-anesthetized aged (12+mo p.i.) male LC-htauE14 and LC-Control rats. The baseline level of firing of LC neurons in LC-htauE14 rats was higher than firing rates of LC-Control rats. Oscillatory patterns in LC firing were increased in amplitude and frequency by LC-htauE14.

PSD95 density measures in piriform cortex were similar for LC-Control and LC-htauE14 male and female rats of young and aged groups. While synaptophysin density was higher in controls of the 1-3mo p.i. groups than in the LC-htauE14 rats, levels did not differ among aged groups.

The increased excitability of LC cells observed may occur in relation to reduced LC axon arbours or may reflect a separate effect of htauE14 in LC neurons. The association of increased tonic LC activity to behavioural changes in the pretangle tau rat model merits further investigation.
A systematic review of quantitative EEG findings in Long COVID, Fibromyalgia and Chronic Fatigue Syndrome
Authors: Silva-Passadouro Bárbara , Tamasauskas Arnas , Khoja Omar , Casson Alexander J. , Delis Ioannis , Brown Christopher , Sivan Manoj
Published: November 2023

Long COVID (LC) is a multisymptom clinical syndrome with similarities to Fibromyalgia Syndrome (FMS) and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). All these conditions are believed to be associated with centrally driven mechanisms such as central sensitisation. There is a lack of consensus on quantitative EEG (qEEG) changes observed in these conditions. This review aims to synthesise and appraise the literature on resting-state qEEG in LC, FMS and CFS/ME, to help uncover possible mechanisms of central sensitisation in these similar clinical syndromes. A systematic search of MEDLINE, Embase, CINHAL, PsycINFO and Web of Science databases for articles published between December 1994 and September 2023 was performed. Following screening for predetermined selection criteria and out of the initial 2510 studies identified, 17 articles were retrieved that met all the inclusion criteria, particularly of assessing qEEG changes in one of the three conditions compared to healthy controls. All studies scored moderate to high quality on the Newcastle-Ottawa scale. There was a general trend for decreased low-frequency EEG band activity (delta, theta, and alpha) and increased high-frequency EEG beta activity in FMS, whereas an opposite trend was found in CFS/ME. The limited LC studies included in this review focused mainly on cognitive impairments and showed mixed findings not consistent with patterns seen in FMS and CFS/ME. Further research is required to explore whether there are phenotypes within LC that have EEG signatures similar to FMS or CFS/ME. This could inform identification of reliable diagnostic markers and possible targets for neuromodulation therapies.
Potassium stimulates fruit sugar accumulation by increasing carbon flow in Citrus
Authors: Wu Kongjie , Hu Chengxiao , Liao Peiyu , Hu Yinlong , Sun Xuecheng , Tan Qiling , Pan Zhiyong , Xu Shoujun , Dong Zhihao , Wu Songwei
Published: November 2023

Soluble sugar is a key factor of flavor quality in citrus. Potassium (K) is known as a quality element, which plays key roles in improving sugar accumulation and fruit quality, but the mechanisms are largely unknown. This study aims to elucidate how K improves sugar accumulation by regulating carbon flow between source and sink in Newhall navel orange (Citrus sinensis). The results demonstrated that appropriate K concentration improved fruit quality and sugar accumulations in citrus, and 1.5% of K concentration in pulp was the optimal concentration for fruit quality. K increased strength of sink and source, as supported by the increased fruit growth rate, gene expressions related to sugar metabolism and sugar transport in fruit, and photosynthesis, gene expressions of sugar metabolism in leaf, respectively, which contributed to increasing sugars accumulation. Further study indicated that K improved carbon flow from source to sink by boosting symplastic and apoplastic loading of phloem, as supported by the increased CF signal intensities, plasmodesmata densities, and the expressions ofCsSUT1andCsSUT2in leaf at early and mid stages of fruit development, finally increasing sugar accumulation in fruit. Conclusively, K stimulates fruit sugar accumulation by increasing carbon flow in Newhall navel orange.

Highlight

K application stimulated carbon flow between source and sink through symplastic and apoplastic loading, which were supported by the structural characteristics of phloem and the expression ofCsSUTsandCsSWEETs, ultimately promoting sugar accumulation inCitrus sinensis.
Climate just entrepreneurship: feminist entrepreneurship for climate action
Authors: Stephenson Elise , Furman Sarah
Published: November 2023

Purpose

This paper aims to explore synergies between feminist, first nations and queer theories and social, circular and climate entrepreneurship, to build a framework for supporting climate just entrepreneurship.

Design/methodology/approach

This paper draws on an extensive qualitative review of the literature on gender justice, equality, social entrepreneurship, the circular economy, climate entrepreneurship and climate action, as well as theorising feminist, first nations and queer approaches to climate action through entrepreneurship.

Findings

Whilst climate change is a “threat multiplier” for existing gender (and other) inequalities, gaps remain in engraining gender equality and gender justice principles in social, circular and climate entrepreneurship. Through analysing the literature for critical gaps and theorising at the intersection of climate entrepreneurship and feminist, first nations and queer theories, the authors advocate that a framework for climate just entrepreneurship could play a pivotal role in combining proactive climate action and gender equality measures through entrepreneurship. It could also be a significant step towards ensuring entrenched, systemic inequalities are not perpetuated in nascent and rapidly evolving fields such as the circular economy, social enterprise and climate entrepreneurship.

Originality/value

The literature on climate entrepreneurship is burgeoning, yet key entrepreneurial concepts lack an explicitly feminist or gender lens approach, even whilst being inextricably linked to effective climate action. This paper seeks to rectify this gap by promoting climate just entrepreneurship as a model for effective climate action.
Structural supply chain complexity index and construct validity: a data-driven empirical approach
Authors: Pant Pushpesh , Dutta Shantanu , Sarmah S.P.
Published: November 2023

Purpose

Given the lack of focus on a standardized measurement framework (e.g. benchmarking tool) to assess and quantify complexity within the supply chain, this study has developed a unified supply chain complexity (SCC) index and validated its utility by examining the relationship with firm performance. More importantly, it examines the role of firm owners' business knowledge, sales strategy and board management on the relationship between SCC and firm performance.

Design/methodology/approach

In this study, the unit of analysis is Indian manufacturing companies listed on the Bombay Stock Exchange (BSE). This research has merged panel data from two secondary data sources: Bloomberg and Prowess and empirically operationalized five key SCC drivers, namely, number of suppliers, the number of supplier countries, the number of products, the number of plants and the number of customers. The study employs panel data regression analyses to examine the proposed conceptual model and associated hypotheses. Moreover, the present study employs models that incorporate robust standard errors to account for heteroscedasticity.

Findings

The results show that complexity has a negative and significant effect on firm performance. Further, the study reveals that an owner's business knowledge and the firm's effective sales strategy and board management can significantly lessen the negative effect of SCC.

Originality/value

This study develops an SCC index and validates its utility. Also, it presents a novel idea to operationalize the measure for SCC characteristics using secondary databases like Prowess and Bloomberg.
Agency and collaboration: an analysis of the relationship between government-certified social enterprises and the public sector in South Korea
Authors: Claassen Casper Hendrik , Bidet Eric , Kim Junki , Choi Yeanhee
Published: November 2023

Purpose

Public sector institutional entrepreneurship efforts may contribute to addressing social challenges by creating an enabling regulatory environment that promotes social enterprise formation and fosters complementarity between the public sector and social enterprises. The outcomes of such public sector institutional entrepreneurship are explored in this study. To assess the outcomes of such public sector initiatives in South Korea, the perspectives of executives (n = 40) of government-certified social enterprises are assessed.

Design/methodology/approach

Several research methodologies were combined, including purposive sampling with an 11-point Likert scale, hierarchical clustering and principal component analysis. The literature on government–nonprofit relations as well as public sector institutional entrepreneurship was leveraged.

Findings

This research results indicate that the enabling regulatory environment with entrenched funding and incubation mechanisms produces mixed-to-positive outcomes if framed with reference to public sector–social enterprise complementarity. The authors identified three perspective-based ideal types that have differential views of isomorphic regulatory pressures, the efficacy of incubation and scaling programs, participation in policymaking and other aspects of public sector patronage.

Originality/value

This study contributes to relating the literature on public sector institutional entrepreneurship and government–third sector relations by empirically assessing how social enterprises attracted by government demand-side signaling to become certified as social enterprises encounter and perceive an ostensibly enabling regulatory ecosystem, with its derivative policies and mechanisms, crafted by the public sector.
Banking sector's reaction during the Russian invasion of Ukraine: who reacted the most?
Authors: Yudaruddin Rizky , Lesmana Dadang
Published: November 2023

Purpose

This study aims to investigate the market reaction to the Russian invasion of Ukraine, specifically in the banking sector.

Design/methodology/approach

The research uses an event study and cross-sectional analysis, with market reaction measured by cumulative abnormal return (CAR). The sample comprised 1,126 banks.

Findings

The results show that the market reacted negatively to the invasion both before and after its announcement. Developed and emerging markets saw a negative impact from the invasion, while frontier markets experienced only a slight impact. The authors also find that the banking markets of North Atlantic Treaty Organization (NATO) members reacted significantly and negatively both before and after the invasion was announced. This demonstrates that the negative market reaction of NATO members was more impactful than that of other markets. Overall, this study shows that investors in the banking market are very sensitive to war.

Originality/value

This is the first study to provide international evidence, specifically on the banking sector's reaction during the Russian invasion of Ukraine.
The enduring political viability of governance models in tourist destinations and their implications for people and planet
Authors: Martins Luis Pedro , Ribeiro Susana
Published: November 2023

Purpose

The objective of this paper is to examine the ways in which tourism can be regarded as a catalyst for positive change, benefiting both people and the planet. The authors consider the integral role of community engagement as a tangible component within the governance frameworks of destination management organizations (DMOs).

Design/methodology/approach

Originating from the authors' professional experience and academic expertise in managing and marketing tourist destinations, both at the local and regional levels, the article explores the pressing requirement for reevaluating policies and strategies. It aims to emphatically underscore and reiterate the role of tourism as a pivotal driver for enhancing peoples' quality of life and ensuring the sustainability of tourist destinations. This effort involves not only maintaining equilibrium among the four widely recognized pillars of sustainability but also pondering the significance of an equally crucial aspect of destination management – the political sustainability of the governance framework of tourist destinations.

Findings

Current realities encourage the authors to contemplate and act, guided by the unfolding of tourism's swift regenerative influence. It is anticipated that people have gleaned vital lessons from the collective pause people underwent during the pandemic, coupled with the stark realization of being unable to partake in the favourable contributions of tourism in everyday life. This article highlights the urgency of implementing DMO models that are capable of conceptualizing and operationalizing a human-centred tourism development policy and the resulting sustainability strategies, enhancing representation and guidance for the satisfaction of stakeholders.

Originality/value

It is neither a widespread practice, nor are there many prior studies that tackle the potential of forecasting the comprehensiveness of governance and management models for tourist destinations that encompass stakeholders who represent the direct interests of local communities within the tourism system. Supported by a literature review, analysis of secondary data and the first-hand experience of the authors, it becomes apparent that the operational landscape of most organizations functioning as tourist destination managers is predominantly at the regional and local tiers. These very organizations are the ones that have been progressively evolving, displaying a readiness to introduce innovation in this realm. Implementing these models would represent an approach to governance more inclined towards a bottom-up style, thereby posing a challenge to the more rigid and commonly employed strategies that emanate from a centrally structured national framework.