bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered Neurotransmitter Ratio in the Prefrontal Cortex is Associated with Pain in Fibromyalgia Syndrome
Authors: Bishop James H. , Faerman Afik , Geoly Andrew , Khan Naushaba , Tischler Claudia , Amin Heer , Maron-Katz Adi , Azeez Azeezat , Yeomans David C. , Hurd Ralph , Gu Meng , Baltusis Laima , Spielman Daniel , Sacchet Matthew D. , Spiegel David , Williams Nolan
Published: October 2021

The central mechanisms underlying fibromyalgia syndrome (FMS) remain undetermined. The dorsolateral prefrontal cortex (DLPFC) is particularly relevant to FMS because it is implicated in cognitive, affective, and top-down pain regulation. Imbalances in excitatory (Glutamate) and inhibitory (Gamma aminobutyric acid; GABA) neurochemicals may play a critical role in the pathophysiology of the condition and more generally in homeostatic function within cortical circuits. Although the balance of excitation and inhibition are intrinsically linked no investigations to date have investigated the E/I ratio in FMS. Thus, the primary objective of this study was to determine whether the E/I ratio in the DLPFC is altered in participants with FMS compared to healthy controls using magnetic resonance spectroscopy. Additionally, we examined the relationship between E/I ratio and pain metrics. We hypothesized that the E/I ratio within the DLPFC would be altered in participants with FMS compared to controls and, secondly, that E/I ratio would be associated with both clinical pain and thermal pain sensitivity. The Brief Pain Inventory (BPI) self-assessment was used to evaluate pain severity and impact on physical functioning and acute pain sensitivity was determined via quantitative sensory testing to define thermal (heat) pain threshold and tolerance. Our results revealed an elevation in the E/I ratio in FMS compared to controls. A positive relationship between E/I ratio and thermal pain sensitivity measures was identified in the FMS cohort. Collapsing across groups, there was a positive relationship between E/I ratio and BPI score. These findings suggest that dysfunction in the balance between excitation and inhibition within cognitive brain circuitry may play a role in pain processing in FMS.
Disordered yet functional atrial t-tubules on recovery from heart failure
Authors: Caldwell Jessica L. , Clarke Jessica D. , Smith Charlotte E.R. , Pinali Christian , Quinn Callum J. , Pearman Charles M. , Adomaviciene Aiste , Radcliffe Emma J. , Watkins Amy E. , Horn Margaux A , Bode Elizabeth F. , Eisner Mark , Eisner David A. , Trafford Andrew W. , Dibb Katharine M.
Published: October 2021

Transverse (t)-tubules drive the rapid and synchronous Ca2+ rise in cardiac myocytes. The virtual complete loss of atrial t-tubules in heart failure (HF) decreases Ca2+ release. It is unknown if or how atrial t-tubules can be restored and if restored t-tubules are functional.

Sheep were tachypaced to induce HF and recovered when pacing was stopped. Serial block face Scanning Electron Microscopy and confocal imaging were used to understand t-tubule ultrastructure and function. Candidate proteins involved in atrial t-tubule recovery were identified by western blot and causality determined using expression studies.

Sheep atrial t-tubules reappeared following recovery from HF. Despite being disordered (branched, longer and longitudinally arranged) recovered t-tubules triggered Ca2+ release and were associated with restoration of systolic Ca2+. Telethonin and myotubularin abundance correlated with t-tubule density and altered the density and structure of BIN1-driven tubules in neonatal myocytes. Myotubularin had a greater effect, increasing tubule length and branching, replicating that seen in the recovery atria.

Recovery from HF restores atrial t-tubules and systolic Ca2+ and myotubularin facilitates this process. Atrial t-tubule restoration could present a new and viable therapeutic strategy.

Brief Summary

The loss of atrial transverse (t)-tubules and the associated dysfunction in heart failure is reversible and the protein myotubularin plays an important role.
Diverse B-cell specific transcriptional contexts of the BCL2 oncogene in mouse models impacts pre-malignant development
Authors: Zawil Lina , Marchiol Tiffany , Brauge Baptiste , Saint-Amand Alexis , Carrion Claire , Dessauge Elise , Oblet Christelle , Le Noir Sandrine , Mourcin Frédéric , Jouan Florence , Brousse Mylène , Derouault Paco , Alizadeh Mehdi , Makhour Yolla El , Monvoisin Céline , Léonard Simon , Durand-Panteix Stéphanie , Tarte Karin , Cogné Michel
Published: October 2021

Follicular lymphoma (FL) is the most common indolent form of non-Hodgkin lymphoma arising from malignant germinal center (GC) B-cells. The genetic hallmark that leads to the development of FL is the t(14:18) which occurs early in the bone marrow during B cell development, thereby placing the anti-apoptoticBCL2gene under the direct control of the transcriptional enhancers in 3’ of immunoglobulin heavy chain locus (IgH 3’RR) and leading to the constitutive expression of the BCL2 protein. To assess the impact of the BCL2 deregulation on B-cell fate and try to reproduce FL development in mice, two models were designed: the Igκ-BCL2 (Knock in of the BCL2 in the light chain Ig kappa locus) and the 3’RR-BCL2 (Transgene containing BCL2 and a micro-3’RR), both containing the full BCL2 promoter region.
The return of the rings: evolutionary role of aromatic residues in liquid-liquid phase separation
Authors: Ho Wen-Lin , Huang Jie-rong
Published: October 2021

Aromatic residues appeared relatively late in the evolution of protein sequences. They stabilize the hydrophobic core of globular proteins and are typically absent from intrinsically disordered regions (IDRs). However, recent advances in protein liquid-liquid phase separation (LLPS) studies have shown that aromatic residues in IDRs often act as important “stickers”, promoting multivalent interactions and the formation of higher-order oligomers. To reconcile this apparent contradiction, we compared levels of sequence disorder in RNA binding proteins and the human proteome and found that aromatic residues appear more frequently than expected in the IDRs of RNA binding proteins, which are often found to undergo LLPS. Phylogenetic analysis shows that aromatic residues are highly conserved among chordates, highlighting their importance in LLPS-driven functional assembly. These results suggest therefore that aromatic residues have contributed twice to evolution: in stabilizing structured proteins and in the assembly of biomolecular condensates.
Large1 Gene Transfer in Older myd Mice with Severe Muscular Dystrophy Restores Muscle Function and Greatly Improves Survival
Authors: Yonekawa Takahiro , Rauckhorst Adam J. , El-Hattab Sara , Cuellar Marco A. , Venzke David , Anderson Mary E. , Okuma Hidehiko , Pewa Alvin D. , Taylor Eric B. , Campbell Kevin P.
Published: October 2021

Muscular dystrophy is a progressive and ultimately lethal neuromuscular disease due to lack of therapeutic options that restore muscle function. Gene editing and gene transfer hold great promise as therapies for various neuromuscular diseases when administered prior to the onset of severe clinical symptoms. However, the efficacy of these strategies for restoring neuromuscular function and improving survival in the late stages of muscular dystrophy with severe muscle pathophysiology is unknown. Dystroglycanopathies are muscular dystrophies characterized by extensive skeletal muscle degeneration and, in many cases, are accompanied by eye and brain abnormalities. Thus far, mutations in at least eighteen human genes are known to cause dystroglycanopathies, including those in the like-acetylglucosaminyltransferase-1 (LARGE1) gene. LARGE1 encodes a xylosyl- and glucuronosyltransferase that modifies α-dystroglycan (α-DG) with matriglycan, a linear repeating disaccharide of alternating xylose and glucuronic acid that binds to the laminin G-like domains of extracellular matrix proteins with high affinity. Largemyd/Largemyd (myd) mice lack expression of Large1, and exhibit severe skeletal muscle pathophysiology, impaired mobility, and a drastically reduced lifespan (50% survivorship at 35 weeks of age). Here, we show that systemic delivery of AAV2/9 CMV Large1 (AAVLarge1) in >34-week-old myd mice with advanced disease restores matriglycan expression, attenuates skeletal muscle pathophysiology, improves motor and respiratory function, and normalizes systemic metabolism, which collectively and dramatically extends survival. Our results demonstrate that in a mouse model of muscular dystrophy, skeletal muscle function can be restored, illustrating its remarkable plasticity, and that survival can be greatly improved even after the onset of severe skeletal muscle pathophysiology.
Crystal structures of glycogen-debranching enzyme mutants in complex with oligosaccharides
Authors: Shen Miaomiao , Gong Xiaoxin , Xiang Song
Published: October 2021

Debranching is a critical step in the mobilization of the important energy store glycogen. In eukaryotes, including fungi and animals, the highly conserved glycogen-debranching enzyme (GDE) debranches glycogen by a glucanotransferase (GT) reaction followed by a glucosidase (GC) reaction. Previous work indicated that these reactions are catalyzed by two active sites located more than 50 Å apart and provided insights into their catalytic mechanisms and substrate recognition. Here, five crystal structures of GDE in complex with oligosaccharides with 4–9 glucose residues are presented. The data suggest that the glycogen main chain plays a critical role in binding to the GT and GC active sites of GDE and that a minimum of five main-chain residues are required for optimal binding.
Vanishing of the atomic form factor derivatives in non-spherical structural refinement – a key approximation scrutinized in the case of Hirshfeld atom refinement
Authors: Midgley Laura , Bourhis Luc J. , Dolomanov Oleg V. , Grabowsky Simon , Kleemiss Florian , Puschmann Horst , Peyerimhoff Norbert
Published: October 2021

When calculating derivatives of structure factors, there is one particular term (the derivatives of the atomic form factors) that will always be zero in the case of tabulated spherical atomic form factors. What happens if the form factors are non-spherical? The assumption that this particular term is very close to zero is generally made in non-spherical refinements (for example, implementations of Hirshfeld atom refinement or transferable aspherical atom models), unless the form factors are refinable parameters (for example multipole modelling). To evaluate this general approximation for one specific method, a numerical differentiation was implemented within the NoSpherA2 framework to calculate the derivatives of the structure factors in a Hirshfeld atom refinement directly as accurately as possible, thus bypassing the approximation altogether. Comparing wR
2 factors and atomic parameters, along with their uncertainties from the approximate and numerically differentiating refinements, it turns out that the impact of this approximation on the final crystallographic model is indeed negligible.
(E)-3-(3-Methylthiophen-2-yl)-1-p-tolylprop-2-en-1-one. Corrigendum
Authors: Naveen S. , Al-Maqtari Helmi Mohammed , Jamalis Joazaizulfazli , Sirat Hasnah Mohd , Lokanath N. K. , Abdoh Muneer
Published: October 2021

In the paper by Naveen et al. [IUCrData (2017), 2, x170234], there was an error in the name of one of the authors.
Pyrazine-2(1H)-thione
Authors: Olszewski Adrian , Wzgarda-Raj Kinga
Published: October 2021

The title compound, C4H4N2S, was obtained by the reduction of 2-mercaptopyrazine (during its crystallization with 2-mercaptopyrazine and isonicotinic acid N-oxide in ethanol solution. It crystallizes in the monoclinic space group P21/m. In the crystal, the molecules are linked by N—H...N and C—H...S hydrogen bonds.
Pandemic, risk-adaptation and household saving: evidence from China
Authors: Zhang Yixing , Lu Xiaomeng , Yin Haitao , Zhao Rui
Published: October 2021

Purpose

Scholars have not agreed with each other on how people would behave after experiencing a catastrophic event. They could save more as a precautionary action for future difficulties or save less with a carpe diem attitude. This study aims to attempt to shed light on this debate with empirical observations on how the Covid-19 pandemic has affected household saving decisions.

Design/methodology/approach

The two waves of the survey data allowed us to investigate both instantaneous and ongoing effects of Covid-19 on household saving decisions. The instantaneous effect refers to the immediate impact of the crisis, while the ongoing effect refers to the lasting impact of the pandemic when economic recovery had started. The variation in the number of confirmed cases across cities during the two waves provides the source of power for identification. The authors extend their analyses of the impact of Covid-19 on the household saving decision by using ordinary least squares models. Due to the ordered nature of survey responses, the authors also rerun all baseline models using the ordered probit regression method.

Findings

This paper studied the impact of the Covid-19 pandemic on household saving decisions in China. This study found that households in the most affected cities would save more during the Covid-19 but tend to save less when the disaster started fading away. Combining findings in Kun et al. (2013) and Filipski et al. (2015), people do become more pessimistic during and after the Covid-19, possibly driving their observed precautionary and cape diem behaviors during the two points of time. Heterogeneity analysis shows that specific households would dramatically change their saving behavior. These observations might be useful for policymakers who concern the economic recovery after this pandemic disaster.

Originality/value

Understanding how the Covid-19 pandemic would affect household consumption vs saving decisions is important for the economic recovery after this disaster comes to an end. The analyses presented in this research could be useful for policymakers who concern appropriate policies aiming to boost consumption and economic activities after Covid.
Disaster conversations: intersecting perspectives on cross-cultural disaster research
Authors: Goodall Susie , Khalid Zainab , Del Pinto Monia
Published: October 2021

Purpose

This paper aims to demonstrate the importance of conversation among disaster studies researchers who may be positioned at times and to varying degrees as both insiders and outsiders in relation to the contexts in which they work. Three key questions are explored: how we identify with and relate to people in our study areas, who we do research for and what this means for knowledge creation and research practice.

Design/methodology/approach

Prompted by the Power Prestige and Forgotten Values manifesto (2019), the authors conversed with one another by email and video call, asking questions that triggered reflection. The emerging themes informed the key questions and the structure of the paper. The authors write with three individual voices to highlight the element of dialogue and our different experiences.

Findings

Sharing in depth with other researchers from different cultural and disciplinary backgrounds created space to both listen and find a voice. Emerging themes were positionality, how knowledge is used and implications for research practice. Researchers are part of a living system with the potential to serve, exploit or damage. Knowledge is generated at multiple scales, and we can act as a bridge between people and policymakers, using networks.

Practical implications

The authors remain open and unbiased to “new” local/contextual knowledge, adopting the attitude of a learner. Knowledge creation should focus on pragmatic outcomes such as informing emergency planning.

Originality/value

A novel dialogical approach is used to demonstrate the value of conversation among researchers from different backgrounds that enables them to question and challenge each other in a supportive environment. This leads to deeper understanding of our role as cross-cultural researchers and reveals unifying questions and implications for research practice.
Communitarian norms and employee performance management in Africa
Authors: Natukunda Loice
Published: October 2021

Purpose

The paper aims to critically evaluate the day-to-day processes of employee performance management and control (EPMC) in an African-based organization and sheds light on formal and informal management controls, social relations and worker responses.

Design/methodology/approach

The paper draws on research undertaken within an Ugandan-based agricultural research organization. A case study approach was used to facilitate an understanding of everyday organizational practices and context. The paper uses ethnographic research and grounded theory, with methods including interviews and observation of work practices.

Findings

The findings provide a nuanced understanding of how performance management and control plays out in practice and show that the unquestioning imposition of Western practices that ignore traditional norms is unlikely to result in desired outcomes.

Research limitations/implications

Since the paper took on a cross-sectional study, a longitudinal study might reveal whether and how the values of managers and employees in Africa-based organizations change over time.

Practical implications

The study's findings indicate the need for a more critical examination of EPMC that takes account of employee attitudes, behaviors and social relations at the intersection of both the formal and informal organization.

Originality/value

Although cultural and institutional approaches have been used to evaluate human resource management (HRM) practices in Africa, organizational behavior approaches to performance and control at the micro-level had been underexplored.
Components of psychosocial health
Authors: Husain Waqar
Published: October 2021

Purpose

“Psychosocial health” is a new term to comprehend the already established factors involved in mental health and psychological well-being. The term has not been specifically defined and explained within the framework of psychology.

Design/methodology/approach

The study proposed and validated a new model of psychosocial health. Principal component analysis, exploratory factor analysis and confirmatory factor analysis were conducted by involving a total of 4,086 participants.

Findings

Psychosocial health was interpreted as the “sexual, emotional, social, environmental, cognitive, religious, moral and spiritual satisfaction” of a person. The proposed model of psychosocial health was statistically validated. The additional findings revealed significantly higher levels of psychosocial health in women and significant inverse correlations between psychosocial health and age.

Originality/value

The current paper provided a comprehensive picture of psychosocial health from a psychological perspective and presented a statistically reliable tool for measuring psychosocial health.
Improving service brand personality with augmented reality marketing
Authors: Plotkina Daria , Dinsmore John , Racat Margot
Published: October 2021

Purpose

Augmented reality (AR) apps offer a great opportunity for brands to provide better service to customers by creating augmented customer service. However, not every AR app is equally effective in improving customer experience. Investigation of underlying processes and brand-related outcomes of AR marketing remains scarce and it is unclear how different types of AR apps influence brand perceptions, such as brand personality. This paper aims to fill in this knowledge gap and provide practical insights on how different AR apps can improve service brand personality.

Design/methodology/approach

Using an experimental plan, the authors investigate how attitudes towards AR apps contribute to customer perceptions of brand personality (i.e. excitement, sincerity, competence and sophistication) according to two different variables, namely, the location of the AR app (location-specific vs non-location-specific) and its orientation (augmenting the product, brand or store experience). The authors also examine the effect of expected customer experience with the AR app (i.e. playfulness and pleasure) and customer technological innovativeness and shopping orientation as predictors of attitudes towards the AR app.

Findings

The findings show that non-location-specific and product-oriented AR apps (i.e. virtual try-on apps) receive more positive evaluations and lead consumers to perceive the brand as more exciting, sincere, competent and sophisticated. Moreover, the playfulness and pleasure experienced with the AR app determine consumers’ attitudes towards the app. Additionally, AR apps improve brand personality perceptions amongst more innovative and adventure-focussed shoppers.

Originality/value

The authors show that brand announcements on high-technology, customer-oriented service offerings are an effective branding tool. Thus, AR apps perceived as pleasant and playful can signal and improve brand personality.
Transportation connectivity strategies and regional tourism economy - empirical analysis of 153 cities in China
Authors: Chen Juan , Li Mingwei , Xie Chen
Published: October 2021

Purpose

A transportation connectivity strategy is a crucial part of an adaptive, congruent and sustainable tourism transportation system and is of concern to countries focusing on growing their tourism economy. This study aims to gain a better understanding of the relationship between transportation connectivity and the tourism economy through a configuration analysis.

Design/methodology/approach

This study uses fuzzy-set qualitative comparative analysis on a sample of 153 cities in China to provide an understanding of the impacts of transportation connectivity strategies, with the co-effecting factors of socio-economic status, tourism resource endowment and hospitality capacity, on the development of regional tourism economies.

Findings

There are multiple paths that lead to regional tourism economic development (a high level of tourist arrivals or a high level of tourism revenue). High-speed rail can play a supportive role, while air travel or traditional rail remains central to the tourism economy. Socio-economic status (i.e. city size and city gross domestic product) and hospitality capacity are identified as crucial influencers for the development of the tourism economy.

Research limitations/implications

This study confirms the validity of deploying configuration analysis (based on the equifinality theory) to establish the relationship between transportation and the tourism economy. The finding of more than one configuration led to a new consensus on how multiple factors influence the tourism economy.

Practical implications

Suggestions on transportation connectivity strategies for different regions are provided.

Originality/value

This study demonstrates the need to place greater emphasis on configurations that lead to tourism economy development instead of the effect of a single transportation mode.
CEO's age and acquisition behaviors of REITs
Authors: Zhang Fan , Ooi Joseph T. L.
Published: October 2021

This paper examines how the investment activities of REITs are affected by the age of their CEOs. Tracking the property acquisition activities of 150 REIT CEOs between 1974 and 2017, we find robust evidence of younger CEOs engaging more frequently and spending more monies on property acquisitions. Our results are consistent with younger CEOs being motivated to acquire aggressively to signal their ability to the market. However, due to reputation and career concerns, younger CEOs tend to hedge their acquisition decisions by preferring local assets and following the herd mentality. Older CEOs may engage less frequently in property acquisitions, but this is not attributed to them slowing down. On the contrary, older CEOs appear to be more confident to venture into new and out‐of‐state markets and to engage in out‐of‐wave acquisitions.
Potential usefulness of otoscopy in the evaluation of hanging deaths: A report of two cases
Authors: Wankhede Ashesh Gunwantrao
Published: October 2021

The significance of examination of the tympanic membrane (TM) has been previously reported in cases of strangulation, traumatic asphyxia, and drowning. We report otoscopic findings in two victims of suicidal hanging, including hemotympanum, bleeding from superficial vessels of the TM, perforation of the TM, and gross bulging of the pars‐tensa with a bluish hue. These two cases also show petechial hemorrhages in the TM, which is a previously reported finding in cases of hanging. Postmortem otoscopic examination of victims of hanging may provide information useful in the determination of vitality of hanging.
Multi‐Scale Hydrologic Evaluation of the National Water Model Streamflow Data Assimilation
Authors: Seo Bong‐Chul , Krajewski Witold F. , Quintero Felipe
Published: October 2021

Streamflow predictions derived from a hydrologic model are subjected to many sources of errors, including uncertainties in meteorological inputs, representation of physical processes, and model parameters. To reduce the effects of these uncertainties and thus improve the accuracy of model prediction, the United States (U.S.) National Water Model (NWM) incorporates streamflow observations in the modeling framework and updates model‐simulated values using the observed ones. This updating procedure is called streamflow data assimilation (DA). This study evaluates the prediction performance of streamflow DA realized in the NWM. We implemented the model using WRF‐Hydro® with the NWM modeling elements and assimilated 15‐min streamflow data into the model, observed during 2016–2018 at 140 U.S. Geological Survey stream gauge stations in Iowa. In its current DA scheme, known as “nudging,” the assimilation effect is propagated downstream only, which allows us to assess the performance of streamflow predictions generated at 70 downstream stations in the study domain. These 70 locations cover basins of a range of scales, thus enabling a multi‐scale hydrologic evaluation by inspecting annual total volume, peak discharge magnitude and timing, and an overall performance indicator represented by the Kling–Gupta efficiency. The evaluation results show that DA improves the prediction skill significantly, compared to open‐loop simulation, and the improvements increase with areal coverage of upstream assimilation points.
Dissecting the salt tolerance potential of cowpea genotypes based on morpho‐physiology and yield‐related attributes
Authors: Akter Mafuza , Mahmud Apple , Akter Munny , Siddiqui Md. Nurealam , Khan Md. Arifur Rahman
Published: October 2021

High salinity is a critical environmental menace hampering crop growth and productivity worldwide. Therefore, dissecting the salt tolerance potentials and identifying resilient genotypes are crucial to secure sustainable crop production. In this study, we explored the salt resistance potentials of three advanced cowpea lines including one check variety exposed to different salinity levels (0, 50 and 100 mM of natural saline water) by quantifying their growth, physiology and yield‐related attributes. Our results implied that salt‐stress resulted in a significant reduction in the morphological, physiological and yield attributes at both 40 and 60 days after sowing when compared to non‐stress plants. Interestingly, we noticed that one of the latest cowpea genotypes (BU‐C‐Acc‐3) sustained better performances in terms of growth, physiology and yield‐related characters at both 50 and 100 mM salt treatments, while other genotypes exhibited varying levels of salt responses. Further, a multivariate analysis showcased that genotype ‘BU‐C‐Acc‐3’ acquired a combination of physiological and yield contributing responses that ultimately induced a higher level of resistance and grain yield. Collectively, our study offers some contrasting genotypes which could be incorporated in current cowpea breeding programmes to improve grain yield and salt tolerance using conventional as well as molecular breeding tools.
A leader in need is a leader indeed? The influence of leaders' stress mindset on their perception of employee well‐being and their intended leadership behavior
Authors: Kaluza Antonia J. , Junker Nina M. , Schuh Sebastian C. , Raesch Pauline , von Rooy Nathalie K. , van Dick Rolf
Published: October 2021

The ability to respond appropriately to employees' work‐related well‐being requires leaders to pay attention to their employees' well‐being in the first place. We propose that leaders' stress mindset, that is, the belief that stress is enhancing versus debilitating, may bias their perception of employees' well‐being. We further propose that this judgment then influences leaders' intention to engage in or refrain from health‐oriented leadership behavior, to express higher performance expectations, or to promote their employees. We expect this process to be stronger if leaders strongly identify with their team, increasing their perceived similarity with their employees. In three experiments (N1 = 198, N2 = 292, N3 = 250), we tested the effect of participants' stress mindset on their intention to show certain leadership behaviors, mediated by their perception of employee well‐being (emotional exhaustion, somatic symptoms, work engagement) and moderated by their team identification. Our findings largely support the association between stress mindset and the perception of well‐being. The results for the proposed mediation and the moderating function of identification were mixed. Overall, the results emphasize the critical role of leaders' stress mindset and may, thus, improve health promotion in organizations by helping leaders to adequately recognize employees' well‐being and respond appropriately.
Review article: insights into the bile acid‐gut microbiota axis in intestinal failure‐associated liver disease—redefining the treatment approach
Authors: Wang Yaoxuan , Zheng Lei , Zhou Zhiyuan , Yao Danhua , Huang Yuhua , Liu Bin , Duan Yantao , Li Yousheng
Published: October 2021

Background

Intestinal failure‐associated liver disease (IFALD) increases mortality of patients with intestinal failure (IF), but lacks effective prevention or treatment approaches. Bile acids, gut microbiota and the host have close and complex interactions, which play a central role in modulating host immune and metabolic homeostasis. Increasing evidence suggests that derangement of the bile acid‐gut microbiota (BA‐GM) axis contributes to the development of IFALD.

Aims

To review the BA‐GM axis in the pathogenesis and clinical applications of IFALD, and to explore future directions for effective disease management.

Methods

We conducted a literature search on bile acid and gut microbiota in IF and liver diseases.

Results

The BA‐GM axis demonstrates a unique IF signature manifesting as an increase in primary‐to‐secondary bile acids ratio, disturbed enterohepatic circulation, blunted bile acid signalling pathways, gut microbial dysbiosis, and altered microbial metabolic outputs. Bile acids and gut microbiota shape the compositional and functional alterations of each other in IF; collaboratively, they promote immune dysfunction and metabolic aberration in the liver. Diagnostic markers and treatments targeting the BA‐GM axis showed promising potential in the management of IFALD.

Conclusions

Bile acids and gut microbiota play a central role in the development of IFALD and make attractive biomarkers as well as therapeutic targets. A multitarget, individualised therapy aiming at different parts of the BA‐GM axis may provide optimal clinical benefits and requires future investigation.
Surgery, cancer and mortality among patients with ulcerative colitis diagnosed 1962‐1987 and followed until 2017 in a Danish population‐based inception cohort
Authors: Burisch Johan , Lophaven Søren , Munkholm Pia , Langholz Ebbe
Published: October 2021

Background

Long‐term data on the natural disease course of unselected patients with ulcerative colitis (UC) are limited.

Aims

To determine the long‐term course and prognosis of UC, including patients’ risks of surgery, cancer and mortality, in a population‐based cohort followed for over 50 years

Methods

All incident patients with UC diagnosed between 1962 and 1987 in Copenhagen County, Denmark were included in a population‐based cohort. We extracted information about IBD‐related surgeries, cancers and mortality from patient files from 1962 to 1987, and from the Danish National Patient Registry, Cancer Registry, and Register of Causes of Death during 1988‐2017. Patients were matched with up to 50 individuals from the general population.

Results

We followed 1161 patients for a median of 34 years (range: 0.1‐56.0). Median age at diagnosis was 33 years (range: 2‐88). The cumulative probability of colectomy 10, 20, 30, 40 and 50 years after diagnosis was 22% (95% CI: 20%‐25%), 27% (95% CI: 25%‐30%), 31% (95% CI: 28%‐34%), 34% (95% CI: 31%‐37%), and 40% (95% CI: 36%‐44%), respectively. The risk of small intestinal, colon, rectal and anal cancer was higher than among controls, as was cancer of the skin, pancreas and thyroid. All‐cause mortality was lower than controls (adjusted RR: 0.90, 95% CI: 0.82‐0.99).

Conclusion

In this population‐based cohort of UC patients diagnosed between 1962 and 1987, 40% underwent colectomy within 50 years of diagnosis. Physicians need to be aware that UC patients are at increased risk of intestinal and extra‐intestinal cancers. However, UC patients’ risk of mortality is comparable to that of the background population.
Characteristics of various fibrolytic isozyme activities in the rumen microbial communities of Japanese Black and Holstein Friesian cattle under different conditions
Authors: Takizawa Shuhei , Asano Ryoki , Fukuda Yasuhiro , Baba Yasunori , Tada Chika , Nakai Yutaka
Published: October 2021

Rumen microorganisms produce various fibrolytic enzymes and degrade lignocellulosic materials into nutrient sources for ruminants; therefore, the characterization of fibrolytic enzymes contributing to the polysaccharide degradation in the rumen microbiota is important for efficient animal production. This study characterized the fibrolytic isozyme activities of a rumen microbiota from four groups of housed cattle (1, breeding Japanese Black; 2, feedlot Japanese Black; 3, lactating Holstein Friesian; 4, dry Holstein Friesian). Rumen fluids in all cattle groups showed similar concentrations of total volatile fatty acids and reducing sugars, whereas acetic acid contents and pH were different among them. Predominant genera were commonly detected in all cattle, although the bacterial compositions were different among cattle groups. Zymograms of whole proteins in rumen fluids showed endoglucanase activities at 55 and 57 kDa and xylanase activity at 44 kDa in all cattle. Meanwhile, several fibrolytic isozyme activities differed among cattle groups and individuals. Treponema, Succinivibrio, Anaeroplasma, Succiniclasticum, Ruminococcus, and Butyrivibrio showed positive correlations with fibrolytic isozyme activities. Further, endoglucanase activity at 68 kDa was positively correlated with pH. This study suggests the characteristics of fibrolytic isozyme activities and their correlations with the rumen microbiota.
Immunogenicity and safety of the BNT162b2 mRNA COVID‐19 vaccine in haematopoietic stem cell transplantation recipients
Authors: Shem‐Tov Noga , Yerushalmi Ronit , Danylesko Ivetta , Litachevsky Vladislav , Levy Itzchak , Olmer Liraz , Lusitg Yaniv , Avigdor Abraham , Nagler Arnon , Shimoni Avichai , Rahav Galia
Published: October 2021

The immunogenicity and safety of Pfizer‐BioNTech BNT162b2 mRNA vaccine in allogeneic haematopoietic stem cell transplantation (HSCT) recipients are unknown. We prospectively followed 152 HSCT recipients who were at least six months following transplantation and with no active acute graft‐versus‐host disease (GVHD). Blood samples were taken 2–4 weeks after the second vaccination and analyzed for receptor‐binding domain (RBD) antibodies and neutralizing antibodies (NA). 272 immunocompetent healthcare workers served as controls. At a median of 28 days after the second vaccination, 118 patients (77·6%) developed RBD immunoglobulin G (IgG) with a geometric mean titre (GMT) of 2·61 [95% CI (confidence interval), 2·16–3·16]. In the control group 269/272 (98·9%) developed RBD IgG, with a GMT of 5·98 (95% CI 5·70–6·28), P < 0·0001. The GMT of NA in HSCT recipients and controls was 116·0 (95% CI 76·5–175·9), and 427·9 (95% CI 354·3–516·7) respectively (P < 0001). Multivariate logistic regression analysis revealed that HSCT recipients with no chronic GVHD and no immunosuppressive therapy at the time of vaccination had significantly higher levels of NA following the second vaccination. Adverse events were minimal and were less common than in healthy controls. In conclusion; the BNT162b2 mRNA vaccination is safe and effective in HSCT recipients, especially those who are immunosuppression‐free. A significant fraction developed protecting NA.
Calycosin ameliorates atherosclerosis by enhancing autophagy via regulating the interaction between KLF2 and MLKL in apolipoprotein E gene‐deleted mice
Authors: Ma Chuanrui , Wu Han , Yang Guangyan , Xiang Jiaqing , Feng Ke , Zhang Jing , Hua Yunqing , Kang Lin , Fan Guanwei , Yang Shu
Published: October 2021

Background and Purpose

Atherosclerosis is one of the underlying causes of cardiovascular disease. Formation of foam cells and necrotic core in the plaque is a hallmark of atherosclerosis, which results from lipid deposition, apoptosis, and inflammation in macrophages. Macrophage autophagy is a critical anti‐atherogenic process and defective autophagy aggravates atherosclerosis by enhancing foam cell formation, apoptosis, and inflammation. Hence, enhancing autophagy can be a strategy for atherosclerosis treatment. Calycosin, a flavonoid from Radix Astragali, displays anti‐oxidant and anti‐inflammatory activities and therefore is potential to reduce the risk of cardiovascular disease. However, the anti‐atherogenic effect of calycosin and the involved mechanism remains unclear. In this study, we assessed the potential benefits of calycosin on autophagy and atherosclerosis, and revealed the underlying mechanism.

Experimental Approach

In this study, apoE−/− mice were fed high‐fat diet for 16 weeks in the presence of calycosin and/or autophagy inhibitor chloroquine, which was followed by determination of atherosclerosis development, autophagy activity, and involved mechanisms.

Key Results

Calycosin protected against atherosclerosis and enhanced plaque stability via promoting autophagy. Calycosin inhibited foam cell formation, inflammation, and apoptosis by enhancing autophagy. MLKL was demonstrated as a new autophagy regulator, which can be negatively regulated by KLF2. Mechanistically, inhibitory effects of calycosin on atherogenesis were via improved autophagy through KLF2‐MLKL signalling pathway modulation.

Conclusions and Implications

This study demonstrated the atheroprotective effect of calycosin was through upregulating KLF2‐MLKL‐mediated autophagy, which not only proposed novel mechanistic insights into t atherogenesis but also identified calycosin as a potential drug candidate for atherosclerosis treatment.
Stemness and immune evasion conferred by the TDO2‐AHR pathway are associated with liver metastasis of colon cancer
Authors: Miyazaki Toshiaki , Chung Suyoun , Sakai Hiroaki , Ohata Hirokazu , Obata Yuuki , Shiokawa Daisuke , Mizoguchi Yukihiro , Kubo Takashi , Ichikawa Hitoshi , Taniguchi Hirokazu , Aoki Kazunori , Soga Tomoyoshi , Nakagama Hitoshi , Okamoto Koji
Published: October 2021

The aryl hydrocarbon receptor (AHR) pathway modulates the immune system in response to kynurenine, an endogenous tryptophan metabolite. IDO1 and TDO2 catalyze kynurenine production, which promotes cancer progression by compromising host immunosurveillance. However, it is unclear whether the AHR activation regulates the malignant traits of cancer such as metastatic capability or cancer stemness. Here, we carried out systematic analyses of metabolites in patient‐derived colorectal cancer spheroids and identified high levels of kynurenine and TDO2 that were positively associated with liver metastasis. In a mouse colon cancer model, TDO2 expression substantially enhanced liver metastasis, induced AHR‐mediated PD‐L1 transactivation, and dampened immune responses; these changes were all abolished by PD‐L1 knockout. In patient‐derived cancer spheroids, TDO2 or AHR activity was required for not only the expression of PD‐L1, but also for cancer stem cell (CSC)‐related characteristics and Wnt signaling. TDO2 was coexpressed with both PD‐L1 and nuclear β‐catenin in colon xenograft tumors, and the coexpression of TDO2 and PD‐L1 was observed in clinical colon cancer specimens. Thus, our data indicate that the activation of the TDO2‐kynurenine‐AHR pathway facilitates liver metastasis of colon cancer via PD‐L1–mediated immune evasion and maintenance of stemness.
A call to embrace jural dualism
Authors: Diesel Jonathon , Klein Daniel B
Published: October 2021

This article explores concepts under a rubric termed ‘jural’, the meaning of which is differentiated from ‘legal’. Within the conceptualisation of the modern nation state, there are two categories of jural relationships. In the first, both parties have equal jural standing (equal–equal), as between neighbours. In the second jural relationship (superior–inferior), one party has standing as a special jural player, essentially the governor. The jural superior wields the coercive powers of government. Human beings, we argue, are predisposed to folding this jural superior back into the equal–equal relationship, thus notionally collapsing two relationships back to one, or collapsing from jural dualism into jural monism. Two varieties of the tendency stand out, namely collectivist thinking that sees government as a set of rules and arrangements arrived at voluntarily, and Rothbardian libertarianism that sees government as a criminal organisation and proposes its elimination. But, beyond those two varieties, we see traces and tinctures of the tendency towards jural monism. We call for a conscious embrace of jural dualism.
Economic complexity and poverty in developing countries
Authors: Gnangnon Sena Kimm
Published: October 2021

This article examines the effect of economic complexity on poverty in developing countries. It shows that greater economic complexity results in lower poverty headcount rates. This is particularly the case for countries that enjoy higher economic growth rates, lower levels of income inequality and lower degrees of economic growth volatility, including volatility due to smaller export demand and financial flows shocks. These findings have important policy implications for those developing countries that are exploring ways and means to recover from the current COVID‐19 pandemic crisis and to prepare for future crises.
What can we learn from the United Kingdom’s post‐1945 economic reforms?
Authors: Crafts Nicholas
Published: October 2021

This article reviews the claim that economic policymakers in the post‐COVID UK should learn the lessons of the 1940s. Post‐1945 policies relating to delivering full employment, levelling up, upgrading social security, dealing with the public debt legacy, and addressing the productivity puzzle are considered. The article finds many reasons to criticise the policies of the 1940s. Although, superficially, outcomes look good, a closer examination reveals significant failings notably concerning design of the welfare state and supply‐side policy for growth. The 1940s do not provide a good way to address the productivity slowdown or twenty‐first‐century social insurance.
The effect of kidney transplantation on left ventricular remodeling and global diastolic strain rate in end‐stage renal disease
Authors: Lassen Mats Christian Højbjerg , Qasim Atif , Webber Allison , Gao Ying , Biering‐Sørensen Tor , Park Meyeon
Published: October 2021

Background

Diastolic dysfunction is an early marker of cardiac pathology in end‐stage kidney disease (ESKD) patients. The ratio of transmitral filling velocity (E) to early diastolic strain rate (E/e'sr) is a novel non‐invasive marker of early left ventricular (LV) filling pressure obtained using two‐dimensional speckle tracking echocardiography (2DSTE).

Methods

In a prospective cohort of kidney transplant (KTX) recipients with echocardiograms performed pre‐transplant we obtained repeat echocardiograms at 6 months following transplant. All echocardiograms were analyzed using 2DSTE where E/e'sr and global longitudinal strain were obtained. Paired tests were used to assess changes to cardiac structure and function following KTX.

Results

A total of 33 patients were included in the study (mean age was 46.6 ± 13.7 years and 42% were males). The primary causes of ESKD in the cohort were glomerular disease (33%), hypertension (30%), and polycystic kidney disease (12%). The median (IQR) time spent on dialysis was 5.4 years [2.9, 7.7 years]. A reverse remodeling of the LV was observed following KTX as LV mass decreased (189.2 ± 57.5 g vs 171.1 ± 56.8 g, P = 0.014). LV filling pressure decreased as assessed by E/e'sr (103.7 ± 51.1 cm vs 72.6 ± 35.5 cm, P = 0.009). E to early diastolic mitral annular tissue velocity (E/e’) did not change following KTX (9.9 ± 4.5 vs 10.3 ± 4.1, P = 0.54). Additionally, both LV internal diastolic and systolic diameter decreased significantly.

Conclusion

Reverse cardiac remodeling following KTX was observed as improvements in LV mass and LV dimensions. LV filling pressure improved as assessed by E/e'sr decreased following KTX, whereas E/e’ did not change.
An unusual case of mitral valve chordal rupture
Authors: Lillo Rosa , Ingrasciotta Gessica , Locorotondo Gabriella , Lombardo Antonella , Graziani Francesca
Published: October 2021

In this report, we present a rare case of severe mitral regurgitation due to isolated mitral valve chordal rupture without valve leaflet prolapse in a patient with Fabry cardiomyopathy. This finding could be due to subvalvular apparatus storage of glycosphingolipids rather than fibro‐elastic deficiency, underlying how close cardiological follow‐up of Fabry patients must be comprehensive and not only focused on left ventricular hypertrophy and arrhythmias.
The role of metabolic syndrome in sudden cardiac death risk: Recent evidence and future directions
Authors: Tirandi Amedeo , Carbone Federico , Montecucco Fabrizio , Liberale Luca
Published: October 2021

Metabolic syndrome (MetS) is a frequent condition whose deleterious effects on the cardiovascular system are often underestimated. MetS is nowadays considered a real pandemic with an estimated prevalence of 25% in general population. Individuals with MetS are at high risk of sudden cardiac death (SCD) as this condition accounts for 50% of all cardiac deaths in such a population. Of interest, recent studies demonstrated that individuals with MetS show 70% increased risk of SCD even without previous history of coronary heart disease (CHD). However, little is known about the interplay between the two conditions. MetS is a complex disease determined by genetic predisposition, unhealthy lifestyle and ageing with deleterious effects on different organs. MetS components trigger a systemic chronic low‐grade pro‐inflammatory state, associated with excess of sympathetic activity, cardiac hypertrophy, arrhythmias and atherosclerosis. Thus, MetS has an important burden on the cardiovascular system as demonstrated by both preclinical and clinical evidence. The aim of this review is to summarize recent evidence concerning the association between MetS and SCD, showing possible common aetiological processes, and to indicate prospective for future studies and therapeutic targets.