bluuebunny/crossref_metadata_2025 huggingface dataset:
Prehabilitative resistance exercise reduces neuroinflammation and improves mitochondrial health in aged mice with perioperative neurocognitive disorders
Authors: Liu Yan , Chu John Man Tak , Ran You , Zhang Yan , Chang Raymond Chuen Chung , Wong Gordon Tin Chun
Published: June 2022

Background

Postoperative neurocognitive dysfunction remains a significant problem in vulnerable groups such as the elderly. While experimental data regarding its possible pathogenic mechanisms accumulate, therapeutic options for this disorder are limited. In this study, we evaluated the neuroprotective effect of a period of preconditioning resistant training on aged mice undergoing abdominal surgery. Further, we examined the underlying mechanisms from the perspective of neuroinflammatory state and synaptic plasticity in the hippocampus.

Methods

18-month-old C57BL/6N mice were trained for 5 weeks using a ladder-climbing protocol with progressively increasing weight loading. Preoperative baseline body parameters, cognitive performance and neuroinflammatory states were assessed and compared between sedentary and trained groups of 9-month-old and 18-month-old mice. To access the neuroprotective effect of resistance training on postoperative aged mice, both sedentary and trained mice were subjected to a laparotomy under 3% sevoflurane anesthesia. Cognitive performance on postoperative day 14, hippocampal neuroinflammation, mitochondrial dysfunction and synaptic plasticity were examined and compared during groups.

Results

18-month-old mice have increased body weight, higher peripheral and central inflammatory status, reduction in muscle strength and cognitive performance compared with middle-aged 9-month-old mice, which were improved by resistance exercise. In the laparotomy group, prehabilitative resistant exercise improved cognitive performance and synaptic plasticity, reduced inflammatory factors and glial cells activation after surgery. Furthermore, resistance exercise activated hippocampal PGC-1α/BDNF/Akt/GSK-3β signaling and improved mitochondrial biogenesis, as well as ameliorated mitochondrial dynamics in postoperative-aged mice.

Conclusions

Resistance exercise reduced risk factors for perioperative neurocognitive disorders such as increased body weight, elevated inflammatory markers, and pre-existing cognitive impairment. Accordantly, preoperative resistance exercise improved surgery-induced adverse effects including cognitive impairment, synaptic deficit and neuroinflammation, possibly by facilitate mitochondrial health through the PGC1-a/BDNF pathway.
A dual-center cohort study on the association between early deep sedation and clinical outcomes in mechanically ventilated patients during the COVID-19 pandemic: The COVID-SED study
Authors: Stephens Robert J. , Evans Erin M. , Pajor Michael J. , Pappal Ryan D. , Egan Haley M. , Wei Max , Hayes Hunter , Morris Jason A. , Becker Nicholas , Roberts Brian W. , Kollef Marin H. , Mohr Nicholas M. , Fuller Brian M.
Published: June 2022

Background

Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes.

Study design and methods

Dual-center, retrospective cohort study conducted over 6 months (March–August, 2020), involving consecutive, mechanically ventilated adults. All sedation-related data during the first 48 h were collected. Deep sedation was defined as Richmond Agitation-Sedation Scale of − 3 to − 5 or Riker Sedation-Agitation Scale of 1–3. To examine impact of early sedation depth on hospital mortality (primary outcome), we used a multivariable logistic regression model. Secondary outcomes included ventilator-, ICU-, and hospital-free days.

Results

391 patients were studied, and 283 (72.4%) experienced early deep sedation. Deeply sedated patients received higher cumulative doses of fentanyl, propofol, midazolam, and ketamine when compared to light sedation. Deep sedation patients experienced fewer ventilator-, ICU-, and hospital-free days, and greater mortality (30.4% versus 11.1%) when compared to light sedation (p < 0.01 for all). After adjusting for confounders, early deep sedation remained significantly associated with higher mortality (adjusted OR 3.44; 95% CI 1.65–7.17; p < 0.01). These results were stable in the subgroup of patients with COVID-19.

Conclusions

The management of sedation for mechanically ventilated patients in the ICU has changed during the COVID pandemic. Early deep sedation is common and independently associated with worse clinical outcomes. A protocol-driven approach to sedation, targeting light sedation as early as possible, should continue to remain the default approach.
SCADIE: simultaneous estimation of cell type proportions and cell type-specific gene expressions using SCAD-based iterative estimating procedure
Authors: Tang Daiwei , Park Seyoung , Zhao Hongyu
Published: June 2022

A challenge in bulk gene differential expression analysis is to differentiate changes due to cell type-specific gene expression and cell type proportions. SCADIE is an iterative algorithm that simultaneously estimates cell type-specific gene expression profiles and cell type proportions, and performs cell type-specific differential expression analysis at the group level. Through its unique penalty and objective function, SCADIE more accurately identifies cell type-specific differentially expressed genes than existing methods, including those that may be missed from single cell RNA-Seq data. SCADIE has robust performance with respect to the choice of deconvolution methods and the sources and quality of input data.
HA gene amino acid mutations contribute to antigenic variation and immune escape of H9N2 influenza virus
Authors: Zhu Rui , Xu Shunshun , Sun Wangyangji , Li Quan , Wang Shifeng , Shi Huoying , Liu Xiufan
Published: June 2022

Based on differences in the amino acid sequence of the protein haemagglutinin (HA), the H9N2 avian influenza virus (H9N2 virus) has been clustered into multiple lineages, and its rapidly ongoing evolution increases the difficulties faced by prevention and control programs. The HA protein, a major antigenic protein, and the amino acid mutations that alter viral antigenicity in particular have always been of interest. Likewise, it has been well documented that some amino acid mutations in HA alter viral antigenicity in the H9N2 virus, but little has been reported regarding how these antibody escape mutations affect antigenic variation. In this study, we were able to identify 15 HA mutations that were potentially relevant to viral antigenic drift, and we also found that a key amino acid mutation, A180V, at position 180 in HA (the numbering for mature H9 HA), the only site of the receptor binding sites that is not conserved, was directly responsible for viral antigenic variation. Moreover, the recombinant virus with alanine to valine substitution at position 180 in HA in the SH/F/98 backbone (rF/HAA180V virus) showed poor cross-reactivity to immune sera from animals immunized with the SH/F/98 (F/98, A180), SD/SS/94 (A180), JS/Y618/12 (T180), and rF/HAA180V (V180) viruses by microneutralization (MN) assay. The A180V substitution in the parent virus caused a significant decrease in cross-MN titres by enhancing the receptor binding activity, but it did not physically prevent antibody (Ab) binding. The strong receptor binding avidity prevented viral release from cells. Moreover, the A180V substitution promoted H9N2 virus escape from an in vitro pAb-neutralizing reaction, which also slightly affected the cross-protection in vivo. Our results suggest that the A180V mutation with a strong receptor binding avidity contributed to the low reactors in MN/HI assays and slightly affected vaccine efficacy but was not directly responsible for immune escape, which suggested that the A180V mutation might play a key role in the process of the adaptive evolution of H9N2 virus.
Alternating 3 different influenza vaccines for swine in Europe for a broader antibody response and protection
Authors: Parys Anna , Vandoorn Elien , Chiers Koen , Van Reeth Kristien
Published: June 2022

Heterologous prime-boost vaccination with experimental or commercial influenza vaccines has been successful in various animal species. In this study, we have examined the efficacy of alternating 3 different European commercial swine influenza A virus (swIAV) vaccines: the trivalent Respiporc® FLU3 (TIV), the bivalent GRIPORK® (BIV) and the monovalent Respiporc® FLUpan H1N1 (MOV). Five groups of 6 pigs each received 3 vaccinations at 4–6 week intervals in a homologous or heterologous prime-boost regimen. A sixth group served as a mock-vaccinated challenge control. Four weeks after the last vaccination, pigs were challenged intranasally with a European avian-like H1N1 (1C.2.1) swIAV, which was antigenically distinct from the vaccine strains. One heterologous prime-boost group (TIV–BIV–MOV) had higher hemagglutination inhibition (HI) and neuraminidase inhibition antibody responses against a panel of antigenically distinct H1N1, H1N2 and H3N2 IAVs than the other heterologous prime-boost group (BIV–TIV–MOV) and the homologous prime-boost groups (3xTIV; 3xBIV; 3xMOV). Group TIV–BIV–MOV had seroprotective HI titers (≥ 40) against 56% of the tested viruses compared to 33% in group BIV–TIV–MOV and 22–39% in the homologous prime-boost groups. Post-challenge, group TIV–BIV–MOV was the single group with significantly reduced virus titers in all respiratory samples compared to the challenge control group. Our results suggest that the use of different commercial swIAV vaccines for successive vaccinations may result in broader antibody responses and protection than the traditional, homologous prime-boost vaccination regimens. In addition, the order in which the different vaccines are administered seems to affect the breadth of the antibody response and protection.
Characterization of siderophores from Escherichia coli strains through genome mining tools: an antiSMASH study
Authors: Cavas Levent , Kirkiz Ibrahim
Published: June 2022

Although urinary tract infections (UTIs) affect many people, they are usually a disease observed in women. UTIs happen when exogenous and endogenous bacteria enter the urinary tract and colonize there. Cystitis and pyelonephritis occur when bacteria infect the bladder and the kidneys, respectively. UTIs become much serious if the bacteria causing the infection are antibiotic resistant. Since the pathogenic microorganisms have been adopted to current antibiotics via genetic variations, UTIs have become an even more severe health problem. Therefore, there is a great need for the discovery of novel antibiotics. Genome mining of nonpathogenic and pathogenic Escherichia coli strains for investigating secondary metabolites were conducted by the antiSMASH analysis. When the resulting secondary metabolites were examined, it was found that some of the siderophores are effective in UTIs. In conclusion, since the siderophore production in E. coli is directly related to UTIs, these molecules can be a good target for development of future pharmaceutical approaches and compounds. Siderophores can also be used in industrial studies due to their higher chelating affinity for iron.
How does the 120-year cycle mast seeding of dwarf bamboo affect the rodent population?
Authors: Suzuki Hanami , Kashiwagi Haruka , Kajimura Hisashi
Published: June 2022

Background

In 2017, large-scale flowering, seeding, and dying events of dwarf bamboo (Sasa borealis) occurred in a wide range in central Japan for the first time in 120 years. This phenomenon of S. borealis, like the mast seeding of trees, could be expected to provide a large amount of food for seed-eating rodents and gradually affect their ecology and population dynamics. We captured rodents in survey plots in a secondary broad-leaved forest with the phenomenon from 2018 to 2019 to investigate the species, the number of individuals, growing stage, sex, and body mass. In addition, we also compared the capture data for 2 years (2018–2019) with that for the mast seeding year (2017) and 6 years before it (2011–2016).

Results

The mast seeding of S. borealis greatly increased the population size of rodents, especially Apodemus speciosus and A. argenteus. Conversely, Eothenomys smithii did not show such an increase. Most of the captured rodent individuals were already adults at the time of new capture, and the proportion of male juveniles was extremely low. These results suggest that the mast seeding of S. borealis created unusually rich food availability for the population concentration of rodents due to their immigration. However, body mass was not significantly different before and after the mast seeding. In addition, the increased populations of the two Apodemus species did not decline 2 years after the S. borealis masting, contrary to the previously reported decrease of rodent populations after tree masting.

Conclusions

Our results indicate that the mast seeding of S. borealis affected the population dynamics of Apodemus species over a long time and their individual composition of different growth stages. However, it did not affect their body mass.
Public expenditure for water facility and road transport infrastructure in Ethiopia: a comparison of impacts using an economy-wide model
Authors: Mosa Abdulaziz Abdulsemed
Published: June 2022

Background

Ethiopian government is investing in a wide range of pro-poor sectors but the economic effects of public investment widely vary across sectors. With a limited public resource, public investment across sectors has to be prioritized based on their potential socio-economic contributions and/or economy-wide benefits. Therefore, the objective of this study is to compare and explore the economy-wide returns of public expenditure on water facility and energy technology (such as improved cooking stoves) on the one hand and public expenditure on road infrastructure on the other hand.

Methods

The source of data for this study is the 2005/06 updated Social accounting matrix (SAM) of Ethiopia. The analysis applies the STAGE Computable General Equilibrium (CGE) model developed by McDonald (2007). This study analyses two policy scenarios; the first scenario is an increase in the total factor productivity (TFP) of water fetching and firewood collection activities due to public investment in water facility and improved cooking stoves and the second scenario is a decrease in the trade and transport margins due to public investment in road transport infrastructure. For ensuring the comparability of the return of public expenditure, the same amount of public capital is invested in both scenarios.

Results

The simulation outcome indicates that public investment in water facility and improved stoves results relatively higher domestic production in most sectors, larger household consumption, improved household welfare and improve in the major macroeconomic indicators (GDP, absorption, private consumption, and total domestic production) as compared to public investment in road transport infrastructure.

Conclusions

It is conducive to explore the potential economic contribution of public expenditure across the different pro-poor sectors before launching public investment in any specific sector. This will ensure limited public budgets are appropriately invested in the sector that can bring relatively highest economic-wide benefits to the wider society.
A focus group study of therapists’ views on using a novel neuroanimation virtual reality game to deliver intensive upper-limb rehabilitation early after stroke
Authors: Stockley Rachel C. , Christian Danielle L.
Published: June 2022

Background

Intensive training can significantly reduce upper-limb impairments after stroke but delivering interventions of sufficiently high intensity is extremely difficult in routine practice. The MindPod Dolphin® system is a novel neuroanimation experience which provides motivating and intensive virtual reality based training for the upper-limb. However several studies report that health professionals have reservations about using technology in rehabilitation. Therefore, this study sought to explore the views of therapists who had used this novel neuroanimation therapy (NAT) in a clinical centre to deliver intensive for the upper-limb of people after stroke in a phase 2 trial (SMARTS2).

Methods

Four therapists (three female, two physical and two occupational therapists) who delivered NAT participated in a focus group conducted by two independent researchers. The theoretical domains framework and COM-B behaviour change models informed the discussion schedule for the focus group. An inductive approach to content analysis was used. Recordings were transcribed, coded and thematically analysed. Generated key themes were cross-checked with participants.

Results

Whilst therapists had some initial concerns about using NAT, these were reduced by training, reference materials and face-to-face technical support. Therapists noted several significant benefits to using NAT including multi-system involvement, carry-over to functional tasks and high levels of patient engagement.

Conclusions

These findings illuminate key areas that clinicians, technology developers and researchers should consider when designing, developing and implementing NAT. Specifically, they highlight the importance of planning the implementation of rehabilitation technologies, ensuring technologies are robust and suggest a range of benefits that might be conferred to patients when using intensive NAT as part of rehabilitation for the upper-limb after stroke.
An explainable framework for load forecasting of a regional integrated energy system based on coupled features and multi-task learning
Authors: Wu Kailang , Gu Jie , Meng Lu , Wen Honglin , Ma Jinghuan
Published: June 2022

To extract strong correlations between different energy loads and improve the interpretability and accuracy for load forecasting of a regional integrated energy system (RIES), an explainable framework for load forecasting of an RIES is proposed. This includes the load forecasting model of RIES and its interpretation. A coupled feature extracting strategy is adopted to construct coupled features between loads as the input variables of the model. It is designed based on multi-task learning (MTL) with a long short-term memory (LSTM) model as the sharing layer. Based on SHapley Additive exPlanations (SHAP), this explainable framework combines global and local interpretations to improve the interpretability of load forecasting of the RIES. In addition, an input variable selection strategy based on the global SHAP value is proposed to select input feature variables of the model. A case study is given to verify the effectiveness of the proposed model, constructed coupled features, and input variable selection strategy. The results show that the explainable framework intuitively improves the interpretability of the prediction model.
Assessment of phytotoxicity of selected botanical insecticides on treated cowpea (Vigna unguiculata) seed
Authors: Ogbonnaya Ewa , Rizwan Ansari Ahmad , Bamidele Emakoji Ile , Ayuba Victoria
Published: June 2022

Background

Synthetic insecticides employed in seed treatment are often phytotoxic, especially at slightest misapplications. Cowpea seed is mainly attacked byCallosobruchus maculatus. It is established that azadirachtin, myristicin and α-humulene based insecticides (botanical insecticides) are eco-friendly and have activity againstC. maculatusand thus are considered ideal candidates in research efforts targeted at developing plant based options for protecting cowpea seed againstC. maculatusattack. Therefore, the aim of this study was to evaluate the toxicity of selected botanical insecticides on treated cowpea (Vigna unguiculata) seed.

Results

Electrical conductivity of leachate obtained from cowpea seed treated with botanical insecticides was significantly (P < 0.05) lower than that recorded on seed treated with chlorpyrifos. Malondialdehyde levels in seed of cowpea cultivars; SAMPEA 11 and 12 was significantly (P < 0.05) higher than that recorded on seed treated with chlorpyrifos. However, malondialdehyde levels in seed of SAMPEA 14 treated with myristicin and azadirachtin based insecticides were not significantly (P > 0.05) different from that reported for cowpea seed treated with chlorpyrifos. Less than 50% of the embryo recovered from seed treated with botanical insecticides was unstained contrary to the observation made on seed of SAMPEA 14 dressed with chlorpyrifos.

Conclusion

This study reveals similarity as well as variation in varietal sensitivity to phytoxicity among the various cultivars of cowpea seed studied implying that a farmer’s choice of botanical insecticides for the protection of cowpea seed againstCallosobruchus maculatuswould strictly depend on the cultivars involved.
Three-dimensional echocardiographic assessment of Chiari’s network relationship with the left ventricular false tendon
Authors: Sumerkan Mutlu Cagan , Cetin Sukru , Helvaci Fusun Behramoglu , Yaslikaya Sendag Satilmis , Karabay Umut , Hamit Turgun , Gurdal Ahmet , Agirbasli Mehmet , Alyan Omer
Published: June 2022

Background

Left ventricular false tendon (LVFT) is a fibromuscular band crossing the left ventricular cavity. And Chiari’s network (CN) is a highly mobile, mesh-like, echogenic structure in right atrium. In this study, we aimed to evaluate the coexistence of LVFT in patients with CN. CN patients were examined with live/real-time three-dimensional transthoracic echocardiography (TTE) for visualization of LVFT.

Results

This is a single-center prospective study of 49 patients with CN. In literature studies, the average ratios of LVFT were 22% in the normal population. In our study, an increased ratio of LVFT (n = 31, 63.3%) was found in CN patients evaluated with a three-dimensional TTE (63.3% versus 22%) (p = 0.01). The interatrial septal aneurysm was found in 31 (63.3%) patients with CN. And, the positive contrast echocardiography examination was determined in 22 (61.1%) patients with CN.

Conclusions

Our study reveals that CN is associated with LVFT and is also associated with cardiac anomalies like an interatrial septal aneurysm, and atrial septal defect. And LVFT can be evaluated better with three-dimensional TTE than with traditional two-dimensional TTE. Patients with CN should be evaluated more carefully by three-dimensional echocardiography as they can be in synergy in terms of the cardiac pathologies they accompany.
Therapeutic potential of venom peptides: insights in the nanoparticle-mediated venom formulations
Authors: Joglekar Aditya Vivek , Dehari Deepa , Anjum Md. Meraj , Dulla Naveen , Chaudhuri Aiswarya , Singh Sanjay , Agrawal Ashish Kumar
Published: June 2022

Background

Venoms are the secretions produced by animals, generally for the purpose of self-defense or catching a prey. Biochemically venoms are mainly composed of proteins, lipids, carbohydrates, ions, etc., and classified into three major classes, viz. neurotoxic, hemotoxic and cytotoxic based upon their mode of action. Venoms are composed of different specific peptides/toxins which are responsible for their unique biological actions. Though venoms are generally seen as a source of death, scientifically venom is a complex biochemical substance having a specific pharmacologic action which can be used as agents to diagnose and cure a variety of diseases in humans.

Main body

Many of these venoms have been used since centuries, and their specified therapies can also be found in ancient texts such as Charka Samhita. The modern-day example of such venom therapeutic is captopril, an antihypertensive drug developed from venom of Bothrops jararaca. Nanotechnology is a modern-day science of building materials on a nanoscale with advantages like target specificity, increased therapeutic response and diminished side effects. In the present review we have introduced the venom, sources and related constituents in brief, by highlighting the therapeutic potential of venom peptides and focusing more on the nanoformulations-based approaches. This review is an effort to compile all such report to have an idea about the future direction about the nanoplatforms which should be focused to have more clinically relevant formulations for difficult to treat diseases.

Conclusion

Venom peptides which are fatal in nature if used cautiously and effectively can save life. Several research findings suggested that many of the fatal diseases can be effectively treated with venom peptides. Nanotechnology has emerged as novel strategy in diagnosis, treatment and mitigation of diseases in more effective ways. A variety of nanoformulation approaches have been explored to enhance the therapeutic efficacy and reduce the toxicity and targeted delivery of the venom peptide conjugated with it. We concluded that venom peptides along with nanoparticles can evolve as the new era for potential treatments of ongoing and untreatable diseases.

Graphical Abstract
Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia
Authors: Kadia Tapan M. , Reville Patrick K. , Wang Xuemei , Rausch Caitlin R. , Borthakur Gautam , Pemmaraju Naveen , Daver Naval G. , DiNardo Courtney D. , Sasaki Koji , Issa Ghayas C. , Ohanian Maro , Montalban-Bravo Guillermo , Short Nicholas J. , Jain Nitin , Ferrajoli Alessandra , Bhalla Kapil N. , Jabbour Elias , Takahashi Koichi , Malla Rashmi , Quagliato Kelly , Kanagal-Shamanna Rashmi , Popat Uday R. , Andreeff Michael , Garcia-Manero Guillermo , Konopleva Marina Y. , Ravandi Farhad , Kantarjian Hagop M.
Published: June 2022

PURPOSE

The combination of venetoclax and 5-azacitidine (5-AZA) for older or unfit patients with acute myeloid leukemia (AML) improves remission rates and survival compared with 5-AZA alone. We hypothesized that the addition of venetoclax to cladribine (CLAD)/low-dose araC (low-dose cytarabine [LDAC]) alternating with 5-AZA backbone may further improve outcomes for older patients with newly diagnosed AML.

METHODS

This is a phase II study investigating the combination of venetoclax and CLAD/LDAC alternating with venetoclax and 5-AZA in older (≥ 60 years) or unfit patients with newly diagnosed AML. The primary objective was composite complete response (CR) rate (CR plus CR with incomplete blood count recovery); secondary end points were overall survival, disease-free survival (DFS), overall response rate, and toxicity.

RESULTS

A total of 60 patients were treated; median age was 68 years (range, 57-84 years). By European LeukemiaNet, 23%, 33%, and 43% were favorable, intermediate, and adverse risk, respectively. Fifty-six of 60 evaluable patients responded (composite CR: 93%) and 84% were negative for measurable residual disease. There was one death (2%) within 4 weeks. With a median follow-up of 22.1 months, the median overall survival and DFS have not yet been reached. The most frequent grade 3/4 nonhematologic adverse events were febrile neutropenia (n = 33) and pneumonia (n = 14). One patient developed grade 4 tumor lysis syndrome.

CONCLUSION

Venetoclax and CLAD/LDAC alternating with venetoclax and 5-AZA is an effective regimen among older or unfit patients with newly diagnosed AML. The rates of overall survival and DFS are encouraging. Further study of this non–anthracycline-containing backbone in younger patients, unfit for intensive chemotherapy, as well as comparisons to standard frontline therapies is warranted.
Molecular Characterization of Mesothelioma: Impact of Histologic Type and Site of Origin on Molecular Landscape
Authors: Dagogo-Jack Ibiayi , Madison Russell W. , Lennerz Jochen K. , Chen Kuei-Ting , Hopkins Julia F. , Schrock Alexa B. , Ritterhouse Lauren L. , Lester Ashley , Wharton Jr Keith A. , Mino-Kenudson Mari , Danziger Natalie , Hung Yin P. , Mata Douglas A. , Ross Jeffrey S.
Published: June 2022

PURPOSE

Mesothelioma is an aggressive malignancy with heterogeneous outcomes that are partly driven by the differential efficacy of existing therapies across histologic types and sites of origin. Large-scale molecular analysis of mesothelioma and its subtypes has the potential to inform future therapeutic strategies.

MATERIALS AND METHODS

We analyzed 1,294 mesotheliomas {980 pleural (malignant pleural mesothelioma [MPM]) and 314 peritoneal (malignant peritoneal mesothelioma [MPeM])} using next-generation sequencing, determined programmed death ligand-1 (PD-L1) expression and histology in a subset of cases, and assessed MTAP /CDKN2A copy-number status by fluorescence in situ hybridization and T-cell infiltration in an independent cohort.

RESULTS

The molecular landscape of MPM was characterized by inactivating alterations in CDKN2A (49%), BAP1 (44%), CDKN2B (42%), MTAP (34%), and NF2 (33%). Compared with epithelioid MPM, nonepithelioid (ie, biphasic and sarcomatoid) MPM had identical tumor mutational burden (median 1.25 mut/Mb, P = .63), more commonly expressed PD-L1 (74% v 51%, P = .02), and was more likely to harbor MTAP, CDKN2A, and CDKN2B copy loss ( P < .05). Fluorescence in situ hybridization confirmed that homozygous MTAP loss was enriched in nonepithelioid MPM. Relative to MPM, MPeM had comparable tumor mutational burden and PD-L1 expression. The molecular profile of MPeM was similar to MPM, with the distinction that PBRM1 alterations occurred at higher frequency (16% v 7%, P < .01). ALK rearrangements were only observed in MPeM.

CONCLUSION

Regardless of histology and location, the molecular landscape of mesothelioma primarily consists of inactivating alterations in tumor suppressor genes, with enrichment of certain alterations in distinct subsets (eg, MTAP loss in nonepithelioid tumors). Given the limited efficacy of current therapies for this disease, novel approaches targeting recurring alterations should be explored.
Metabolomic Changes Upon Conjugated Linoleic Acid Supplementation and Predictions of Body Composition Responsiveness
Authors: He Yafang , Xu Kun , Li Yunfeng , Chang Huan , Liao Xia , Yu Hang , Tian Tian , Li Chao , Shen Yuan , Wu Qian , Liu Xin , Shi Lin
Published: June 2022

Context

Conjugated linoleic acid (CLA) may optimize body composition, yet mechanisms underlining its benefits are not clear in humans.

Objective

We aimed to reveal the CLA-induced changes in the plasma metabolome associated with body composition improvement and the predictive performance of baseline metabolome on intervention responsiveness.

Methods

Plasma metabolome from overnight fasted samples at pre- and post-intervention of 65 participants in a 12-week randomized, placebo-controlled trial (3.2 g/day CLA vs 3.2 g/day sunflower oil) were analyzed using untargeted LC-MS metabolomics. Mixed linear model and machine learning were applied to assess differential metabolites between treatments, and to identify optimal panel (based on baseline conventional variables vs metabolites) predicting responders of CLA-derived body composition improvement (increased muscle variables or decreased adiposity variables) based on dual-energy x-ray absorptiometry.

Results

Compared with placebo, CLA altered 57 metabolites (P < 0.10) enriched in lipids/lipid-like molecules including glycerophospholipids (n = 7), fatty acyls (n = 6), and sphingolipids (n = 3). CLA-upregulated cholic acid (or downregulated aminopyrrolnitrin) was inversely correlated with changes in muscle and adiposity variables. Inter-individual variability in response to CLA-derived body composition change. The areas under the curves of optimal metabolite panels were higher than those of optimal conventional panels in predicting favorable response of waist circumference (0.93 [0.82-1.00] vs 0.64 [0.43-0.85]), visceral adiposity index (0.95 [0.88-1.00] vs 0.58 [0.35-0.80]), total fat mass (0.94 [0.86-1.00] vs 0.69 [0.51-0.88]) and appendicular fat mass (0.97 [0.92-1.00] vs 0.73 [0.55-0.91]) upon CLA supplementation (all FDR P < 0.05).

Conclusion

Post-intervention metabolite alterations were identified, involving in lipid/energy metabolism, associated with body composition changes. Baseline metabolite profiling enhanced the prediction accuracy for responsiveness of CLA-induced body composition benefits.
George Lamming: Reflections on Writing, Politics, and Caribbean Society
Authors: Farah Nuruddin , Bogues Anthony
Published: June 2022

This interview was conducted in September 2014 by the noted African novelist and writer Nuruddin Farah and the Caribbean intellectual historian and scholar Anthony Bogues. George Lamming, a seminal Caribbean novelist, writer, and thinker, is the author of six novels and a remarkable volume of essays, along with several other works. He belongs to a generation of Caribbean writers and intellectuals who carved out a space for Caribbean literature and thought in the twentieth century. In 2014 he was awarded the Anisfield-Wolf Book Award.
The Experience of Peril in Secular Criticism
Authors: Zartaloudis Thanos
Published: June 2022

This essay offers a reading of Stathis Gourgouris's The Perils of the One (2019). The peril of the One is primarily, Zartaloudis suggests, its poverty of experience. The impoverishment of experience is the purpose of transcendental foundations of the One, which, in Western traditions, is presupposed through a binary schema of power whereby potency is exhausted in actuality. This binary of power corresponds historically to the Christian Trinitarian oikonomia that predates the transcendental foundationalism of sovereign power/law and secular government. Hence, the age-old discourses that have been produced over many centuries over heteronomy and/or autonomy, across the theological, philosophical, juridical, and political spectrum, revolve around the same false paradox of how to form order in the world from a transcendental vantage point, without being able, by definition, to unfold it in the world. Determined to separate the false paradox (the “world” according to the One) from the true paradox (the cosmological abyss) within which it unfolds, humanity is thought to be destined to an inevitable state of war as if by nature. Secular criticism (in the manner of Edward Said and Gourgouris) as a tradition of thought offers an alternative to the polemic between traditions that are structured according to a false paradox (a world as the world) attempting to erase the unmappable cosmos. Such criticism, it is proposed, could become ever more creative and inviting if it reached out across traditions to compose an impassioned poietic thread that is premised on the negation neither of traditions nor of the irreparable cosmological abyss that marks our species.
Dorsal Root Entry Zone Lesioning for the Treatment of Pain After Brachial Plexus Avulsion Injury: 2-Dimensional Operative Video and Technical Report
Authors: Khalifeh Jawad M. , Lubelski Daniel , Ochuba Arinze , Belzberg Allan J.
Published: June 2022

BACKGROUND:

Neuropathic pain after nerve root or plexus avulsion injury is disabling and often refractory to medical therapy. Dorsal root entry zone (DREZ) lesioning is a neurosurgical procedure that disrupts the pathological generation and transmission of nociceptive signaling through the selective lesioning of culprit neurons within the dorsal horn of the spinal cord.

OBJECTIVE:

To present a case report and describe the operative technique for cervical spinal cord DREZ lesioning using radiofrequency thermocoagulation.

METHODS:

We present the case of a 29-year-old man who experienced a traumatic right-sided brachial plexus avulsion injury. The patient experienced severe neuropathic pain in his distal right upper extremity. He underwent cervical spinal DREZ lesioning. Postoperatively, he reported immediate and total pain relief that was sustained on follow-up at 3 months. We describe the operative technique for DREZ lesioning, including preoperative considerations, patient position, incision, approach, exposure, microsurgical dissection, DREZ lesioning, fixation, and closure.

RESULTS:

The goal of DREZ lesioning is the selective destruction of nociceptive fibers within the lateral bundle of the dorsal rootlet and superficial layers of the dorsal horn gray matter, while preserving the medial inhibitory fibers. DREZ lesioning targets the putative pain generator and ascending pain pathways that mediate the characteristic neuropathic pain after avulsion injury. Neurological complications include worsening pain or motor and sensory deficits of the ipsilateral lower extremity.

CONCLUSION:

DREZ lesioning provides an effective and durable treatment for neuropathic pain after nerve root or plexus avulsion injury.
Rac1, the actin cytoskeleton and microtubules are key players in clathrin-independent endophilin-A3-mediated endocytosis
Authors: Tyckaert François , Zanin Natacha , Morsomme Pierre , Renard Henri-François
Published: June 2022

Endocytic mechanisms actively regulate plasma membrane composition and sustain fundamental cellular functions. Recently, we identified a clathrin-independent endocytic (CIE) modality mediated by the BAR domain protein endophilin-A3 (endoA3, encoded by SH3GL3), which controls the cell surface homeostasis of the tumor marker CD166 (also known as ALCAM). Deciphering the molecular machinery of endoA3-dependent CIE should therefore contribute to a better understanding of its pathophysiological role, which remains so far unknown. Here, we investigate the role of actin, Rho GTPases and microtubules, which are major players in CIE processes, in this mechanism. We show that the actin cytoskeleton is dynamically associated with endoA3- and CD166-positive endocytic carriers, and that its perturbation strongly inhibits the process of CD166 uptake. We also reveal that the Rho GTPase Rac1, but not Cdc42, is a master regulator of this endocytic route. Finally, we provide evidence that microtubules and kinesin molecular motors are required to potentiate endoA3-dependent endocytosis. Of note, our study also highlights potential compensation phenomena between endoA3-dependent CIE and macropinocytosis. Altogether, our data deepen our understanding of this CIE modality and further differentiate it from other unconventional endocytic mechanisms.

This article has an associated First Person interview with the first author of the paper.
Physiological responses and adjustments of corals to strong seasonal temperature variations (20–28°C)
Authors: Sawall Yvonne , Nicosia Anna M. , McLaughlin Kathryn , Ito Maysa
Published: June 2022

Temperature is a key driver of metabolic rates. So far, we know little about potential physiological adjustments of subtropical corals to seasonal temperature changes (>8°C) that substantially exceed temperature fluctuation experienced by their counterparts in the tropics. This study investigated the effect of temperature reductions on Montastraea cavernosa and Porites astreoides in Bermuda (32°N; sea surface temperature ∼19–29°C) over 5 weeks, applying the following treatments: (i) constant control temperature at 28°C, and (ii) temperature reduction (0.5°C day−1) followed by constant temperature (20 days; acclimatization period) at 24°C and (iii) at 20°C. Both species decreased photosynthesis and respiration during temperature reduction as expected, which continued to decrease during the acclimatization period, indicating adjustment to a low energy turnover rather than thermal compensation. Trajectories of physiological adjustments and level of thermal compensation, however, differed between species. Montastraea cavernosa zooxanthellae metrics showed a strong initial response to temperature reduction, followed by a return to close to control values during the acclimatization period, reflecting a high physiological flexibility and low thermal compensation. Porites astreoides zooxanthellae, in contrast, showed no initial response, but an increase in pigment concentration per zooxanthellae and similar photosynthesis rates at 24°C and 20°C at the end of the experiment, indicating low acute thermal sensitivity and the ability for thermal compensation at the lowest temperature. Respiration decreased more strongly than photosynthesis, leading to significant build-up of biomass in both species (energy reserves). Results are important in the light of potential poleward migration of corals and of potential latitudinal and species-specific differences in coral thermal tolerance.
Acupuncture and Dry Needling for Sports Performance and Recovery
Authors: Tang Chi-Tsai , Song Bo
Published: June 2022

Acupuncture and dry needling share many similarities in their proposed mechanisms of action and their sports medicine-related applications. Pain is the most common indication for these needling treatments, but there also are some limited studies on their use for ergogenic purposes. Needling can likely improve muscular strength and power, including increasing jump height, and it also can increase flexibility. In terms of sports recovery, acupuncture can not only be used for pain relief after injury, but also can help with routine recovery, such as in delayed onset muscle soreness. There are numerous case reports of acupuncture and dry needling being used to treat athletes for various diagnoses and conditions, however more high quality studies are needed in order to make more specific evidence-based recommendations. Given the high degree of safety and limited adverse events associated with needling treatments, it can likely be promoted in athletes.
Optimization of scan parameters to reduce acquisition time for RESOLVE-based diffusion kurtosis imaging (DKI) in nasopharyngeal carcinoma (NPC)
Authors: He Yaoyao , Chen Hao , Zhang Huiting , Grimm Robert , Zhao Cecheng , Guo Xiaofang , Liu Yulin , Yuan Zilong
Published: June 2022

Objective:

To shorten acquisition time of readout segmentation of long variable echo trains (RESOLVE)-based diffusion kurtosis imaging (DKI) via Readout Partial Fourier (RPF) and b-value combinations.

Methods:

The RESOLVE-based DKI images of 38 patients with nasopharyngeal carcinoma (NPC) were prospectively enrolled. For RESOLVE-based DKI images with 5/8 RPF and without RPF, objective and subjective evaluations of image quality were performed. A total of nine groups with different b-value combinations were simulated, and the influence of different b-value combinations for RESOLVE-RPF-based DKI sequences was assessed using the intraclass correlation coefficient (ICC).

Results:

The mean values of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in DKI images without RPF were higher than those with 5/8 RPF (252.9 ± 77.7 vs 247.3 ± 85.5 and 5.8 ± 2.8 vs 5.4 ± 2.3, respectively), but not significantly (p = 0.460 and p = 0.180, respectively). In comparing the ICCs between nine groups of different b-value combinations in RESOLVE-RPF-based DKI, group (200, 800, 2000 s/mm2), group (200, 400, 800, 2000 s/mm2) and group (200, 800, 1500, 2000 s/mm2) were not significantly different (p > 0.001) and showed excellent agreement (0.81–1.00) with that of group (200, 400, 800, 1500, 2000 s/mm2). Using b-value optimization and RPF technology, the group with RPF (200, 400, 800, 2000 s/mm2) showed a 56% reduced scanning compared with the group without RPF (200, 400, 800, 1500, 2000 s/mm2; 3 min 46 s vs 8 min 31 s, respectively).

Conclusion:

DKI with RPF did not significantly affect image quality, but both RPF and different b-value combinations can affect the scanning time. The combination of RPF and b-value optimization can ensure the stability of DKI parameters and reduce the scanning time by 56%.

Advances in knowledge:

This work is to optimize scan parameters, e.g. RPF and b-value combinations, to reduce acquisition time for RESOLVE-based DKI in NPC. To our knowledge, the effect of RESOLVE-RPF and b-value combinations on DKI has not been reported.
The differentiation of mesenchymal bone marrow stem cells into nerve cells induced by Chromolaena odorata extracts
Authors: Eriani Kartini , Desriani Desriani , Suhartono Suhartono , Br Sibarani Miftahul Jannah , Ichsan Ichsan , Syafrizal Dedy , Asmara Hadhymulya
Published: June 2022

Background: Mesenchymal stem cells (MSCs) can differentiate into nerve cells with an induction from chemical compounds in medium culture. Chromolaena odorata contains active compounds, such as alkaloids and flavonoids, that can initiate the transformation of MSCs into nerve cells. The aim of this study was to determine the potential of methanol extracted C. odorata leaf to induce the differentiation of bone marrow MSCs into nerve cells.

Methods: A serial concentration of C. odorata leaf extract (0.7–1.0 mg/mL) with two replications was used. The parameters measured were the number of differentiated MSCs into nerve cells (statistically analyzed using ANOVA) and cell confirmation using reverse transcription polymerase chain reaction (RT-PCR).

Results: The results showed that the C. odorata extract had a significant effect on the number MSCs differentiating into nerve cells (p < 0.05) on the doses of 0.8 mg/ml with 22.6%. Molecular assay with RT-PCR confirmed the presence of the nerve cell gene in all of the samples.

Conclusions: In conclusion, this study showed the potential application of C. odorata leaf extract in stem cell therapy for patients experiencing neurodegeneration by inducing the differentiation of MSCs into nerve cells.
Transfer of maternal immunity using a polyvalent vaccine and offspring protection in Nile tilapia, Oreochromis niloticus
Authors: Amrullah Amrullah , Wahidah Wahidah , Ardiansyah Ardiansyah , Indrayani Indrayani
Published: June 2022

Background: Vaccination is an effective and alternative means of disease prevention, however, it cannot be conducted on the offspring of fish.  For this process to take place, the transfer of maternal immunity must be implemented. This study aims to determine the effectiveness of transferring immunity from the broodstock to the offspring using a polyvalent vaccine against Aeromonas hydrophila, Streptococcus agalactiae, and Pseudomonas fluorescens in Nile tilapia, Oreochromis niloticus.

Methods: Nile tilapia broodstock, with an average weight of 203g (±SD 23 g) was injected with a vaccine used as a treatment. Example include A. hydrophila monovalent (MA), S. agalactiae monovalent (MS), P. fluorescens monovalent (MP), A. hydrophila and S. agalactiae bivalent (BAS), A. hydrophila and P. fluorescens bivalent (BAP), P. fluorescens and S. agalactiae bivalent (BPS), and A. hydrophila, S. agalactiae, and P. fluorescens polyvalent vaccines (PAPS). While the control was fish that were injected with a PBS solution. The broodstock’s immune response was observed on the 7th, 14th, 21st, and 28th day, while the immune response and challenge test on the offspring was conducted on the 10th, 20th, 30th, and 40th day during the post-hatching period.

Result: The application of PAPS in broodstock could significantly induce the best immune response and immunity to multiple diseases compared to other treatments. The RPS of the PAPS was also higher than the other types of vaccines. This showed that the transfer of immunity from the broodstock to the Nile tilapia offspring could protect it against bacterial diseases such as A. hydrophila, S. agalactiae, and P. fluorescens.

Conclusion: The application of PAPS A. hydrophila, S. agalactiae, P. fluorescens vaccines increased the broodstock’s immune response and it was transferred to their offsprings. They were able to produce tilapia seeds that are immune to diseases caused by A. hydrophila, S. agalactiae, and P. fluorescens.