bluuebunny/crossref_metadata_2025 huggingface dataset:
Four Quartets: Criticism in a New Key
Authors: Burns William
Published: April 2024

Many passages in T. S. Eliot’s Four Quartets (1943) are frequently described as ‘prosaic’ and sometimes even directly categorized as ‘prose’. In exploring what might thus be called Eliot’s mimesis of prose style, I consider what it might mean for the poem’s relationship to other forms of discursive writing, chiefly the kind of specialist discourse with which poetry, by the time Four Quartets was first published as a whole, was most frequently in contact: literary criticism. Whereas previous approaches have viewed the poem’s discursiveness as a form of exposition, or otherwise as expressing a newly sceptical relationship to poetry, I suggest that these so-called ‘antipoetic’ passages are actually anticritical, insofar as they serve to radically qualify the claims of academic interpretation, while conversely affording a greater role to an earlier mode of reading displaced by the institutionalisation of literary criticism: judgement. In this way, Four Quartets demands that we temporarily suspend our modern allegiance to interpretation as a means of participating in the Christianized sensus communis that the poem projects for us. In concluding, I ask whether this is a practice of reading that we can ultimately assent to, that is, whether the poem’s mysticism is compatible with professionalized literary study.
How do countries shift their export specialization? The role of technological capabilities and industrial policy in Ireland, Spain and Sweden (1995–2018)
Authors: Anzolin Guendalina , Benassi Chiara
Published: April 2024

This article contributes to the Comparative Political Economy discourse on countries’ export specialization transitions. While current growth model literature often highlights producer coalitions’ influence, we present a complementary perspective emphasizing industrial policies. These policies, we argue, are not solely shaped by politics but are also deeply influenced by sectoral technological capabilities. By strategically engaging in both demand and supply-side sectoral innovation processes, industrial policies deepen existing technological capabilities with spillover effects into new sectors or foster new sector-specific capabilities. Our empirical analysis comprises two main steps. First, we create export profiles for eight European nations, using OECD TiVA data from 1995 to 2018. These profiles are categorized based on their technological and innovation content. Second, we identify significant shifts in export structures within Ireland, Sweden and Spain. Through thorough case studies, we illustrate the role of industrial policies in cultivating sector-specific technological capabilities.
SKF82958, a dopamine D1 receptor agonist, disrupts prepulse inhibition in the medial prefrontal cortex and nucleus accumbens in C57BL/6J mice
Authors: Yang Chengmei , Chen Xiaoyu , Xu Jingyang , Chen Weihai
Published: April 2024

Prepulse inhibition (PPI) is a crucial indicator of sensorimotor gating that is often impaired in neuropsychiatric diseases. Although dopamine D1 receptor agonists have been found to disrupt PPI in mice, the underlying mechanisms are not fully understood. In this study, we aimed to identify the brain regions responsible for the PPI-disruptive effect of the D1 agonist in mice. Results demonstrated that intraperitoneal administration of the selective dopamine D1 receptor agonist SKF82958 dramatically inhibited PPI, while the dopamine D1 receptor antagonist SCH23390 enhanced PPI. Additionally, local infusion of SKF82958 into the nucleus accumbens and medial prefrontal cortex disrupted PPI, but not in the ventral hippocampus. Infusion of SCH23390 into these brain regions also failed to enhance PPI. Overall, the study suggests that the nucleus accumbens and medial prefrontal cortex are responsible for the PPI-disruptive effect of dopamine D1 receptor agonists. These findings provide essential insights into the cellular and neural circuit mechanisms underlying the disruptive effects of dopamine D1 receptor agonists on PPI and may contribute to the development of novel treatments for neuropsychiatric diseases.
Intimate Partner Violence Among Rwandan Women With HIV: A Cross-Sectional Study
Authors: Hatoum Sandy , Mukamana Donatilla , Gishoma Darius , Kayiranga Dieudonne , Pan Wei , Relf Michael V.
Published: April 2024

In Rwanda, women have higher incidence of HIV and intimate partner violence (IPV). This study aimed to estimate the prevalence of IPV among women living with HIV (WWH) in Rwanda and measure the difference in psychological outcomes, demographic data, and HIV-related outcomes using a cross-sectional, descriptive, observational design. A convenience sample of 162 Rwandan WWH were purposefully recruited to participate. The study collected demographic data and data about IPV, depression, HIV-related stigma, coping, self-esteem, and hope. The prevalence of any form of IPV in the sample was 27% with psychological IPV being the most prevalent. Demographic data had no statistical significance with the prevalence of IPV. WWH who experienced IPV had higher HIV stigma, lower coping self-efficacy, lower self-esteem, and less hope and worse HIV psychological outcomes. Further studies are needed to look into the correlation between the two and interventions addressing IPV prevention.
Single-use Duodenoscope
Authors: Lanka Chandana , Bhenswala Prashant , Lakhana Muhddesa , Shah Neal C. , Srivastava Pranay , Andalib Iman , Gress Frank
Published: April 2024

Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard in the endoscopic management of biliary disease. An average of 700,000 ERCPs are performed every year, and most are performed using a reusable flexible duodenoscope. The innovation of disposable duodenoscopes has changed the dynamic in the advanced endoscopy field of study to primarily reduce or eliminate the risk of cross-contamination between patients. Many factors affect whether institutions can convert from standard reusable duodenoscopes to single-use duodenoscopes including the cost of the devices, reimbursement from insurance companies for the new devices, and the overall environmental impact. However, the reduction of cross-contamination leading to active infection in patients, environmental waste produced with high-level disinfection procedures, staff and equipment required for reprocessing, and the inability to frequently upgrade duodenoscopes for optimal performance are all factors that favor transitioning to single-use duodenoscopes. As these devices are new to the field of gastroenterology, the purpose of this review is to analyze the advantages and disadvantages of transitioning to single-use devices and a brief mention of alternative options for institutions unable to make this change.
ABCD1 as a Novel Diagnostic Marker for Solid Pseudopapillary Neoplasm of the Pancreas
Authors: Liu Ying-ao , Liu Yuanhao , Tu Jiajuan , Shi Yihong , Pang Junyi , Huang Qi , Wang Xun , Lin Zhixiang , Zhao Yupei , Wang Wenze , Peng Junya , Wu Wenming
Published: April 2024

The diagnosis of solid pseudopapillary neoplasm of the pancreas (SPN) can be challenging due to potential confusion with other pancreatic neoplasms, particularly pancreatic neuroendocrine tumors (NETs), using current pathological diagnostic markers. We conducted a comprehensive analysis of bulk RNA sequencing data from SPNs, NETs, and normal pancreas, followed by experimental validation. This analysis revealed an increased accumulation of peroxisomes in SPNs. Moreover, we observed significant upregulation of the peroxisome marker ABCD1 in both primary and metastatic SPN samples compared with normal pancreas and NETs. To further investigate the potential utility of ABCD1 as a diagnostic marker for SPN via immunohistochemistry staining, we conducted verification in a large-scale patient cohort with pancreatic tumors, including 127 SPN (111 primary, 16 metastatic samples), 108 NET (98 nonfunctional pancreatic neuroendocrine tumor, NF-NET, and 10 functional pancreatic neuroendocrine tumor, F-NET), 9 acinar cell carcinoma (ACC), 3 pancreatoblastoma (PB), 54 pancreatic ductal adenocarcinoma (PDAC), 20 pancreatic serous cystadenoma (SCA), 19 pancreatic mucinous cystadenoma (MCA), 12 pancreatic ductal intraepithelial neoplasia (PanIN) and 5 intraductal papillary mucinous neoplasm (IPMN) samples. Our results indicate that ABCD1 holds promise as an easily applicable diagnostic marker with exceptional efficacy (AUC=0.999, sensitivity=99.10%, specificity=100%) for differentiating SPN from NET and other pancreatic neoplasms through immunohistochemical staining.
Application of Oral Retractor for Lip Injury Protection in Oral and Maxillofacial Surgeries: A Randomized Controlled Trial
Authors: Li Honglin , Paka Lubamba Grace , Zhang Gaowei , Li Chunjie , Han Bo , Gao Ning , Wang Lei , Chen Yafei , Yan Bing
Published: April 2024

Purpose:

Iatrogenic lip injury may occur during oral and maxillofacial surgical procedures. This study aimed to evaluate the effect of oral retractors on iatrogenic lip injury prevention during intraoral procedures of oral and maxillofacial surgery.

Methods:

We conducted a randomized controlled trial and included patients who underwent intraoral procedures of oral and maxillofacial surgery. Patients were randomly allocated to receive oral retractor (intervention group) or traditional procedure without lip protection (control group). The incidence of lip injury was the outcome variable. Other study variables included surgical time and satisfaction of patients and surgeons with treatment experience evaluated by visual analog scale (VAS). Student t test and χ2 test were used to compare both groups’ variables and measure the relationship between the predictor variable and the outcome variable. P<0.05 was considered significant for all analyses.

Results:

A total of 114 patients were included, with 56 allocated to intervention group and 58 to control group. The results showed that the application of an oral retractor did not significantly increase surgical time (P=0.318). A total of 12 patients had lip injury, with 1 in the intervention group and 11 in the control group (P=0.003). For the assessment of satisfaction with treatment experience, the intervention group had significantly higher VAS scores for doctors and patients (P<0.05).

Conclusions:

We found that the oral retractor was a good tool for iatrogenic lip injury prevention in oral and maxillofacial surgical procedures and could be considered in clinical treatment.
Irregular warfare must combine good medicine, with both good tactics and good strategies: Position paper by the French Special Operations Forces Medical Command
Authors: Pasquier Pierre , David Mathieu , Petit Ludovic , Chery Morgan , Habas Sébastien , Patey Edouard , Conort Sébastien , Zeller Nicolas , Gelmann Marc-Olivier , Peyrefitte Sébastien , Castel Fabrice , Travers Stéphane , Mahé Pierre
Published: April 2024

INTRODUCTION

Military operations are no longer limited to the application of counterterrorism and counterinsurgency strategies; they are now characterized by hybrid, irregular, and unconventional features. While some authors have indicated the need for medical support to adapt to these new modes of military operations, they have focused mainly on the tactical level of care on the battlefield. As Sun Tzu states, “Strategy without tactics is the slowest route to victory. Tactics without strategy is the noise before defeat,” further proposals are still needed on the application of both medical tactics and medical strategies in irregular warfare.

METHODS

Medical experts from the French Special Operations Forces (SOF) Medical Command have identified specific medical challenges that special operations face in the context of the current transformation of armed confrontations into irregular warfare.

RESULTS

This position paper presents original tactical medical proposals for improving medical support in irregular warfare, ranging from the definition of a Primary-Alternate-Contingency-Emergency medical plan to the promotion of telemedical support. Original strategic medical proposals have highlighted the importance of recognizing medical issues in irregular warfare, including the medical actions carried out through and with local partners and the multiple approaches to countering medical threats.

CONCLUSION

The SOF medical community must be closely involved with and facilitate the responses to the shift to irregular warfare. International collaboration and interoperability are more necessary than ever, as they will enable a more effective combination of good medicine with both good tactics and good strategies. These perspectives can also be extended to improve medical care in the conventional armed forces and austere civilian settings.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level V
Stress response of fire salamander larvae differs between habitat types
Authors: Schulte Laura , Oswald Pia , Mühlenhaupt Max , Ossendorf Edith , Kruse Sabine , Kaiser Sylvia , Caspers Barbara A.
Published: April 2024

The larvae of the European fire salamander (
Salamandra salamandra
) can inhabit two different habitats: streams and ponds. Streams are characterized by lower predation risks and higher food availability. Thus, ponds are considered a less suitable habitat. To investigate the differential impacts of these two habitats on larval physiology, we measured the stress response of larvae. After successfully validating the measure of water-borne corticosterone release rates in fire salamander larvae, we measured the baseline and stress-induced corticosterone of 64 larvae from ponds and streams in the field. We found that larvae in ponds have a higher baseline and stress-induced corticosterone levels. Additionally, we performed a reciprocal transplant experiment (RTE) and tested whether larvae can adapt their stress responses to changing habitats. After two weeks, we did not find an increase in corticosterone levels when comparing stress-induced corticosterone values with baseline corticosterone values in larvae transferred into ponds, irrespective of their habitat of origin. However, larvae transferred into streams still exhibited an increase in the stress-induced corticosterone response in comparison with the baseline values. These results show that non-invasive hormone measurements can provide information on the habitat quality and potential adaptation and thus emphasize the potential for its use in conservation efforts.
Energy gap and aromatic molecular rings
Authors: Ismael Ali K. , Al-Jobory Alaa
Published: April 2024

The manuscript combines rational density functional theory simulations and experimental data to investigate the electrical properties of eight polycyclic aromatic hydrocarbons (PAHs). The optimized geometries reveal a preference for one-row, two-row and three-row ring distributions. Band structure plots demonstrate an inverse correlation between the number of aromatic rings and band gap size, with a specific order observed across the PAHs. Gas phase simulations support these findings, though differences in values are noted compared to the literature. Introducing a two-row ring distribution concept resolves discrepancies, particularly in azulene. The B3LYP function successfully bridges theoretical and experimental gaps, particularly in large PAHs. The manuscript highlights the potential for designing electronic devices based on different-sized PAHs, emphasizing a multi-ring distribution approach and opening new avenues for practical applications.
Navigating sex and sex roles: deciphering sex-biased gene expression in a species with sex-role reversal (
Syngnathus typhle
)
Authors: Pappert Freya A. , Dubin Arseny , Torres Guillermo G. , Roth Olivia
Published: April 2024

Sexual dimorphism, the divergence in morphological traits between males and females of the same species, is often accompanied by sex-biased gene expression. However, the majority of research has focused on species with conventional sex roles, where females have the highest energy burden with both egg production and parental care, neglecting the diversity of reproductive roles found in nature. We investigated sex-biased gene expression in
Syngnathus typhle
, a sex-role reversed species with male pregnancy, allowing us to separate two female traits: egg production and parental care. Using RNA sequencing, we examined gene expression across organs (brain, head kidney and gonads) at various life stages, encompassing differences in age, sex and reproductive status. While some gene groups were more strongly associated with sex roles, such as stress resistance and immune defence, others were driven by biological sex, such as energy and lipid storage regulation in an organ- and age-specific manner. By investigating how genes regulate and are regulated by changing reproductive roles and resource allocation in a model system with an unconventional life-history strategy, we aim to better understand the importance of sex and sex role in regulating gene expression patterns, broadening the scope of this discussion to encompass a wide range of organisms.
Marinobacter azerbaijanicus sp. nov., a moderately halophilic bacterium from Urmia Lake, Iran
Authors: Sánchez-Porro Cristina , Aghdam Elnaz Mehdizadeh , Montazersaheb Soheila , Tarhriz Vahideh , Kazemi Elham , Amoozegar Mohammad Ali , Ventosa Antonio , Hejazi Mohammad Saeid
Published: April 2024

A novel moderately halophilic, Gram-stain-negative and facultatively anaerobic bacterium, designated as strain TBZ242T, was isolated from water of Urmia Lake in the Azerbaijan region of Iran. The cells were found to be rod-shaped and motile by a single polar flagellum, producing circular and yellowish colonies. The strain could grow in the presence of 0.5–10 % (w/v) NaCl (optimum, 2.5–5 %). The temperature and pH ranges for growth were 15–45 °C (optimum 30 °C) and pH 7.0–11.0 (optimum pH 8.0) on marine agar. The 16S rRNA gene sequence analysis revealed that strain TBZ242T belonged to the genus Marinobacter, showing the highest similarities to Marinobacter algicola DG893T (98.8 %), Marinobacter vulgaris F01T (98.8 %), Marinobacter salarius R9SW1T (98.5 %), Marinobacter panjinensis PJ-16T (98.4 %), Marinobacter orientalis W62T (98.0 %) and Marinobacter denitrificans JB2H27T (98.0 %). The 16S rRNA and core-genome phylogenetic trees showed that strain TBZ242T formed a distinct branch, closely related to a subclade accommodating M. vulgaris, M. orientalis, M. panjinensis, M. denitrificans, M. algicola, M. salarius and M. iranensis, within the genus Marinobacter. Average nucleotide identity and digital DNA–DNA hybridization values between strain TBZ242T and the type strains of the related species of Marinobacter were ≤85.0 and 28.6 %, respectively, confirming that strain TBZ242T represents a distinct species. The major cellular fatty acids of strain TBZ242T were C16 : 0 and C16 : 1
 ω7c/C16 : 1 ω6c and the quinone was ubiquinone Q-9. The genomic DNA G+C content of strain TBZ242T is 57.2 mol%. Based on phenotypic, chemotaxonomic and genomic data, strain TBZ242T represents a novel species within the genus Marinobacter, for which the name Marinobacter azerbaijanicus sp. nov. is proposed. The type strain is TBZ242T (= CECT 30649T = IBRC-M 11466T). Genomic fragment recruitment analysis showed that this species prefers aquatic saline environments with intermediate salinities, being detected on metagenomic databases of Lake Meyghan (Iran) with 5 and 18 % salinity, respectively.
Blastococcus brunescens sp. nov., a member of the Geodermatophilaceae isolated from sandstone collected from the Sahara Desert in Tunisia
Authors: Hezbri Karima , kammoun Ikram , Sbissi Imed , Klenk Hans-Peter , Montero-Calasanz Maria del Carmen , Ghodhbane-Gtari Faten , Gtari Maher
Published: April 2024

The taxonomic position of strain BMG 8361T, isolated from sandstone collected in the Sahara Desert of Southern Tunisia, was refined through a polyphasic taxonomic investigation. Colonies of BMG 8361T were pale-orange coloured, irregular with a dry surface and produced a diffusible pink or brown pigment depending on media. The Gram-positive cells were catalase-positive and oxidase-negative. The strain exhibited growth at 10–40 °C and pH values ranging from 5.5 to 9.0, with optima at 28–35 °C and pH 6.5–8.0. Additionally, BMG 8361T demonstrated the ability to grow in the presence of up to 1 % NaCl (w/v) concentration. The peptidoglycan of the cell wall contained meso-diaminopimelic acid, glucose, galactose, xylose, ribose, and rhamnose. The predominant menaquinones consisted of MK-9(H4) and MK-9. The main polar lipids were phosphatidylcholine, phosphatidylinositol, glycophosphatidylinositol, diphosphatidylglycerol, phosphatidylethanolamine, and two unidentified lipids. Major cellular fatty acids were iso-C16 : 0, iso-C16 : 1 h, and C17 : 1
 ω8c. Phylogenetic analyses based on both the 16S rRNA gene and whole-genome sequences assigned strain BMG 8361T within the genus Blastococcus. The highest pairwise sequence similarity observed in the 16S rRNA gene was 99.5 % with Blastococcus haudaquaticus AT 7-14T. However, when considering digital DNA–DNA hybridization and average nucleotide identity, the highest values, 48.4 and 86.58 %, respectively, were obtained with Blastococcus colisei BMG 822T. These values significantly undershoot the recommended thresholds for establishing new species, corroborating the robust support for the distinctive taxonomic status of strain BMG 8361T within the genus Blastococcus. In conjunction with the phenotyping results, this compelling evidence leads to the proposal of a novel species we named Blastococcus brunescens sp. nov. with BMG 8361T (=DSM 46845T=CECT 8880T) as the type strain.
Mapping immunodominant sites on the MERS-CoV spike glycoprotein targeted by infection-elicited antibodies in humans
Authors: Addetia Amin , Stewart Cameron , Seo Albert J. , Sprouse Kaitlin R. , Asiri Ayed Y , Al-Mozaini Maha , Memish Ziad A , Alshukairi Abeer , Veesler David
Published: April 2024

Middle-East respiratory syndrome coronavirus (MERS-CoV) first emerged in 2012 and causes human infections in endemic regions. Most vaccines and therapeutics in development against MERS-CoV focus on the spike (S) glycoprotein to prevent viral entry into target cells. These efforts, however, are limited by a poor understanding of antibody responses elicited by infection along with their durability, fine specificity and contribution of distinct S antigenic sites to neutralization. To address this knowledge gap, we analyzed S-directed binding and neutralizing antibody titers in plasma collected from individuals infected with MERS-CoV in 2017-2019 (prior to the COVID-19 pandemic). We observed that binding and neutralizing antibodies peak 1 to 6 weeks after symptom onset/hospitalization, persist for at least 6 months, and broadly neutralize human and camel MERS-CoV strains. We show that the MERS-CoV S1subunit is immunodominant and that antibodies targeting S1, particularly the RBD, account for most plasma neutralizing activity. Antigenic site mapping revealed that polyclonal plasma antibodies frequently target RBD epitopes, particularly a site exposed irrespective of the S trimer conformation, whereas targeting of S2subunit epitopes is rare, similar to SARS-CoV-2. Our data reveal in unprecedented details the humoral immune responses elicited by MERS-CoV infection, which will guide vaccine and therapeutic design.
Ready-To-Use Investigational Stem Cells, MiSaver, in Patients with Recent Acute Myocardial Infarction, 1 year follow up from a Phase 1 Safety Study
Authors: Ueng KC , Tsai CF , Su CH , Chuang YT , Liu JTK
Published: April 2024

Objectives

The aim of this study was to investigate the safety of MiSaver stem cells and their preliminary efficacy in improving left ventricular ejection function and functional activity in patients with acute myocardial infarction (AMI)

Background

Cardiovascular diseases (CVDs) are the leading cause of death globally. In 2019, an estimated 17.9 million people died from CVDs, accounting for 32% of all global deaths. Among these deaths, 85% were due to heart attacks and strokes.

Left ventricular ejection fraction (LVEF) recovery after myocardial infarction (MI) is an important prognostic indicator, and patients who do not recover LVEF after MI are at high risk of sudden cardiac arrest events and death.

Stem cell therapy holds promise for cardiovascular diseases, offering regenerative potential through cell differentiation. However, limited access exists for clinicians and patients. This study investigates the safety and efficacy of MiSaver (Myocardial Infarction Functional Saver), a prefabricated stem cell investigational product, in recent AMI patients. Findings contribute to advancing stem cell treatments, improving accessibility and patient outcomes.

Methods

Patients who were admitted for AMI within 7 days and had reduced LVEF (.45%) were eligible for the study. MiSaver were matched for blood group and administered in participants in cohorts of five, each receiving escalating dosages (0.5×10^7, 1.6×10^7, and 5.0×10^7 cells/kg, respectively). Patients were assessed for symptoms of graft-versus-host disease (GVHD) and treatment-related adverse events (AE). LVEF measured by echocardiographic on admission, at 6 months, and at 12 months after treatment. Patients functional activity status evalution ( using the New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) classification systems.

Results

Out of the initially planned 15 participants, eleven were enrolled in the study. The trial was halted prematurely due to challenges associated with the COVID-19 pandemic and impractical transportation logistics. Patients received MiSaver infusions within 2-5 days post-AMI onset. During the 12-month follow-up period, no study-related adverse events or signs of graft-versus-host disease were reported. At 12 months post-treatment, both the low and middle dose groups, as well as participant 11, showed improved LVEF, accompanied by enhanced Canadian Cardiovascular Society (CCS) class grades compared to baseline.

Conclusion

The intravenous infusion of MiSaver stem cells in AMI patients demonstrated safety and tolerability for low and middle dosage groups. The study provides promising insights into the potential of stem cells therapy in improving left ventricular function following AMI. However, further research with larger cohorts and a controlled placebo is warranted to confirm these findings and address limitations encountered during this trial.
Twin pair analysis uncovers novel links between DNA methylation, mitochondrial DNA quantity and obesity
Authors: Heikkinen Aino , Esser Vivienne F C , Lundgren Sara , Lee Seung Hyuk T , Hakkarainen Antti , Lundbom Jesper , Kuula Juho , Groop Per-Henrik , Heinonen Sini , Pajukanta Päivi , Kaprio Jaakko , Pietiläinen Kirsi H , Li Shuai , Ollikainen Miina
Published: April 2024

Alterations in mitochondrial metabolism in obesity may indicate disrupted communication between mitochondria and nucleus, crucial for adapting to changing metabolic demands. Epigenetic modifications, particularly DNA methylation, may influence this intricate interplay, though the specifics remain poorly understood. Leveraging data from the subcohort of the Finnish Twin Cohort (n=173; 86 full twin pairs) that includes comprehensive measurements of obesity-related outcomes, mitochondrial DNA quantity (mtDNAq) and nuclear DNA methylation levels in adipose and muscle tissue, we identified one locus atSH3BP4(cg19998400) significantly associated with mtDNAq in adipose tissue (FDR<0.05).SH3BP4methylation correlated with its gene expression. Additionally, 14 out of the 35 obesity-related traits displayed significant associations with bothSH3BP4methylation and mtDNAq in adipose tissue. Using the method that infers causality from examination of familial confounding (ICE FALCON) our data suggests that mtDNAq, insulin sensitivity and certain body fat measures are causal toSH3BP4methylation. The examination of mtDNAq and obesity-related traits suggested causation from mtDNAq to obesity which could not, however, be distinguished from potential unmeasured within-individual confounding. In conclusion, our findings underscore the impact of mtDNAq on DNA methylation and expression of theSH3BP4gene within adipose tissue, with potential implications for obesity.
Effectiveness of Non-Pharmacological Interventions to Improve Cognition in Cancer: A Protocol for an Overview of Systematic Reviews
Authors: Haywood Darren , Henneghan Ashley M. , MclinPsych Evan Dauer , Vasan Sherry , Franco-Rocha Oscar Y. , Wilding Helen , Hart Nicolas H.
Published: April 2024

Many cancer survivors, including those with a current or previous diagnosis of cancer, experience cancer-related cognitive impairments (CRCI). CRCI can impact their ability to think quickly, clearly, make decisions and perform daily actions. There have been a variety of non-pharmacological interventions developed and trialed with the aim of reducing CRCI or mitigating its impact. The aim of this work is to provide an overall picture of the effectiveness of non-pharmacological interventions to improve cognition in cancer survivors by providing an overview and synthesis of systematic reviews.

Review Title

Effectiveness of Non-Pharmacological Interventions to Improve Cognition in Cancer: An Overview of Systematic Reviews
Anthelminthic treatment modifies cytokine profiles and improves the performance of tuberculin test in helminth-Mycobacterium bovisco-infection in cattle herds
Authors: Akinseye Victor O. , Jarikre Theophilus A , Tijani Moshood O , Alaka Olugbenga O , Cadmus Simeon I.
Published: April 2024

While enormous efforts are directed at tackling the problems of human tuberculosis (TB) globally, the aspect of bovine TB (bTB) has received limited attention particularly in developing countries, where control policies are non-existent or inadequate. We compared the results of a single intradermal comparative cervical tuberculin test (SICCTT) with cytokine profiles before and after anti-helminthic treatment in cattle in their natural environment. Cattle were initially subjected to SICCTT and their helminth status assessed by coprological testing forStrongyle-type, Strongyloides sp.,Toxocara vitulorum, Nematodirus sp.,Paraphistomum cervi, Fasciola gigantica, Dicrocoelium dendriticum and Moniezia benedeni.; 60 days after, they were dewormed and the SICCTT was repeated with coprological testing; SICCTT-positives underwent post mortem examination and mycobacterial culture to confirm TB infection. Also, we measured the level of circulating type 1 (gamma interferon [IFN-γ]), type 2 (interleukine-4 [IL-4]) and regulatory (transforming growth factor-beta [TGF-β]) cytokines before and after anthelminthic therapy. Results revealed that cattle positive by SICCTT showed typical granulomatous lesions suggestive of TB which was confirmed by positive culture. The proportion of SICCTT positive cattle increased to about two folds following anthelminthic treatment. Cattle co-infected with helminth-bTB have significantly (p = 0.000) lower levels of IFN-γ and higher levels of IL-4 and TGF-β. Conversely, anthelminthic therapy led to significantly (p=0.000) elevated levels of IFN-γ, concomitant (p =0.000) decreased levels of IL-4 and TGF-β. Overall, we show that anthelminthic treatment can improve the rate of SICCTT positivity and reverse the modulation of cytokine responses in helminth-bTB co-infection.
Optimised methods for the targeted surveillance of extended-spectrum beta-lactamase producingEscherichia coliin human stool
Authors: Gallichan Sarah , Forrest Sally , Picton-Barlow Esther , McKeown Claudia , Moore Maria , Heinz Eva , Feasey Nicholas A , Lewis Joseph M , Graf Fabrice E
Published: April 2024

Understanding transmission pathways of important opportunistic, drug resistant pathogens, such as extended-spectrum beta-lactamase (ESBL) producingEscherichia coli,is essential to implementing targeted prevention strategies to interrupt transmission and reduce the number of infections. To link transmission of ESBL-producingE. coli(ESBL-EC) between two sources, single nucleotide resolution ofE. colistrains as well asE. colidiversity within and between samples is required. However, the microbiological methods to best track these pathogens are unclear. Here we compared different steps in the microbiological workflow to determine the impact different pre-enrichment broths, pre-enrichment incubation times, selection in pre-enrichment, selective plating, and DNA extraction methods had on recovering ESBL-EC from human stool samples, with the aim to acquire high quality DNA for sequencing and genomic epidemiology. We demonstrate that using a 4-hour pre-enrichment in Buffered Peptone Water, plating on cefotaxime supplemented MacConkey agar and extracting DNA using Lucigen MasterPure DNA Purification kit improves the recovery of ESBL-EC from human stool and produced high-quality DNA for whole genome sequencing. We conclude that our optimised workflow can be applied for single nucleotide variant analysis of an ESBL-EC from stool.
Tracing Alzheimer’s Genetic Footprints: A Pioneering Longitudinal Study Using Artificial Intelligence to Unravel Mutation- Driven Risks and Progression in Virtual Patients; Part 1 – The APOE genotypes
Authors: Danter WR
Published: April 2024

Alzheimer’s Disease (AD), the most common neurodegenerative disorder, presents a significant challenge for early detection and intervention due to its complex etiology involving genetic, environmental, and lifestyle factors. This study harnesses the innovative potential of artificial intelligence (AI) through the aiHumanoid platform to simulate AD progression. In this study, we focus on the impact of two APOE genotypes on disease development and progression. Our longitudinal virtual subject simulations, grounded in extensive medical literature and genetic information, explore the nuanced interplay between specific genetic variants, APOE ε3/4 and ε4/4, and their role in AD’s heterogeneity. Despite the potential limitations associated with emerging technologies, including the translatability of AI simulations to real-world scenarios and the scope of genetic variants, this research provides key insights into early biomarkers and the progression patterns of AD. Future segments of this study (Part 2 and Part 3) will broaden the analysis to encompass a wider array of genetic factors and their interactions, enhancing the understanding of AD and paving the way for personalized intervention strategies. Ethical considerations surrounding the use of AI in medical research are acknowledged, emphasizing the need for responsible integration of technology in healthcare. Our findings underscore the transformative potential of AI in advancing AD research, offering a foundation for future studies aimed at refining diagnostic and therapeutic approaches through enhanced realism in simulations and a comprehensive exploration of genetic and environmental factors.
Structural characterization of thePseudomonas AeruginosaMexR–mexRrepressor-operator complex: a small-angle X-ray and neutron scattering perspective
Authors: Pietras Zuzanna , Caporaletti Francesca , Jeffries Cy M. , Morad Vivian , Wallner Björn , Martel Anne , Sunnerhagen Maria
Published: April 2024

The rapid spread of acquired multidrug resistance (MDR) in bacteria is a world-wide health threat. The MexR protein regulates the expression of the MexAB-OprM efflux pump, which actively extrudes chemical compounds with high toxicity to the host organismPseudomonas Aeruginosa. In repression mode, two MexR dimers bind to an operator with two homologous pseudo-palindromic boxes located in proximity (named PI and PII). Here we report a first structural characterization of the complex in solution using small angle X-ray scattering (SAXS), small-angle neutron scattering (SANS) and rigid body modelling. The spacing between the PI and PII boxes is rich in AT base pairs indicate possible flexibility between the two MexR dimer binding sites. In agreement, our best modelling fits show a requirement for DNA bending between the two MexR binding sites to optimally fit SAS data as well as known biological properties of the MexR operons. Taken together, this study contributes to better understanding of the structural properties of bacterial operators and their repressor proteins.
Responses to membrane potential-modulating ionic solutions measured by magnetic resonance imaging of cultured cells andin vivorat cortex
Authors: Min Kyeongseon , Chung Sungkwon , Lee Seung-Kyun , Lee Jongho , Toi Phan Tan , Kim Daehong , Lee Jung Seung , Park Jang-Yeon
Published: April 2024

Membrane potential plays a crucial role in various cellular functions. However, existing techniques for measuring membrane potential are often invasive or have limited recording depth. In contrast, magnetic resonance imaging (MRI) offers noninvasive imaging with desirable spatial resolution over large areas. This study investigates the feasibility of utilizing MRI to detect responses of cultured cells andin vivorat cortex to membrane potential-modulating ionic solutions by measuring magnetic resonance parameters. Our findings reveal that depolarizing (or hyperpolarizing) ionic solutions increase (or decrease) theT2relaxation time, while the ratio of bound to free water proton shows the opposite trend. These findings also suggest a potential approach to noninvasively detect changes in membrane potential using MRI.
Analysis of predation-driven inoculum loss and carbon flow in bioaugmented soils through DNA-SIP
Authors: Nieto Esteban E. , Jurburg Stephanie D. , Steinbach Nicole , Festa Sabrina , Morelli Irma S. , Coppotelli Bibiana M. , Chatzinotas Antonis
Published: April 2024

Bioaugmentation is considered as a sustainable and cost-effective methodology to recover contaminated environments, but its outcome is highly variable. Predation is a key top-down control mechanism affecting inoculum establishment, however its effects on this process have received little attention. This study focused on the impact of trophic interactions on bioaugmentation success in two soils with different pollution exposure histories We inoculated a 13C-labelled pollutant-degrading consortium in these soils and tracked the fate of the labelled biomass through stable isotope probing (SIP) of DNA. We identified active bacterial and eukaryotic inoculum-biomass consumers through amplicon sequencing of 16S rRNA and 18S rRNA genes coupled to modified enrichment factor calculation. Inoculation effectively increased PAH removal in short-term polluted soils but not in long-term polluted soils. A decrease in the relative abundance of the inoculated genera was observed already on day 15 in the long-term polluted soil, while growth of these genera was observed in the short-term polluted soil, indicating establishment of the inoculum. In both soils, eukaryotic genera dominated as early incorporators of 13C-labelled biomass, while bacteria incorporated the labelled biomass at the end of the incubation period, probably through cross-feeding. We also found different successional patterns between the two soils. In the short-term polluted soil, Cercozoa and Fungi genera predominated as early incorporators, whereas Ciliophora, Ochrophyta and Amoebozoa were the predominant genera in the long-term polluted soil. Our results showed differences in the inoculum establishment and predator community behaviours, affecting bioaugmentation efficiency. This highlights the need to further study predation effects on inoculum survival to increase the applicability of inoculation-based technologies.
A platform for mapping reactive cysteines within the immunopeptidome
Authors: Zhang Chenlu , Zhou Chen , Magassa Assa , Fang Deyu , Zhang Xiaoyu
Published: April 2024

The major histocompatibility complex class I (MHC-I) antigen presentation pathways play pivotal roles in orchestrating immune responses. Recent studies have begun to utilize cysteines within the immunopeptidome for therapeutic applications, such as using covalent ligands to create haptenated neoantigens for inducing an immune response. In this study, we report a platform for mapping reactive cysteines present on MHC-I-bound peptide antigens. We have developed cell-impermeable sulfonated maleimide probes capable of effectively capturing reactive cysteines on antigens. Utilizing these probes in chemoproteomic experiments, we discovered that cysteines on MHC-I-bound antigens exhibit various degrees of reactivity. Furthermore, interferon-gamma stimulation produces increased reactivity of cysteines at position 8 of 9-mer MHC-I-bound antigens. Our findings may open up new avenues for understanding the distinctive roles of cysteine within the MHC-I immunopeptidome and leveraging the differentially reactive cysteines for therapeutic intervention.
Empowering STEM Students: A University-wide Mentorship Program Fostering Retention and Belonging
Authors: Ravishankar Sumedha , Spencer-Drakes Tara C.J. , Fernandes Ivy H. , Hayes Megan I. , Coopwood Shelby , Spencer Ilya , Neal Sonya E.
Published: April 2024

In the face of a challenging climate that is resistant to Diversity, Equity, and Inclusion (DEI) efforts, there is a critical need for a support structure for retaining students, particularly those from historically excluded groups (HEGs), in STEM. The Biology Undergraduate and Master’s Mentorship Program (BUMMP) embodies this commitment to fostering scientific identity, efficacy, and sense of belonging for 1stgeneration and historically underserved undergraduate and master’s students at UC San Diego. The mission of BUMMP is to cultivate a sense of belonging, instill confidence, and nurture a strong scientific identity amongst all of its participants. At its core, the three pillars of BUMMP are: 1) mentorship, 2) professional development, and 3) research. Quality mentorship is provided where students receive personal guidance from faculty, graduate students, postdocs, and industry leaders in navigating their career pathways. Complementing mentorship, BUMMP provides paid research opportunities and prioritizes professional development by offering workshops designed to enhance students’ professional skills. These three pillars form the backbone of BUMMP, empowering students from all backgrounds and ensuring their retention and persistence in STEM. So far, we’ve served over 1,350 mentees, collaborated with 809 mentors, and had over 180 mentees actively engaged in BUMMP-sponsored research activities. Overall, BUMMP’s expansive efforts have made a tremendous impact at UC San Diego and will continue to foster a community of future leaders who will be prepared to make meaningful contributions to the scientific community and beyond.
Whole-brain functional connectivity predicts groupwise and sex-specific tau PET in preclincal Alzheimer’s disease
Authors: Abuwarda Hamid , Trainer Anne , Horien Corey , Shen Xilin , Ju Suyeon , Constable R. Todd , Fredericks Carolyn
Published: April 2024

Preclinical Alzheimer’s disease, characterized by the initial accumulation of amyloid and tau pathologies without symptoms, presents a critical opportunity for early intervention. Yet, the interplay between these pathological markers and the functional connectome during this window remains understudied. We therefore set out to elucidate the relationship between the functional connectome and amyloid and tau, as assessed by PET imaging, in individuals with preclinical AD using connectome-based predictive modeling (CPM). We found that functional connectivity predicts tau PET, outperforming amyloid PET models. These models were predominantly governed by linear relationships between functional connectivity and tau. Tau models demonstrated a stronger correlation to global connectivity than underlying tau PET. Furthermore, we identify sex-based differences in the ability to predict regional tau, without any underlying differences in tau PET or global connectivity. Taken together, these results suggest tau is more closely coupled to functional connectivity than amyloid in preclinical disease, and that multimodal predictive modeling approaches stand to identify unique relationships that any one modality may be insufficient to discern.
Imaging the dynamics of initial laser-driven shocks and blowoff plasmas in polystyrene under laser-direct-drive fusion conditions
Authors: Kafka K. R. P. , Hu S. X. , Huang H. , Goncharov V. N. , Demos S. G.
Published: April 2024

The dynamics of laser-driven shock propagation in solid ablator material, along with the concomitant processes of shinethrough and blowoff plasma plume expansion, at conditions relevant to laser-direct-drive fusion are measured using a tabletop system capable of supporting rapid dataset development with significantly higher resolution compared to existing methods. The experimental results are directly compared with current radiation-hydrodynamic simulations using the two-dimensional code . Discrepancies between experiments and simulations are evidenced and attributed to limitation of simulation to account for important processes involved in the solid-to-plasma transition.

Published by the American Physical Society
2024
Deciphering non-Gaussianity of diffusion based on the evolution of diffusivity
Authors: Xu Haolan , Zheng Xu , Shi Xinghua
Published: April 2024

Non-Gaussian diffusion of nanoparticles in complex media disrupts Einstein's picture of Brownian motion, and non-Gaussianity is thought to be closely related to diffusing diffusivity generated by spatiotemporal heterogeneities. However, the correlation between non-Gaussianity and the dynamics of heterogeneous environments in anomalous diffusion remains uncertain. Inspired by a recent study by Alexandre [], we demonstrate that non-Gaussianity can be deciphered through the spatiotemporal evolution of heterogeneity-dependent diffusivity distribution. Using diffusion experiments in a linear temperature field and Brownian dynamics simulations, we found that short-time non-Gaussianity can be predicted based on the boundary ratio of the diffusivity distribution; the long-time non-Gaussianity either approaches an asymptotic value of −2 or scales with 1/t, depending on the dominance of particle migration. The temporal variation of non-Gaussianity is determined by an effective Péclet number, which represents a competition between the varying rate of diffusivity and the diffusivity of diffusivity and reveals whether the tail distribution expands or contracts. The tail is more Gaussian than exponential over long times, with exceptions significantly dependent on the diffusivity distribution. Our findings provide a versatile framework for understanding non-Gaussian diffusion in probability space, and shed light on establishing a diffusion spectrum in cells and characterizing nanomedicine transport in biological microenvironment using non-Gaussian statistics.

Published by the American Physical Society
2024
Tuning the Josephson diode response with an ac current
Authors: Seoane Souto Rubén , Leijnse Martin , Schrade Constantin , Valentini Marco , Katsaros Georgios , Danon Jeroen
Published: April 2024

Josephson diodes are superconducting elements that show an asymmetry in the critical current depending on the direction of the current. Here, we theoretically explore how an alternating current bias can tune the response of such a diode. We show that for slow driving there is always a regime where the system can only carry zero-voltage dc current in one direction, thus effectively behaving as an ideal Josephson diode. Under fast driving, the diode efficiency is also tunable, although the ideal regime cannot be reached in this case. We also investigate the residual dissipation due to the time-dependent current bias and show that it remains small. All our conclusions are solely based on the critical current asymmetry of the junction, and are thus compatible with any Josephson diode.

Published by the American Physical Society
2024