bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted metabolomics characterizes metabolite occurrence and variability in stable freshwater mussel populations
Authors: Waller Diane , Putnam Joel , Steiner J Nolan , Fisher Brant , Burcham Grant N , Oliver John , Smith Stephen B , Erickson Richard , Remek Anne , Bodoeker Nancy
Published: June 2023

Freshwater mussels (order Unionida) play a key role in freshwater systems as ecosystem engineers and indicators of aquatic ecosystem health. The fauna is globally imperilled due to a diversity of suspected factors; however, causes for many population declines and mortality events remain unconfirmed due partly to limited health assessment tools. Mussel-monitoring activities often rely on population-level measurements, such as abundance and age structure, which reflect delayed responses to environmental conditions. Measures of organismal health would enable preemptive detection of declining condition before population-level effects manifest. Metabolomic analysis can identify shifts in biochemical pathways in response to stressors and changing environmental conditions; however, interpretation of the results requires information on inherent variability of metabolite concentrations in mussel populations. We targeted metabolites in the haemolymph of two common mussels, Lampsilis cardium and Lampsilis siliquoidea, from three Indiana streams (USA) using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectroscopy. The influence of species, stream and sex on metabolite variability was examined with distance-based redundancy analysis. Metabolite variability was most influenced by species, followed by site and sex. Inter- and intraspecies metabolite variability among sexes was less distinct than differences among locations. We further categorized metabolites by occurrence and variability in mussel populations. Metabolites with high occurrence (Categories 1 and 2) included those indicative of energy status (catabolism versus anabolism; arginine, proline, carnitine, nicotinic acid, pantothenic acid), oxidative stress (proline, glutamine, glutamate) and protein metabolism (thymidine, cytidine, inosine). Metabolites with lower occurrence (Category 3) are constituents of assorted metabolic pathways and can be important biomarkers with additional temporal sampling to characterize their variability. These data provide a reference for future temporal (before/after) monitoring and for studies of stressor–metabolite linkages in freshwater mussels.
A systematization of voter registration security
Authors: Cable Jack , Fábrega Andrés , Park Sunoo , Specter Michael A
Published: June 2023

Voter registration is an essential part of almost any election process, and its security is a critical component of election security. Yet, despite notable compromises of voter registration systems, relatively little academic work has been devoted to securing voter registration systems, compared to research on other aspects of election security. In this paper, we present a systematic treatment of voter registration system security. We propose the first rigorous definitional framework for voter registration systems, describing the entities and core functionalities inherent in most voter registration systems, the jurisdictional policies that constrain specific implementations, and key security properties. Our definitions are configurable based on jurisdiction-specific parameters and policies. We provide a template for the structured presentation of detailed jurisdictional policy information, via a series of tables, and illustrate its application with detailed case studies of the voter registration systems of three US states and Panama. Throughout our research, with the aim of realism and practical applicability, we consulted current and former US election officials, civil society, and nonprofits in the elections space. We conclude with a list of critical questions regarding voter registration security.
PLBD: protein–ligand binding database of thermodynamic and kinetic intrinsic parameters
Authors: Lingė Darius , Gedgaudas Marius , Merkys Andrius , Petrauskas Vytautas , Vaitkus Antanas , Grybauskas Algirdas , Paketurytė Vaida , Zubrienė Asta , Zakšauskas Audrius , Mickevičiūtė Aurelija , Smirnovienė Joana , Baranauskienė Lina , Čapkauskaitė Edita , Dudutienė Virginija , Urniežius Ernestas , Konovalovas Aleksandras , Kazlauskas Egidijus , Shubin Kirill , Schiöth Helgi B , Chen Wen-Yih , Ladbury John E , Gražulis Saulius , Matulis Daumantas
Published: June 2023

We introduce a protein–ligand binding database (PLBD) that presents thermodynamic and kinetic data of reversible protein interactions with small molecule compounds. The manually curated binding data are linked to protein–ligand crystal structures, enabling structure–thermodynamics correlations to be determined. The database contains over 5500 binding datasets of 556 sulfonamide compound interactions with the 12 catalytically active human carbonic anhydrase isozymes defined by fluorescent thermal shift assay, isothermal titration calorimetry, inhibition of enzymatic activity and surface plasmon resonance. In the PLBD, the intrinsic thermodynamic parameters of interactions are provided, which account for the binding-linked protonation reactions. In addition to the protein–ligand binding affinities, the database provides calorimetrically measured binding enthalpies, providing additional mechanistic understanding. The PLBD can be applied to investigations of protein–ligand recognition and could be integrated into small molecule drug design.

Database URL https://plbd.org/
Hypomethylation and Overexpression of Th17-Associated Genes is a Hallmark of Intestinal CD4+ Lymphocytes in Crohn’s Disease
Authors: Sun Zhifu , Braga-Neto Manuel B , Xiong Yuning , Bhagwate Adytia V , Gibbons Hunter R , Sagstetter Mary R , Hamdan Feda H , Baheti Saurabh , Friton Jessica , Nair Asha , Ye Zhenqing , Faubion William A
Published: June 2023

Background

The development of Crohn’s disease [CD] involves immune cell signalling pathways regulated by epigenetic modifications. Aberrant DNA methylation has been identified in peripheral blood and bulk intestinal tissue from CD patients. However, the DNA methylome of disease-associated intestinal CD4+ lymphocytes has not been evaluated.

Materials and Methods

Genome-wide DNA methylation sequencing was performed from terminal ileum CD4+ cells from 21 CD patients and 12 age- and sex-matched controls. Data were analysed for differentially methylated CpGs [DMCs] and methylated regions [DMRs]. Integration was performed with RNA-sequencing data to evaluate the functional impact of DNA methylation changes on gene expression. DMRs were overlapped with regions of differentially open chromatin [by ATAC-seq] and CCCTC-binding factor [CTCF] binding sites [by ChIP-seq] between peripherally derived Th17 and Treg cells.

Results

CD4+ cells in CD patients had significantly increased DNA methylation compared to those from the controls. A total of 119 051 DMCs and 8113 DMRs were detected. While hypermethylated genes were mostly related to cell metabolism and homeostasis, hypomethylated genes were significantly enriched within the Th17 signalling pathway. The differentially enriched ATAC regions in Th17 cells [compared to Tregs] were hypomethylated in CD patients, suggesting heightened Th17 activity. There was significant overlap between hypomethylated DNA regions and CTCF-associated binding sites.

Conclusions

The methylome of CD patients shows an overall dominant hypermethylation yet hypomethylation is more concentrated in proinflammatory pathways, including Th17 differentiation. Hypomethylation of Th17-related genes associated with areas of open chromatin and CTCF binding sites constitutes a hallmark of CD-associated intestinal CD4+ cells.
Pan trapping is an effective method to trap adults of the jujube gall midge, Dasineura jujubifolia (Diptera: Cecidomyiidae)
Authors: Wang Hainuo , Yang Long , Pan Yunfei , Zhang Jianmin , Lu Yanhui
Published: June 2023

Jujube gall midge (Dasineura jujubifolia Jiao & Bu) (Diptera: Cecidomyiidae) is an important pest in jujube (Ziziphus jujuba Mill.) orchards in Aksu, Xinjiang, China. Yellow sticky traps are the main device used for monitoring jujube gall midge adults, but their efficacy is low. Here, we compared the effectiveness of yellow sticky traps with water pan traps (are commonly used for trapping Diptera insects) to monitor jujube gall midge adults. Yellow sticky traps and pan traps were deployed for 2 consecutive years in jujube orchards in Aksu, Xinjiang, China. The midge’s population dynamics as revealed by these 2 trap types were consistent, but the effectiveness of pan traps was about 5 times greater than that of the yellow sticky traps. In addition, pan traps captured fewer non-target species (e.g., parasitic wasps, lacewings, and lady beetles) than yellow sticky traps. Our study suggests that pan trap is an effective device to monitor jujube gall midge adults with minimal harm to natural enemies.
Impact of annual volume of cases and intensive cardiac care unit availability on mortality of patients with acute myocardial infarction-related cardiogenic shock treated at revascularization capable centres
Authors: Barrionuevo-Sánchez M Isabel , Viana-Tejedor Ana , Ariza-Solé Albert , del Prado Náyade , Rosillo Nicolás , Sánchez-Salado José Carlos , Lorente Victòria , Jorge-Pérez Pablo , Noriega Francisco Javier , Ferrera Carlos , Alegre Oriol , Llaó Isaac , Bernal José Luis , Triguero Laura , Fernández-Pérez Cristina , González-Costello José , Marcos Marta , de la Cuerda Francisco , Carmona Jesús , Cequier Angel , Fernández-Ortiz Antonio , Pérez-Villacastín Julián , Comin-Colet Josep , Elola Francisco Javier
Published: June 2023

Aims

Cardiogenic shock (CS) is associated with high mortality. The purpose of this study was to assess the impact of hospital structure-related variables on mortality in patients with CS treated at percutaneous and surgical revascularization capable centres (psRCC) from a large nationwide registry.

Methods and results

Retrospective observational study including consecutive patients with main or secondary diagnosis of CS and ST elevation myocardial infarction (STEMI). Patients discharged from Spanish National Healthcare System psRCC were included (2016–20). The association between the volume of CS cases attended by each centre, availability of intensive cardiac care unit (ICCU) and heart transplantation (HT) programmes, and in-hospital mortality was assessed by multilevel logistic regression models. The study population consisted of 3074 CS-STEMI episodes, of whom 1759 (57.2%) occurred in 26 centres with ICCU. A total of 17/44 hospitals (38.6%) were high-volume centres, and 19/44 (43%) centres had HT programmes availability. Treatment at HT centres was not associated with a lower mortality (P = 0.121). Both high volume of cases and ICCU showed a trend to an association with lower mortality in the adjusted model [odds ratio (OR): 0.87 and 0.88, respectively]. The interaction between both variables was significantly protective (OR 0.72; P = 0.024). After propensity score matching, mortality was lower in high-volume hospitals with ICCU (OR 0.79; P = 0.007).

Conclusion

Most CS-STEMI patients were attended at psRCC with high volume of cases and ICCU available. The combination of high volume and ICCU availability showed the lowest mortality. These data should be taken into account when designing regional networks for CS management.
Complete revascularization is associated with higher mortality in patients with ST-elevation myocardial infarction, multi-vessel disease and shock defined by hyperlactataemia: results from the Harefield Shock Registry incorporating explainable machine learning
Authors: Tindale Alexander , Cretu Ioana , Meng Hongying , Panoulas Vasileios
Published: June 2023

Aims

Revascularization strategy for patients with ST-elevation myocardial infarction (STEMI) and multi-vessel disease varies according to the patient’s cardiogenic shock status, but assessing shock acutely can be difficult. This article examines the link between cardiogenic shock defined solely by a lactate of ≥2 mmol/L and mortality from complete vs. culprit-only revascularization in this cohort.

Methods and results

Patients presenting with STEMI, multi-vessel disease without severe left main stem stenosis and a lactate ≥2 mmol/L between 2011 and 2021 were included. The primary endpoint was mortality at 30 days by revascularization strategy for shocked patients. Secondary endpoints were mortality at 1 year and over a median follow-up of 30 months. Four hundred and eight patients presented in shock. Mortality in the shock cohort was 27.5% at 30 days. Complete revascularization (CR) was associated with higher mortality at 30 days [odds ratio (OR) 2.1 (1.02–4.2), P = 0.043], 1 year [OR 2.4 (1.2–4.9), P = 0.01], and over 30 months follow-up [hazard ratio (HR) 2.2 (1.4–3.4), P < 0.001] compared with culprit lesion-only percutaneous coronary intervention (CLOP). Mortality was again higher in the CR group after propensity matching (P = 0.018) and inverse probability treatment weighting [HR 2.0 (1.3–3.0), P = 0.001]. Furthermore, explainable machine learning demonstrated that CR was behind only blood gas parameters and creatinine levels in importance for predicting 30-day mortality.

Conclusion

In patients presenting with STEMI and multi-vessel disease in shock defined solely by a lactate of ≥2 mmol/L, CR is associated with higher mortality than CLOP.
Multimodality imaging for patient selection, procedural guidance, and follow-up of transcatheter interventions for structural heart disease: a consensus document of the EACVI Task Force on Interventional Cardiovascular Imaging: part 1: access routes, transcatheter aortic valve implantation, and transcatheter mitral valve interventions
Authors: Agricola Eustachio , Ancona Francesco , Bartel Thomas , Brochet Eric , Dweck Marc , Faletra Francesco , Lancellotti Patrizio , Mahmoud-Elsayed Hani , Marsan Nina Ajmone , Maurovich-Hovart Pal , Monaghan Mark , Pontone Gianluca , Sade Leyla Elif , Swaans Martin , Von Bardeleben Ralph Stephan , Wunderlich Nina , Zamorano Jose-Luis , Popescu Bogdan A , Cosyns Bernard , Donal Erwan
Published: June 2023

Transcatheter therapies for the treatment of structural heart diseases (SHD) have expanded dramatically over the last years, thanks to the developments and improvements of devices and imaging techniques, along with the increasing expertise of operators. Imaging, in particular echocardiography, is pivotal during patient selection, procedural monitoring, and follow-up. The imaging assessment of patients undergoing transcatheter interventions places demands on imagers that differ from those of the routine evaluation of patients with SHD, and there is a need for specific expertise for those working in the cath lab. In the context of the current rapid developments and growing use of SHD therapies, this document intends to update the previous consensus document and address new advancements in interventional imaging for access routes and treatment of patients with aortic stenosis and regurgitation, and mitral stenosis and regurgitation.
Physiological declines in sex steroid exposure in relation to changes in body composition in healthy men—a prospective cohort study
Authors: Banica Thiberiu , Verroken Charlotte , Reyns Tim , T’Sjoen Guy , Fiers Tom , Kaufman Jean-Marc , Lapauw Bruno
Published: June 2023

Objective

Androgen levels decline from early adulthood and decreases are steeper in men with increasing body mass index. It is, however, unclear to what extent changes in other indices of body composition and metabolism associate with changes in sex steroid levels in healthy men. Therefore, this study investigated longitudinal changes in body composition and metabolic health in relation to sex steroid levels in healthy adult men.

Design

This is a longitudinal, population-based study. A total of 676 healthy men aged 24-46 years were measured at baseline and after ±12 years.

Methods

Serum sex hormone-binding globulin (SHBG) was measured by immunoassay, testosterone (T), estradiol (E2), and dihydrotestosterone byliquid chromatography with tandem mass spectrometry (LC-MS/MS), calculated free T and calculated free E2 (cFE2), and homeostasis model assessment for insulin resistance (HOMA-IR) were calculated. Grip strength was measured by hand-grip dynamometry. Body composition was determined using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography.

Results

Mean fat mass (FM), lean mass (LM), and HOMA-IR increased (all P < .001). Decreasing androgen and SHBG levels was associated with increasing FM, whereas decreasing (cF)E2 levels were associated with decreasing FM (all P < .005). Decreasing (cF)E2 levels and increasing SHBG levels associated with decreasing LM (all P < .002). Changes in sex steroid levels and HOMA-IR or grip strength were not interrelated.

Conclusion

Aging leads to increases in FM indices and insulin resistance, whereas changes in parameters of LM are less unequivocal. In healthy adult men, physiological changes in sex steroid exposure clearly correlate with changes in adiposity but not so with lean mass, insulin resistance, or grip strength.

Clinical Trial

The SIBEX study was registered on ClinicalTrials.gov (#NVT02997033).
Novel aldo-keto reductase 1C3 inhibitor affects androgen metabolism but not ovarian function in healthy women: a phase 1 study
Authors: Gashaw Isabella , Reif Stefanie , Wiesinger Herbert , Kaiser Andreas , Zollmann Frank S , Scheerans Christian , Grevel Joachim , Piraino Paolo , Seidel Henrik , Peters Michaele , Rottmann Antje , Rohde Beate , Arlt Wiebke , Hilpert Jan
Published: June 2023

Objective

Aldo-keto reductase 1C3 (AKR1C3) has been postulated to be involved in androgen, progesterone, and estrogen metabolism. Aldo-keto reductase 1C3 inhibition has been proposed for treatment of endometriosis and polycystic ovary syndrome. Clinical biomarkers of target engagement, which can greatly facilitate drug development, have not yet been described for AKR1C3 inhibitors. Here, we analyzed pharmacodynamic data from a phase 1 study with a new selective AKR1C3 inhibitor, BAY1128688, to identify response biomarkers and assess effects on ovarian function.

Design

In a multiple-ascending-dose placebo-controlled study, 33 postmenopausal women received BAY1128688 (3, 30, or 90 mg once daily or 60 mg twice daily) or placebo for 14 days. Eighteen premenopausal women received 60 mg BAY1128688 once or twice daily for 28 days.

Methods

We measured 17 serum steroids by liquid chromatography–tandem mass spectrometry, alongside analysis of pharmacokinetics, menstrual cyclicity, and safety parameters.

Results

In both study populations, we observed substantial, dose-dependent increases in circulating concentrations of the inactive androgen metabolite androsterone and minor increases in circulating etiocholanolone and dihydrotestosterone concentrations. In premenopausal women, androsterone concentrations increased 2.95-fold on average (95% confidence interval: 0.35-3.55) during once- or twice-daily treatment. Note, no concomitant changes in serum 17β-estradiol and progesterone were observed, and menstrual cyclicity and ovarian function were not altered by the treatment.

Conclusions

Serum androsterone was identified as a robust response biomarker for AKR1C3 inhibitor treatment in women. Aldo-keto reductase 1C3 inhibitor administration for 4 weeks did not affect ovarian function.

ClinicalTrials.gov Identifier: NCT02434640; EudraCT Number: 2014-005298-36
At the intersection of race and immigration: a comprehensive review of depression and related symptoms within the US Black population
Authors: Esie Precious , Bates Lisa M
Published: June 2023

Although the literature on the differences between Black people and White people in terms of differences in major depressive disorder and related self-reported symptoms is robust, less robust is the literature on how these outcomes are patterned within the US Black population and why differences exist. Given increased ethnic diversity of Black Americans due to increases in immigration, continued aggregation may mask differences between Black ethnic-immigrant groups and Black Americans with more distant ancestral ties to Africa (African Americans). The purpose of this narrative review was to comprehensively synthesize the literature on depression and related symptoms within the US Black population across immigration- and ethnicity-related domains and provide a summary of mechanisms proposed to explain variation. Findings revealed substantial variation in the presence of these outcomes within the US Black population by nativity, region of birth, age at immigration, and Caribbean ethnic origin. Racial context and racial socialization were identified as important, promising mechanisms for better understanding variations by region of birth and among those born or socialized in the United States, respectively. Findings warrant data collection efforts and measurement innovation to better account for within-racial differences in outcomes under study. A greater appreciation of the growing ethnic-immigrant diversity within the US Black population may improve understanding of how racism differentially functions as a cause of depression and related symptoms within this group.
International validation of the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score in heart failure
Authors: Adamopoulos Stamatis , Miliopoulos Dimitris , Piotrowicz Ewa , Snoek Johan Aernout , Panagopoulou Niki , Nanas Serafim , Niederseer David , Mazaheri Reza , Ma Jing , Chen Yundai , Popovic Dejana , Seferovic Petar , Girola Davide , Corrà Ugo , Coats Andrew J S , Metra Marco , Rosano Giuseppe M C , Volterrani Maurizio , Apostolo Anna , Campodonico Jeness , Salvioni Elisabetta , Agostoni Piergiuseppe , Piepoli Massimo
Published: June 2023

Aims

Current European heart failure (HF) guidelines suggest the use of risk score: among them, the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score has demonstrated to be one of the most accurate. However, the risk scores are still poorly implemented in clinical practice, also due to the lack of strong evidence regarding their external validation in different populations. Thus, the current study was designed as an external validation test of the MECKI score in an international multicentre setting.

Methods and results

The study cohort consisted of patients diagnosed with HF with reduced ejection fraction (HFrEF) across international centres (not Italian), retrospectively recruited. Collected data included demographics, HF aetiology, laboratory testing, electrocardiogram (ECG), echocardiographic findings, and cardiopulmonary exercise testing (CPET) results as described in the original MECKI score publication. A total of 1042 patients across 8 international centres (7 European and 1 Asian) were included and followed up from 1998 till 2019. Patients were divided according to the calculated MECKI scores into three subgroups: (i) MECKI score <10%, (ii) 10–20%, and (iii) ≥ 20%. Survival analysis comparison among the three MECKI score subgroups showed a worse prognosis in patients with higher MECKI score value: median event-free survival times were 4396 days for MECKI score <10%, 3457 days for 10–20%, and 1022 days for ≥20% (P < 0.0001). Receiver operating characteristic (ROC) curves and area under the ROC curves (AUC) were like those reported in the original internal validation studies.

Conclusion

In patients diagnosed with HFrEF, the power of the MECKI score was confirmed in terms of prognosis and risk stratification, supporting its implementation as advised by the HF guidelines.
Conspiracy beliefs, COVID-19 vaccine uptake and adherence to public health interventions during the pandemic in Europe
Authors: Regazzi Luca , Lontano Alberto , Cadeddu Chiara , Di Padova Pasquale , Rosano Aldo
Published: June 2023

Background

Conspiracy beliefs can be a major hindrance causing a lack of compliance with public health measures, including vaccination. We examined the relationship between individual attitudes, socio-demographic factors, conspiracy beliefs, COVID-19 vaccine hesitancy and preferences about pandemic policies in Europe.

Methods

We used data from the 10th round of the European Social Survey, conducted in 2021–22 in 17 European countries. Both a conspiracy index and a personal attitude index for each participant were built by using a Latent Class Analysis model. Then, we used a multilevel regression model to investigate the relationship between a personal attitudes index, socio-demographic factors and country of residence, and a conspiracy index. We descriptively analyse the relationship between the conspiracy index and four main items related to COVID-19.

Results

We found that a higher probability of believing in conspiracy theories was associated with male gender, middle age, lower levels of education, unemployment, lower levels of trust and satisfaction and right-wing political orientation. The country of residence was a contextual factor, with eastern European countries having higher levels of conspiracy beliefs. Individuals who expressed conspiracy beliefs had lower COVID-19 vaccine uptake, were less satisfied with the way health services coped with the pandemic and less supportive of governmental restrictions.

Conclusions

This study provides valuable insights into the factors associated with conspiracy beliefs and their potential impact on public health. The findings highlight the need for effective strategies to address the underlying factors driving conspiracy beliefs, reduce vaccine hesitancy and promote acceptance of public health interventions.
Return on investment of workplace-based prevention interventions: a systematic review
Authors: Thonon Frédérique , Godon-Rensonnet Anne-Sophie , Perozziello Anne , Garsi Jérôme-Philippe , Dab William , Emsalem Philippe
Published: June 2023

Background

Occupational Safety and Health is an important public health topic. Many employers may regard health promotion or prevention initiatives as an additional cost with few benefits. The aim of this systematic review is to identify the studies conducted on the return on investment (ROI) of preventive health interventions conducted within workplaces, and to describe their designs, topics and calculation methods.

Methods

We searched PubMed, Web of Science, Science Direct, National Institute for Occupational Safety and Health, International Labour Organization and Occupational Safety and Health Administration from 2013 to 2021. We included studies that evaluated prevention interventions in the workplace setting and reported an economic outcome or company-related benefits. We report the findings according to PRISMA reporting guidelines.

Results

We included 141 articles reporting 138 interventions. Of them, 62 (44.9%) had an experimental design, 29 (21.0%) had a quasi-experimental design, 37 (26.8%) were observational studies and 10 (7.2%) were modelling studies. The interventions’ objectives were mostly related to psychosocial risks (N = 42; 30.4%), absenteeism (N = 40; 29.0%), general health (N = 35; 25.4%), specific diseases (N = 31; 22.5%), nutrition (N = 24; 17.4%), sedentarism (N = 21; 15.2%) musculoskeletal disorders (N = 17; 12.3%) and accidents (N = 14; 10.1%). The ROI calculation was positive for 78 interventions (56.5%), negative for 12 (8.7%), neutral for 13 (9.4%) and undetermined for 35 (25.4%).

Conclusion

There were many different ROI calculations. Most studies have a positive result but randomized controlled trials have fewer positive results than other designs. It is important to conduct more high-quality studies so that results can inform employers and policy-makers.
Probiotics in vaginal health
Authors: Mashatan Noushin , Heidari Reza , Altafi Mana , Amiri Amin , Ommati Mohammad Mehdi , Hashemzaei Masoud
Published: June 2023

Bacterial vaginosis, a type of vaginal inflammation, can be considered the main reason for abnormal discharges of the vagina and vaginal dysbiosis during reproductive years. Epidemiological investigations of females suffering from vaginitis demonstrated that at least 30% to 50% of all women had Bacterial vaginosis (BV). One of the fields of treatment is the use of probiotics, probiotics are commonly defined as viable microorganisms (yeasts or bacteria) that can positively affect the health of their hosts. They are used in foods, notably fermented milk products, and medicine-related products. The development of new probiotic strains is aimed at more active advantageous organisms. Lactobacillus species are the dominant bacteria in a normal vagina that can decrease the pH of the vagina by the production of lactic acid. A number of lactobacilli types can produce hydrogen peroxide as well. The presence of hydrogen peroxide-induced low pH can prevent the growth of several other microorganisms. The vaginal flora of BV cases can modify by replacing the Lactobacillus species with a high density of anaerobic bacteria (i.e. Mobiluncus sp. Bacteroides sp.), Mycoplasma hominis, and Gardnerella vaginalis. More vaginal infections are treated with medications, while there is a possibility of recurrence and chronic infection because of the adverse effects on the indigenous lactobacilli. Probiotics and prebiotics have shown capacities for optimizing, maintaining, and restoring the vaginal microflora. Therefore, biotherapeutics can offer alternative approaches to reduce infections of the vagina and thus promote consumers' health.
From genotype to phenotype: computational approaches for inferring microbial traits relevant to the food industry
Authors: Karlsen Signe T , Rau Martin H , Sánchez Benjamín J , Jensen Kristian , Zeidan Ahmad A
Published: June 2023

When selecting microbial strains for the production of fermented foods, various microbial phenotypes need to be taken into account to achieve target product characteristics, such as biosafety, flavor, texture, and health-promoting effects. Through continuous advances in sequencing technologies, microbial whole-genome sequences of increasing quality can now be obtained both cheaper and faster, which increases the relevance of genome-based characterization of microbial phenotypes. Prediction of microbial phenotypes from genome sequences makes it possible to quickly screen large strain collections in silico to identify candidates with desirable traits. Several microbial phenotypes relevant to the production of fermented foods can be predicted using knowledge-based approaches, leveraging our existing understanding of the genetic and molecular mechanisms underlying those phenotypes. In the absence of this knowledge, data-driven approaches can be applied to estimate genotype–phenotype relationships based on large experimental datasets. Here, we review computational methods that implement knowledge- and data-driven approaches for phenotype prediction, as well as methods that combine elements from both approaches. Furthermore, we provide examples of how these methods have been applied in industrial biotechnology, with special focus on the fermented food industry.
Evaluation of early liquid drinking after radical gastrectomy in gastric cancer: a Chinese multicenter propensity score matching analysis
Authors: Zhang Yue , Tao Kaixiong , Yu Jinlong , Chen Chao , Zheng Quan , Lei Sanlin , Zhong Xiaogang , Liu Lixin , Wang Wei , Wang Qiang , Li En , Luo Yuwen , Zhang Guanrong , Feng Xingyu , Li Yong , Wang Junjiang
Published: June 2023

Background

Enhanced recovery after surgery is used in gastrointestinal surgery. This study aimed to access the effects of early liquid drinking (ELD) on gastrointestinal function recovery in patients with gastric cancer (GC) who underwent radical gastrectomy, as high-quality evidence on the outcomes of ELD after gastrectomy is currently lacking.

Methods

Clinicopathological data of patients with GC from 11 centers were retrospectively analysed. Clinical outcomes were investigated in 555 patients, including 225 who started drinking liquid within 48 h (ELD group) of surgery and 330 who started drinking liquid after flatus resumption (traditional liquid drinking [TLD] group). Propensity score matching (PSM) analysis was performed using a match ratio of 1:1 and 201 patients were selected from each group for the analysis. Primary outcome was time to first passage of flatus. Secondary outcomes included time to first defecation, post-operative hospitalization days, occurrence of short-term post-operative complications, and hospitalization costs.

Results

After PSM, baseline characteristics were not significantly different between the two groups. The time to first flatus (2.72 ± 1.08 vs 3.36 ± 1.39 days), first defecation (4.34 ± 1.85 vs 4.77 ± 1.61 days), and post-operative hospital stay (8.27 ± 4.02 vs 12.94 ± 4.43 days) were shorter in the ELD group than in the TLD group (all P < 0.05). The ELD group had lower hospitalization costs than the TLD group ([7.83 ± 2.44 vs 8.78 ± 3.41] × 104 RMB, P = 0.041). No significant differences were observed in the incidence of post-operative complications.

Conclusions

Compared with TLD, post-operative ELD could promote rapid recovery of gastrointestinal function and reduce hospitalization costs; moreover, ELD does not increase the risk of post-operative complications.
Can a Y Chromosome Degenerate in an Evolutionary Instant? A Commentary on Fong et al. 2023
Authors: Charlesworth Deborah , Hastings Abigail , Graham Chay
Published: June 2023

It is well known that the Y chromosomes of Drosophila and mammals and the W chromosomes of birds carry only small fractions of the genes carried by the homologous X or Z chromosomes, and this “genetic degeneration” is associated with loss of recombination between the sex chromosome pair. However, it is still not known how much evolutionary time is needed to reach such nearly complete degeneration. The XY pair of species in a group of closely related poecilid fish is homologous but has been found to have either nondegenerated or completely degenerated Y chromosomes. We evaluate evidence described in a recent paper and show that the available data cast doubt on the view that degeneration has been extraordinarily rapid in the latter (Micropoecilia species).
Interrogating the Etiology of Sporadic Alzheimer’s Disease Using Aging Rhesus Macaques: Cellular, Molecular, and Cortical Circuitry Perspectives
Authors: Datta Dibyadeep
Published: June 2023

Aging is the most significant risk factor for neurodegenerative disorders such as Alzheimer’s disease (AD) associated with profound socioeconomic and personal costs. Consequently, there is an urgent need for animal models that recapitulate the age-related spatial and temporal complexity and patterns of pathology identical to human AD. Our research in aging nonhuman primate models involving rhesus macaques has revealed naturally occurring amyloid and tau pathology, including the formation of amyloid plaques and neurofibrillary tangles comprising hyperphosphorylated tau. Moreover, rhesus macaques exhibit synaptic dysfunction in association cortices and cognitive impairments with advancing age, and thus can be used to interrogate the etiological mechanisms that generate neuropathological cascades in sporadic AD. Particularly, unique molecular mechanisms (eg, feedforward cyclic adenosine 3ʹ,5ʹ-monophosphate [cAMP]-Protein kinase A (PKA)-calcium signaling) in the newly evolved primate dorsolateral prefrontal cortex are critical for persistent firing required for subserving higher-order cognition. For example, dendritic spines in primate dorsolateral prefrontal cortex contain a specialized repertoire of proteins to magnify feedforward cAMP-PKA-calcium signaling such as N-methyl-d-aspartic acid receptors and calcium channels on the smooth endoplasmic reticulum (eg, ryanodine receptors). This process is constrained by phosphodiesterases (eg, PDE4) that hydrolyze cAMP and calcium-buffering proteins (eg, calbindin) in the cytosol. However, genetic predispositions and age-related insults exacerbate feedforward cAMP-Protein kinase A-calcium signaling pathways that induce a myriad of downstream effects, including the opening of K+ channels to weaken network connectivity, calcium-mediated dysregulation of mitochondria, and activation of inflammatory cascades to eliminate synapses, thereby increasing susceptibility to atrophy. Therefore, aging rhesus macaques provide an invaluable model to explore novel therapeutic strategies in sporadic AD.
Chronic Stress and Latent Virus Reactivation: Effects on Immune Aging, Chronic Disease Morbidity, and Mortality
Authors: Klopack Eric T
Published: June 2023

Objectives

Social stress has been shown to affect immune functioning. Past research has found that chronic social stress and latent viral infections accelerate immune aging, leading to chronic disease morbidity and mortality. Chronic stress may also reactivate latent viral infections, like cytomegalovirus (CMV), accelerating the aging of the immune system.

Method

Utilizing panel survey data from 8,995 U.S. adults aged 56 or older from the Health and Retirement Study, this study investigates whether chronic stress interacts with CMV positivity to drive aging of the immune system, multimorbidity, and mortality.

Results

Results of moderated mediation analysis indicate that the effect of CMV positivity on morbidity and mortality as mediated by immune aging indicators is amplified by chronic stress.

Discussion

These findings suggest that immune aging is a biological pathway underlying the stress process and help explain past findings in the literature on stress and health.
Single-cell transcriptome atlas reveals spatiotemporal developmental trajectories in the basal roots of moso bamboo (Phyllostachys edulis)
Authors: Cheng Zhanchao , Mu Changhong , Li Xiangyu , Cheng Wenlong , Cai Miaomiao , Wu Chongyang , Jiang Jutang , Fang Hui , Bai Yucong , Zheng Huifang , Geng Ruiman , Xu Junlei , Xie Yali , Dou Yuping , Li Juan , Mu Shaohua , Gao Jian
Published: June 2023

Roots are essential for plant growth and development. Bamboo is a large Poaceae perennial with 1642 species worldwide. However, little is known about the transcriptional atlas that underpins root cell-type differentiation. Here, we set up a modified protocol for protoplast preparation and report single-cell transcriptomes of 14 279 filtered single cells derived from the basal root tips of moso bamboo. We identified four cell types and defined new cell-type-specific marker genes for the basal root. We reconstructed the developmental trajectories of the root cap, epidermis, and ground tissues and elucidated critical factors regulating cell fate determination. According to in situ hybridization and pseudotime trajectory analysis, the root cap and epidermis originated from a common initial cell lineage, revealing the particularity of bamboo basal root development. We further identified key regulatory factors for the differentiation of these cells and indicated divergent root developmental pathways between moso bamboo and rice. Additionally, PheWOX13a and PheWOX13b ectopically expressed in Arabidopsis inhibited primary root and lateral root growth and regulated the growth and development of the root cap, which was different from WOX13 orthologs in Arabidopsis. Taken together, our results offer an important resource for investigating the mechanism of root cell differentiation and root system architecture in perennial woody species of Bambusoideae.
Characteristics, Clinical Outcomes, and Prognosis of Anal and Pouch-related Carcinoma in Patients With Crohn’s Disease
Authors: Suttichaimongkol Tanita , Loftus Edward V
Published: June 2023

Background

This study described the clinical characteristics, outcomes, and prognosis of Crohn’s disease (CD) patients with anal cancer in a tertiary referral center.

Methods

The electronic medical records of 35 adult CD patients, including CD of the pouch, with anal carcinoma evaluated at Mayo Clinic Rochester, Florida, or Arizona between January 1989 and August 2022 were retrospectively reviewed.

Results

Before cancer diagnosis, patients with pouch-related carcinoma had a shorter median duration of inflammatory bowel disease than those with anal carcinoma (10 vs 26 years). Twenty-six patients (74%) had perianal diseases or rectovaginal fistula, and 35% had a history of human papillomavirus infection. Twenty-one patients (60%) were diagnosed with cancer by anal examination under anesthesia (EUA). More than half of adenocarcinomas were mucinous. Sixteen patients (47%) were American Joint Committee on Cancer (AJCC) Tumor Nodes Metastasis (TNM) stage 3, and 83% were treated by surgery. At last follow-up, 57% of patients were alive without cancer. The 1-, 3- and 5-year overall survival rates were 93.8% (95% confidence interval [CI], 85.7%-100%), 71.5% (95% CI, 56.4%-90.7%), and 67.7% (95% CI, 51.2%-87.7%), respectively. Advanced AJCC TNM stage (hazard ratio, 3.20 per stage; 95% CI, 1.05-9.72; P = .040) was significantly associated with increased risk of death, whereas the period of cancer diagnosis in 2011-2022 (HR, relative to 1989-2000, 0.16; 95% CI, 0.04-0.72; P = .017) was significantly related to decreased risk of death.

Conclusions

Anal and pouch-related carcinomas were rare complications of CD, and long-standing perianal diseases were an important risk factor. Anal EUA improved the diagnostic yield. Newer cancer treatment strategies and surgery were associated with excellent survival outcome.
Pro-inflammatory Cytokines Promote the Occurrence and Development of Colitis-associated Colorectal Cancer by Inhibiting miR-615-5p
Authors: Sun Danping , Gong Lingqi , Wang Xiaotong , Chen Shuijiao , Yi Jun , Liu Xiaowei
Published: June 2023

Background

Patients with ulcerative colitis (UC) may be prone to colitis-associated colorectal cancer (CAC), but there is still a poor understanding of the underlying mechanism so far. This study intended to clarify the role of pro-inflammatory cytokines and miR-615-5p in this process.

Methods

This experiment first detected miR-615-5p expressions in paraffin-embedded sections of colonic tissues from patients with UC and CAC. Then, we investigated the mechanism through which pro-inflammatory cytokines affected miR-615-5p. Furthermore, in vivo and in vitro tests were performed to identify how miR-615-5p affected colorectal cancer (CRC). Dual-luciferase reporter assay was then employed to identify the targeting relationship between miR-615-5p and stanniocalcin-1 (STC1).

Results

The miR-615-5p was lowly expressed in both cancerous and noncancerous colonic tissues of patients with CAC. Pro-inflammatory cytokines downregulated miR-615-5p expression. Overexpression of miR-615-5p reduced the proliferation and migration of CRC cells and had a certain therapeutic effect on in human CRC xenograft mice. Stanniocalcin-1 was identified to be a target gene of miR-615-5p and was involved in the effect of miR-615-5p on CRC.

Conclusions

During the progression from UC to CAC, pro-inflammatory cytokines downregulate miR-615-5p, which may induce the upregulation of STC1, and promote the occurrence and development of tumors. These findings offer new insights into the mechanism of CAC and may indicate novel tumor markers or therapeutic targets.
Peer Effects in Productivity and Differential Growth: A Global Value-Chain Perspective
Authors: Mundt Philipp , Savin Ivan , Cantner Uwe , Inoue Hiroyasu , Vannuccini Simone
Published: June 2023

Using multinational input–output data, we analyze how the productivity of countries adjusted for participation in global value chains affects their output growth in manufacturing sectors. Based on parametric and non-parametric methods, we find that value-chain linkages are critical to the productivity–growth nexus and help to explain cross-country differences in sectoral output growth rates compared to the situation where these linkages are ignored. Our results have implications for macroeconomics, where they point to peer effects in productivity as drivers of growth, and for economic development, where they illustrate how the participation in global value chains may outweigh disadvantages in productive performance at the level of individual countries. They may also encourage future empirical tests of replicator dynamics to verify whether global value chains can explain the weak evidence of selection forces at the firm level.
A New Era: Power in Partnership Peacekeeping
Authors: Schumann Maurice P , Bara Corinne
Published: June 2023

UN blue helmets increasingly deploy in partnership with regional organizations and coalitions of states. While this development is hailed as a way out of geopolitical fragmentation and capacity overstretch, little is known about the effectiveness of these peacekeeping partnerships. We argue that UN and non-UN operations exercise different forms of power, which reinforce each other to reduce battle violence in active wars. If non-UN military operations actively engage in combat, the UN can focus on what it does best—employing its broad toolbox to coerce, induce, and persuade. Our quantitative analysis of the interaction between UN and non-UN peacekeeping supports these expectations: partnership peacekeeping works. With a non-UN partner, UN troops can reduce battlefield violence more effectively, that is, with fewer blue helmets. Importantly, non-UN missions need UN operations to successfully curb violence. The UN’s multidimensional engagement offsets the potential negative effects of an all-too militarized approach to violence reduction. Regional and coalition peacekeeping can only support the UN, not replace it.
Crisis Bargaining in the Shadow of Third-Party Opportunism
Authors: Tarar Ahmer
Published: June 2023

The prospect of a rival opportunistically pressing for gains while one is at war with another rival highly influenced Britain's “two-power standard” as well as the US's “two-war standard.” Conflict scholars have documented numerous instances of third-party opportunism. I analyze a game-theoretic model of crisis bargaining in the shadow of third-party opportunism. Under complete information, a country with multiple rivals, that lacks overwhelming military power, incurs bargaining vulnerabilities with each rival due to potential opportunism by the others. Under incomplete information, uncertainty across dyads can lead to war even if there is complete information within dyads, adding more uncertainty to the interaction can actually reduce the likelihood of war, resolve across disputes can be endogenously correlated in equilibrium (in contrast to the exogenous assumption of reputational models), and a commitment problem can be conducive to peace rather than war.
Historical Claims to the International: The Case of the Suez Canal Experts
Authors: Eijking Jan
Published: June 2023

What IR scholars refer to as “the international” gets constructed and performed to specific ends, depending on time and place. This results in a plurality of claims to the international, subject to historical variation. To bring such variation into view, this article shows how nineteenth-century claims to internationality were tied to particular conceptions of legitimacy. The article explores this legitimation-by-experts through a case study of the 1855–56 Suez Canal Commission. Based on original archival research, the article shows that expert advice played an important role in claiming the internationality of the Suez Canal by limiting contestation to technical aspects. The central argument is that expertise and claims to the international can get co-constituted in arrangements that are intended to produce legitimacy. These arrangements narrow the terms of contestation in self-serving ways. A technocratic claim to the international was tightly linked to the mobilization and making of the Suez Canal experts, on two fronts. One, expertise and internationality were repeatedly articulated in conjunction, so they would signify each other. Two, the article shows that expert involvement was driven by legitimation concerns more than by epistemic optimization purposes. In sum, the article proposes a new way of historicizing internationality claims and sheds light on the distinctiveness of international expertise.