bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting ferroptosis with miR-144-3p to attenuate pancreatic β cells dysfunction via regulating USP22/SIRT1 in type 2 diabetes
Authors: Zhang Shanshan , Liu Xiao , Wang Jihong , Yuan Fengjuan , Liu Yali
Published: June 2022

Background

Recently, ferroptosis has been implicated in the pathologic process of several diseases including type 2 diabetes mellitus (T2DM). However, molecular mechanisms underlying ferroptosis in T2DM remain obscure.

Methods

Twenty four mice were included in this study. T2DM model mice were established by a high-fat diet combined with streptozotocin injection. INS-1 cells were stimulated with high glucose (HG). Cell viability was detected by CCK-8 kit. The levels of GSH, MDA, iron, and lipid ROS, and SOD activity, were detected by the corresponding kits. The interaction between miR-144-3p and USP22 was validated by dual-luciferase reporter assay. The relationship between USP22 and its substrate was verified using Co-IP and ubiquitination assays. The mRNA and protein expressions were examined by RT-qPCR and western blot, respectively. The functions of β cells in vitro and in vivo were evaluated glucose-stimulated insulin secretion test and HOMA-β, respectively.

Results

Ferroptosis occurred in the pancreas of T2DM mice and HG-induced INS-1 cells. Silencing miR-144-3p blocked the effect of HG on the cell viability and accumulation of lipid peroxides, thereby improving the insulin secretion in INS-1 cells. Mechanistically, USP22 is a direct target of miR-144-3p, which could stabilize SIRT1 expression, thereby suppressing ferroptosis. Overexpressing USP22 attenuated deleterious roles of HG in INS-1 cells; but its roles were reversed by up-regulating miR-144-3p. In vivo study demonstrated that miR-144-3p antagomir exerted an anti-hyperglycemic effect and regulated the ferroptosis-related proteins in the pancreas.

Conclusion

The up-regulation of miR-144-3p suppressed USP22/SIRT1 to induce ferroptosis, which causes pancreatic β cells dysfunction, thereby promoting T2DM development.
Income disparities in driving distance to health care infrastructure in the United States: a geographic information systems analysis
Authors: Guo Jingchuan , Hernandez Inmaculada , Dickson Sean , Tang Shangbin , Essien Utibe R. , Mair Christina , Berenbrok Lucas A.
Published: June 2022

Objective

Inequities in access to health care contribute to persisting disparities in health care outcomes. We constructed a geographic information systems analysis to test the association between income and access to the existing health care infrastructure in a nationally representative sample of US residents. Using income and household size data, we calculated the odds ratio of having a distance > 10 miles in nonmetropolitan counties or > 1 mile in metropolitan counties to the closest facility for low-income residents (i.e., < 200% Federal Poverty Level), compared to non-low-income residents.

Results

We identified that in 954 counties (207 metropolitan counties and 747 nonmetropolitan counties) representing over 14% of the US population, low-income residents have poorer access to health care facilities. Our analyses demonstrate the high prevalence of structural disparities in health care access across the entire US, which contribute to the perpetuation of disparities in health care outcomes.
Kimura disease with Allergic Bronchopulmonary Aspergillosis: a case report
Authors: Fan Ruiyun , Xu Guopeng , Chen Ying , Lv Jinghuan , Zhang Zhongwei
Published: June 2022

Background

Kimura disease (KD) is a rare chronic idiopathic condition of unknown etiology that is prevalent in Asian males. It often causes subcutaneous lumps and enlarged lymph nodes, especially in head and neck region. But KD is also a systemic disease that can involve multiple organs, such as the kidneys and skin.

Case presentation

We report a 62-year-old Chinese man who presented with paroxysmal cough, enlarged inguinal lymph nodes, recurrent skin itching, and elevated IgE antibodies specific to A. fumigatus. After a comprehensive review, the final diagnosis for this patient was KD with Allergic Bronchopulmonary Aspergillosis (ABPA).

Conclusions

The age of onset and the location of the lump involved were not characteristic for the illness. This case report described the patient’s diagnosis and treatment process. This case report serves to arouse the attention of multidisciplinary team to explore the potential relationship between KD and ABPA. It will contribute to preventing the misdiagnosis and missed diagnosis of KD.
Prognostic impact of an integrative analysis of [18F]FDG PET parameters and infiltrating immune cell scores in lung adenocarcinoma
Authors: Choi Jinyeong , Sarker Azmal , Choi Hongyoon , Lee Dong Soo , Im Hyung-Jun
Published: June 2022

Background

High levels of 18F-fluorodeoxyglucose (18F-FDG) tumor uptake are associated with worse prognosis in patients with non-small cell lung cancer (NSCLC). Meanwhile, high levels of immune cell infiltration in primary tumor have been linked to better prognosis in NSCLC. We conducted this study for precisely stratified prognosis of the lung adenocarcinoma patients using the integration of 18F-FDG positron emission tomography (PET) parameters and infiltrating immune cell scores as assessed by a genomic analysis.

Results

Using an RNA sequencing dataset, the patients were divided into three subtype groups. Additionally, 24 different immune cell scores and cytolytic scores (CYT) were obtained. In 18F-FDG PET scans, PET parameters of the primary tumors were obtained. An ANOVA test, a Chi-square test and a correlation analysis were also conducted. A Kaplan–Meier survival analysis with the log-rank test and multivariable Cox regression test was performed to evaluate prognostic values of the parameters. The terminal respiratory unit (TRU) group demonstrated lower 18F-FDG PET parameters, more females, and lower stages than the other groups. Meanwhile, the proximal inflammatory (PI) group showed a significantly higher CYT score compared to the other groups (P = .001). Also, CYT showed a positive correlation with tumor-to-liver maximum standardized uptake value ratio (TLR) in the PI group (P = .027). A high TLR (P = .01) score of 18F-FDG PET parameters and a high T follicular helper cell (TFH) score (P = .005) of immune cell scores were associated with prognosis with opposite tendencies. Furthermore, TLR and TFH were predictive of overall survival even after adjusting for clinicopathologic features and others (P = .024 and .047).

Conclusions

A high TLR score was found to be associated with worse prognosis, while high CD8 T cell and TFH scores predicted better prognosis in lung adenocarcinoma. Furthermore, TLR and TFH can be used to predict prognosis independently in patients with lung adenocarcinoma.
Bacterial community structure and bacterial isolates having antimicrobial potential in shrimp pond aquaculture
Authors: Ali Sardar , Xie Jianmin , Zada Sahib , Hu Zhong , Zhang Yueling , Cai Runlin , Wang Hui
Published: June 2022

Diseases outbreaks in pond aquaculture have resulted in huge losses to the aquaculture industry. The emergence of non-antimicrobial and environment friendly agents (probiotics) is the potential consideration for the healthy shrimp aquaculture. The present study was aimed to compare the bacterial community compositions in shrimp ponds and surrounding seawater, as well as isolate probiotic bacteria from the shrimp ponds. Based on the high-throughput of 16S rRNA gene sequencing, all sequences were assigned to 3584 unique operational taxonomic units (OTUs) at 97% similarity levels, which were affiliated with 24 phyla, 54 classes, 235 families, and 367 genera. The 10 most abundant phyla were Bacteroidota, Proteobacteria, Actinobacteriota, Planctomycetota, Cyanobacteria, Chloroflexi, Firmicutes, Desulfobacterota, Patescibacteria and Verrucomicrobiota. Notably, the alpha diversity (Shannon diversity) of shrimp ponds was significantly differences (P < 0.05) with that of surrounding seawater. There were 2498 and 791 unique OTUs in shrimp ponds and surrounding seawater, respectively. A total of 15 isolates were obtained in the culturable bacterial diversity, and the antibacterial activities were recorded for potential probiotic bacterial isolates against different tested bacterial isolates including pathogenic bacteria. An isolate Hallobacillusmarinus HMALI004 showed strong inhibitory effects against three pathogenic bacteria, Vibrio cholerae CECT 514, non AHPND V. parahaemolyticus BCRC12959 and AHPND V. parahaemolyticus PD-2. The isolates Algophigussanaruensis AGALI005, Algoriphagus taiwanensis ATALI009 and Bacillusaequororis BAALI008 were also identified as potential probiotics strains.
Hybrid intrusion detection system using blockchain framework
Authors: Khonde S. R. , Ulagamuthalvi V.
Published: June 2022

Data security and confidentiality are major goals now days due to the extensive use of the internet for data sharing. In modern era, most of the networks are compromised by intruders to grab access to private, confidential, and highly secured data. An intrusion detection system (IDS) is widely used to secure the network from getting compromised by intruders. Most of the IDS share the signatures of the novel attacks detected by anomaly approach for improving the detection rate and processing time. Security of signature shared by nodes is becoming a considerable problem. This paper presents a novel framework blockchain based hybrid intrusion detection system (BC-HyIDS), which uses the blockchain framework for exchanging signatures from one node to the other in distributed IDS. BC-HyIDS works in three phases where it uses both detection methods and blockchain in the third phase to provide security to data transferred through the network. This system makes use of a cryptosystem to encrypt the data stored in blocks to improve security one level higher. Hyperledger fabric v2.0 and Hyperledger sawtooth is used to implement system. Blockchain framework is created as a prototype using distributed ledger technology which helps in securing signature exchange. Performance of BC-HyIDS is evaluated in terms of accuracy, detection rate, and false alarm rate. From results, it is observed that a 2.8% increase in accuracy, 4.3% increase in detection rate, and a reduction of 2.6% in FAR is achieved. Blockchain performance is evaluated using Hyperledger fabric v2.0 and Hyperledger sawtooth on throughput, processing time, and average latency. BC-HyIDS shows improved performance when used with blockchain.
Targeting metabolic reprogramming in chronic lymphocytic leukemia
Authors: Nie Yu , Yun Xiaoya , Zhang Ya , Wang Xin
Published: June 2022

Metabolic reprogramming, fundamentally pivotal in carcinogenesis and progression of cancer, is considered as a promising therapeutic target against tumors. In chronic lymphocytic leukemia (CLL) cells, metabolic abnormalities mediate alternations in proliferation and survival compared with normal B cells. However, the role of metabolic reprogramming is still under investigation in CLL. In this review, the critical metabolic processes of CLL were summarized, particularly glycolysis, lipid metabolism and oxidative phosphorylation. The effects of T cells and stromal cells in the microenvironment on metabolism of CLL were also elucidated. Besides, the metabolic alternation is regulated by some oncogenes and tumor suppressor regulators, especially TP53, MYC and ATM. Thus, the agents targeting metabolic enzymes or signal pathways may impede the progression of CLL. Both the inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) statins and the lipoprotein lipase inhibitor orlistat induce the apoptosis of CLL cells. In addition, a series of oxidative phosphorylation inhibitors play important roles in decreasing the proliferation of CLL cells. We epitomized recent advancements in metabolic reprogramming in CLL and discussed their clinical potentiality for innovative therapy options. Metabolic reprogramming plays a vital role in the initiation and progression of CLL. Therapeutic approaches targeting metabolism have their advantages in improving the survival of CLL patients. This review may shed novel light on the metabolism of CLL, leading to the development of targeted agents based on the reshaping metabolism of CLL cells.
Anti-bacterial and anti-inflammatory activities of lactic acid bacteria-bioconversioned indica rice (Oryza sativa L.) extract
Authors: Kwon Hyuk-Ju , Ahn Hyunwoo , Kim Bong Sun , Kang Seok-Seong , Lee Kwang-Geun
Published: June 2022

Background

In this study, indica rice (Oryza sativa L.) was bioconversioned using Lactobacillus plantarum ATCC14917 and Lactobacillus rhamnosus GG KCTC5033.

Results

Compared to the control treatment (RE), rice extract fermented with Lactobacillus plantarum ATCC14917 (LP-RE) and Lactobacillus rhamnosus GG KCTC5033 (LR-RE) inhibited the growth of pathogenic bacteria significantly except for E. coli O157:H7 (p < 0.05). The LR-RE treatment had the strongest inhibitory effect on Staphylococcus aureus biofilm formation (10.81 ± 1.98%). Additionally, real-time PCR analyses confirmed that LP-RE inhibited S. aureus-induced IL-8 expression in Caco-2 cells by 60%. HPLC-orbitrap analysis indicated that this treatment increased the levels of key metabolites with therapeutic properties such as acetophenone, 9-oxo-10(E), 12(E)-octadecadienoic acid, nicotinic acid, and indol-3-lactic acid.

Conclusions

This study demonstrated that the secondary metabolites were linked to antibacterial and anti-inflammatory effects, suggesting that bioconversion is a promising means to produce dietary supplements with therapeutic properties.

Graphical Abstract
Efficient emotion recognition using hyperdimensional computing with combinatorial channel encoding and cellular automata
Authors: Menon Alisha , Natarajan Anirudh , Agashe Reva , Sun Daniel , Aristio Melvin , Liew Harrison , Shao Yakun Sophia , Rabaey Jan M.
Published: June 2022

In this paper, a hardware-optimized approach to emotion recognition based on the efficient brain-inspired hyperdimensional computing (HDC) paradigm is proposed. Emotion recognition provides valuable information for human–computer interactions; however, the large number of input channels (> 200) and modalities (> 3 ) involved in emotion recognition are significantly expensive from a memory perspective. To address this, methods for memory reduction and optimization are proposed, including a novel approach that takes advantage of the combinatorial nature of the encoding process, and an elementary cellular automaton. HDC with early sensor fusion is implemented alongside the proposed techniques achieving two-class multi-modal classification accuracies of > 76% for valence and > 73% for arousal on the multi-modal AMIGOS and DEAP data sets, almost always better than state of the art. The required vector storage is seamlessly reduced by 98% and the frequency of vector requests by at least 1/5. The results demonstrate the potential of efficient hyperdimensional computing for low-power, multi-channeled emotion recognition tasks.
How sign language expertise can influence the effects of face masks on non-linguistic characteristics
Authors: Lau Wee Kiat , Chalupny Jana , Grote Klaudia , Huckauf Anke
Published: June 2022

Face masks occlude parts of the face which hinders social communication and emotion recognition. Since sign language users are known to process facial information not only perceptually but also linguistically, examining face processing in deaf signers may reveal how linguistic aspects add to perceptual information. In general, signers could be born deaf or acquire hearing loss later in life. For this study, we focused on signers who were born deaf. Specifically, we analyzed data from a sample of 59 signers who were born deaf and investigated the impacts of face masks on non-linguistic characteristics of the face. Signers rated still-image faces with and without face masks for the following characteristics: arousal and valence of three facial expressions (happy, neutral, sad), invariant characteristics (DV:sex, age), and trait-like characteristics (attractiveness, trustworthiness, approachability). Results indicated that, when compared to masked faces, signers rated no-masked faces with stronger valence intensity across all expressions. Masked faces also appeared older, albeit a tendency to look more approachable. This experiment was a repeat of a previous study conducted on hearing participants, and a post hoc comparison was performed to assess rating differences between signers and hearing people. From this comparison, signers exhibited a larger tendency to rate facial expressions more intensely than hearing people. This suggests that deaf people perceive more intense information from facial expressions and face masks are more inhibiting for deaf people than hearing people. We speculate that deaf people found face masks more approachable due to societal norms when interacting with people wearing masks. Other factors like age and face database’s legitimacy are discussed.
The development, paradigm and academic values of enterprise anthropology—the “fourth revolution” of anthropology
Authors: Wang Zhuo
Published: June 2022

As an emerging interdisciplinary field in anthropology, enterprise anthropology (EA) has experienced five historical stages of development since its inception in the 1930s. 2008 marked the first year of internationalized enterprise anthropology, thus prompting the “fourth revolution” of anthropology. Since then, the sub-discipline of enterprise anthropology has entered its fifth stage of development. This stage of enterprise anthropology has witnessed new research subjects, concepts, and theories. Breakthroughs have been made in theoretical research and methodological innovation, and a unique paradigm has been established. In terms of discipline and era, the fifth stage is characterized by: innovative transformation and creative development, integration of Chinese and Western channels for anthropology research, building of international academic networks, and the practice of “people-centered” research. As a result, this stage of enterprise anthropology holds profound theoretical and practical significance for interdisciplinary and academic equity, new ideas and methods for studying the transformation of Chinese society, and establishment of an internationalized research paradigm for the Chinese academic community.
Computational evaluation of bioactive compounds from Vitis vinifera as a novel β-catenin inhibitor for cancer treatment
Authors: Adebesin Ayomide Oluwadarasimi , Ayodele Abigail Oluwakemi , Omotoso Olabode , Akinnusi Precious Ayorinde , Olubode Samuel Olawale
Published: June 2022

Background

β-catenin is an important unit of the Wnt/β-catenin signaling pathway, a conserved process involving several physiological activities, encompassing differentiation and cell proliferation, etc. The dysfunction or mutation in β-catenin causing the initiation and advancement of various neoplasm types, including colorectal cancer, breast cancer, etc., has been reported. Therefore, β-catenin is a therapeutic target. Hence, designing new inhibitors targeted against β-catenin will prevent cancerous cells’ involvement and eliminate the diseases. Studies showed that Vitis vinifera, a well-known grape species, contains different phytochemical substances, including aromatic acids, flavonoids, phenolic compounds, proanthocyanins, etc. V.vinifera exerts different anticancer properties such as apoptosis, cell proliferation, cell cycle arrest, and inhibition in cancerous cells. Structural bioinformatics methods, including molecular docking, molecular mechanics generalized Born surface area (MM/GBSA), absorption, distribution, metabolism, excretion studies (ADMET), and pharmacophore modeling approach, were used to determine the potential β-catenin inhibitors from V.vinifera bioactive compounds.

Result

Cis-astringin, rutin, caftaric acid, trans-caftaric acid, procyanidin B3, cis-Miyabenol C, and ampelopsin H are shown to be suitable inhibitors against β-catenin due to their binding affinity and interaction with the amino acids residues at the binding sites of β-catenin compared to Food and Drug Administration (FDA) approved drugs leucovorin Calcium and Xeloda prescribed to cure colorectal cancer.

Conclusions

This study suggests that V. vinifera could be a good plant source for compounds that might treat cancer by inhibiting the Wnt/β-catenin signaling pathway.
Subcutaneous progesterone (Prolutex) versus vaginal (Cyclogest) for luteal phase support in IVF/ICSI cycles: a randomized controlled clinical trial
Authors: Moini Ashraf , Arabipoor Arezoo , Zolfaghari Zahra , Sadeghi Maria , Ramezanali Fariba
Published: June 2022

Background

To compare the safety, efficacy, and tolerability of subcutaneous vaginal progesterone suppository for luteal phase support (LPS) in assisted reproduction technology (ART) cycles in patients referred to the Royan Institute.

Methods

This randomized clinical trial was conducted from August 2016 to March 2018. The infertile patients undergoing in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) were evaluated. The controlled ovarian stimulation (COH) was performed in all of the patients with standard long GnRH agonist protocol. After ovum pickup, eligible women were randomly allocated into two groups. In group A, since oocyte retrieval day, subcutaneous injections of progesterone (50 mg) (Prolutex®) were used daily, and in group B, two vaginal suppositories (Cyclogest ®) were administrated for LPS. The clinical pregnancy and miscarriage rates and the drug’s side effect were compared between two groups by appropriate statistical tests.

Results

Finally, 40 patients in each group were enrolled, and the IVF/ICSI outcomes were compared between groups. The data analysis showed that no significant differences were found between groups in terms of the demographic, infertility characteristics, and the COH outcome between groups. The chemical and clinical pregnancy rates (CPR) in group A were significantly higher than those of group B (P = 0.04, P = 0.02, respectively). The implantation and twin pregnancy rates in group B were significantly higher than those in group A (P = 0.009, P = 0.02, respectively).

Conclusion

The subcutaneous administration of progesterone 25 mg twice daily for LPS was associated with higher CPR versus vaginal progesterone, and it was safe and well-tolerated in the follow-up. In addition, it can be a suitable replacement in cases of allergic reactions to vaginal suppositories. However, further study is required to compare the cost-effectiveness of these medications.

Trial registration

The study was also registered in the Iranian Registry of Clinical Trials on February 19, 2015 (IRCT201402191141N18 at www.irct.ir, registered prospectively).
A study of emotional intelligence in an Egyptian sample of offspring of patients with schizophrenia
Authors: ElSehrawy Tarek M. K. , Elela Eman Abo , Hassan Ghada A. M. , Missiry Marwa El , Nabi Sohayla Abdel , Soliman Mahmoud Farag
Published: June 2022

Background

Emotional intelligence is usually a construct measured in healthy children, now it may be used for relatives of schizophrenia, and considered as trait marker for schizophrenia. Offspring of parents with schizophrenia are considered children with high familial risk for major mental disorder. The aim of the study is to assess emotional intelligence in a group of off springs of a parent with schizophrenia and compare them to healthy control subjects, and to find possible relation between emotional intelligence in offspring and profile of symptoms in schizophrenic parents.

Results

Offspring of parents with schizophrenia had lower scores of emotional intelligences than their matched controls in emotion perception, self-esteem, low impulsivity and emotion regulation’s subsets of TEIQue-CF. There was correlation between offspring trait emotional intelligence and their parent’s duration of illness. There was no correlation found between schizophrenia severity in the parents and their offspring’s trait emotional intelligence.

Conclusions

Offspring of parents with schizophrenia had impaired trait emotional intelligence in some of its facets when compared to normal healthy subjects.
Leukocyte-specific DNA methylation biomarkers and their implication for pathological epigenetic analysis
Authors: Dunnet M. J. , Ortega-Recalde O. J. , Waters S. A. , Weeks R. J. , Morison I. M. , Hore T. A.
Published: June 2022

Background

Distinct cell types can be identified by their DNA methylation patterns. Much research over the last decade has focused on DNA methylation changes in cancer or the use of cell-free circulating DNA in plasma to identify damaged tissue in cases of trauma or organ transplantation. However, there has been little research into the differential methylation patterns between leukocytes and other tissues and how they can be used as a detection tool for immune activity in a range of contexts.

Results

We have identified several loci that are fully methylated in leukocytes but virtually devoid of methylation in a range of other mesoderm-, ectoderm-, and endoderm-derived tissues. We validated these biomarkers using amplicon-bisulphite-sequencing on saliva and in vitro mixing of peripheral blood mononuclear cells and intestinal organoid cells combined at a defined range of ratios. Interestingly, these methylation biomarkers have previously been identified as altered in various inflammatory diseases, including Alzheimer disease, inflammatory bowel disease, and psoriasis. We hypothesise this is due to leukocyte infiltration rather than being a feature of the diseased cells themselves. Moreover, we show a positive linear relationship between infiltrating leukocytes and DNA methylation levels at the HOXA3 locus in six cancer types, indicative of further immune cell infiltration.

Conclusions

Our data emphasise the importance of considering cellular composition when undertaking DNA methylation analysis and demonstrate the feasibility of developing new diagnostic tests to detect inflammation and immune cell infiltration.
The interplay between psychopathological symptoms: transdiagnostic cross-lagged panel network model
Authors: Chavez-Baldini UnYoung , Verweij Karin , de Beurs Derek , Bockting Claudi , Lok Anja , Sutterland Arjen L. , van Rooijen Geeske , van Wingen Guido , Denys Damiaan , Vulink Nienke , Nieman Dorien
Published: June 2022

Background

Recent paradigm shifts suggest that psychopathology manifests through dynamic interactions between individual symptoms.

Aims

To investigate the longitudinal relationships between symptoms in a transdiagnostic sample of patients with psychiatric disorders.

Method

A two-wave, cross-lagged panel network model of 15 nodes representing symptoms of depression, (social) anxiety and attenuated psychotic symptoms was estimated, using baseline and 1-year follow-up data of 222 individuals with psychiatric disorders. Centrality indices were calculated to determine important predictors and outcomes.

Results

Our results demonstrated that the strongest relationships in the network were between (a) more suicidal ideation predicting more negative self-view, and (b) autoregressive relationships of social anxiety symptoms positively reinforcing themselves. Negative self-view was the most predictable node in the network as it had the highest ‘in-expected influence’ centrality, and may be an important transdiagnostic outcome symptom.

Conclusions

The results give insight into longitudinal interactions between symptoms, which interact in ways that do not adhere to broader diagnostic categories. Our results suggest that self-view can also be a transdiagnostic outcome of psychopathology rather than just a predictor, as is normally posited, and may especially have an important relationship with suicidal ideation. Overall, our study demonstrates the dynamic complexity of psychopathology, and further supports the importance of investigating symptom interactions of different psychopathological dimensions over time and across disorders.
Escape dynamics in an anisotropically driven Brownian magneto-system
Authors: Abdoli I. , Sommer J.-U. , Löwen H. , Sharma A.
Published: June 2022

Thermally activated escape of a Brownian particle over a potential barrier is well understood within Kramers theory. When subjected to an external magnetic field, the Lorentz force slows down the escape dynamics via a rescaling of the diffusion coefficient without affecting the exponential dependence on the barrier height. Here, we study the escape dynamics of a charged Brownian particle from a two-dimensional truncated harmonic potential under the influence of Lorentz force due to an external magnetic field. The particle is driven anisotropically by subjecting it to noises with different strengths along different spatial directions. We show that the escape time can largely be tuned by the anisotropic driving. While the escape process becomes anisotropic due to the two different noises, the spatial symmetry is restored in the limit of large magnetic fields. This is attributed to the Lorentz-force–induced coupling between the spatial degrees of freedom which makes the difference between two noises irrelevant at high magnetic fields. The theoretical predictions are verified by Brownian dynamics simulations. In principle, our predictions can be tested by experiments with a Brownian gyrator in the presence of a magnetic field.
Obstetric Anesthesia Procedure-Based Workload and Facility Utilization of Society of Obstetric Anesthesia and Perinatology Centers of Excellence Designated Institutions
Authors: Im Mary , Riley Edward T. , Hoang Dan , Lim Grace , Zakowski Mark , Carvalho Brendan
Published: June 2022

BACKGROUND:

Optimal workload and staffing for obstetric anesthesia services have yet to be determined. We surveyed Society of Obstetric Anesthesia and Perinatology (SOAP) Centers of Excellence (COE) for Obstetric Anesthesia Care institutions to evaluate procedure-based obstetric anesthesia workload and facility use.

METHODS:

After institutional review board (IRB) exemption, an online survey instrument (REDCap) was sent by email (1 initial and 2 reminders) to all SOAP COEs. Survey data included the number of deliveries, cesarean delivery rate, neuraxial labor analgesia rate, the number of labor and operating rooms, and the number of in-house and backup obstetric anesthesia providers. Obstetric anesthesia activity was estimated using a time-based workload ratio per provider (Stanford Work Index, 1.0 = clinically working every minute of every hour on duty) during weekday, weeknight, and weekend shifts. We compared workload between academic and nonacademic centers and correlated operating and labor rooms with cesarean and vaginal delivery volume.

RESULTS:

Fifty-one of 53 surveys were returned (96% response rate). Data from 33 academic and 14 nonacademic US institutions were analyzed. For academic centers, median Stanford Work Index for all staff (included trainees and Certified Registered Nurse Anesthetists) was 0.20 (weekday) and 0.19 (weeknight and weekends); nonacademic centers were 0.33 (weekday, P < .001 versus academic), 0.23 (weeknight, P = .009 versus academic), and 0.23 (weekends, P = .03 versus academic practices). Attending-only Stanford Work Indices were similar between academic and nonacademic centers. Total number of rooms on the obstetric suite (operating, labor, or triage room) was strongly correlated with delivery volume (R
2 = 0.55).

CONCLUSIONS:

The results outline staffing procedure-based workload ratios and facility utilization at SOAP COEs in the United States. These data can be used by other institutions that provide obstetric anesthesia services to guide their obstetric anesthesia staffing. The importance of considering the workload associated with different shifts and between academic and nonacademic centers is also highlighted. The results show that approximately one-third of an obstetric anesthesiologist’s workload is spent on performing procedures. We did not, however, measure the other tasks anesthesiologists practice as peripartum physicians (eg, managing critically ill parturients, doing pre- and postprocedural evaluations, or performing emergent and unexpected procedures), and future studies are required to determine the time required to perform these tasks. Studies to determine the optimal staffing models to handle workload fluctuations and improve outcomes are also required.
Dexmedetomidine Diminishes, but Does Not Prevent, Developmental Effects of Sevoflurane in Neonatal Rats
Authors: Yang Zhengbo , Tong Yuanyuan , Brant Jason O. , Li Ningtao , Ju Ling-Sha , Morey Timothy E. , Gravenstein Nikolaus , Setlow Barry , Zhang Jiaqiang , Martynyuk Anatoly E.
Published: June 2022

BACKGROUND:

Sevoflurane (SEVO) increases neuronal excitation in neonatal rodent brains through alteration of gamma aminobutyric acid (GABA)(A) receptor signaling and increases corticosterone release. These actions may contribute to mechanisms that initiate the anesthetic’s long-term neuroendocrine and neurobehavioral effects. Dexmedetomidine (DEX), a non-GABAergic α2-adrenergic receptor agonist, is likely to counteract SEVO-induced neuronal excitation. We investigated how DEX pretreatment may alter the neurodevelopmental effects induced by SEVO in neonatal rats.

METHODS:

Postnatal day (P) 5 Sprague-Dawley male rats received DEX (25 µg/kg, intraperitoneal) or vehicle before exposure to 2.1% SEVO for 6 hours (the DEX + SEVO and SEVO groups, respectively). Rats in the DEX-only group received DEX without exposure to SEVO. A subcohort of P5 rats was used for electroencephalographic and serum corticosterone measurements. The remaining rats were sequentially evaluated in the elevated plus maze on P80, prepulse inhibition of the acoustic startle response on P90, Morris water maze (MWM) starting on P100, and for corticosterone responses to physical restraint for 30 minutes on P120, followed by assessment of epigenomic DNA methylation patterns in the hippocampus.

RESULTS:

Acutely, DEX depressed SEVO-induced electroencephalogram-detectable seizure-like activity (mean ± SEM, SEVO versus DEX + SEVO, 33.1 ± 5.3 vs 3.9 ± 5.3 seconds, P < .001), but it exacerbated corticosterone release (SEVO versus DEX + SEVO, 169.935 ± 20.995 versus 280.853 ± 40.963 ng/mL, P = .043). DEX diminished, but did not fully abolish, SEVO-induced corticosterone responses to restraint (control: 11625.230 ± 877.513, SEVO: 19363.555 ± 751.325, DEX + SEVO: 15012.216 ± 901.706, DEX-only: 12497.051 ± 999.816; F
[
3,31] = 16.878, P < .001) and behavioral deficiencies (time spent in the target quadrant of the MWM: control: 31.283% ± 1.722%, SEVO: 21.888% ± 2.187%, DEX + SEVO: 28.617% ± 1.501%, DEX-only: 31.339% ± 3.087%; F
[3,67] = 3.944, P = .012) in adulthood. Of the 391 differentially methylated genes in the SEVO group, 303 genes in the DEX + SEVO group had DNA methylation patterns that were not different from those in the control group (ie, they were normal). DEX alone did not cause acute or long-term functional abnormalities.

CONCLUSIONS:

This study suggests that the ability of DEX to depress SEVO-induced neuronal excitation, despite increasing corticosterone release, is sufficient to weaken mechanisms leading to long-term neuroendocrine/neurobehavioral abnormalities. DEX may prevent changes in DNA methylation in the majority of genes affected by SEVO, epigenetic modifications that could predict abnormalities in a wide range of functions.
Interpreting protein variant effects with computational predictors and deep mutational scanning
Authors: Livesey Benjamin J. , Marsh Joseph A.
Published: June 2022

Computational predictors of genetic variant effect have advanced rapidly in recent years. These programs provide clinical and research laboratories with a rapid and scalable method to assess the likely impacts of novel variants. However, it can be difficult to know to what extent we can trust their results. To benchmark their performance, predictors are often tested against large datasets of known pathogenic and benign variants. These benchmarking data may overlap with the data used to train some supervised predictors, which leads to data re-use or circularity, resulting in inflated performance estimates for those predictors. Furthermore, new predictors are usually found by their authors to be superior to all previous predictors, which suggests some degree of computational bias in their benchmarking. Large-scale functional assays known as deep mutational scans provide one possible solution to this problem, providing independent datasets of variant effect measurements. In this Review, we discuss some of the key advances in predictor methodology, current benchmarking strategies and how data derived from deep mutational scans can be used to overcome the issue of data circularity. We also discuss the ability of such functional assays to directly predict clinical impacts of mutations and how this might affect the future need for variant effect predictors.
Dyspnea Is Attenuated by Auditory Distraction via Music with Headphones during Exercise in Healthy Individuals
Authors: GABLER MIKAELA C. , GOSS CURTIS S. , FREEMAS JESSICA A. , BARANAUSKAS MARISSA N. , SOGARD ABIGAIL S. , CHAPMAN ROBERT F.
Published: June 2022

Listening to music while exercising can alter afferent feedback from breathing sounds; however, it is currently unknown whether auditory distraction with music mitigates exertional dyspnea in healthy individuals.

Purpose

This study aimed to determine whether listening to music through headphones (a) affects the sensory (breathing intensity [BI]) and/or affective (breathing unpleasantness [BU]) components of dyspnea during exercise at different intensities and (b) affects exercise performance.

Methods

Twenty-two recreationally active individuals (24 ± 3 yr, 10 women) performed two 5-min constant loads (10% below/above gas exchange threshold [GET]) and an 8-km cycling time trial with ambient laboratory noise or self-selected music in a randomized crossover design. BI, BU, and ventilation (V̇
E) were measured at each minute of the constant loads and every 2 km of the time trial. Ratios of BU/V̇
E and BI/V̇
E were used to examine the gain in dyspnea during the time trial.

Results

In the 10% below GET trial, BU was reduced in the first (P = 0.03) and final (P = 0.04) minutes. In the 10% above GET trial, BU and BI were reduced with music (P < 0.05). During the time trial with music, BU/V̇
E was significantly attenuated by 9%–13% (P < 0.05) despite a greater heart rate and self-selected power output (P < 0.05).

Conclusions

Music through headphones mitigated the sensation of dyspnea and changed the accretion of dyspnea per unit increase in V̇
E leading to a higher self-selected workload during self-paced exercise. The dyspnea-reducing intervention of self-selected music may improve exercise tolerance and performance and promote adherence to regular aerobic exercise.
Case studies from the experience of early career researchers in East Africa in building community engagement in research
Authors: Bargul Joel L. , Mkwashapi Denna M. , Namagembe Imelda , Nakityo Immaculate , Nakimuli Annettee , Byamugisha Josaphat , Semakula Daniel , Seeley Janet , Sewankambo Nelson K.
Published: June 2022

Background: In this paper, we explain how three early career researchers actively engaged community members in their health research projects in Kenya, Tanzania and Uganda, and what was learnt from the experience. The research project in Kenya was on camel trypanosomiasis and the role of camel biting keds (or louse flies) in disease transmission. The project in Tanzania looked at the effect of human immunodeficiency virus and antiretroviral therapy on fertility and ascertained the trends in the use of family planning services amongst women of reproductive age. The focus of the project in Uganda was the implementation of maternal death surveillance and the response policy to determine the cause of maternal deaths and how they might be prevented.

Methods: In the three different settings, efforts to ensure local community engagement provided a focus for the researchers to hone their skills in explaining research concepts and working in partnership with community members to co-develop ideas, their research methods and outputs.

Results: Involvement of communities in scientific research, which entailed a two-way mutual engagement process, led to (i) generation of new research ideas that shaped the work, (ii) strengthened mutual trust, and (iii) promoted uptake of research findings.

Conclusion: Our key findings strongly support the need for considering community engagement as one of the key components in research studies.
Targeted protein degradation using deGradFP in Trypanosoma brucei
Authors: Ishii Midori , Akiyoshi Bungo
Published: June 2022

Targeted protein degradation is an invaluable tool in studying the function of proteins. Such a tool was not available in Trypanosoma brucei, an evolutionarily divergent eukaryote that causes human African trypanosomiasis. Here, we have adapted deGradFP (degrade green fluorescent protein [GFP]), a protein degradation system based on the SCF E3 ubiquitin ligase complex and anti-GFP nanobody, in T. brucei. As a proof of principle, we targeted a kinetoplastid kinetochore protein (KKT3) that constitutively localizes at kinetochores in the nucleus. Induction of deGradFP in a cell line that had both alleles of KKT3 tagged with yellow fluorescent protein (YFP) caused a more severe growth defect than RNAi in procyclic (insect form) cells. deGradFP also worked on a cytoplasmic protein (COPII subunit, SEC31). Given the ease in making GFP fusion cell lines in T. brucei, deGradFP can serve as a powerful tool to rapidly deplete proteins of interest, especially those with low turnover rates.
Derechos humanos e inteligencia artificial.
Authors: Grigore Andrea Elena
Published: June 2022

La inteligencia artificial (IA) puede tener un impacto positivo en el ejercicio de determinados derechos, pero otros pueden verse menoscabados por su uso como: la libertad de expresión (incluyendo el derecho a comunicar o recibir información libremente), la privacidad, la prohibición de la discriminación, y el derecho a la tutela judicial efectiva. Las organizaciones internacionales dedicadas a la protección de los derechos humanos están actualmente reflexionando sobre estos riesgos y las posibles soluciones para ayudar a sus Estados miembros a responder a estos retos, así se presentan las acciones llevadas a cabo en el marco universal por las Naciones Unidas y en el ámbito europeo por el Consejo de Europa y la Unión Europea. La Inteligencia Artificial es una herramienta sumamente poderosa y necesaria para ayudarnos a abordar los inmensos retos que debemos superar como especie. Pero si a la hora de desarrollarla pasamos por alto los factores sociales, laborales y éticos, la Inteligencia Artificial puede convertirse en arma a favor de la desigualdad, el control y la destrucción.
Summer poisoning hazards to pets
Authors: Bates Nicola
Published: June 2022

As the spring turns to summer, owners and their pets will spend even more time out of doors. Some venomous animals are more active in the warmer months and there is risk of adder bites or stings from bees, wasps and hornets. Adder bites can result in significant morbidity but low mortality. Insect stings commonly cause local reactions and although these are generally mild, stings involving the airway are more hazardous since there is risk of respiratory obstruction. In addition, there is also a risk of anaphylaxis in sensitive individuals (just as in people) and multiple stings can cause multiorgan damage. Slug and snail killer products are more commonly used in the summer and are therefore more accessible to pets. These commonly contain ferric phosphate rather than metaldehyde which has been banned in the UK, and are less hazardous. Harmful summer plants include those containing cardiac glycosides such as foxglove and oleander. Some plants such as hogweed contain compounds that cause skin damage following dermal contact in combination with exposure to sunlight, and are therefore a particular risk on sunny days.
Evaluating Verbal Fluency Outcome Measures in Children With Down Syndrome
Authors: Smeyne Catelyn N. , Esbensen Anna J. , Schworer Emily K. , Belizaire Shequanna , Hoffman Emily K. , Beebe Dean W. , Wiley Susan
Published: June 2022

This study evaluates the psychometric properties of a verbal fluency task for potential use as an outcome measure in future clinical trials involving children with Down syndrome. Eighty-five participants attempted a modified version of the Neuropsychological Assessment of Children, Second Edition Word Generation Task at two time points. In the full sample, the measure fell below a priori reliability and feasibility criteria, though feasibility of the semantic trials were higher than feasibility of the phonemic trials. Performance on the measure correlated with chronological age and IQ scores, and no sex-related effects were found. Additional analyses suggested that the semantic verbal fluency trials might be appropriate for children with Down syndrome 10 years of age and older.
Temporal compression of high-power IR laser pulses in a KDP
crystal
Authors: Mironov S. Yu. , Mukhin I. B. , Lozhkarev V. V. , Potemkin A. K. , Martyanov M. A. , Kuzmin I. V. , Khazanov E. A.
Published: June 2022

It is shown that a KDP crystal can be used for temporal compression of
powerful pulses of the near-IR range. A method of searching for laser
beam and crystal parameters suitable for compression is proposed.
Temporal compression of laser pulses at a central wavelength of
1034 nm from 266 fs to 94 fs during propagation along the optical axis
in a 21 cm thick KDP crystal is demonstrated experimentally.
Label-free metabolic imaging of non-alcoholic-fatty-liver-disease (NAFLD) liver by volumetric dynamic optical coherence tomography
Authors: Mukherjee Pradipta , Fukuda Shinichi , Lukmanto Donny , Yamashita Toshiharu , Okada Kosuke , Makita Shuichi , Abd El-Sadek Ibrahim , Miyazawa Arata , Zhu Lida , Morishita Rion , Lichtenegger Antonia , Oshika Tetsuro , Yasuno Yoshiaki
Published: June 2022

Label-free metabolic imaging of non-alcoholic fatty liver disease (NAFLD) mouse liver is demonstrated ex vivo by dynamic optical coherence tomography (OCT). The NAFLD mouse is a methionine choline-deficient (MCD)-diet model, and two mice fed the MCD diet for 1 and 2 weeks are involved in addition to a normal-diet mouse. The dynamic OCT is based on repeating raster scan and logarithmic intensity variance (LIV) analysis that enables volumetric metabolic imaging with a standard-speed (50,000 A-lines/s) OCT system. Metabolic domains associated with lipid droplet accumulation and inflammation are clearly visualized three-dimensionally. Particularly, the normal-diet liver exhibits highly metabolic vessel-like structures of peri-vascular hepatic zones. The 1-week MCD-diet liver shows ring-shaped highly metabolic structures formed with lipid droplets. The 2-week MCD-diet liver exhibits fragmented vessel-like structures associated with inflammation. These results imply that volumetric LIV imaging is useful for visualizing and assessing NAFLD abnormalities.
Spatial encoding of modulated pump–probe signals with slow area detectors
Authors: Schick Daniel , Steinbach Felix , Noll Tino , Strueber Christian , Engel Dieter , von Korff Schmising Clemens , Pfau Bastian , Eisebitt Stefan
Published: June 2022

We present a novel concept for acquiring fast signal modulations with slow area detectors. The modulation is spatially encoded by alternatingly blocking the signal in front of the detector with two inverted masks.
Ultrafast HHG source delivering 13 mW of average power
Authors: Klas Robert , Kirsche Alexander , Gebhardt Martin , Buldt Joachim , Stark Henning , Hädrich Steffen , Rothhardt Jan , Limpert Jens
Published: June 2022

In this contribution, a record-high XUV average power of 12.9 mW in a single harmonic line at 26.5 eV is reported, surpassing previously reported HHG sources by one order of magnitude.
High-Order Harmonic Generation in Laser-Produced Aluminium Plasmas
Authors: Mathijssen J. , Mazzotta Z. , Eikema K. S. E. , Witte S.
Published: June 2022

We present a pump-probe experiment in which high-order harmonics are generated in a laser-produced plasma as a bright EUV photon source and as a tool for plasma characterization.