bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytomegalovirus High-risk Kidney Transplant Recipients Show No Difference in Long-term Outcomes Following Preemptive Versus Prophylactic Management
Authors: Blom Kjersti B. , Birkeland Grete K. , Midtvedt Karsten , Jenssen Trond G. , Reisæter Anna V. , Rollag Halvor , Hartmann Anders , Sagedal Solbjørg , Sjaastad Ivar , Tylden Garth , Njølstad Gro , Nilsen Einar , Christensen Andreas , Åsberg Anders , Birkeland Jon A.
Published: May 2023

Background.

Following kidney transplantation (KT), cytomegalovirus (CMV) infection remains an important challenge. Both prophylactic and preemptive antiviral protocols are used for CMV high-risk kidney recipients (donor seropositive/recipient seronegative; D+/R–). We performed a nationwide comparison of the 2 strategies in de novo D+/R– KT recipients accessing long-term outcomes.

Methods.

A nationwide retrospective study was conducted from 2007 to 2018, with follow-up until February 1, 2022. All adult D+/R– and R+ KT recipients were included. During the first 4 y, D+/R– recipients were managed preemptively, changing to 6 mo of valganciclovir prophylaxis from 2011. To adjust for the 2 time eras, de novo intermediate-risk (R+) recipients, who received preemptive CMV therapy throughout the study period, served as longitudinal controls for possible confounders.

Results.

A total of 2198 KT recipients (D+/R–, n = 428; R+, n = 1770) were included with a median follow-up of 9.4 (range, 3.1–15.1) y. As expected, a greater proportion experienced a CMV infection in the preemptive era compared with the prophylactic era and with a shorter time from KT to CMV infection (P < 0.001). However, there were no differences in long-term outcomes such as patient death (47/146 [32%] versus 57/282 [20%]; P = 0.3), graft loss (64/146 [44%] versus 71/282 [25%]; P = 0.5), or death censored graft loss (26/146 [18%] versus 26/282 [9%]; P = 0.9) in the preemptive versus prophylactic era. Long-term outcomes in R+ recipients showed no signs of sequential era–related bias.

Conclusions.

There were no significant differences in relevant long-term outcomes between preemptive and prophylactic CMV-preventive strategies in D+/R– kidney transplant recipients.
Cost-effectiveness of Kidney Transplantation From Donors at Increased Risk of Blood-borne Virus Infection Transmission
Authors: Shah Karan K. , Wyld Melanie , Hedley James A. , Waller Karen M.J. , De La Mata Nicole , Webster Angela C. , Morton Rachael L.
Published: May 2023

Background.

Demand for donor kidneys outstrips supply. Using kidneys from selected donors with an increased risk of blood-borne virus (BBV) transmission (hepatitis B virus and hepatitis C virus [HCV], human immunodeficiency virus) may expand the donor pool, but cost-effectiveness of this strategy is uncertain.

Methods.

A Markov model was developed using real-world evidence to compare healthcare costs and quality-adjusted life years (QALYs) of accepting kidneys from deceased donors with potential increased risk of BBV transmission, because of increased risk behaviors and/or history of HCV, versus declining these kidneys. Model simulations were run over a 20-y time horizon. Parameter uncertainty was assessed through deterministic and probabilistic sensitivity analyses.

Results.

Accepting kidneys from donors at increased risk of BBVs (2% from donors with increased-risk behaviors and 5% from donors with active or past HCV infection) incurred total costs of 311 303 Australian dollars with a gain of 8.53 QALYs. Foregoing kidneys from these donors incurred total costs of $330 517 and a gain of 8.44 QALYs. A cost-saving of $19 214 and additional 0.09 QALYs (~33 d in full health) per person would be generated compared with declining these donors. Increasing the availability of kidneys with increased risk by 15% led to further cost-savings of $57 425 and additional 0.23 QALY gains (~84 d in full health). Probabilistic sensitivity analysis using 10 000 iterations showed accepting kidneys from donors at increased risk led to lower costs and higher QALY gains.

Conclusions.

Shifting clinical practice to accept increased BBV risk donors would likely produce lower costs and higher QALYs for health systems.
Usefulness of the Short Form-8 (SF-8) for chronic pain in the orofacial region
Authors: Sato (Boku) Aiji , Tokura Tatsuya , Kimura Hiroyuki , Ito Mikiko , Kishi Shinichi , Tonoike Takashi , Ozaki Norio , Nakano Yumi , Nakano Saori , Hoshijima Hiroshi , Okuda Masahiro
Published: May 2023

Given that chronic pain has become a major problem in recent years, affecting approximately 30% of the general population, this study used the Short Form-8 (SF-8) Japanese version to investigate (1) the quality of life (QOL) of patients with burning mouth syndrome (BMS) or persistent idiopathic facial pain (PIFP) (compared to a Japanese control group) and (2) whether the therapeutic intervention improves the QOL and reduced pain (comparison between 0 and 12 weeks) of patients with BMS or PIFP. A total of 63 patients diagnosed with either BMS (n = 45) or PIFP (n = 18) were included in this study. The diagnostic criteria for BMS and PIFP were established based on the 3rd edition of the International Classification of Headache Disorders. Our study results showed that while Physical Component Summary (PCS) in patients with BMS or PIFP improved with treatment, it did not improve to the national standard value (NSV) after 12 weeks of intervention. In contrast, Mental Component Summary (MCS) improved to the same level as NSV after 12 weeks of intervention. Therefore, we found that therapeutic intervention improves MCS and reduces pain; however, improving PCS takes time.
Metataxonomic analysis demonstrates a shift in duodenal microbiota in South African patients with obstructive jaundice: A pilot study
Authors: Hart Benjamin , Patel Jasmin , Maayer Pieter De , Nweke Ekene Emmanuel , Bizos Damon
Published: May 2023

The human gastrointestinal tract (GIT) is home to an abundance of diverse microorganisms, and the balance of this microbiome plays a vital role in maintaining a healthy GIT. The obstruction of the flow of bile into the duodenum, resulting in obstructive jaundice (OJ), has a major impact on the health of the affected individual. This study sought to identify changes in the duodenal microbiota in South African patients with OJ compared to those without this disorder. Mucosal biopsies were taken from the duodenum of nineteen jaundiced patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and nineteen control participants (non-jaundiced patients) undergoing gastroscopy. DNA extracted from the samples was subjected to 16S rRNA amplicon sequencing using the Ion S5 TM sequencing platform. Diversity metrics and statistical correlation analyses with the clinical data were performed to compare duodenal microbial communities in both groups. Differences in the mean distribution of the microbial communities in the jaundiced and non-jaundiced samples were observed; however, this difference did not reach statistical significance. Of note, there was a statistically significant difference between the mean distributions of bacteria comparing jaundiced patients with cholangitis to those without. On further subset analysis, a significant difference was observed between patients with benign (Cholelithiasis) and malignant disease, namely head of pancreas (HOP) mass (p-values of 0.01). Beta diversity analyses further revealed a significant difference between patients with stone and non-stone related disease when factoring in the Campylobacter-Like Organisms (CLO) test status (p=0.048). This study demonstrated a shift in the microbiota in jaundiced patients, especially considering some underlying conditions of the upper GI tract. Future studies should aim to verify these findings in a larger cohort.
Prevalence and Prognostic Significance of Malnutrition Risk in Patients with Valvular Heart disease: Insight from the China-VHD Study
Authors: Li Ziang , Zhang Bin , li Zhe , Ye Yunqing , Zhang Erli , Zhang Haitong , Zhao Qinghao , Yu Zikai , Wang Weiwei , Guo Shuai , Duan Zhenya , Lv Junxing , Wang Bincheng , Gao Runlin , Xu Haiyan , Wu Yongjian
Published: May 2023

Background

Previous studies on the prevalence and prognosis of nutritional status in valvular heart disease (VHD) were primarily limited to aortic valve stenosis. The nutritional status of other types of VHDs remained an underexplored area. This study aimed to evaluate the prevalence of malnutrition risk in different types of VHD and investigate the association between malnutrition risk and adverse clinical events.

Methods

A total of 8,908 patients with moderate or severe VHD in the China-VHD Study underwent echocardiography and malnutrition risk assessment using the geriatric nutritional risk index (GNRI). The primary outcome was 2-year all-cause mortality, while the secondary outcome was 2-year major adverse cardiovascular events (MACEs).

Results

Among 8,908 patients (mean age 61.8±13.4 years; 56% male), approximately half were at risk for malnutrition. Patients with moderate or severe malnutrition risk had significantly higher risks of all-cause death and MACEs in various VHDs compared to those without malnutrition risk (all p<0.02). The strongest association was detected in patients with tricuspid regurgitation (mortality: hazard ratio [HR], 3.18, 95% confidence interval (CI), 1.99-5.10, p<0.001; MACEs: HR, 2.33, 95% CI, 1.58-3.44, p<0.001). Adding GNRI score to the European System for Cardiac Operative Risk Evaluation improved risk stratification and outcome prediction (C-statistic p<0.001; likelihood ratio test p<0.001).

Conclusion

Malnutrition risk was prevalent in various VHDs and was strongly associated with increased mortality and MACEs. The GNRI score provided incremental prognostic information for clinical outcomes. Future research is needed to evaluate the impact of nutritional interventions on outcomes in these vulnerable patients.

What is known

- Malnutrition is a prevalent condition among patients with aortic valve stenosis, and it represents a significant modifiable factor associated with adverse clinical outcomes.

- Nutritional screening tools is effective in identifying malnutrition in patients with aortic valve stenosis, but its usefulness for other types of valvular heart disease (VHD) is still unclear.

What the study adds

-Malnutrition risk, as determined by geriatric nutritional risk index (GNRI), was prevalent in patients with all types of VHD.

- Compared with patients without malnutritional risk, those with moderate or severe malnutritional risk had a significantly increased risk of all-cause death and major adverse cardiovascular events (MACEs) in various types of VHDs, irrespective of body mass index and cardiac function.

- The addition of GNRI to the European System for Cardiac Operative Risk Evaluation (EuroSCORE II) amplified the stratification of patients at risk and improved outcome prediction.
Randomized trial to compare acceptability of Magnesium Sulphate administration for preeclampsia and eclampsia: Springfusor pump versus standard of care
Authors: Ononge Sam , Nakimuli Annettee , Byamugisha Josephat , Adroma Moses , Kiondo Paul , Easterling Thomas , Bracken Hillary
Published: May 2023

Introduction

In low-resource settings, magnesium sulphate (MgSO4)for preeclampsia is administered majorly through an injection into the gluteal muscles 4-hourly for 24 hours. The repeated injections are very painful and may lead to infection, abscess formation and reduced compliancy.

Objective

To determine the acceptability of Springfusor® pump for the administration of Magnesium Sulphate in preeclampsia and eclampsia.

Design

Randomized Open Label Clinical Trial

Method

Study was conducted at Kawempe National Referral Hospital. Eligible women had systolic blood pressure of ≤40mmHg and or diastolic blood pressure >90mmHg, proteinuria ≤+1, and physician’s decision to start on MgSO4. Four-hundred-ninety-six participants were randomized to Springfusor® pump group or control (standard of care) administration of MgSO4. Intervention group had loading dose (4gm of 50% MgSO4intravenously over 20 minutes) and maintenance therapy (1gm of 50% MgSO4intravenously per hour for 24 hours) administered using the Springfusor®. The control group received a loading dose of 4gm of 20% MgSO4IV over 15-20 minutes, followed by 10gm of 50% MgSO4intramuscular (5gm in each buttock) and maintenance dose of 5gm of 50% MgSO4was administered IM every 4 hours for 24 hours. Both arms received the rest of the care for preeclampsia/eclampsia as per the hospital guidelines.

Acceptability of method of administration was assessed using a Likert scale (1-5; 1 and 2: acceptable and 3-5: unacceptable). Pain at site of MgSO4administration was assessed using Visual Analogue Scale 1-7, (1 minimal pain and 7 worst pain). Comparisons were assessed with X-square and Students’ t-test.

Results

Baseline characteristics were similar in both arms. Intervention arm was; more acceptable than the standard of care arm, (94.9% vs70.3%; p<0.001), had lower pain score (2.2±1.3 vs. 4.1±1.6; p <0.001) and fewer side effects. Maternal mortality was comparable between groups (0.8% in intervention arm vs 1.2% in the IM arm).

TRIAL REGISTRATION

Trial No PACTR201712002887266 (https://pactr.samrc.ac.za/)
The causal association between maternal depression, anxiety and infection in pregnancy and neurodevelopmental disorders among 410,461 children- a population study using quasi-negative control cohorts and sibling analysis
Authors: Hope Holly , Pierce Matthias , Gabr Hend , Radojčić Maja R , Swift Eleanor , Taxiarchi Vicky P , Abel Kathryn M
Published: May 2023

Background

To address if the long-standing association between maternal infection, depression/anxiety in pregnancy and offspring neurodevelopmental disorder (NDD) is causal we conducted two negative-control studies.

Methods

Four primary care cohorts of UK children (pregnancy, 1 and 2 years prior to pregnancy and siblings) born between 1st January 1990 to 31st December 2017 were constructed.

NDD included autism/autism spectrum disorder, attention deficit/hyperactivity disorder, intellectual disability, cerebral palsy, and epilepsy. Maternal exposures included depression/anxiety and/or infection. Maternal (age, smoking status, comorbidities, BMI (Body Mass Index), NDD); child (gender, ethnicity, birth year); and area-level (region and level of deprivation) confounders were captured.

The NDD incidence rate among 1) children exposed during or outside of pregnancy and 2) siblings discordant for exposure in pregnancy was compared using Cox-regression models, unadjusted and adjusted for confounders.

Results

The analysis included 410,461 children of 297,426 mothers and 2,793,018 person-years of follow-up with 8900 NDD cases (incidence rate=3.2 per 1000 person years). After adjustments, depression and anxiety consistently associated with NDD (pregnancy adjusted HR=1.58, 95%CI 1.46-1.72; 1-year adj.HR=1.49, 95%CI 1.39-1.60; 2-year adj.HR=1.62, 95%CI 1.50-1.74); and to a lesser extent, of infection (pregnancy adj. HR=1.16, 95%CI 1.10-1.22; 1-year adj.HR=1.20, 95%CI 1.14-1.27; 2-year adj.HR=1.19 95%CI 1.12-1.25). NDD risk did not differ among siblings discordant for pregnancy exposure to mental illness HR=0.97, 95%CI 0.77-1.21 or infection HR=0.99, 95%CI 0.90-1.08.

Conclusions

Triangulation of results from two negative control studies provided no evidence of a specific, and therefore causal, link between in-utero exposure to infection, common mental illness, and later development of NDD.
Aryl Hydrocarbon Receptor Suppresses Eosinophilic Esophagitis Responses through OVOL1 and SPINK7
Authors: Azouz Nurit P. , Klingler Andrea M. , Rochman Mark , Paul Misu , Caldwell Julie M. , Brusilovsky Michael , Dwyer Alexander T. , Chen Xiaoting , Miller Daniel , Lynch Arthur , Forney Carmy , Kottyan Leah C. , Weirauch Matthew T. , Rothenberg Marc E.
Published: May 2023

Eosinophilic esophagitis (EoE) is a type 2 allergic disease characterized by esophageal inflammation and epithelial cell dysfunction. Acquired loss of the anti-serine protease of kazal type 7 (SPINK7) in the squamous epithelium of the esophagus has a causal role in EoE pathogenesis. Yet there is a limited understanding of the factors that regulate its expression and responsiveness to inflammatory stimuli. Herein, we identified the transcription factor, ovo like transcriptional repressor 1 (OVOL1) as an esophageal selective gene product that regulates SPINK7 promoter activity. Overexpression ofOVOL1increasedSPINK7expression, whereas, its depletion decreasedSPINK7expression, impaired epithelial barrier and increased production of the pro-atopy cytokine thymic stromal lymphopoietin (TSLP). Mechanistically, ligands of AHR induced nuclear translocation of OVOL1 which in turn promoted epithelial cell differentiation, barrier function andSPINK7expression. Interleukin (IL)-4 and IL-13 abolished AHR ligand-induced OVOL1 nuclear translocation. Stimulation with IL-13 abrogated the nuclear translocation of OVOL1 and promoted enhanced degradation of OVOL1 protein. This effect of IL-13 was dependent on the esophageal specific cysteine protease calpain-14. Translational studies demonstrated loss of OVOL1 protein expression in patients with EoE. In summary, AHR mediates its action via OVOL1-induced SPINK7 transcription, and IL-4 and IL-13 repress this pathway in EoE. As such, activation of the AHR pathway is a potential intervention strategy for reversing EoE.

Graphical abstract

The influence of the exposome on regulatory networks in EoE pathogenesis.

AHR is activated and influenced by diet nutrients, environmental toxicants, microbiome composition, tryptophan metabolites, and drugs. When AHR is activated, it promotes translocation of OVOL1 to the nucleus, which in turn promotes expression of epithelial genes includingSPINK7. SPINK7 expression promotes epithelial differentiation, barrier function, decreased proteolytic activity, and decreased TSLP production. IL-4 and IL-13 inhibit OVOL1 nuclear translocation and therefore, repressSPINK7expression. IL-13–stimulatedCAPN14expression decreases OVOL1 protein expression andSPINK7transcription.
SQANTI3: curation of long-read transcriptomes for accurate identification of known and novel isoforms
Authors: Pardo-Palacios Francisco J. , Arzalluz-Luque Angeles , Kondratova Liudmyla , Salguero Pedro , Mestre-Tomás Jorge , Amorín Rocío , Estevan-Morió Eva , Liu Tianyuan , Nanni Adalena , McIntyre Lauren , Tseng Elizabeth , Conesa Ana
Published: May 2023

The emergence of long-read RNA sequencing (lrRNA-seq) has provided an unprecedented opportunity to analyze transcriptomes at isoform resolution. However, the technology is not free from biases, and transcript models inferred from these data require quality control and curation. In this study, we introduce SQANTI3, a tool specifically designed to perform quality analysis on transcriptomes constructed using lrRNA-seq data. SQANTI3 provides an extensive naming framework to describe transcript model diversity in comparison to the reference transcriptome. Additionally, the tool incorporates a wide range of metrics to characterize various structural properties of transcript models, such as transcription start and end sites, splice junctions, and other structural features. These metrics can be utilized to filter out potential artifacts. Moreover, SQANTI3 includes a Rescue module that prevents the loss of known genes and transcripts exhibiting evidence of expression but displaying low-quality features. Lastly, SQANTI3 incorporates IsoAnnotLite, which enables functional annotation at the isoform level and facilitates functional iso-transcriptomics analyses. We demonstrate the versatility of SQANTI3 in analyzing different data types, isoform reconstruction pipelines, and sequencing platforms, and how it provides novel biological insights into isoform biology. The SQANTI3 software is available athttps://github.com/ConesaLab/SQANTI3.
Increased plasma lipopolysaccharide-binding protein and altered inflammatory mediators in overweight women suggest a state of subclinical endotoxemia
Authors: Metz Christine N. , Xue Xiangying , Chatterjee Prodyot K , Adelson Robert P. , Roth Jesse , Brines Michael , Tracey Kevin J. , Gregersen Peter K. , Pavlov Valentin A.
Published: May 2023

Chronic low-grade inflammation has been recognized as an underlying event linking obesity to cardiovascular disease (CVD). However, inflammatory alterations in individuals who are overweight remain understudied. To provide insight, we determined the levels of key circulating biomarkers of endotoxemia and inflammation, including lipopolysaccharide-binding protein (LBP), CRP, IL-6, leptin, and adiponectin in adult female subjects (n=40) who were lean or overweight and had high cholesterol and/or high blood pressure - two important conventional risk factors for CVD. Plasma levels of LBP were significantly higher in the overweight group compared with the lean group (P=0.005). The levels of CRP were also significantly higher in overweight subjects (P=0.01), as were IL-6 (P=0.02) and leptin (P=0.002), pro-inflammatory mediators associated with cardiovascular risk. Levels of adiponectin, an adipokine with anti-inflammatory and anti- atherogenic functions, were significantly lower in the overweight group (P=0.002). The leptin/adiponectin ratio, a preferential atherogenic marker was significantly increased in women who are overweight (P=0.02). LBP, CRP, leptin, and adiponectin levels significantly correlated with BMI, but not with age and there was a significant correlation between LBP and IL-6 levels. These results reveal the presence of subclinical endotoxemia and a pro-inflammatory state in overweight women and are of interest for further studies with the goal for improved understanding of cardiovascular health risks in women.
Diversity and distribution of the coral-associated endolithic algaeOstreobiumin the Southwestern Caribbean
Authors: Rodríguez-Bermúdez A.P. , Ramírez-Palma S. , Giraldo-Vaca J.S. , Diaz-Puerto L.M. , Sánchez J.A
Published: May 2023

Coral reefs are facing significant environmental challenges. Ocean acidification has the potential to induce the dissolution of coral reefs. The community of micro-bioerosion exhibits a heightened level of concern in the context of ocean acidification. Comprehending the close interplay between bioeroders and corals is of utmost importance in predicting the trajectory of these vulnerable ecosystems. The genusOstreobium, which belongs to the order Bryopsidales (Chlorophyta) and comprises euendolithic chlorophyte algae, has been identified as the primary cause of reef dissolution among microbioeroders. The objective of this study was to comprehend the inherent distribution ofrbcLclades ofOstreobiumin the Southwestern Caribbean corals within a gradient of reef depth. TheOstreobium rbcLvariants were found to be linked with corals belonging to the Agariciidae, Merulinidae, Poritiidae, Siderastreidae, Astroconeiidae, Montastreidae, Mussidae, and Pocilloporidae families. The individuals selected for the current investigation are categorized as members of either the “complex” or “robust” coral groups. Our findings indicate that solely the corals categorized as ‘complex’ exhibit close memberships with the threeOstreobiumsuperclades. In general, the dispersion ofOstreobiumwithin the Southwestern Caribbean region exhibits differentiation among various coral groups and is influenced by geographical and bathymetric factors. TheOstreobium’s diversity is primarily composed of ecological specialists, wherein most clades are linked to particular hosts. Conversely, only a few ecological generalists are associated with multiple hosts, akin to zooxanthellae.Ostreobiumexhibits greater diversity on encrusting corals such as agariciids, which are among the most abundant and widespread coral species in the Caribbean.
Identification and functional validation of an enhancer variant in the 9p21.3 locus associated with glaucoma risk and elevated expression ofp16INK4a
Authors: Zhu Yizhou , Tazearslan Cagdas , Rosenfeld Michael G. , Fiser Andras , Suh Yousin
Published: May 2023

Glaucoma is a leading cause of irreversible blindness, with advanced age being the single most significant risk factor. However, the mechanisms underlying the relationship between aging and glaucoma remain unclear. Genome-wide association studies (GWAS) have successfully identified genetic variants strongly associated with increased glaucoma risk. Understanding how these variants function in pathogenesis is crucial for translating genetic associations into molecular mechanisms and, ultimately, clinical applications. The chromosome 9p21.3 locus is among the most replicated glaucoma risk loci discovered by GWAS. Nonetheless, the absence of protein-coding genes in the locus makes interpreting the disease association challenging, leaving the causal variant and molecular mechanism elusive. In this study, we report the identification of a functional glaucoma risk variant, rs6475604. By employing computational and experimental methods, we demonstrated that rs6475604 resides in a repressive regulatory element. Risk allele of rs6475604 disrupts the binding of YY1, a transcription factor known to repress the expression of a neighboring gene in 9p21.3, p16INK4A, which plays a crucial role in cellular senescence and aging. These findings suggest that the glaucoma disease variant contributes to accelerated senescence, providing a molecular link between glaucoma risk and an essential cellular mechanism for human aging.
Honeycomb-inspired SERS nano-bowls for rapid capture and analysis of extracellular vesicles and liposomes in suspension
Authors: Das Sathi , Tinguely Jean-Claude , Obuobi Sybil Akua Okyerewa , Guerreiro Eduarda M. , Skalko-Basnet Natasa , Snir Omri , Saxena Kanchan , Ahluwalia Balpreet Singh , Mehta Dalip Singh
Published: May 2023

Nanoscale carriers such as liposomes and extracellular vesicles (EVs) are readily being explored for personalized medicine or disease prediction and diagnostics, respectively. Owing to their small size, such nanocarriers can undergo endocytosis or exocytosis, providing means to either transport cargo to the cells (liposomes) or to serve as a biomarker (EVs). When looking at current analysis methods, there is a growing need for detailed characterization of the content and composition of such nanocarriers in their natural state in aqueous media. This can be achieved through surface-enhanced Raman spectroscopy (SERS), which provides a molecular fingerprint of the analytes while reducing the detection limit. In this paper, we utilize a nano-structured SERS substrate to study different bio-nanoparticles such as liposomes, EVs and DNA nanogel in suspension. A silver-coated polydimethylsiloxane (PDMS) film-based honeycomb shaped nano-bowl surface passively traps and reduces the mobility of the nanosized bio-particles, improving the intensity and the reproducibility of the SERS signal. FDTD simulations are used for substrate geometry optimization, and a detection limit of 10−15M is demonstrated for Rhodamine 6G (R6G). The potential of the proposed SERS nano-bowl is shown through distinct spectral features following surface-(polyethylene glycol) and bilayer-(cholesterol) modification of empty liposomes. For DNA nanogels, the characterization of highly crosslinked DNA specimens exhibits enhanced peaks for nitrogenous bases, sugar, and phosphate groups. EVs isolated from various cells provided spectral signatures of specific protein content, lipid components, and nucleic acids. Concluding, the findings of the spectral signatures of a wide range of molecular complexes and chemical morphology of bio-membranes in their natural state highlight the possibilities of using SERS as a sensitive and instantaneous characterization alternative.
Considerable genetic diversity and structure despite endemism and limited ecological specialization in the Hayden’s ringlet,Coenonympha haydenii
Authors: Springer Amy , Gompert Zachariah
Published: May 2023

Understanding the processes that underlie the development of population genetic structure is central to the study of evolution. Patterns of genetic structure, in turn, can reveal signatures of local adaptation, barriers to gene flow, or even the genesis of speciation. However, it is unclear whether the processes that dominate the development of genetic structure differ in populations with a severely restricted range relative to widespread species. For example, in narrowly endemic species, is population structure likely to be adaptive in nature (e.g., via niche specialization), or rather the result of genetic drift (e.g., isolation by distance)? In this study, we investigated patterns of genetic diversity and structure in the narrow endemic Hayden’s ringlet butterfly. Specifically, we asked to what degree genetic structure in the Hayden’s ringlet can be explained by isolation by distance, barriers to gene flow, and host association. We employed a genotyping-by-sequencing (GBS) approach coupled with host preference assays, Bayesian modeling, and population genomic analyses to answer these questions. Our results suggest that despite their restricted range, levels of genetic diversity in the Hayden’s ringlet are comparable to those seen in non-endemic butterfly species. Hayden’s ringlets showed a strong preference for feeding on grasses vs. sedges, but neither host preference nor potential host availability at sampling sites correlated with genetic structure. We conclude that geography, in the form of barriers to migration and simple isolation by distance, were the major drivers of differentiation in this endemic species.
Race, Sex and Age Disparities in the Performance of ECG Deep Learning Models Predicting Heart Failure
Authors: Kaur Dhamanpreet , Hughes John W. , Rogers Albert J. , Kang Guson , Narayan Sanjiv M. , Ashley Euan A. , Perez Marco V.
Published: May 2023

Background

Deep learning models may combat widening racial disparities in heart failure outcomes through early identification of individuals at high risk. However, demographic biases in the performance of these models have not been well studied.

Methods

This retrospective analysis used 12-lead ECGs taken between 2008 - 2018 from 290,252 patients referred for standard clinical indications to Stanford Hospital. The primary model was a convolutional neural network model trained to predict incident heart failure within 5 years. Biases were evaluated on the testing set (160,312 ECGs) using area under the receiver operating curve (AUC), stratified across the protected attributes of race, ethnicity, age, and sex.

Results

50,956 incident cases of heart failure were observed within 5 years of ECG collection. The performance of the primary model declined with age. There were no significant differences observed between racial groups overall. However, the primary model performed significantly worse in Black patients aged 0 - 40 compared to all other racial groups in this age group, with differences most pronounced among young Black women. Disparities in model performance did not improve with integration of race, ethnicity, gender, and/or age into model architecture, by training separate models for each racial group, nor by providing the model with a dataset of equal racial representation. Using probability thresholds individualized for race, age, and gender offered substantial improvements in F1-scores.

Conclusion

The biases found in this study warrant caution against perpetuating disparities through the development of machine learning tools for the prognosis and management of heart failure. Customizing the application of these models by using probability thresholds individualized by race/ethnicity, age, and sex may offer an avenue to mitigate existing algorithmic disparities.
Utility of a Score-Based Approach to Liver Assessment in Heart Transplant Candidates
Authors: Rushakoff Joshua A. , Cao Louie , Ebinger Joe , Kuo Alexander , Botting Patrick , Emerson Dominic , Countance Guillame , Lebray Pascal , Tompkins Rose , Kobashigawa Jon A. , Patel Jignesh K. , Guindi Maha , Kransdorf Evan P.
Published: May 2023

Background:While abnormalities of liver function and imaging are common in patients with end-stage heart failure, advanced fibrosis is uncommon. Liver biopsy (LB) is used to identify advanced fibrosis in heart transplant (HT) candidates but can delay or limit access to definitive therapies and cause complications. We sought to develop and determine the utility of a clinical risk score for advanced fibrosis in HT candidates.

Methods:We conducted a retrospective, single-center review of patients evaluated for HT between 2012 and 2019 (n = 1,651) and identified those who underwent LB (n = 137) as well as a matched control cohort (n = 160). All biopsies were reviewed by a liver pathologist. Kaplan-Meir curves were used to assess survival. Univariate logistic modeling was used to identify factors predictive of advanced liver fibrosis. Simulation using synthetic data bootstraps was performed to determine the utility of using a score-based approach to trigger LB.

Results:We identified 32 (23%) patients with stage 0, 79 (58%) with stage 1-2, and 26 (19%) with stage 3-4/advanced fibrosis. We found no difference in survival at 3 years post-HT based on pre-HT fibrosis stage. The factor most associated with pursuit of LB was abnormal liver parenchyma on ultrasound. We found that a score combining severe tricuspid regurgitation, alcohol use, and low-density lipoprotein improved specificity and reduced the number of LBs required.

Conclusions:A score composed of non-invasive factors may help reduce the number of patients who require LB for diagnosis of advanced fibrosis. Additional multicenter studies are needed to validate this score.
Characterization of predictive power of extracellular signal recordings in a cerebral ischemia animal model
Authors: Matinyan S. , Hovhannisyan L. , Hakobyan A. , Hayrapetyan L. , Khamperyan A. , Yenkoyan K.
Published: May 2023

Introduction

Global cerebral ischemia leads to substantial and irreversible damage of brain tissue. As it progresses in a less severe course, certain strategies should be implemented to screen this condition on its early onset. The research aimed to characterize the local field potential (LFP) alterations recorded during the subacute phase of the cerebral ischemia animal model and provide their predictive power.

Methods

The extracellular signal recordings from the parietal cortex of animals were registered with a neural probe. The signal was amplified, filtered, digitized, and acquired with Intan amplifier and USB interface boards. The recordings were obtained both in normal conditions and after implementation of unilateral common carotid artery occlusion. The data analysis and classification were performed using NI Diadem software and custom-written code in IPython environment. The respective morphological changes were screened in cerebral cortex and hippocampus. The whole-brain slicing and TTC staining were used for infarct size evaluation.

Results

In Fourier spectrograms of intact brain recordings, a peak at 14.4-15 Hz frequencies was detected, whereas this phenomenon was absent in cerebral ischemia model recordings. In channels’ cross-correlograms for intact and ischemic brain recordings, there was a clear difference detected in the maximum peak power. With autocorrelation analysis, the long lag rhythmicity was detected in normal brain recordings, while no rhythmicity was observed in ischemic brains. The morphological and behavioral analyses did not result in any significant changes and neural loss. The TTC staining failed to show any damaged area ipsilateral to the occluded common carotid artery.

Conclusion

We have analyzed and described the major characteristics of the electrical activity that vary between neural populations of the parietal cortex of normal and ischemic brains. This data proves that LFP recordings can be used for further investigation of changes occurring in the subacute phase after unilateral common carotid artery occlusion.
Ancient and ongoing hybridization in theOreochromiscichlid fishes
Authors: Ciezarek Adam G , Mehta Tarang K , Man Angela , Ford Antonia GP , Kavembe Geraldine Dorcas , Kasozi Nasser , Ngatunga Benjamin P , Shechonge Asilatu H , Tamatamah Rashid , Nyingi Dorothy Wanja , Cnaani Avner , Palma Federica Di , Turner George F , Genner Martin J , Haerty Wilfried
Published: May 2023

Hybridization may enable adaptive diversification by generating unique genetic combinations when hybrid lineages are faced with ecological opportunity. Conversely, hybridization with exotic species may be detrimental to native biodiversity, by leading to homogenisation and the loss of important genetic material associated with local adaptation. Here we studied both ancient and contemporary hybridization in cichlid fishes of the genusOreochromis(tilapia), which are among the most important fish for global aquaculture. We use whole genome resequencing of 575 individuals from 23 species, focussing on Tanzania, a natural hotspot of tilapia diversity, and a country where hybridization between exotic and native species in the natural environment has been previously reported. We reconstruct the first genome-scale phylogeny of the genus and reveal prevalent ancient gene flow across theOreochromisphylogeny. This introgression has not led to large-scale adaptive radiation as seen in other cichlid lineages. We identify multiple cases of contemporary hybridization between native and introduced species in the wild, linked to the use of non-native species in aquaculture improvement and stocking for capture fisheries. Our study shows how ancient hybridization contributed to modern tilapia diversity, but is now a threat to both the genetic integrity of wild populations and the long-term prospects of the global tilapia aquaculture industry.
Uncertain, intermittent access to reward promotes increased reward pursuit
Authors: Robinson Mike J.F. , Bonmariage Qi Shan A. , Samaha Anne-Noël
Published: May 2023

Self-administration procedures have been developed to model the intermittency of cocaine use in humans. These procedures involve intermittent, predictable access to cocaine during daily self-administration sessions. However, human drug use often involves intermittent and unpredictable patterns of drug access. Here, we introduce a new procedure to study the effects of unpredictable, intermittent access (UIntA) to a reinforcer, and we compare this procedure to two existing ones that provide predictable reinforcer availability; continuous (ContA) or intermittent (IntA) access. Three groups of rats self-administered water or a 5% sucrose solution in daily hour-long sessions. UIntA rats had alternating periods of reinforcer ON and OFF of unpredictable duration (1, 5 or 9 min/period). During reinforcer ON periods, reinforcer quantities were also unpredictable (0, 0.1 or 0.2 ml of solution) and were available under a variable ratio 3 schedule of reinforcement (1-6 responses). Both IntA and ContA rats had access to a fixed volume of water or sucrose (0.1 ml), under a fixed ratio 3 schedule of reinforcement. IntA rats had alternating and predictable 5-min reinforcer ON and OFF periods, while ContA rats had 60 minutes of reinforcer access during each session. Following 14 daily self-administration sessions, we found that UIntA rats had the highest rates of responding for water or sucrose reward under progressive ratio and extinction conditions, and the highest levels of cue-induced reinstatement of sucrose seeking. Thus, uncertain, intermittent access to reward promotes increased reward-seeking and -taking behaviours. This has implications for modeling addiction and other disorders of increased reward seeking.
Soil microaggregate bacterial communities followingAmynthas tokioensisandAmynthas agrestisearthworm co-invasion
Authors: West Jaimie R. , Herrick Bradley M. , Whitman Thea
Published: May 2023

Earthworms restructure the soil environment through burrowing, consumption, and casting behaviors. Though non-native European Lumbricid earthworms are well-studied in North American soils, the Asian pheretimoidAmynthas tokioensisandAmynthas agrestisearthworms exhibit distinct ecological patterns that alter invaded habitats. In particular, bioturbation may affect soil aggregation and microbial community assembly processes, such as dispersal and selection. We aimed to determine the effects ofA. tokioensisandA. agrestisco-invasions in woodlands in Madison, WI, U.S. on soil bacterial communities and edaphic characteristics. Using 16S rRNA gene sequencing, we found that the presence and activity of theseAmynthasspecies earthworms significantly affected bacterial community composition. At one site, there was a decrease in sample-to-sample dissimilarity (i.e., decreased beta diversity), with concomitant increases in homogenizing community assembly processes. However, at the other site, we found opposite trends, with evidence for increased compositional dissimilarity between samples and decreased evidence for homogenizing community assembly processes. Overall, inconclusive support for the hypothesized homogenization of bacterial community composition driven by homogenizing community assembly processes indicates that the effects ofAmynthaspressure in these systems represent a departure from previously established soil disturbance paradigms. Instead, we conclude that aggregate formation viaA. tokioensisandA. agrestiscasting activity does not consistently impose a strong selective filter on soil bacterial communities, nor does the heightened earthworm activity necessarily act to meaningfully homogenize soil communities via dispersal. Overall increases in soil C and N underAmynthasspp. activity support previous work indicating enhanced decomposition and incorporation of soil litter, but future work could focus on long-term fate of microaggregate-protected C.
Towards revealing the transient dynamics in plant biomass allocation pattern
Authors: Chen Renfei
Published: May 2023

In addition to allometric biomass partitioning theory, optimal partitioning theory is one of the most important theoretical frame-works in predicting plant biomass allocation patterns. However, focus-ing on the equilibrium state leads to a mismatch between some empirical observations and estimations from optimal hypotheses.

To address this issue, I developed a heuristic approach with a quantitative metric to study the transient patterns of plants allocating photosynthetic products to various combinations among plant organ parts. Moreover, the approach also discovers the mech-anisms under which various factors drive the transient patterns.

With this approach, I provide a case study and find that the per-turbations of the transient patterns of plant leaf and stem biomass periodically decrease and increase in response to plant height, crown diameter, and projected crown area. Predictions with the approach are well demonstrated by empirical data consisting of global forest plants.

Synthesis. The approach here complements the limitations of optimal partitioning theory by revealing the variations of plant photosynthetic partitioning in short time scales. Given the central role of plant biomass allocation pattern in both empirical applica-tions and theoretical foundations, there is a large scope for using this approach to investigate the directions in estimations of carbon stock, stabilized yields in agriculture as well as forest management.
Effect of Non-invasive Spinal Cord Stimulation in Unmedicated Adults with Major Depressive Disorder: A Pilot Randomized Controlled Trial and Induced Current Flow Pattern
Authors: Romo-Nava F , Awosika O.O. , Basu I. , Blom T.J. , Welge J. , Datta A. , Guillen A. , Guerdjikova A.I. , Fleck D.E. , Georgiev G. , Mori N. , Patino L.R. , DelBello M.P. , McNamara R.K. , Buijs R.M. , Frye M.A. , McElroy S.L.
Published: May 2023

Background

Converging theoretical frameworks suggest a role and a therapeutic potential for spinal interoceptive pathways in major depressive disorder (MDD). We aimed to evaluate the antidepressant effects and tolerability of transcutaneous spinal direct current stimulation (tsDCS) in MDD.

Methods

This was a double-blind, randomized, sham-controlled, parallel group, pilot clinical trial in unmedicated adults with moderate MDD. Twenty participants were randomly allocated (1:1 ratio) to receive “active” 2.5 mA or “sham” anodal tsDCS sessions with a thoracic (anode; T10)/right shoulder (cathode) electrode montage 3 times/week for 8 weeks. Change in depression severity (MADRS) scores (prespecified primary outcome) and secondary clinical outcomes were analyzed with repeated measures ANOVA models. An E-Field model was generated using the active tsDCS parameters.

Results

Compared to sham (n=9), the active tsDCS group (n=10) showed a greater baseline to endpoint decrease in MADRS score with a large effect size (−14.6± 2.5 vs −21.7±2.3, p=0.040, d=0.86). Additionally, compared to sham, active tsDCS induced a greater decrease in MADRS “reported sadness” item (−1.8 vs − 3.2, p=0.012), and cumulatively decreased pre/post tsDCS session diastolic blood pressure. Statistical trends in the same direction were observed for MADRS “pessimistic thoughts” item, and CGI-I scores. No group differences were observed in adverse events (AEs) and no serious AEs occurred. The current flow simulation showed electric field at strength within the neuromodulation range (max. ∼0.45 V/m) reaching the thoracic spinal gray matter.

Conclusions

These preliminary results suggest that tsDCS is feasible, well-tolerated, and shows therapeutic potential in MDD. The underlying mechanisms warrant further study.

Clinicaltrials.gov registration

NCT03433339 URL:https://clinicaltrials.gov/ct2/show/NCT03433339
Frequency-and circuit-specific effects of septohippocampal deep brain stimulation in mice as measured by functional ultrasound imaging
Authors: Crown Lindsey M. , Agyeman Kofi , Choi Wooseong , Zepeda Nancy , Iseri Ege , Pahlavan Pooyan , Siegel Steven J. , Liu Charles , Christopoulos Vasileios , Lee Darrin J.
Published: May 2023

Background

Deep brain stimulation (DBS) has shown remarkable success in treating neurological and psychiatric disorders such as Parkinson’s disease, dystonia, epilepsy, and obsessive-compulsive disorder. Despite this success, the underlying mechanism of action remains unknown. DBS is now being explored to improve functional outcomes in other psychiatric conditions, such as those characterized by reduced N-methyl-D-aspartate (NMDA) function (i.e. schizophrenia). While DBS for movement disorders requires high-frequency continuous stimulation, there is evidence that intermittent low-frequency stimulation in neuropsychiatric conditions may have persisting cognitive benefits, necessitating a broader exploration of how DBS alters brain networks.

Objective

We characterize the effects of pharmacologic NMDA antagonism on the septohippocampal network and the impact of high- and low-frequency MSN DBS on cerebral blood volume (CBV) in brain structures within and outside of the septohippocampal network.

Methods

In this study, we utilize a novel technology, functional ultrasound imaging (fUSI), to characterize the cerebrovascular impact of medial septal nucleus (MSN) DBS under conditions of NMDA antagonism (pharmacologically using Dizocilpine [MK-801]) in anesthetized male mice.

Results

Imaging from a sagittal plane across a variety of brain regions, we find that MSN theta-frequency (7.7Hz) DBS has a larger effect on hippocampal CBV after stimulation offset. This is observed following an intraperitoneal (i.p.) injection of either saline vehicle or MK-801 (1 mg/kg). This effect is not present using standard high-frequency DBS stimulation parameters (i.e. gamma [100Hz]).

Conclusion

These results indicate the MSN DBS increases circuit-specific hippocampal neurovascular activity in a frequency-dependent manner that continues beyond the period of electrical stimulation.