bluuebunny/crossref_metadata_2025 huggingface dataset:
Oligometastatic disease from differentiated thyroid cancer: best treatment schemes
Authors: Colombo Elena , Ottini Arianna , Licitra Lisa
Published: December 2022

Purpose of review

Patients with slowly progressive and/or symptomatic oligometastatic radioactive iodine refractory (RAIR) differentiated thyroid carcinomas (DTCs) are candidates to receive locoregional treatment to delay the start of systemic therapy with multikinase inhibitors. Information provided by the recent literature has not been extensively reviewed in previous published works, thus we aim to bridge this gap.

Recent findings

We present for each metastatic site the different locoregional treatment options, contraindications and potential adverse events. Some techniques can be combined together, whereas others are discouraged in certain situations, requiring a high level of expertise and multidisciplinarity in the treatment algorithm.

Different techniques of radiation therapy and interventional radiology allow to control the metastatic spread. However, as no clinical trials are available to compare the treatment schemes in terms of safety and potential impact on the prognosis, the most appropriate option for each patient should be selected within a multidisciplinary decision making, taking into account the clinical conditions and the pattern/rapidity of metastatic disease.
Post-COVID-19 syndrome in a sample of climacteric women living in Latin America
Authors: Blümel Juan Enrique , Vallejo María Soledad , Bencosme Ascanio , Calle Andrés , Dextre Maribel , Díaz Karen , López Marcela , Miranda Carlos , Ñañez Mónica , Ojeda Eliana , Rey Claudia , Rodrigues Marcio Alexandre Hipólito , Salinas Carlos , Tserotas Konstantinos , Aedo Sócrates , Pérez-López Faustino R.
Published: December 2022

Objective

The aim of this study was to assess resilience, fear of COVID-19, sleep disorders, and menopause-related symptoms after the acute phase of COVID-19 in middle-aged women with positive reverse transcription-polymerase chain reaction and noninfected women.

Methods

This is a cross-sectional, analytical study of climacteric women from 9 Latin American countries, aged 40-64 years, attending a routine health checkup. We evaluated clinical characteristics and used the Connor-Davidson Resilience Scale, the Fear of COVID-19 Scale, the Jenkins Sleep Scale, and the Menopause Rating Scale to evaluate their health.

Results

A total of 1,238 women were studied, including 304 who were positive for COVID-19 reverse transcription-polymerase chain reaction. The median (interquartile range) age was 53 (12) years; years of studies, 16 (6); body mass index, 25.6 (5.1) kg/m2; and time since first COVID-19 symptom, 8 (6) months. COVID-19 patients reported fatigability (18.8%), joint and muscular discomfort (14.1%), and anosmia (9.5%). They had a significantly lower resilience score (26.87 ± 8.94 vs 29.94 ± 6.65), higher Fear of COVID-19 score (17.55 ± 7.44 vs 15.61 ± 6.34), and a higher Jenkins Scale score (6.10 ± 5.70 vs 5.09 ± 5.32) compared with control women. A logistic regression model confirmed these results. There was not a significant difference in the total Menopause Rating Scale score, although the odds ratios for both severe menopausal symptoms (1.34; 95% confidence interval, 1.02-1.76) and the use of hypnotics were higher in women with COVID-19 (1.80; 95% confidence interval, 1.29-2.50) compared with those without infection. We found no decrease in studied outcomes between the initial 7 months versus those reported after 8 to 18 months since first COVID-19 symptoms.

Conclusions

COVID-19 climacteric women have sleep disorders, lower resilience and higher fear of COVID-19.
Supply Issues in Nuclear Medicine
Authors: Jadvar Delara A. , Colletti Patrick M.
Published: December 2022

Issues related to the distribution and availability of supplies and personnel in nuclear medicine are well known and episodic. The combination of COVID-related restrictions and the unprecedented growth of our specialty have acutely exacerbated these supply and demand mismatches.
CircKlhl2 knockdown alleviates acute lung injury by regulating miR-29b-3p-mediated ROCK1 expression
Authors: Li Nan , Li Yuqiang , Wu Bin , Sun Rongli , Zhao Mingzhou , Hu Zhansheng
Published: December 2022

Background

Acute lung injury (ALI) induced by sepsis is distinguished by an inflammatory progression. Herein, we investigated the action of circular RNA kelch like family member 2 (circKlhl2) in sepsis-induced ALI.

Methods

The animal or cell model of sepsis-ALI was established by lipopolysaccharide (LPS) stimulation. The contents of circKlhl2, microRNA-29b-3p (miR-29b-3p), Rho associated coiled-coil containing protein kinase 1 (ROCK1), CyclinD1, B-cell lymphoma-2 (Bcl-2) and cleaved-caspase 3 (C-caspase3) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. Cell viability was assessed by Cell Counting Kit 8 (CCK8) assay. Cell cycle and apoptosis were evaluated by flow cytometry. The abundances of pro-inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Besides, the targeted relationship between miR-29b-3p and circKlhl2 or ROCK1 was verified by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay.

Results

Loss of circKlhl2 mitigated lung injury and pro-inflammatory cytokine expression in sepsis-ALI mice model and alleviated LPS-induced apoptosis and inflammatory response in MPVECs in vitro. The abundances of circKlhl2 and ROCK1 were boosted, while the miR-29b-3p level was diminished in the animal or cell model of sepsis-ALI. MiR-29b-3p inhibition abrogated circKlhl2 knockdown-mediated effects on MPVECs injury. Moreover, miR-29b-3p overexpression promoted cell proliferation and inhibited apoptosis and inflammation in LPS-treated MPVECs, while ROCK1 enhancement reversed these effects.

Conclusion

CircKlhl2 expedited the sepsis-induced acute lung injury by adjusting miR-29b-3p/ROCK1 axis.
SHORT-TERM INFLAMMATORY BIOMARKER PROFILES ARE ASSOCIATED WITH DEFICIENT MITOCHONDRIAL BIOENERGETICS IN LYMPHOCYTES OF SEPTIC SHOCK PATIENTS—A PROSPECTIVE COHORT STUDY
Authors: Nedel Wagner L. , Strogulski Nathan R. , Rodolphi Marcelo S. , Kopczynski Afonso , Montes Tiago H. M. , Portela Luis V.
Published: December 2022

Introduction: A biomarker strategy based on the quantification of an immune profile could provide a clinical understanding of the inflammatory state in patients with sepsis and its potential implications for the bioenergetic state of lymphocytes, whose metabolism is associated with altered outcomes in sepsis. The objective of this study is to investigate the association between mitochondrial respiratory states and inflammatory biomarkers in patients with septic shock. Methods: This prospective cohort study included patients with septic shock. Routine, complex I, complex II respiration, and biochemical coupling efficiency were measured to evaluate mitochondrial activity. We measured IL-1ß, IL-6, IL-10, total lymphocyte count, and C-reactive protein levels on days 1 and 3 of septic shock management as well as mitochondrial variables. The variability of these measurements was evaluated using delta counts (days 3–1 counts). Results: Sixty-four patients were included in this analysis. There was a negative correlation between complex II respiration and IL-1ß (Spearman ρ, −0.275; P = 0.028). Biochemical coupling efficiency at day 1 was negative correlated with IL-6: Spearman ρ, −0.247; P = 0.05. Delta complex II respiration was negatively correlated with delta IL-6 (Spearman ρ, −0.261; P = 0.042). Delta complex I respiration was negatively correlated with delta IL-6 (Spearman ρ, −0.346; P = 0.006), and delta routine respiration was also negatively correlated with both delta IL-10 (Spearman ρ, −0.257; P = 0.046) and delta IL-6 (Spearman ρ, −0.32; P = 0.012). Conclusions: The metabolic change observed in mitochondrial complex I and complex II of lymphocytes is associated with a decrease in IL-6 levels, which can signal a decrease in global inflammatory activity.
Prevalence and Characteristics of Patients with Median Arcuate Ligament Syndrome in a Cohort Diagnosed with Celiac Artery Compression
Authors: Kozhimala Meagan , Chan Shin Mei , Weininger Gabe , Sumpio Brandon J , Levine Louis J , Harris Sean , Zheng Sijin , Longo Walter E , Chaar Cassius Ochoa , Guzman Raul J , Sumpio Bauer E
Published: December 2022

Background:

Median arcuate ligament syndrome (MALS) is a frequent differential diagnosis in patients with post-prandial abdominal symptoms, but diagnosis remains challenging. The aim of this study was to identify characteristics of patients who had MALS compared to non-MALS patients amongst a cohort of patients diagnosed with celiac artery compression (CAC).

Study Design:

An IRB approved retrospective chart review (2000-2021) of patients at our institution with a discharge diagnosis of CAC was performed. Medical record review for clinical symptoms and findings consistent with MALS was performed.

Results:

293 patients with a diagnosis of CAC were identified. 59.7% were female and average age was 63.9 ± 20.2 years. 69 (23.5%) patients with CAC had MALS. There were no significant differences in sex or race between MALS and non-MALS patients, but MALS patients were younger (55.7 vs 68.1, p<0.001). There was no significant difference in gastrointestinal comorbidities between the two groups. Patients with MALS were less likely to have diabetes (12.5% vs. 26.9%), renal disease (4.6% vs 8.2%) and hypertension (41.5% vs. 70.3%), mesenteric atherosclerotic disease (14% vs 61.9%) and peripheral artery disease (15.0% vs 39.7%).

Conclusion:

We demonstrate a novel observation that MALS patients tend to have less atherosclerotic characteristics than non-MALS patients with CAC. Patients in our study with MALS were more likely to be younger, female, and presenting with epigastric pain. MALS patients had a significantly lower incidence of diabetes, hypertension, renal disease, mesenteric artery disease and peripheral arterial disease compared to the non-MALS group. An important clinically relevant feature of MALS patients may be their lack of atherosclerotic phenotype compared with non- MALS patients with CAC.
Biological control interventions reduce pest abundance and crop damage while maintaining natural enemies in sub-Saharan Africa: a meta-analysis
Authors: Ratto Fabrizia , Bruce Toby , Chipabika Gilson , Mwamakamba Sithembile , Mkandawire Rachel , Khan Zeyaur , Mkindi Angela , Pittchar Jimmy , Sallu Susannah M. , Whitfield Stephen , Wilson Kenneth , Sait Steven M.
Published: December 2022

Insect pests are a major challenge to smallholder crop production in sub-Saharan Africa (SSA), where access to synthetic pesticides, which are linked to environmental and health risks, is often limited. Biological control interventions could offer a sustainable solution, yet an understanding of their effectiveness is lacking. We used a meta-analysis approach to investigate the effectiveness of commonly used biocontrol interventions and botanical pesticides on pest abundance (PA), crop damage (CD), crop yield (Y) and natural enemy abundance (NEA) when compared with controls with no biocontrol and with synthetic pesticides. We also evaluated whether the magnitude of biocontrol effectiveness was affected by type of biocontrol intervention, crop type, pest taxon, farm type and landscape configuration. Overall, from 99 studies on 31 crops, we found that compared to no biocontrol, biocontrol interventions reduced PA by 63%, CD by over 50% and increased Y by over 60%. Compared to synthetic pesticides, biocontrol resulted in comparable PA and Y, while NEA was 43% greater. Our results also highlighted that the potential for biocontrol to be modulated by landscape configuration is a critical knowledge gap in SSA. We show that biocontrol represents an effective tool for smallholder farmers, which can maintain yields without associated negative pesticide effects. Furthermore, the evidence presented here advocates strongly for including biocontrol practices in national and regional agricultural policies.
Metabolic perturbations and key pathways associated with the antibacterial activity of Clitoria ternatea flower anthocyanin fraction against Escherichia coli
Authors: Jeyaraj Ethel Jeyaseela , Han Mei-Ling , Li Jian , Choo Wee Sim
Published: December 2022

Clitoria ternatea flowers are rich in anthocyanins and possess various biological activities. Specifically, the antibacterial mechanism of action of C. ternatea anthocyanins remains unknown and was investigated in Escherichia coli. Time-kill assay was used to assess the antibacterial activity and the metabolic perturbations in E. coli were investigated utilising LC-MS-based metabolomics. Pathway analyses were carried out for metabolites showing ≥ 2-fold changes. The anthocyanin fraction remarkably reduced the growth of E. coli at 4 h by 95.8 and 99.9% at minimum inhibitory concentration (MIC) and 2 × MIC, respectively. The antibacterial activity of the anthocyanin fraction (MIC) was shown to have perturbed glycerophospholipids (1-Acyl-sn-glycero-3-phosphoethanolamine, phosphatidylglycerol, diacylglycerol and cardiolipin), amino acids (valine, tyrosine and isoleucine) and energy (ubiquinone and NAD) metabolites at 1 and 4 h. This study demonstrated significant metabolic perturbations of the glycerophospholipid, amino acid and energy metabolism being the key pathways involved in the antibacterial activity of anthocyanins from C. ternatea and has promising potential as antibacterial agents for E. coli-related infections.
Genetic diversity of Staphylococcus aureus wall teichoic acid glycosyltransferases affects immune recognition
Authors: Tamminga Sara M. , Völpel Simon L. , Schipper Kim , Stehle Thilo , Pannekoek Yvonne , van Sorge Nina M.
Published: December 2022

Staphylococcus aureus

is a leading cause of skin and soft tissue infections and systemic infections. Wall teichoic acids (WTAs) are cell wall-anchored glycopolymers that are important for

S. aureus

nasal colonization, phage-mediated horizontal gene transfer, and antibiotic resistance. WTAs consist of a polymerized ribitol phosphate (RboP) chain that can be glycosylated with N-acetylglucosamine (GlcNAc) by three glycosyltransferases: TarS, TarM, and TarP. TarS and TarP modify WTA with β-linked GlcNAc at the C-4 (β1,4-GlcNAc) and the C-3 position (β1,3-GlcNAc) of the RboP subunit, respectively, whereas TarM modifies WTA with α-linked GlcNAc at the C-4 position (α1,4-GlcNAc). Importantly, these WTA glycosylation patterns impact immune recognition and clearance of

S. aureus

. Previous studies suggest that tarS is near-universally present within the

S. aureus

population, whereas a smaller proportion co-contain either tarM or tarP. To gain more insight into the presence and genetic variation of tarS, tarM and tarP in the

S. aureus

population, we analysed a collection of 25 652

S

.

aureus

genomes within the PubMLST database. Over 99 % of isolates contained tarS. Co-presence of tarS/tarM or tarS/tarP occurred in 37 and 7 % of isolates, respectively, and was associated with specific

S. aureus

clonal complexes. We also identified 26 isolates (0.1 %) that contained all three glycosyltransferase genes. At sequence level, we identified tar alleles with amino acid substitutions in critical enzymatic residues or with premature stop codons. Several tar variants were expressed in a S. aureus tar-negative strain. Analysis using specific monoclonal antibodies and human langerin showed that WTA glycosylation was severely attenuated or absent. Overall, our data provide a broad overview of the genetic diversity of the three WTA glycosyltransferases in the

S. aureus

population and the functional consequences for immune recognition.
Increased migratory/activated CD8+ T cell and low avidity SARS-CoV-2 reactive cellular response in post-acute COVID-19 syndrome
Authors: Paniskaki Krystallenia , Konik Margarethe J. , Anft Moritz , Heidecke Harald , Meister Toni L. , Pfaender Stephanie , Krawczyk Adalbert , Zettler Markus , Jäger Jasmin , Gaeckler Anja , Dolff Sebastian , Westhoff Timm H. , Rohn Hana , Stervbo Ulrik , Scheibenbogen Carmen , Witzke Oliver , Babel Nina
Published: December 2022

The role of autoimmunity in post-acute sequelae of COVID-19 (PASC) is not well explored, although clinicians observe a growing population of convalescent COVID-19 patients with manifestation of post-acute sequelae of COVID-19. We analyzed the immune response in 40 post-acute sequelae of COVID-19 patients with non-specific PASC manifestation and 15 COVID-19 convalescent healthy donors. The phenotyping of lymphocytes showed a significantly higher number of CD8+ T cells expressing the Epstein-Barr virus induced G protein coupled receptor 2, chemokine receptor CXCR3 and C-C chemokine receptor type 5 playing an important role in inflammation and migration in PASC patients compared to controls. Additionally, a stronger, SARS-CoV-2 reactive CD8+ T cell response, characterized by IFNγ production and predominant TEMRAphenotype but low SARS-CoV-2 avidity was detected in PASC patients compared to controls. Furthermore, higher titers of several autoantibodies were detected among PASC patients. Our data suggest that a persistent inflammatory response triggered by SARS-CoV-2 might be responsible for the observed sequelae in PASC patients. These results may have implications on future therapeutic strategies.
Discordant results among MHC binding affinity prediction tools
Authors: Nguyen Austin , Nellore Abhinav , Thompson Reid F.
Published: December 2022

A large number of machine learning-based Major Histocompatibility Complex (MHC) binding affinity (BA) prediction tools have been developed and are widely used for both investigational and therapeutic applications, so it is important to explore differences in tool outputs. We examined predictions of four popular tools (netMHCpan, HLAthena, MHCflurry, and MHCnuggets) across a range of possible peptide sources (human, viral, and randomly generated) and MHC class I alleles. We uncovered inconsistencies in predictions of BA, allele promiscuity and the relationship between physical properties of peptides by source and BA predictions, as well as quality of training data. Our work raises fundamental questions about the fidelity of peptide-MHC binding prediction tools and their real-world implications.
Longitudinal improvement in postural instability is distinct from gait in treated adult hydrocephalus
Authors: Wacek Amber , Jean James , Jonason Alec , Hanson Jacob T. , Mavanji Vibha , Palzer Elise F. , Lewis Scott , Ashe James , Looft John M. , McGovern Robert A.
Published: December 2022

Background

Ventriculoperitoneal shunting improves gait in patients with normal pressure hydrocephalus. Postural instability is a major concern, but mostly ignored in the evaluation and treatment of these patients. This study quantified postural instability using kinematics via a prospective cohort design.

Methods

Seventeen patients with suspected normal pressure hydrocephalus and twenty age-matched, healthy controls underwent quantitative pull test and gait examinations while wearing inertial measurement units at baseline. Patients with suspected normal pressure hydrocephalus who were shunted (n=13) and not shunted (n=4) underwent further testing after a lumbar drain trial and at follow-up visits 6 and 12 months post-operatively.

Results

While most gait improvement in patients who were shunted was seen immediately after the lumbar drain trial, measures of their postural response continued to improve after the lumbar drain trial through one year of follow-up. Patients who were not shunted showed no statistically significant changes in gait and postural instability measures.

Conclusions

After shunting, postural instability improves continuously over one year. In contrast, a large improvement in gait is seen immediately with minimal change over the subsequent year. This difference in timing may implicate two distinct neurophysiological mechanisms of recovery and provides novel evidence that postural instability improves in response to long-term CSF diversion.
SAYSD1 senses UFMylated ribosome to safeguard co-translational protein translocation at the endoplasmic reticulum
Authors: Wang Lihui , Xu Yue , Yun Sijung , Yuan Quan , Satpute-Krishnan Prasanna , Ye Yihong
Published: December 2022

Translocon clogging at the endoplasmic reticulum (ER) as a result of translation stalling triggers ribosome UFMylation, activating aTranslocation-AssociatedQualityControl (TAQC) mechanism that degrades clogged substrates. How cells sense ribosome UFMylation to initiate TAQC is unclear. Here we use a genome-wide CRISPR/Cas9 screen to identify an uncharacterized membrane protein named SAYSD1 that facilitates TAQC. SAYSD1 associates with the Sec61 translocon, and also recognizes both ribosome and UFM1 directly, engaging a stalled nascent chain to ensure its transport via the TRAPP complex to lysosomes for degradation. Like UFM1 deficiency, SAYSD1 depletion causes the accumulation of translocation-stalled proteins at the ER and triggers ER stress. Importantly, disrupting UFM1- and SAYSD1-dependent TAQC inDrosophilaleads to intracellular accumulation of translocation-stalled collagens, defective collagen deposition, abnormal basement membranes, and reduced stress tolerance. Together, our data support a model that SAYSD1 acts as a UFM1 sensor that collaborates with ribosome UFMylation at the site of clogged translocon, safeguarding ER homeostasis during animal development.
Visualizing somatic alterations in spatial transcriptomics data of skin cancer
Authors: Chen Limin , Chang Darwin , Tandukar Bishal , Deivendran Delahny , Cho Raymond , Cheng Jeffrey , Bastian Boris C. , Ji Andrew L. , Shain A. Hunter
Published: December 2022

Tools to visualize genetic alterations within tissues remain underdeveloped despite the growth of spatial transcriptomic technologies, which measure gene expression in different regions of tissues. Since genetic alterations can be detected in RNA-sequencing data, we explored the feasibility of observing somatic alterations in spatial transcriptomics data. Extracting genetic information from spatial transcriptomic data would illuminate the spatial distribution of clones and allow for correlations with regional changes in gene expression to support genotype-phenotype studies. Recent work demonstrates that copy number alterations can be inferred from spatial transcriptomics data1. Here, we describe new software to further enhance the inference of copy number from spatial transcriptomics data. Moreover, we demonstrate that single nucleotide variants are also detectable in spatial transcriptomic data. We applied these approaches to map the location of point mutations, copy number alterations, and allelic imbalances in spatial transcriptomic data of two cutaneous squamous cell carcinomas. We show that both tumors are dominated by a single clone of cells, suggesting that their regional variations in gene expression2are likely driven by non-genetic factors. Furthermore, we observe mutant cells in histologically normal tissue surrounding one tumor, which were not discernible upon histopathologic evaluation. Finally, we detected mono-allelic expression of immunoglobulin heavy chains in B-cells, revealing clonal populations of plasma cells surrounding one tumor. In summary, we put forward solutions to add the genetic dimension to spatial transcriptomic datasets, augmenting the potential of this new technology.
Stat3 has a different role in axon growth during development than it does in axon regeneration after injury
Authors: Duan Qinwen , Zheng Hongfei , Qin Yanjun , Yan Jizhou , Burgess Shawn , Wang Jian , Fan Chunxin
Published: December 2022

Signal transducer and activator of transcription 3 (STAT3) is essential for neural development and regeneration as a key transcription factor and mitochondrial activator. In this study, using zebrafish posterior lateral line (PLL) axons, we demonstrate that Stat3 plays distinct roles in PLL axon embryonic growth and regeneration. In zebrafishstat3mutants the PLL axons were truncated during embryonic growth. Expressingstat3in neurons of the PLL ganglion rescued their axon growth suggestingstat3promoted PLL axon growth in a cell-autonomous manner. Using Jak/Stat signaling inhibitors or modified Stat3, we found Jak/Stat signaling was dispensable for PLL axon growth. We showed that Stat3 was co-localized with mitochondria in PLL axon and lower ATPase activity instat3mutant embryos than wild-type embryos. The PLL axon growth was affected by mitochondrial modulators indicating that Stat3 regulated PLL axon growth through mitochondrial Stat3 function. Mutation ofstat3or treating with Jak/Stat signaling inhibitors retarded PLL axon regeneration and Schwann cell migration. Taken together, Stat3 is required for embryonic PLL axon growth by regulating the ATP synthesis efficiency of mitochondria, whereas Stat3 stimulates PLL axon regeneration through regulating Schwann cell migration via Jak/Stat signaling. Our findings show a new mechanism of Stat3 in axon growth and regeneration.

Author Summary

Neurons are one of the most specialized cell type in our body. A slender axon used for transmitting information between neuron and target cell extends from the cell body. Axon extension during both development and regeneration is regulated by intrinsic and extrinsic factors. In this study, we used the zebrafish posterior lateral line (PLL) axons which extends a long distance to study the regulation of axon extension. Signal transducer and activator of transcription 3 (STAT3) is a key transcription factor in Jak/Stat signaling and an activator for mitochondria functions. Our results demonstrate that Stat3 plays distinct roles in PLL axons development and regeneration. During embryonic development, Jak/Stat signaling is dispensable for PLL axons extension, whereas the mitochondrial Stat3 is required for embryonic axon growth through promoting ATP synthesis. During PLL axons regeneration, Jak/Stat is essential for Schwann cells migration which mediates axon regeneration.
Convergent deployment of ancestral programs during the evolution of mammalian flight membranes
Authors: Feigin Charles Y. , Moreno Jorge A. , Ramos Raul , Mereby Sarah A. , Alivisatos Ares , Wang Wei , van Amerongen Renée , Camacho Jasmin , Rasweiler John J. , Behringer Richard R. , Ostrow Bruce , Plikus Maksim V. , Mallarino Ricardo
Published: December 2022

Lateral flight membranes, or patagia, have evolved repeatedly in diverse mammalian lineages. While little is known about patagium development, its recurrent evolution may suggest a shared molecular basis. By combining transcriptomics, developmental experiments, and mouse transgenics, we demonstrate that lateral WNT5A expression in the marsupial sugar glider (Petaurus breviceps) promotes the differentiation of its patagium primordium. We further show that this function of WNT5A reprises ancestral roles in skin morphogenesis predating mammalian flight and has been convergently employed during patagium evolution in eutherian bats. Moreover, we find that many genes involved in limb development have been re-deployed during patagium outgrowth in both the sugar glider and bat. Taken together, our findings reveal that deeply conserved molecular toolkits underpin the evolutionary transition to flight in mammals.
Histone monoaminylation dynamics are regulated by a single enzyme and promote neural rhythmicity
Authors: Zheng Qingfei , Bastle Ryan M. , Zhao Shuai , Kong Lingchun , Vostal Lauren , Ramakrishnan Aarthi , Shen Li , Fulton Sasha L. , Wang Haifeng , Zhang Baichao , Upad Akhil , Dierdorff Lauren , Thompson Robert E. , Molina Henrik , Stransky Stephanie , Sidoli Simone , Muir Tom W. , Li Haitao , David Yael , Maze Ian
Published: December 2022

Histone H3 monoaminylations at glutamine(Q) 5 represent an important family of epigenetic markers in neurons that play critical roles in the mediation of permissive gene expression (1, 2). We previously demonstrated that H3Q5 serotonylation(ser) and dopaminylation(dop) are catalyzed by the Transglutaminase 2 (TGM2) enzyme and alter both local and global chromatin states (3, 4). Here, we found that TGM2 additionally functions as an “eraser” of H3 monoaminylations that is capable of “re-writing” these epigenetic marks in cells, including a new class of this modification, H3Q5 histaminylation(his), which displays dynamic diurnal expression in brain and contributes to neural rhythmicity. We found that H3Q5his inhibits binding of the MLL1 complex to the H3 N-terminus and attenuates its methyltransferase activity on H3 lysine(K) 4. We determined that H3Q5 monoaminylation dynamics are dictated by local monoamine concentrations, which are utilized by TGM2. Taken together, we present here a novel mechanism through which a single chromatin regulatory enzyme is capable of sensing chemical microenvironments to affect the epigenetic states of cells.

One sentence summary

A single enzyme, TGM2, bidirectionally controls H3 monoaminylation dynamics, which, in turn, facilitate neural rhythmicity.
Asymmetric effect of renewable energy consumption and economic growth on environmental degradation in sub-Saharan Africa
Authors: Abdul-Mumuni Abdallah , Mensah Barbara Deladem , Amankwa Fosu Richard
Published: December 2022

Purpose

While there are enormous studies on the determinants of environmental degradation, empirical studies on the effect of renewable energy consumption and economic growth on the environment remain limited. The purpose of this paper is to examine the asymmetric effect of renewable energy consumption and economic growth on environmental degradation in 31 selected sub-Saharan African countries spanning from 1990 to 2018.

Design/methodology/approach

To examine possible asymmetric effects of the exogenous variables on environmental degradation, we used the panel nonlinear autoregressive distributed lag approach and secondary data was sourced from the World Bank (2021).

Findings

The cointegration test results suggest that there is a long-run cointegration among the variables whereas our main findings indicate that environmental degradation responds asymmetrically to changes in renewable energy consumption and economic growth. The results further reveal that both positive and negative shocks in renewable energy consumption reduce environmental degradation. On the other hand, positive and negative shocks in economic growth increase environmental degradation in the long run.

Research limitations/implications

The implications of this study include the need for policymakers in sub-Saharan Africa to encourage the utilization of renewable energy as it reduces environmental degradation. Also, governments in the subregion should gradually replace the usage of fossil fuels by adapting renewable energy sources so as to achieve higher economic growth.

Originality/value

The positive and negative shocks of renewable energy consumption and economic growth on environmental degradation are examined to ascertain their asymmetric relationships.
Green knowledge management and organizational green culture: an interaction for organizational green innovation and green performance
Authors: Abbas Jawad , Khan Shumaila Mazhar
Published: December 2022

Purpose

Based on the sharp decline in the quantity and quality of natural resources, many organizations are shifting their operations to an eco-friendly system. However, this objective cannot be achieved without capitalizing on green knowledge and innovation. The purpose of this study is to examine whether green knowledge management (GKM) strengthens organizational green innovation capabilities, leading to green performance. Moreover, considering culture as the buffering condition, the authors took it as the conditional boundary between GKM and green innovation and investigated if it impacts their relationship.

Design/methodology/approach

The authors focused on the manufacturing and services firms’ managerial and non-managerial staff and collected data following the non-probability convenience sampling technique. The collected data were examined through structural equation modeling.

Findings

It is found that GKM is a significant positive predictor of organizational green innovation and green performance and strengthens their abilities in these areas. However, green innovation partially mediates between GKM and corporate green performance. It is also found that green culture strengthens the relationship between GKM and organizational green innovation.

Originality/value

This study’s findings provide confidence to organizational managers and related stakeholders to achieve sustainability goals by capitalizing on GKM and promoting green culture in their setup. This study is also among the pioneer studies investigating GKM as a unified system and linking it with environmental performance domains.
B‐cell targeted therapy of pemphigus
Authors: Yamagami Jun
Published: December 2022

Pemphigus is an autoimmune disease that causes blistering and erosion of the skin and mucous membranes because of autoantibodies against desmoglein, which plays an important role in adhesion between epidermal keratinocytes. Treatment of pemphigus has long been centered on corticosteroids, and the guidelines for management of pemphigus have recommended high‐dose systemic corticosteroids as the first‐line treatment. While guideline‐based treatment has been shown to be beneficial in patients with pemphigus, it has also become clear that this treatment is accompanied by significant burden and risk. The challenge for future pemphigus treatment is to maximize efficacy while minimizing risk during the course of the disease. In this regard, treatment targeting B cells is expected to become increasingly important as autoreactive B cells in pemphigus patients are thought to play a major role in the production of autoantibodies, which form the basis of the pathogenesis. The recent expansion of insurance coverage to rituximab, a monoclonal antibody against CD20, for refractory pemphigus in the USA, Europe, and Japan has opened up a new era of pemphigus treatment by enabling treatment strategies with drugs targeting B cells in patients. Here, we discuss the current status and future prospects of pemphigus treatment, focusing on rituximab and Bruton's tyrosine kinase inhibitors, which are expected to become essential drugs for pemphigus treatment in the future.
Age and support for public debt reduction
Authors: ASPIDE ALESSIA , BROWN KATHLEEN J. , DIGIUSEPPE MATTHEW , SLASKI ALEXANDER
Published: December 2022

Many scholars and policymakers see rising debt burdens in the industrialised world as the product of ageing populations. Prominent theoretical models of government debt accumulation – used to justify fiscal rules and austerity measures – explicitly assume that support for debt reduction decreases with age. While such models have been influential, the fundamental relationship between age and preferences for debt has not been tested empirically. We test this argument but further theorise that the relationship between age and debt preferences is non‐linear. While the elderly have a clear preference for ignoring debt burdens, we add that the young should also prefer to delay reckoning with high national debts given their low income and expectations of higher future earnings. Using survey data (N = 112,689), we find that age does have a small to modest non‐linear impact on concern for national deficits and debt burdens. Middle‐aged respondents are most concerned about debt reduction, while the young and old view reducing government debt as less of a policy priority. Notably, the relationship is strongest in countries with more generous old‐age benefits.
Catheter‐directed thrombolysis for lower limb ischaemia: A retrospective study of treatment outcomes
Authors: Parker Sophie , Midgley David John , Iosua Ella , Galletly Anna , Durran Alexandra , Lau Gabriel , Reddy Michael , Abcarian Peter , Letts James
Published: December 2022

Introduction

Lower limb ischaemia secondary to occlusion of a lower limb artery is a limb‐threatening condition that can be effectively treated by catheter‐directed thrombolysis (CDT). The purpose of this study was to examine treatment outcomes of CDT both at the time of treatment and ongoing patency up to 12 months following treatment. The secondary aim of the study was to investigate the influence of age of occlusion and treatment duration on success and complication rates.

Method

A retrospective observational study was performed at a single institution over a 10‐year period from 2010 to 2019. Data for patient demographics, vessel occlusion factors and treatment information were obtained and analysed. Patency data were investigated using Kaplan–Meier analyses.

Results

A total of 218 limbs in 159 patients were treated during the study period. The aetiology of vessel occlusion was in situ thrombosis or occluded bypass graft in 74.5%. Technical success was achieved in 55.5% with CDT alone and 84.4% by using CDT in combination with adjunctive endovascular procedures (angioplasty or stenting). The overall probability of patency was 0.65 at 3 months and 0.44 at 12 months. The overall rate of major amputation within 30 days of thrombolysis was 8.2%. Thirty‐day mortality was 6.3% and was secondary to intracranial haemorrhage in three patients.

Conclusion

Technical success of CDT was found to be significantly higher when combined with adjunctive endovascular procedures at the time of CDT. Despite an initial moderate technical success, the probability of patency at 12 months was only 44%. The likelihood of bleeding complications and technical and long‐term success remain key considerations when selecting patients for CDT.
Remembering Fraud in the Future: Investigating and Improving Auditors' Attention to Fraud during Audit Testing*
Authors: Austin Ashley A.
Published: December 2022

During the testing stages of the audit, auditors must divide their attention simultaneously between (i) performing the planned audit procedures and (ii) remaining broadly skeptical and alert for fraud. Regulators note instances in which auditors do not take actions that effectively respond to fraud risks during these later stages, suggesting auditors may devote insufficient attention to fraud while they are busy executing the planned audit procedures. Leveraging prospective memory theory, I identify and test an intervention that can improve auditors' attention to fraud by encouraging auditors to have implementation intentions—that is, more detailed plans about when and how they will consider fraud. I find that encouraging implementation intentions interacts with auditors' perceived fraud task importance to increase auditors' attention to fraud when this attention would otherwise be lower, making auditors more likely to take effective fraud actions. Importantly, these results also indicate that, even in a high fraud risk setting, auditors may devote insufficient attention to fraud while performing the planned audit procedures, confirming concerns voiced by regulators. However, my study also highlights concerns about regulators' inspection processes prompting auditors to focus too heavily on inspection risk, as the results suggest auditors are less likely to detect fraud in high‐risk audit areas thought to have low inspection risk.
Impacts of relatively rational and irrational investor sentiment on realized volatility
Authors: Tseng Tseng‐Chan , Lai Hung‐Cheng , Chen Jih‐Kuang
Published: December 2022

We adopt intraday data in this study to facilitate an exploration of the influences of relatively rational and irrational investor sentiment on volatility within the Taiwan stock markets. Following the decomposition of daily trading volume within the Taiwan Stock Exchange Capitalization Weighted Stock Index (TWSE) into two subsets, comprising the trading volume of institutional investors and individual investors, we go on to investigate the influence of each subset on realized volatility. We reveal that the relatively rational sentiment of institutional investors plays a stabilizing role in future volatility, whereas the relatively irrational sentiment of individual investors tends to exacerbate such volatility. Therefore, we suggest that our modified model, which takes into account the relatively rational and irrational sentiment of investors, is capable of more accurately predicting volatility than the benchmark model.
Chemotherapy‐induced phlebitis via the GBP5/NLRP3 inflammasome axis and the therapeutic effect of aescin
Authors: Liu Peng , Ye Lichun , Ren Yongshen , Zhao Guodun , Zhang Yun , Lu Shaojuan , Li Qiang , Wu Chen , Bai Lijie , Zhang Zhongyun , Zhao Zhongqiu , Shi Zhaohua , Yin Shijin , Liao Maochuan , Lan Zhou , Feng Jing , Chen Lvyi
Published: December 2022

Background and Purpose

Intravenous infusion of chemotherapy drugs can cause severe chemotherapy‐induced phlebitis (CIP) in patients. However, the underlying mechanism of CIP development remains unclear.

Experimental Approach

RNA‐sequencing analysis was used to identify potential disease targets in CIP. Guanylate binding protein‐5 (GBP5) genetic deletion approaches also were used to investigate the role of GBP5 in NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in lipopolysaccharide (LPS) primed murine bone‐marrow‐derived macrophages (BMDMs) induced by vinorelbine (VIN) in vitro and in mouse models of VIN‐induced CIP in vivo. The anti‐CIP effect of aescin was evaluated, both in vivo and in vivo.

Key Results

Here, we show that the expression of GBP5 was upregulated in human peripheral blood mononuclear cells from CIP patients. Genetic ablation of GBP5 in murine macrophages significantly alleviated VIN‐induced CIP in the experimental mouse model. Mechanistically, GBP5 contributed to the inflammatory responses through activating NLRP3 inflammasome and driving the production of the inflammatory cytokine IL‐1β. Moreover, aescin, a mixture of triterpene saponins extracted from horse chestnut seed, can alleviate CIP by inhibiting the GBP5/NLRP3 axis.

Conclusion and Implications

These findings suggest that GBP5 is an important regulator of NLRP3 inflammasome in CIP mouse model. Our work further reveals that aescin may serve as a promising candidate in the clinical treatment of CIP.
Commentary: Commentary on the Twitter comments evoked by the May 2022 debate on diagnosing personality disorders in adolescents
Authors: Cavelti Marialuisa , Sharp Carla , Chanen Andrew M. , Kaess Michael
Published: December 2022

The debate about the value and utility of personality disorder (PD) diagnosis in adolescence published in the May 2022 issue of CAMH generated fervent Twitter discussion. This commentary addresses some points raised in the Twitter discussion that represent important social and/or cultural beliefs that are often presented in day‐to‐day practice but are rarely tested in the context of scientific evidence. This includes, in particular, the assertion that symptoms used to diagnose personality disorder are better described as sequelae of trauma, and the assertion that effective treatment for PD is possible without a diagnosis. The call for a fundamental transformation of mental health services that currently do not meet the needs of people with PD and for the involvement of people with lived experience as equal partner in this process is supported by evidence and might represent common ground among those clinician‐scientist advocating for early intervention for PD and those expressing their concerns about this issue.
CD34dim cells identified as pluripotent stem cell‐derived definitive hemogenic endothelium purified using bone morphogenetic protein 4
Authors: Jeon Soo‐Been , Han A‐Reum , Lee Sunghun , Lee Seung Chan , Lee Min Ji , Park Soon‐Jung , Moon Sung‐Hwan , Lee Ji Yoon
Published: December 2022

Hemogenic endothelium (HE) plays a pivotal and inevitable role in haematopoiesis and can generate all blood and endothelial lineage cells in the aorta‐gonad‐mesonephros of mouse embryos. Whether definitive HE can prospectively isolate pure HE from human pluripotent stem cells that can spontaneously differentiate into heterogeneous cells remains unknown. Here, we identified and validated a CD34dim subpopulation with hemogenic potential. We also purified CD34 cells with a CXCR4−CD73− phenotype as a definitive HE population that generated haematopoietic stem cells and lymphocytes. The frequency of CXCR4−CD73−CD34dim was evidently increased by bone morphogenetic protein 4, and purified HE cells differentiated into haematopoietic cells with myeloid and T lymphoid lineages including Vδ2+ subset of γ/δ T cells. We developed a simple method to purify HE cells that were enriched in CD34dim cells. We uncovered an initial step in differentiating haematopoietic lineage cells that could be applied to basic and translational investigations into regenerative medicine.
Visiting migrants: An introduction
Authors: Miah Md Farid , King Russell , Lulle Aija
Published: December 2022

This paper offers an overview of the origins and dynamics of the concept of migrant visits and introduces the key contributions of the special issue. We highlight the significance of visits that criss‐cross many forms of migration and centre on these visits’ bilateral and multilateral nature. Furthermore, we emphasize emotional, sensory and bodily implications, which almost always shape encounters between migrants and others in such visits. The papers of this special issue contribute to a broad interdisciplinary agenda highlighting familial ties, networks and transnational spaces at the core of migration and mobility scholarship. Together, we offer new perspectives on the multidirectionality of visits and the role of relationships which drive, connect and diversify forms of migration and are facilitated by broader developments in technology, tourism and diasporic practices.
Efficacy of minocycline hydrochloride aspiration sclerotherapy with additional monoethanolamine oleate aspiration sclerotherapy for symptomatic hepatic cysts
Authors: Kimura Yoshihide , Fujiwara Kei , Matsuura Kentaro , Suzuki Takanori , Senoo Kyouji , Tsuchida Kenji , Mori Yoshinori , Hirano Atsuyuki , Nomura Satoshi , Kitagawa Mika , Tomita Yusaku , Kanaiwa Hiroki , Imazu Mitsuki , Nagura Yoshihito , Nojiri Shunsuke , Kataoka Hiromi
Published: December 2022

Aim

Minocycline hydrochloride (MINO) aspiration sclerotherapy (AS) has been widely used for treating hepatic cysts (HC). However, cyst recurrence remains problematic. Information on monoethanolamine oleate (EO) AS, another effective HC treatment, is currently limited. We investigated the efficacy of EO on ineffective MINO treatments, and the relationship between MINO AS and cyst fluid pH.

Methods

A total of 22 cases with symptomatic HC underwent AS with 500 mg of MINO from January 2016 to June 2021. Cyst fluid pH was measured before and after MINO injection. Cyst volume ratio (CVR, %) after 2 weeks was calculated as follows:cyst volume 2 weeks after MINO injection / pre‐treatment cyst volume × 100. Treatment was completed if CVR after 2 weeks was ≤35% (MINO‐group). For patients with CVR >35%, 2 g of EO was added (MINO/EO‐group). Cyst volume ratio was measured every 12 months thereafter.

Results

There were no recurrence symptoms in any of the patients during follow‐up. Of the 22 cases, 21 had CVR ≤20% after 12 months. The MINO/EO‐group (n = 8) tended to have smaller CVRs after 12 months than the MINO‐group (n = 14). Cyst volume ratio after 2 weeks was correlated to pH change (p = 0.012) and was larger in patients whose pH decreased by <1.5 (p = 0.015). All adverse events were mild, including in elderly patients.

Conclusion

Adding EO is an effective and safe treatment for symptomatic HC when MINO AS alone is insufficient. Patients with pH decreases of <1.5 should be considered for additional EO treatment.