bluuebunny/crossref_metadata_2025 huggingface dataset:
Perioperative Complications and Health-related Quality of Life Outcomes in Severe Pediatric Spinal Deformity
Authors: Gupta Munish C. , Lenke Lawrence G. , Gupta Sachin , Farooqi Ali S. , Asghar Jahangir K. , Boachie-Adjei Oheneba , Cahill Patrick J. , Erickson Mark A. , Garg Sumeet , Newton Peter O. , Samdani Amer F. , Shah Suken A. , Shufflebarger Harry L. , Sponseller Paul D. , Sucato Daniel J. , Bumpass David B. , McCarthy Richard E. , Yaszay Burt , Pahys Joshua M. , Ye Jichao ,   The Fox Pediatric Spinal Deformity Study Group, Kelly Michael P.
Published: May 2023

Study Design.

Prospective multicenter cohort study.

Objective.

To evaluate perioperative complications and mid-term outcomes for severe pediatric spinal deformity.

Summary of Background Data.

Few studies have evaluated the impact of complications on health-related quality of life (HRQoL) outcomes in severe pediatric spinal deformity.

Methods.

Patients from a prospective, multicenter database with severe pediatric spinal deformity (minimum of 100 degree curve in any plane or planned vertebral column resection (VCR)) with a minimum of 2-years follow-up were evaluated (n=231). SRS-22r scores were collected preoperatively and at 2-years postoperatively. Complications were categorized as intraoperative, early postoperative (within 90-days of surgery), major, or minor. Perioperative complication rate was evaluated between patients with and without VCR. Additionally, SRS-22r scores were compared between patients with and without complications.

Results.

Perioperative complications occurred in 135 (58%) patients, and major complications occurred in 53 (23%) patients. Patients that underwent VCR had a higher incidence of early postoperative complications than patients without VCR (28.9% vs. 16.2%, P=0.02). Complications resolved in 126/135 (93.3%) patients with a mean time to resolution of 91.63 days. Unresolved major complications included motor deficit (n=4), spinal cord deficit (n=1), nerve root deficit (n=1), compartment syndrome (n=1), and motor weakness due to recurrent intradural tumor (n=1). Patients with complications, major complications, or multiple complications had equivalent postoperative SRS-22r scores. Patients with motor deficits had lower postoperative satisfaction subscore (4.32 vs. 4.51, P=0.03), but patients with resolved motor deficits had equivalent postoperative scores in all domains. Patients with unresolved complications had lower postoperative satisfaction subscore (3.94 vs. 4.47, P=0.03) and less postoperative improvement in self-image subscore (0.64 vs. 1.42, P=0.03) as compared to patients with resolved complications.

Conclusion.

Most perioperative complications for severe pediatric spinal deformity resolve within 2-years postoperatively and do not result in adverse HRQoL outcomes. However, patients with unresolved complications have decreased HRQoL outcomes.
Regulatory mucosa-associated invariant T cells controlled by β1 adrenergic receptor signaling contribute to hepatocellular carcinoma progression
Authors: Fu Sicheng , Liu Muziying , Zhu Chenwen , Zhang Huimin , Zhao Changfeng , Xie Yaping , Chen Guanghou , Sheng Daping , Pan Jun , He Ziqing , Dai Ying , Gao Yufeng , Li Xiaomei , Chen Lijian , Qian Yeben , Jin Tengchuan , Sun Cheng , Tian Zhigang , Wang Hua , Bai Li
Published: May 2023

Background and Aims:

The innate-like mucosa-associated invariant T (MAIT) cells are enriched in human liver and have been linked to human HCC. However, their contributions to the progression of HCC are controversial due to the heterogeneity of MAIT cells, and new MAIT cell subsets remain to be explored.

Approach and Results:

Combining single cell RNA sequencing (scRNA-seq) and flow cytometry analysis, we performed phenotypic and functional studies and found that FOXP3+ CXCR3+ MAIT cells in HCC patients were regulatory MAIT cells (MAITregs) with high immunosuppressive potential. These MAITregs were induced under Treg-inducing condition and predominantly from FOXP3− CXCR3+ MAIT cells, which displayed mild Treg-related features and represented a pre-MAITreg reservoir. In addition, the induction and function of MAITregs were promoted by β1 adrenergic receptor signaling in pre-MAITregs and MAITregs, respectively. In HCC patients, high proportion of the intratumoral MAITregs inhibited antitumor immune responses and was associated with poor clinical outcomes.

Conclusions:

Together, we reveal an immunosuppressive subset of MAIT cells in HCC patients that contributes to HCC progression, and propose a control through neuroimmune crosstalk.
Paradoxical Associations of Occupational and Nonoccupational Sedentary Behavior With Cardiovascular Disease Risk Measures in Desk Workers
Authors: Alansare Abdullah B. , Paley Joshua L. , Quinn Tyler D. , Gibbs Bethany B.
Published: May 2023

Objectives

We assessed sedentary behavior (SB) patterns and examined its associations, by domain, with cardiovascular disease (CVD) risk measures in desk workers (N = 273).

Methods

Sedentary behavior was measured by activPAL3 and partitioned into occupational and nonoccupational SB. Cardiovascular disease risk measures included blood pressure, pulse wave velocity, heart rate, and heart rate variability. Paired t tests evaluated patterns of SB across domains. Linear regressions estimated associations of occupational and nonoccupational SB with CVD risk measures.

Results

Participants spent 69% of their time in SB; higher proportions were accumulated during occupational versus nonoccupational time. Higher all-domain SB was only associated with higher pulse wave velocity. Paradoxically, greater nonoccupational SB unfavorably associated with CVD risk measures, while higher occupational SB favorably correlated to CVD risk measures.

Conclusions

Observed paradoxical associations suggest that domain should be considered in efforts to improve cardiovascular health by reducing SB.
The impact of surgery and survival prediction in patients with gastroenteropancreatic neuroendocrine tumors: a population-based cohort study
Authors: Wu Zenghong , Wang Weijun , Zhang Kun , Fan Mengke , Lin Rong
Published: May 2023

Objective:

This study aimed at assessing the impact of surgical treatments in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Methods:

A propensity score-matched analysis based on data in the Surveillance, Epidemiology, and End Results database was used to assess the efficacy of surgical treatment in patients with GEP-NETs.

Results:

A total of 7515 patients diagnosed with GEP-NETs from 2004 to 2015 were evaluated from the Surveillance, Epidemiology, and End Results database. There were 1483 patients in the surgery group and 6032 patients in the nonsurgery group. Compared with patients in the surgery group, patients in the nonsurgery group were inclined to receive chemotherapy (50.8 vs. 16.7%) and radiation (12.9 vs. 3.7%) as treatment options. Multivariate Cox regression analysis revealed higher rates of overall survival (OS) outcomes for GEP-NETs patients who had been subjected to surgery (hazard ratio=0.483, 95% CI=0.439–0.533, P<0.001). Then, to reduce the impact of bias, a 1 : 1 propensity score-matched analysis was performed for the two groups of patients. A total of 1760 patients were assessed and each subgroup included 880 patients. In the matched population, the patients exhibited the ability to significantly benefit from surgery (hazard ratio=0.455, 95% CI=0.439–0.533, P<0.001). The OS outcomes for radiation or chemotherapy patients who had been treated with surgery were better than those of patients who had not been treated with surgery (P<0.001). In addition, it was found that the OS of patients was not significant after rectum and small intestine surgery, whereas there was a significant difference in OS after colon, pancreas, and stomach surgery on the patients. Patients who had been subjected to surgery in the rectum and small intestines exhibited better therapeutic benefits.

Conclusion:

Patients with GEP-NETs who are treated with surgery have better OS outcomes. Therefore, surgery is recommended for specified selected patients with metastatic GEP-NETs.
External validation of 18F-FDG PET-based radiomic models on identification of residual oesophageal cancer after neoadjuvant chemoradiotherapy
Authors: Valkema Maria J. , Beukinga Roelof J. , Chatterjee Avishek , Woodruff Henry C. , van Klaveren David , Noordzij Walter , Valkema Roelf , Bennink Roel J. , Roef Mark J. , Schreurs Wendy , Doukas Michail , Lagarde Sjoerd M. , Wijnhoven Bas P.L. , Lambin Philippe , Plukker John T.M. , van Lanschot J. Jan B.
Published: May 2023

Objectives

Detection of residual oesophageal cancer after neoadjuvant chemoradiotherapy (nCRT) is important to guide treatment decisions regarding standard oesophagectomy or active surveillance. The aim was to validate previously developed 18F-FDG PET-based radiomic models to detect residual local tumour and to repeat model development (i.e. ‘model extension’) in case of poor generalisability.

Methods

This was a retrospective cohort study in patients collected from a prospective multicentre study in four Dutch institutes. Patients underwent nCRT followed by oesophagectomy between 2013 and 2019. Outcome was tumour regression grade (TRG) 1 (0% tumour) versus TRG 2-3-4 (≥1% tumour). Scans were acquired according to standardised protocols. Discrimination and calibration were assessed for the published models with optimism-corrected AUCs >0.77. For model extension, the development and external validation cohorts were combined.

Results

Baseline characteristics of the 189 patients included [median age 66 years (interquartile range 60–71), 158/189 male (84%), 40/189 TRG 1 (21%) and 149/189 (79%) TRG 2-3-4] were comparable to the development cohort. The model including cT stage plus the feature ‘sum entropy’ had best discriminative performance in external validation (AUC 0.64, 95% confidence interval 0.55–0.73), with a calibration slope and intercept of 0.16 and 0.48 respectively. An extended bootstrapped LASSO model yielded an AUC of 0.65 for TRG 2-3-4 detection.

Conclusion

The high predictive performance of the published radiomic models could not be replicated. The extended model had moderate discriminative ability. The investigated radiomic models appeared inaccurate to detect local residual oesophageal tumour and cannot be used as an adjunct tool for clinical decision-making in patients.
Physical Training and Healthy Diet Improved Bowel Symptoms, Quality of Life, and Fatigue in Children With Inflammatory Bowel Disease
Authors: Scheffers Linda Elisabeth , Vos Iris K. , Utens E.M.W.J. , Dieleman G.C. , Walet S. , Escher J.C. , van den Berg L.E.M. ,   on behalf of the Rotterdam Exercise Team
Published: May 2023

Objectives:

Physical activity programs have been suggested as adjunctive therapy in adult inflammatory bowel disease (IBD) patients. We assessed the effects of a 12-week lifestyle intervention in children with IBD.

Methods:

This study was a randomized semi-crossover controlled trial, investigating a 12-week lifestyle program (3 physical training sessions per week plus personalized healthy dietary advice) in children with IBD. Endpoints were physical fitness (maximal and submaximal exercise capacity, strength, and core stability), patient-reported outcomes (quality of life, fatigue, and fears for exercise), clinical disease activity (fecal calprotectin and disease activity scores), and nutritional status (energy balance and body composition). Change in maximal exercise capacity (peak VO2) was the primary endpoint; all others were secondary endpoints.

Results:

Fifteen patients (median age 15 [IQR: 12–16]) completed the program. At baseline, peak VO2 was reduced (median 73.3% [58.8–100.9] of predicted). After the 12-week program, compared to the control period, peak VO2 did not change significantly; exercise capacity measured by 6-minute walking test and core-stability did. While medical treatment remained unchanged, Pediatric Crohn's Disease Activity Index decreased significantly versus the control period (15 [3–25] vs 2.5 [0–5], P = 0.012), and fecal calprotectin also decreased significantly but not versus the control period. Quality of life (IMPACT-III) improved on 4 out of 6 domains and total score (+13 points) versus the control period. Parents-reported quality of life on the child health questionnaire and total fatigue score (PedsQoL Multidimensional Fatigue Scale) also improved significantly versus the control period.

Conclusions:

A 12-week lifestyle intervention improved bowel symptoms, quality of life, and fatigue in pediatric IBD patients.
Rewarming Young Children After Drowning-Associated Hypothermia and Out-of-Hospital Cardiac Arrest: Analysis Using the CAse REport Guideline
Authors: Andre Maya Caroline , Vuille-Dit-Bille Raphael Nicolas , Berset Andreas , Hammer Jürg
Published: May 2023

OBJECTIVES:

Extracorporeal membrane oxygenation (ECMO) is recommended in adults with drowning-associated hypothermia and out-of-hospital cardiac arrest (OHCA). Our experience of managing a drowned 2-year-old girl with hypothermia (23°C) and cardiac arrest (58 min) prompted this summary using the CAse REport (CARE) guideline to address the question of optimal rewarming procedure in such patients.

DESIGN/PATIENTS:

Following the CARE guideline, we identified 24 reports in the “PubMed database” describing children less than or equal to 6 years old with a temperature less than or equal to 28°C who had been rewarmed using conventional intensive care ± ECMO. Adding our patient, we were able to analyze a total of 57 cases.

MAIN RESULTS:

The two groups (ECMO vs non-ECMO) differed with respect to submersion time, pH and potassium but not age, temperature or duration of cardiac arrest. However, 44 of 44 in the ECMO group were pulseless on arrival versus eight of 13 in the non-ECMO group. Regarding survival, 12 of 13 children (92%) undergoing conventional rewarming survived compared with 18 of 44 children (41%) undergoing ECMO. Among survivors, 11 of 12 children (91%) in the conventional group and 14 of 18 (77%) in the ECMO group had favorable outcome. We failed to identify any correlation between “rewarming rate” and “outcome.”

CONCLUSIONS:

In this summary analysis, we conclude that conventional therapy should be initiated for drowned children with OHCA. However, if this therapy does not result in return of spontaneous circulation, a discussion of withdrawal of intensive care might be prudent when core temperature has reached 34°C. We suggest further work is needed using an international registry.
Intensive Care Interventions Among Children With Toxicologic Exposures to Cardiovascular Medications
Authors: Simpson Michael D. , Watson C. James , Whitledge James D. , Monuteaux Michael C. , Burns Michele M. ,   on behalf of the Toxicology Investigators Consortium (ToxIC)
Published: May 2023

OBJECTIVES:

Interventions requiring a PICU are rare in toxicologic exposures, but cardiovascular medications are high-risk exposures due to their hemodynamic effects. This study aimed to describe prevalence of and risk factors for PICU interventions among children exposed to cardiovascular medications.

DESIGN:

Secondary analysis of Toxicology Investigators Consortium Core Registry from January 2010 to March 2022.

SETTING:

International multicenter research network of 40 sites.

PATIENTS:

Patients 18 years old or younger with acute or acute-on-chronic toxicologic exposure to cardiovascular medications. Patients were excluded if exposed to noncardiovascular medications or if symptoms were documented as unlikely related to exposure.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Of 1,091 patients in the final analysis, 195 (17.9%) received PICU intervention. One hundred fifty-seven (14.4%) received intensive hemodynamic interventions and 602 (55.2%) received intervention in general. Children less than 2 years old were less likely to receive PICU intervention (odds ratio [OR], 0.42; 95% CI, 0.20–0.86). Exposures to alpha-2 agonists (OR, 2.0; 95% CI, 1.11–3.72) and antiarrhythmics (OR, 4.26; 95% CI, 1.41–12.90) were associated with PICU intervention. In the sensitivity analysis removing atropine from the composite outcome PICU intervention, only exposures to calcium channel antagonists (OR, 2.12; 95% CI, 1.09–4.11) and antiarrhythmics (OR, 4.82; 95% CI, 1.57–14.81) were independently associated with PICU intervention. No independent association was identified between PICU intervention and gender, polypharmacy, intentionality or acuity of exposure, or the other medication classes studied.

CONCLUSIONS:

PICU interventions were uncommon but were associated with exposure to antiarrhythmic medications, calcium channel antagonists, and alpha-2 agonists. As demonstrated via sensitivity analysis, exact associations may depend on institutional definitions of PICU intervention. Children less than 2 years old are less likely to require PICU interventions. In equivocal cases, age and exposure to certain cardiovascular medication classes may be useful to guide appropriate disposition.
Effectiveness of implementation strategies to improve nutrition education interventions in adults living in rural and/or low-income communities
Authors: Gholar Victoria M. , Christian Robin
Published: May 2023

Objective:

The objective of this project was to promote evidence-based practice and identify how to best implement nutrition education interventions for adults living in rural and/or low-income communities.

Introduction:

Adults living in rural and/or low-income communities are at increased risk for poor nutrition and chronic health conditions. Patients are referred to the EversCare Clinic (ECC), an ambulatory clinic at an academic medical center in Mississippi, USA, to receive assistance with social needs. In addition to living in rural and/or low-income communities, over 90% of the patients seen at the ECC are food-insecure, yet nutrition education is inconsistently provided.

Methods:

The JBI Practical Application of Clinical Evidence System (PACES) and the Getting Research into Practice (GRiP) audit and feedback tools were used. The ECC team conducted a baseline audit of 30 patient electronic health records, designed and implemented best-practice nutrition education strategies, and completed a follow-up audit of 30 patient electronic health records. Four evidence-based criteria for nutrition education in adults living in rural and/or low-income communities were audited, and various interventions were used to address multiple levels.

Results:

The baseline audit revealed patients were not receiving recommended nutrition education interventions. Following the implementation, there was a 64.2% improvement in compliance with all four best practice criteria. Involving nursing students proved to be an effective method of improving compliance.

Conclusion:

Adherence to best practices regarding implementing nutrition education interventions was satisfactory, with 80% of patients receiving interventions at individual, interpersonal, community, and societal levels. Future audits are planned to ensure sustainability.
Here comes the sun: music features of popular songs reflect prevailing weather conditions
Authors: Anglada-Tort Manuel , Lee Harin , Krause Amanda E. , North Adrian C.
Published: May 2023

We examine associations between prevailing weather conditions and music features in all available songs that reached the United Kingdom weekly top charts throughout a 67-year period (1953–2019), comprising 23 859 unique entries. We found that music features reflecting high intensity and positive emotions were positively associated with daily temperatures and negatively associated with rainfall, whereas music features reflecting low intensity and negative emotions were not related to weather conditions. These results held true after controlling for the mediating effects of year (temporal patterns) and month (seasonal patterns). However, music–weather associations were more nuanced than previously assumed by linear models, becoming only meaningful in those months and seasons when changes in weather were the most notable. Importantly, the observed associations depended on the popularity of the music: while songs in the top 10 of the charts exhibited the strongest associations with weather, less popular songs showed no relationship. This suggests that a song's fit with prevailing weather may be a factor pushing a song into the top of the charts. Our work extends previous research on non-musical domains (e.g. finance, crime, mental health) by showing that large-scale population-level preferences for cultural phenomena (music) are also influenced by broad environmental factors that exist over long periods of time (weather) via mood-regulation mechanisms. We discuss these results in terms of the limited nature of correlational studies and cross-cultural generalizability.
ACOX-driven peroxisomal heterogeneity and functional compartmentalization in brown adipocytes of hypothyroid rats
Authors: Aleksic Marija , Golic Igor , Jankovic Aleksandra , Cvoro Aleksandra , Korac Aleksandra
Published: May 2023

We previously demonstrated that hypothyroidism increases peroxisomal biogenesis in rat brown adipose tissue (BAT). We also showed heterogeneity in peroxisomal origin and their unique structural association with mitochondria and/or lipid bodies to carry out β-oxidation, contributing thus to BAT thermogenesis. Distinctive heterogeneity creates structural compartmentalization within peroxisomal population, raising the question of whether it is followed by their functional compartmentalization regarding localization/colocalization of two main acyl-CoA oxidase (ACOX) isoforms, ACOX1 and ACOX3. ACOX is the first and rate-limiting enzyme of peroxisomal β-oxidation, and, to date, their protein expression patterns in BAT have not been fully defined. Therefore, we used methimazole-induced hypothyroidism to study ACOX1 and ACOX3 protein expression and their tissue immunolocalization. Additionally, we analysed their specific peroxisomal localization and colocalization in parallel with peroxisomal structural compartmentalization in brown adipocytes. Hypothyroidism caused a linear increase in ACOX1 expression, while a temporary decrease in ACOX3 levels is only recovered to the control level at day 21. Peroxisomal ACOX1 and ACOX3 localization and colocalization patterns entirely mirrored heterogeneous peroxisomal biogenesis pathways and structural compartmentalization, e.g. associations with mitochondria and/or lipid bodies. Hence, different ACOX isoforms localization/colocalization creates distinct functional heterogeneity of peroxisomes and drives their functional compartmentalization in rat brown adipocytes.
Vulture culture: dietary specialization of an obligate scavenger
Authors: Arrondo Eneko , Sebastián-González Esther , Moleón Marcos , Morales-Reyes Zebensui , María Gil-Sánchez José , Cortés-Avizanda Ainara , Ceballos Olga , Donázar José Antonio , Sánchez-Zapata José Antonio
Published: May 2023

Individual dietary variation has important ecological and evolutionary consequences. However, it has been overlooked in many taxa that are thought to have homogeneous diets. This is the case of vultures, considered merely as ‘carrion eaters’. Given their high degree of sociality, vultures are an excellent model to investigate how inter-individual transmissible behaviours drive individual dietary variation. Here, we combine GPS-tracking and accelerometers with an exhaustive fieldwork campaign to identify the individual diet of 55 griffon vultures (
Gyps fulvus
) from two Spanish populations that partially overlap in their foraging areas. We found that individuals from the more humanized population consumed more anthropic resources (e.g. stabled livestock or rubbish), resulting in more homogeneous diets. By contrast, individuals from the wilder population consumed more wild ungulates, increasing their dietary variability. Between sexes, we found that males consumed anthropic resources more than females did. Interestingly, in the shared foraging area, vultures retained the dietary preference of their original population, highlighting a strong cultural component. Overall, these results expand the role of cultural traits in shaping key behaviours and call for the need of including cultural traits in Optimal Foraging models, especially in those species that strongly rely on social information while foraging.
Conversion efficiency of flight power is low, but increases with flight speed in the migratory bat
Pipistrellus nathusii
Authors: Currie Shannon E. , Johansson L. Christoffer , Aumont Cedric , Voigt Christian C. , Hedenström Anders
Published: May 2023

The efficiency with which flying animals convert metabolic power to mechanical power dictates an individual's flight behaviour and energy requirements. Despite the significance of this parameter, we lack empirical data on conversion efficiency for most species as
in vivo
measurements are notoriously difficult to obtain. Furthermore, conversion efficiency is often assumed to be constant across flight speeds, even though the components driving flight power are speed-dependent. We show, through direct measurements of metabolic and aerodynamic power, that conversion efficiency in the migratory bat (
Pipistrellus nathusii
) increases from 7.0 to 10.4% with flight speed. Our findings suggest that peak conversion efficiency in this species occurs near maximum range speed, where the cost of transport is minimized. A meta-analysis of 16 bird and 8 bat species revealed a positive scaling relationship between estimated conversion efficiency and body mass, with no discernible differences between bats and birds. This has profound consequences for modelling flight behaviour as estimates assuming 23% efficiency underestimate metabolic costs for
P. nathusii
by almost 50% on average (36–62%). Our findings suggest that conversion efficiency may vary around an ecologically relevant optimum speed and provide a crucial baseline for investigating whether this drives variation in conversion efficiency between species.
Temperature-independent telomere lengthening with age in the long-lived human fish (
Proteus anguinus
)
Authors: Voituron Yann , Guillaume Olivier , Dumet Adeline , Zahn Sandrine , Criscuolo Francois
Published: May 2023

Despite a number of studies showing a negative relationship between age and telomere length, the universality of this pattern has been recently challenged, mainly in ectothermic animals exhibiting diverse effects of age on telomere shortening. However, data on ectotherms may be strongly affected by the thermal history of the individuals. We thus investigated the age-related changes in relative telomere length in the skin of a small but long-lived amphibian living naturally in a stable thermal environment over its entire life, allowing comparison with other homeothermic animals like birds and mammals. The present data showed a positive relation between telomere length and individual age, independent of sex and body size. A segmented analysis highlighted a breakpoint in the telomere length–age relationship, suggesting that telomere length reached a plateau at the age of 25 years. Further studies focusing on the biology of animals that live much longer than expected based on body mass will contribute to our better understanding of how ageing processes evolved and may also bring innovation for extending human health span.
Evaluation of core genome and whole genome multilocus sequence typing schemes for Campylobacter jejuni and Campylobacter coli outbreak detection in the USA
Authors: Joseph Lavin A. , Griswold Taylor , Vidyaprakash Eshaw , Im Sung B. , Williams Grant M. , Pouseele Hannes A. , Hise Kelley B. , Carleton Heather A.
Published: May 2023

Campylobacter

is a leading causing of bacterial foodborne and zoonotic illnesses in the USA. Pulsed-field gene electrophoresis (PFGE) and 7-gene multilocus sequence typing (MLST) have been historically used to differentiate sporadic from outbreak

Campylobacter

isolates. Whole genome sequencing (WGS) has been shown to provide superior resolution and concordance with epidemiological data when compared with PFGE and 7-gene MLST during outbreak investigations. In this study, we evaluated epidemiological concordance for high-quality SNP (hqSNP), core genome (cg)MLST and whole genome (wg)MLST to cluster or differentiate outbreak-associated and sporadic

Campylobacter jejuni

and

Campylobacter coli

isolates. Phylogenetic hqSNP, cgMLST and wgMLST analyses were also compared using Baker’s gamma index (BGI) and cophenetic correlation coefficients. Pairwise distances comparing all three analysis methods were compared using linear regression models. Our results showed that 68/73 sporadic

C. jejuni

and

C. coli

isolates were differentiated from outbreak-associated isolates using all three methods. There was a high correlation between cgMLST and wgMLST analyses of the isolates; the BGI, cophenetic correlation coefficient, linear regression model R
2 and Pearson correlation coefficients were >0.90. The correlation was sometimes lower comparing hqSNP analysis to the MLST-based methods; the linear regression model R
2 and Pearson correlation coefficients were between 0.60 and 0.86, and the BGI and cophenetic correlation coefficient were between 0.63 and 0.86 for some outbreak isolates. We demonstrated that

C. jejuni

and

C. coli

isolates clustered in concordance with epidemiological data using WGS-based analysis methods. Discrepancies between allele and SNP-based approaches may reflect the differences between how genomic variation (SNPs and indels) are captured between the two methods. Since cgMLST examines allele differences in genes that are common in most isolates being compared, it is well suited to surveillance: searching large genomic databases for similar isolates is easily and efficiently done using allelic profiles. On the other hand, use of an hqSNP approach is much more computer intensive and not scalable to large sets of genomes. If further resolution between potential outbreak isolates is needed, wgMLST or hqSNP analysis can be used.
Distribution of mutation rates challenges evolutionary predictability
Authors: Sun T. Anthony , Lind Peter A.
Published: May 2023

Natural selection is commonly assumed to act on extensive standing genetic variation. Yet, accumulating evidence highlights the role of mutational processes creating this genetic variation: to become evolutionarily successful, adaptive mutants must not only reach fixation, but also emerge in the first place, i.e. have a high enough mutation rate. Here, we use numerical simulations to investigate how mutational biases impact our ability to observe rare mutational pathways in the laboratory and to predict outcomes in experimental evolution. We show that unevenness in the rates at which mutational pathways produce adaptive mutants means that most experimental studies lack power to directly observe the full range of adaptive mutations. Modelling mutation rates as a distribution, we show that a substantially larger target size ensures that a pathway mutates more commonly. Therefore, we predict that commonly mutated pathways are conserved between closely related species, but not rarely mutated pathways. This approach formalizes our proposal that most mutations have a lower mutation rate than the average mutation rate measured experimentally. We suggest that the extent of genetic variation is overestimated when based on the average mutation rate.
Phylogenomics and Biogeography of North American Trechine Cave Beetles (Coleoptera: Carabidae)
Authors: Benito Joseph B. , Ober Karen A. , Niemiller Matthew L. , Ober Karen A.
Published: April 2023

Cave trechines beetles (Coleoptera: Carabidae: Trechini) are members of cave communities globally and important models for understanding the colonization of caves, adaptation to cave life, and the diversification of cave-adapted lineages. In eastern North America, cave trechines are the most species-rich group of terrestrial troglobionts, comprised of over 150 taxa in six genera with no extant surface members. Previous studies have hypothesized the climate change during the Pleistocene was a major driver of cave colonization and diversification in this and other temperate terrestrial cave fauna. However, our time-calibrated molecular phylogeny resulting from the analysis of 16,794 base pairs (bp) from 68 UCE loci for 45 species of the clade supports an alternative hypothesis whereby cave colonization of the surface ancestor of eastern North American cave trechines likely began in the middle Miocene in the Appalachians Ridge and Valley (APP) and dispersed into the Interior Low Plateau (ILP) in an east to west manner around 11.5 Mya. The APP served as a cradle for diversification and also as a bridge linking the southern Appalachians and Interior Low Plateau enabling the dispersal and subsequent diversification of these cave beetles. Major clades in our time-calibrated phylogeny attained their present-day geographic distributions by the early Miocene followed by multiple additional episodes of cave colonization and diversification occurring throughout the Pliocene and Pleistocene. The generaNeaphanops,Darlingtonea,Nelsonites, andAmeroduvaliuswere nested within specious genusPseudanopthalmussupporting the hypothesis that these genera are derived Pseudanophtlamus. Moreover, while several morphologically-derived species groups ofPseudanopthalmuswere recovered as monophyletic, others were not warranting future taxonomic and systematic research. The molecular systematics and biogeography of these unique cave beetles offer a model for other comparative evolutionary and ecological studies of troglobionts to further our understanding of factors driving speciation and biogeographic patterns.
Express barcoding with NextGenPCR and MinION for species-level sorting of ecological samples
Authors: Vasilita Cristina , Feng Vivian , Hansen Aslak Kappel , Hartop Emily , Srivathsan Amrita , Struijk Robin , Meier Rudolf
Published: April 2023

DNA barcodes are useful for species-level sorting of specimen samples, but rarely used in time-sensitive projects that require species richness estimates or identification of pest or invasive species within hours. The main reason is that existing express barcoding workflows are either too expensive or can only be carried out in very well equipped laboratories by highly trained staff.

We here introduce a simple workflow that combines rapid DNA extraction with HotSHOT, amplicon production with the aid of NextGenPCR® thermocyclers, and sequencing with low-cost MinION sequencers.

We demonstrate the power of the approach by generating and identifying 250 barcodes for 285 specimens within 6 hours. The workflow only required the following major equipment that easily fits onto a lab bench: Conventional thermocycler, NextGenPCR® thermocycler, microplate sealer, Qubit, and MinION.

We argue that species-level sorting with simplified barcoding workflows is now faster, more accurate, and sufficiently cost-effective that it can and should replace morphospecies sorting in many projects.
Effect of an intensive lifestyle intervention on circulating biomarkers of atrial fibrillation-related pathways
Authors: Li Linzi , Alonso Alvaro , Romaguera Dora , Alonso-Gómez Angel M. , Razquin Cristina , Tojal-Sierra Lucas , Fiol Miquel , Martínez-González Miguel Angel , Subramanya Vinita , Salas-Salvadó Jordi , Fito Montserrat , Toledo Estefanía
Published: May 2023

Determining the effect of lifestyle interventions on blood concentrations of biomarkers of atrial fibrillation (AF)-related pathways could help understand AF pathophysiology and contribute to AF prevention. We studied 471 participants enrolled in the PREDIMED-Plus trial, a Spanish randomized trial in adults with metabolic syndrome. Eligible participants were randomized 1:1 to an intensive lifestyle intervention, emphasizing physical activity, weight loss, and adherence to an energy-reduced Mediterranean diet or to a control group. Serum biomarkers [carboxy-terminal propeptide of procollagen type I (PICP), high-sensitivity troponin T (hsTnT), high-sensitivity C reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and N-terminal propeptide of B-type natriuretic peptide (NT-proBNP)] were measured at baseline, 3 and 5 years after randomization. Mixed models were used to evaluate the effect of intervention on changes in biomarkers through year 5. Mediation analysis was performed to examine the proportion mediated by each component of the intervention. Compared to the control group, participants in the intervention group experienced greater decreases in hsCRP (-16%, 95% confidence interval (CI) - 28%, -1%) or smaller increases in 3-NT (-15%, 95% CI -25%, -4%) and NT-proBNP (-13%, 95% CI - 25%, 0%). The intervention had minimal impact on hsTnT (-3%, 95% CI -8%, 2%) or PICP concentrations (-0%, 95% CI -9%, 9%). The effect of the intervention on hsCRP was primarily mediated by weight loss (73% and 66% at years 3 and 5). In conclusion, a dietary and lifestyle intervention for weight-loss favorably affected concentrations of hsCRP, 3-NT, and NT-proBNP, pointing to specific mechanisms in pathways linking lifestyles and AF.

Condensed abstract

In this study, we assessed the impact of an intensive lifestyle intervention on blood biomarkers related to atrial fibrillation (AF) pathways in 471 participants from the PREDIMED-Plus trial. The intervention focused on physical activity, weight loss, and an energy-reduced Mediterranean diet. Over five years, the intervention group showed greater decreases in high-sensitivity C reactive protein and smaller increases in 3-nitrotyrosine and N-terminal propeptide of B-type natriuretic peptide. Weight loss primarily mediated the effect of the intervention on high-sensitivity C reactive protein. These findings suggest that dietary and lifestyle changes may influence biomarkers involved in AF pathophysiology.

Key points

Randomized clinical trial, lifestyle, biomarker, atrial fibrillation
Clinical Gait Analysis for Hip Osteoarthritis Diagnostic Model and Arthroplasty Treatment’s Evaluation
Authors: Zhang Weiheng
Published: May 2023

I.

Osteoarthritis (OA) is a degenerative joint disease that seriously disturbs the patients’ motor ability [7]. To quantify gait kinematic impairments from such bone diseases, clinical gait analysis is widely used. Based on the motion-captured gait analysis data published by Bertaux et al., stratified by the subjects’ body mass index (BMI), we built a computational pipeline to extract seven gait kinematic features that can significantly distinguish hip OA (HOA) patients from healthy subjects [3], [5]. These features, along with demographic variables, were utilized to fit regression models for HOA predictor interpretation and classification models for HOA diagnosis. CV results showed that the final diagnostic model could achieve 90%+ sensitivity under 90% specificity, with AUC up to 0.96. We also analyzed the HOA patients 6 months post arthroplasty treatment: patients showed a trend of improvement in most kinematics variables and Ground Reaction Force similarities compared to healthy controls. Although differences between the treated patients and the healthy control still persist. Clinical gait analysis, along with data science strategies, can have substantial potential for HOA diagnosis and evaluation of the arthroplasty treatment.
Community-level variation in TB testing history: analysis of a prevalence survey in Blantyre, Malawi
Authors: Nightingale Emily S , Feasey Helena R A , Khundi McEwen , Soko Rebecca Nzawa , Burke Rachael M , Nliwasa Marriott , Twabi Hussein , Mpunga James A , Fielding Katherine , MacPherson Peter , Corbett Elizabeth L
Published: May 2023

Equitable access to tuberculosis testing is vital for achieving global treatment targets, but access to diagnostic services is often worse in poorer communities. The SCALE survey to estimate TB prevalence in Blantyre city, Malawi, also recorded engagement with TB services. We explored variation in self-reported TB testing history between 72 community clusters - adjusting for sex, age and HIV status - and investigated whether residual differences could be explained by household poverty. We observed substantial variation between clusters in the prevalence of ever-testing for TB, with little correlation between neighbouring clusters. Participants in poorer households had, on average, lower odds of ever-testing, yet adjusting for poverty did not reduce cluster-level variation. We conclude that, despite a decade of increased active case finding efforts, access to TB testing is inconsistent across the population of Blantyre, likely reflecting health inequities that also apply to TB testing in many other settings.
Task-induced changes in brain entropy
Authors: Camargo Aldo , Mauro Gianpaolo Del , Wang Ze
Published: May 2023

Abstract (TBD)

Entropy indicates irregularity of a dynamic system with higher entropy indicating higher irregularity and more transit states. In the human brain, regional entropy has been increasingly assessed using resting state fMRI. Response of regional entropy to task has been scarcely studied. The purpose of this study is to characterize task-induced regional brain entropy (BEN) alterations using the large Human Connectome Project (HCP) data. To control the potential modulation by the block-design, BEN of task-fMRI was calculated from the fMRI images acquired during the task conditions only and then compared to BEN of rsfMRI. Compared to resting state, task-performance unanimously induced BEN reduction in the peripheral cortical area including both the task activated regions and task non-specific regions such as the task negative area and BEN increase in the centric part of the sensorimotor and perception networks. Task control condition showed large residual task effects. After controlling the task non-specific effects using the control BEN vs task BEN comparison, regional BEN showed task specific effects in target regions.
Preparation of robust Synthetic Control samples and their use in a metatranscriptomic clinical test
Authors: Toma Ryan , Hu Lan , Banavar Guru , Vuyisich Momchilo
Published: May 2023

Metatranscriptomics (MT), or RNA sequencing, has the potential to revolutionize the field of molecular diagnostics. Due to the complexity of MT diagnostic models, positive and negative control materials for specific disease indications can be difficult to obtain. Controls must often be sourced directly from patients. This introduces logistical burdens, assay variability, and limits high throughput clinical laboratory operations. To overcome this limitation, we developed a method for generating Synthetic Control (SC) samples, which duplicate the nucleic acid signature of complex clinical specimens and produce the desired test outcome. SCs can be easily and cost-effectively produced in large quantities (>100,000 SCs per amplification cycle), enabling high throughput diagnostic testing. Here, we report the generation of Synthetic Positive Control (SPC) samples. SPCs were validated and implemented in a clinical laboratory. The SPCs produced robust positive signals (average OC risk score of 0.997) and high levels of reproducibility (%CV of 0.2%) in a high throughput automated CLIA laboratory. SCs are a novel and useful method for the generation of high quality controls for MT-based diagnostic tests, and their adoption could herald the widespread use of MT tests in molecular diagnostics.
Expansion of Disease Specific Cardiac Macrophages in Immune Checkpoint Inhibitor Myocarditis
Authors: Ma Pan , Liu Jing , Qin Juan , Lai Lulu , Heo Gyu Seong , Luehmann Hannah , Sultan Deborah , Bredemeyer Andrea , Bajapa Geetika , Feng Guoshuai , Jimenez Jesus , Parks Antanisha , Amrute Junedh , Villanueva Ana , Liu Yongjian , Lin Chieh-Yu , Mack Matthias , Amancherla Kaushik , Moslehi Javid , Lavine Kory J.
Published: April 2023

Background

Immune checkpoint inhibitors (ICIs), antibodies targeting PD-1/PD-L1 or CTLA4 have revolutionized cancer management but are associated with devastating immune-related adverse events (irAEs) including myocarditis. The main risk factor for ICI myocarditis is the use of combination PD-1 and CTLA4 inhibition. ICI-myocarditis is often fulminant and is pathologically characterized by myocardial infiltration of T lymphocytes and macrophages. While much has been learned regarding the role of T-cells in ICI-myocarditis, little is understood regarding the identity, transcriptional diversity, and functions of infiltrating macrophages.

Methods

We employed an established murine ICI myocarditis model (Ctla4+/-Pdcd1-/-mice) to explore the cardiac immune landscape using single-cell RNA-sequencing, immunostaining, flow cytometry, in situ RNA hybridization and molecular imaging and antibody neutralization studies.

Results

We observed marked increases in CCR2+monocyte-derived macrophages and CD8+T-cells in this model. The macrophage compartment was heterogeneous and displayed marked enrichment in an inflammatory CCR2+subpopulation highly expressingCxcl9,Cxcl10,Gbp2b, andFcgr4that originated from CCR2+monocytes. Importantly, a similar macrophage population expressingCXCL9,CXCL10, and CD16α (human homologue of mouse FcgR4) was found selectively expanded in patients with ICI myocarditis compared to other forms of heart failure and myocarditis.In silicoprediction of cell-cell communication suggested interactions between T-cells andCxcl9+Cxcl10+macrophages via IFN-γ and CXCR3 signaling pathways. Depleting CD8+T-cells, macrophages, and blockade of IFN-γ signaling blunted the expansion ofCxcl9+Cxcl10+macrophages in the heart and attenuated myocarditis suggesting that this interaction was necessary for disease pathogenesis.

Conclusion

These data demonstrate that ICI-myocarditis is associated with the expansion of a specific population of IFN-γ induced inflammatory macrophages and suggest the possibility that IFN-γ blockade may be considered as a treatment option for this devastating condition.
Negligible effects of read trimming on the accuracy of germline short variant calling in the human genome
Authors: Barbitoff Yury A , Predeus Alexander V
Published: April 2023

Next generation sequencing (NGS) has become a standard tool in the molecular diagnostics of Mendelian disease, and the precision of such diagnostics is greatly affected by the accuracy of variant calling from sequencing data. Recently, we have made a comprehensive evaluation of the performance of multiple variant calling pipelines, showing that state-of-the-art neural network-based methods show the best accuracy of variant discovery in the coding genome. In this work, we systematically evaluated the effects of adapters on the performance of variant calling tools using standard reference Genome-in-a-Bottle (GIAB) samples. We show that adapter trimming has no effect on the accuracy of the best-performing variant callers (e.g., DeepVariant) on whole-genome sequencing (WGS) data. For whole-exome sequencing (WES) datasets subtle improvement of accuracy was observed in some of the samples. In high-coverage WES data (~200x mean coverage), adapter removal allowed for discovery of 2-4 additional true positive variants in only two out of seven datasets tested. Moreover, this effect was not dependent on the median insert size and proportion of adapter sequences in reads. Surprisingly, the effect of trimming on variant calling was reversed when moderate coverage (~80-100x) WES data was used. Finally, we show that some of the recently developed machine learning-based variant callers demonstrate greater dependence on the presence of adapters in reads. Taken together, our results indicate that adapter removal is unnecessary when calling germline variants, but suggest that preprocessing methods should be carefully chosen when developing and using machine learning-based variant analysis methods.