bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential screening for non-viral sexually transmitted infections by type of vaginitis testing
Authors: Pinto Casey N. , Jung Molly , Wimmer Megan , Goldblatt Claudia , Sweeney Nicole , Broache Molly , Van Der Pol Barbara
Published: April 2023

Background

Data are lacking on adherence to Centers for Disease Control and Prevention testing guidelines among insured US women presenting with vaginal health complaints; thus, we quantified vaginitis testing frequency and assessed the co-testing rate for causes of vaginitis and Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG).

Methods

This was a retrospective analysis of de-identified data from a medical database. Information from women, ages 18-50 years, was obtained from the Truven MarketScan Commercial Database (2012-2017) using Current Procedural Technology codes; chi-square testing was applied to determine co-testing differences for CT/NG based on vaginitis test type. Odds ratios were calculated to determine the association with CT/NG screening across vaginitis testing categories.

Results

Approximately 48% of 1,359,289 women received a vaginitis diagnosis that involved a laboratory-based test. Of these women only 34% were co-tested for CT/NG. CT/NG co-testing was highest for those with nucleic acid amplification testing for vaginitis and lowest for those with no vaginitis testing Current Procedural Technology code (respectively, 71% vs 23%, P < 0.0001).

Conclusions

The vaginitis nucleic acid amplification test, indicated by CPT code, was associated with statistically significant, higher CT/NG testing rates. Molecular diagnostics may support vaginitis testing in settings that have limited opportunities for microscopy and clinical exams and offer greater opportunity to offer comprehensive women’s healthcare that includes testing for chlamydia and/or gonorrhea infections.
Characterization of Vaginal Microbial Community Dynamics in the Pathogenesis of Incident Bacterial Vaginosis, a Pilot Study
Authors: Elnaggar Jacob H. , Lammons John W. , Taylor Christopher M. , Toh Evelyn , Ardizzone Caleb M. , Dong Amy , Aaron Kristal J. , Luo Meng , Tamhane Ashutosh , Lefkowitz Elliot J. , Quayle Alison J. , Nelson David E. , Muzny Christina A.
Published: April 2023

Background

Despite over 60 years of research, the etiology of bacterial vaginosis (BV) remains controversial. In this pilot study, we utilized shotgun metagenomic sequencing to characterize vaginal microbial community changes prior to the development of incident BV (iBV).

Methods

A cohort of African American women with a baseline healthy vaginal microbiome (no Amsel Criteria, Nugent Score 0-3 with no Gardnerella vaginalis morphotypes) were followed for 90 days with daily self-collected vaginal specimens for iBV (≥2 consecutive days of a Nugent score of 7-10). Shotgun metagenomic sequencing was performed on select vaginal specimens from 4 women, every other day for 12 days prior to iBV diagnosis. Sequencing data were analyzed through Kraken2 and bioBakery 3 workflows, and specimens were classified into community state types (CSTs). Quantitative PCR (qPCR) was performed to compare the correlation of read counts to bacterial abundance.

Results

Common BV-associated bacteria such as G. vaginalis, Prevotella bivia, and Fannyhessea vaginae were increasingly identified in the participants prior to iBV. Linear modeling indicated significant increases in G. vaginalis and F. vaginae relative abundance prior to iBV, while the relative abundance of Lactobacillus spp. declined over time. The Lactobacillus spp. decline correlated with the presence of Lactobacillus phages. We observed enrichment in bacterial adhesion factor genes on days prior to iBV. There were also significant correlations between bacterial read counts and abundances measured by qPCR.

Conclusions

This pilot study characterizes vaginal community dynamics prior to iBV and identifies key bacterial taxa and mechanisms potentially involved in the pathogenesis of iBV.
Artificial Intelligence: Singularity Approaches
Authors: TerKonda Sarvam P. , TerKonda Anurag A. , Sacks Justin M. , Kinney Brian M. , Gurtner Geoff C. , Nachbar James M. , Reddy Sashank K. , Jeffers Lynn L.
Published: April 2023

Artificial intelligence (AI) has been a disruptive technology within health care, from the development of simple care algorithms to complex deep-learning models. AI has the potential to reduce the burden of administrative tasks, advance clinical decision-making, and improve patient outcomes. Unlocking the full potential of AI requires the analysis of vast quantities of clinical information. Although AI holds tremendous promise, widespread adoption within plastic surgery remains limited. Understanding the basics is essential for plastic surgeons to evaluate the potential uses of AI. This review provides an introduction of AI, including the history of AI, key concepts, applications of AI in plastic surgery, and future implications.
Evaluation of Safety, Biodistribution, and Dosimetry of a Long-Acting Radiolabeled Somatostatin Analog 177Lu-DOTA-EB-TATE With and Without Amino Acid Infusion
Authors: Jiang Yuanyuan , Liu Qingxing , Wang Guochang , Zhang Jingjing , Zhu Zhaohui , Chen Xiaoyuan
Published: April 2023

Purpose

Kidney is considered to be one of the dose-limiting organs in peptide receptor radionuclide therapy (PRRT). Amino acid cocktail infusion has been applied to reduce renal absorbed dose by inhibiting the proximal tubular reabsorption of the radiopeptide. An Evans blue-modified 177Lu-labeled octreotate (177Lu-DOTA-EB-TATE) has an extended circulation in the blood, which may make the amino acid infusion unnecessary. The aim of this study was to evaluate the safety, biodistribution, and dosimetry of 177Lu-DOTA-EB-TATE with and without amino acid infusion.

Patients and Methods

Ten patients with metastatic neuroendocrine tumors were randomly divided into 2 groups. The effect of amino acid infusion on renal uptake was assessed in a crossover randomized setting. Group A received 177Lu-DOTA-EB-TATE at a dose of 3.7 GBq without amino acid infusion for the first cycle and with amino acid infusion for the second cycle; group B received 177Lu-DOTA-EB-TATE at a dose of 3.7 GBq with amino acid infusion for the first cycle and without amino acid infusion for the second cycle. All patients underwent serial whole-body planar imaging at 1, 24, 96, and 168 hours and SPECT scan at 24 hours after radioligand administration. Abdominal CT was performed 2 days before PRRT for SPECT/CT fusion. The dosimetry was calculated using the HERMES software. Dosimetry evaluation was compared on a between-group and intrapatient basis.

Results

Administrations of 177Lu-DOTA-EB-TATE with or without amino acids were well tolerated. No grade 4 hematotoxicity was observed in any of the patients. Grade 3 thrombocytopenia was reported in 1 patient. No nephrotoxicity of any grade was recorded. No significant difference was observed in creatinine (75.1 ± 21.7 vs 67.5 ± 18.1 μmol/L, P = 0.128), blood urea nitrogen (4.5 ± 0.8 vs 5.1 ± 1.4 mmol/L, P = 0.612), or GFR (109.3 ± 25.2 vs 100.9 ± 24.9 mL/min, P = 0.398) before and after PRRT. For each cycle, there was no significant difference in whole-body effective dose, kidney effective dose, as well as residence time of the kidneys between group A and B (P > 0.05). By intrapatient comparison, without and with amino acid infusion also did not show significant difference in whole-body effective dose (0.14 ± 0.05 vs 0.12 ± 0.04 mSv/MBq, P = 0.612), kidney effective dose (1.09 ± 0.42 vs 0.73 ± 0.31 mSv/MBq, P = 0.093), and residence time of the kidneys (2.95 ± 1.58 vs 3.13 ± 1.11 hours, P = 0.674).

Conclusions

177Lu-DOTA-EB-TATE PRRT with and without amino acid infusion demonstrated a favorable safety profile in neuroendocrine tumor patients. Administration of 177Lu-DOTA-EB-TATE without amino acid infusion has acceptable slightly increased kidney absorbed dose and residence time of the kidneys, and does not affect kidney function. Further investigation in a larger cohort and long-term follow-up are warranted.
68Ga-PSMA PET/CT Detecting Metastatic Lesion of RCC
Authors: Jha Saurav , Hemrom Angel , Shamim Shamim Ahmed , Barwad Adarsh , Batra Atul
Published: April 2023

Renal cell carcinoma (RCC) accounts for ~2% of global cancers and deaths. Survival depends on initial staging and shows poor survival rate in metastatic disease. CT and MRI are used for evaluating RCC, and PET/CT is used for metastatic disease assessment. We report a case of RCC, where both 18F-FDG and 68Ga-PSMA PET/CT showed increased uptake in liver metastatic lesions; however, a subhepatic peritoneal deposit showed uptake only in PSMA. Also, liver lesions were seen better in PSMA owing to lesser background uptake, suggesting a possibility of 68Ga-PSMA being a potential tracer for RCC evaluation.
Cyclic Vomiting Syndrome and Cannabis Hyperemesis Syndrome
Authors: Lathrop James R. , Rosen Sheldon N. , Heitkemper Margaret M. , Buchanan Diana Taibi
Published: April 2023

This article provides a narrative review of the state of the science for both cyclic vomiting syndrome and cannabis hyperemesis syndrome along with a discussion of the relationship between these 2 conditions. The scope of this review includes the historical context of these conditions as well as the prevalence, diagnostic criteria, pathogenesis, and treatment strategies for both conditions. A synopsis of the endocannabinoid system provides a basis for the hypothesis that a lack of cannabidiol in modern high-potency Δ9-tetrahydrocannabinol cannabis may be contributory to cannabis hyperemesis syndrome and possibly other cannabis use disorders. In concluding assessment, though the publications addressing both adult cyclic vomiting syndrome and cannabis hyperemesis syndrome are steadily increasing overall, the state of the science supporting the treatments, prognosis, etiology, and confounding factors (including cannabis use) is of moderate quality. Much of the literature portrays these conditions separately and as such sometimes fails to account for the confounding of adult cyclic vomiting syndrome with cannabis hyperemesis syndrome. The diagnostic and therapeutic approaches are, at present, based generally on case series publications and expert opinion, with a very limited number of randomized controlled trials and a complete absence of Level 1 evidence within the cyclic vomiting literature overall as well as for cannabis hyperemesis syndrome specifically.
Pediatric cervical spine clearance: A 10-year evaluation of multidetector computed tomography at a level 1 pediatric trauma center
Authors: Russell Katie W. , Iantorno Stephanie E. , Iyer Rajiv R. , Brockmeyer Douglas L. , Smith Karch M. , Polukoff Natalya E. , Larsen Kezlen E. , Barnes Kacey L. , Bell Teresa M. , Fenton Stephen J. , Inaba Kenji , Swendiman Robert A.
Published: April 2023

INTRODUCTION

Efficient and accurate evaluation of the pediatric cervical spine (c-spine) for both injury identification and posttraumatic clearance remains a challenge. We aimed to determine the sensitivity of multidetector computed tomography (MDCT) for identification of cervical spine injuries (CSIs) in pediatric blunt trauma patients.

METHODS

A retrospective cohort study was conducted at a level 1 pediatric trauma center from 2012 to 2021. All pediatric trauma patients age younger than 18 years who underwent c-spine imaging (plain radiograph, MDCT, and/or magnetic resonance imaging [MRI]) were included. All patients with abnormal MRIs but normal MDCTs were reviewed by a pediatric spine surgeon to assess specific injury characteristics.

RESULTS

A total of 4,477 patients underwent c-spine imaging, and 60 (1.3%) were diagnosed with a clinically significant CSI that required surgery or a halo. These patients were older, more likely to be intubated, have a Glasgow Coma Scale score of <14, and more likely to be transferred in from a referring hospital. One patient with a fracture on radiography and neurologic symptoms got an MRI and no MDCT before operative repair. All other patients who underwent surgery including halo placement for a clinically significant CSI had their injury diagnosed by MDCT, representing a sensitivity of 100%. There were 17 patients with abnormal MRIs and normal MDCTs; none underwent surgery or halo placement. Imaging from these patients was reviewed by a pediatric spine surgeon, and no unstable injuries were identified.

CONCLUSION

Multidetector computed tomography appears to have 100% sensitivity for detecting clinically significant CSIs in pediatric trauma patients, regardless of age or mental status. Forthcoming prospective data will be useful to confirm these results and inform recommendations for whether pediatric c-spine clearance can be safely performed based on the results of a normal MDCT alone.

LEVEL OF EVIDENCE

Diagnostic Tests or Criteria; Level IV.
Contemporary management and outcomes of penetrating colon injuries: Validation of the 2020 AAST Colon Organ Injury Scale
Authors: Zeineddin Ahmad , Tominaga Gail T. , Crandall Marie , Almeida Mariana , Schuster Kevin M. , Jawad Ghassan , Maqbool Baila , Sheffield Abby C. , Dhillon Navpreet K. , Radow Brandon S. , Moorman Matthew L. , Martin Niels D. , Jacovides Christina L. , Lowry Debra , Kaups Krista , Horwood Chelsea R. , Werner Nicole L. , Proaño-Zamudio Jefferson A. , Kaafarani Haytham M. A. , Marshall William A. , Haines Laura N. , Schaffer Kathryn B. , Staudenmayer Kristan L. , Kozar Rosemary A.
Published: April 2023

INTRODUCTION

The American Association for the Surgery of Trauma Colon Organ Injury Scale (OIS) was updated in 2020 to include a separate OIS for penetrating colon injuries and included imaging criteria. In this multicenter study, we describe the contemporary management and outcomes of penetrating colon injuries and hypothesize that the 2020 OIS system correlates with operative management, complications, and outcomes.

METHODS

This was a retrospective study of patients presenting to 12 Level 1 trauma centers between 2016 and 2020 with penetrating colon injuries and Abbreviated Injury Scale score of <3 in other body regions. We assessed the association of the new OIS with surgical management and clinical outcomes and the association of OIS imaging criteria with operative criteria. Bivariate analysis was done with χ2, analysis of variance, and Kruskal-Wallis, where appropriate. Multivariable models were constructed in a stepwise selection fashion.

RESULTS

We identified 573 patients with penetrating colon injuries. Patients were young and predominantly male; 79% suffered a gunshot injury, 11% had a grade V destructive injury, 19% required ≥6 U of transfusion, 24% had an Injury Severity Score of >15, and 42% had moderate-to-large contamination. Higher OIS was independently associated with a lower likelihood of primary repair, higher likelihood of resection with anastomosis and/or diversion, need for damage-control laparotomy, and higher incidence of abscess, wound infection, extra-abdominal infections, acute kidney injury, and lung injury. Damage control was independently associated with diversion and intra-abdominal and extra-abdominal infections. Preoperative imaging in 152 (27%) cases had a low correlation with operative findings (κ coefficient, 0.13).

CONCLUSION

This is the largest study to date of penetrating colon injuries and the first multicenter validation of the new OIS specific to these injuries. While imaging criteria alone lacked strong predictive value, operative American Association for the Surgery of Trauma OIS colon grade strongly predicted type of interventions and outcomes, supporting use of this grading scale for research and clinical practice.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level III.
Cervical Radiofrequency Ablation Artifact Mimicking an Electrographic Seizure on RNS
Authors: Sánchez-Boluarte Sofía S. , Feyissa Anteneh M. , Freund Brin , Khan Aafreen , Middlebrooks Erik H. , Grewal Sanjeet S. , Tatum William O.
Published: April 2023

The responsive neurostimulator continuously monitors the electrocorticogram. It delivers short bursts of high-frequency electrical stimulation when personalized patterns are detected. Intracranial EEG recording including electrocorticography is susceptible to artifacts, albeit at a lesser frequency compared with scalp recording. The authors describe a novel case of a patient with focal epilepsy, bitemporal responsive neurostimulation, and seizures without self-awareness manifest as focal impaired awareness seizures adversely affecting memory. At follow-up evaluation, the patient reported being clinically seizure-free although a single long episode was detected using the Patient Data Management System over the course of 3 years. Initial review identified a left-sided rhythmic discharge with a bilateral spatial field of involvement. In response to detection, the responsive neurostimulation delivered a series of five electrical stimulations. On further review, the patient recalled undergoing cervical radiofrequency ablation, which coincided with the appearance of the “electrographic seizure.” Extrinsic electrical artifact involving monomorphic nonevolving waveforms confirmed electrical artifact identified and treated by responsive neurostimulation as an epileptic seizure. On rare occasion, implanted electrical devices may lead to misdiagnosis and mistreatment of patients because of intracranial artifact.
Bayesian phylogenetic inference of HIV latent lineage ages using serial sequences
Authors: Nagel Anna A. , Rannala Bruce
Published: April 2023

HIV evolves rapidly within individuals, allowing phylogenetic studies to infer histories of viral lineages on short time scales. Latent HIV sequences are an exception to this rapid evolution, as their transcriptional inactivity leads to negligible mutation rates compared with non-latent HIV lineages. This difference in mutation rates generates potential information about the times at which sequences entered the latent reservoir, providing insight into the dynamics of the latent reservoir. A Bayesian phylogenetic method is developed to infer integration times of latent HIV sequences. The method uses informative priors to incorporate biologically sensible bounds on inferences (such as requiring sequences to become latent before being sampled) that many existing methods lack. A new simulation method is also developed, based on widely used epidemiological models of within-host viral dynamics, and applied to evaluate the new method—showing that point estimates and credible intervals are often more accurate than existing methods. Accurate estimates of latent integration dates are crucial in relating integration times to key events during HIV infection, such as treatment initiation. The method is applied to publicly available sequence data from four HIV patients, providing new insights regarding the temporal pattern of latent integration.
Computational capability of ecological dynamics
Authors: Ushio Masayuki , Watanabe Kazufumi , Fukuda Yasuhiro , Tokudome Yuji , Nakajima Kohei
Published: April 2023

Ecological dynamics is driven by complex ecological networks. Computational capabilities of artificial networks have been exploited for machine learning purposes, yet whether an ecological network possesses a computational capability and whether/how we can use it remain unclear. Here, we developed two new computational/empirical frameworks based on reservoir computing and show that ecological dynamics can be used as a computational resource.
In silico
ecological reservoir computing (ERC) reconstructs ecological dynamics from empirical time series and uses simulated system responses for information processing, which can predict near future of chaotic dynamics and emulate nonlinear dynamics. The real-time ERC uses real population dynamics of a unicellular organism,
Tetrahymena thermophila
. The temperature of the medium is an input signal and population dynamics is used as a computational resource. Intriguingly, the real-time ecological reservoir has necessary conditions for computing (e.g. synchronized dynamics in response to the same input sequences) and can make near-future predictions of empirical time series, showing the first empirical evidence that population-level phenomenon is capable of real-time computations. Our finding that ecological dynamics possess computational capability poses new research questions for computational science and ecology: how can we efficiently use it and how is it actually used, evolved and maintained in an ecosystem?
L-2L ladder digital-to-analogue converter for dynamics generation of chemical concentrations
Authors: Chatani Tomohito , Shiraishi Suguru , Miyazako Hiroki , Onoe Hiroaki , Hori Yutaka
Published: April 2023

Cellular response to dynamic chemical stimulation encodes rich information about the underlying reaction pathways and their kinetics. Microfluidic chemical stimulators play a key role in generating dynamic concentration waveforms by mixing several aqueous solutions. In this article, we propose a multi-layer microfluidic chemical stimulator capable of modulating chemical concentrations by a simple binary logic based on the electronic-hydraulic analogy of electronic R-2R ladder circuits. The proposed device, which we call L-2L ladder digital-to-analogue converter (DAC), allows us to systematically modulate 2

n

levels of concentrations from single sources of solution and solvent by a single operation of 2
n
membrane valves, which contrasts with existing devices that require complex channel geometry with multiple input sources and valve operations. We fabricated the L-2L ladder DAC with
n
= 3 bit resolution and verified the concept by comparing the generated waveforms with computational simulations. The response time of the proposed DAC was within the order of seconds because of its simple operation logic of membrane valves. Furthermore, detailed analysis of the waveforms revealed that the transient concentration can be systematically predicted by a simple addition of the transient waveforms of 2
n
= 6 base patterns, enabling facile optimization of the channel geometry to fine-tune the output waveforms.
Genome-based reclassification of Picrophilus torridus Zillig et al. 1996 as a later heterotypic synonym of Picrophilus oshimae Schleper et al. 1996
Authors: Habib Neeli , Narsing Rao Manik Prabhu , Jan Sohail Ahmad , Banerjee Aparna , Thamchaipenet Arinthip , Li Wen-Jun
Published: April 2023

In the present study, we attempt to clarify the taxonomic positions of

Picrophilus oshimae

and

Picrophilus torridus

. The 16S rRNA gene sequence similarity between

P. oshimae

DSM 9789T and

P. torridus

DSM9790T (99.4 %) was above the threshold value (98.6 %) for bacterial species delineation. The average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between

P. oshimae

DSM 9789T and

P. torridus

DSM9790T were higher than the threshold values (95–96 % for ANI and 70 % for dDDH) for bacterial species delineation. The present results indicate that

Picrophilus torridus

Zillig et al. 1996 is a later heterotypic synonym of

Picrophilus oshimae

Schleper et al. 1996.
Evaluation of variant calling algorithms for wastewater-based epidemiology using mixed populations of SARS-CoV-2 variants in synthetic and wastewater samples
Authors: Bassano Irene , Ramachandran Vinoy K. , Khalifa Mohammad S. , Lilley Chris J. , Brown Mathew R. , van Aerle Ronny , Denise Hubert , Rowe William , George Airey , Cairns Edward , Wierzbicki Claudia , Pickwell Natalie D. , Carlile Matthew , Holmes Nadine , Payne Alexander , Loose Matthew , Burke Terry A. , Paterson Steve , Wade Matthew J. , Grimsley Jasmine M. S.
Published: April 2023

Wastewater-based epidemiology has been used extensively throughout the COVID-19 (coronavirus disease 19) pandemic to detect and monitor the spread and prevalence of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and its variants. It has proven an excellent, complementary tool to clinical sequencing, supporting the insights gained and helping to make informed public-health decisions. Consequently, many groups globally have developed bioinformatics pipelines to analyse sequencing data from wastewater. Accurate calling of mutations is critical in this process and in the assignment of circulating variants; yet, to date, the performance of variant-calling algorithms in wastewater samples has not been investigated. To address this, we compared the performance of six variant callers (VarScan, iVar, GATK, FreeBayes, LoFreq and BCFtools), used widely in bioinformatics pipelines, on 19 synthetic samples with known ratios of three different SARS-CoV-2 variants of concern (VOCs) (Alpha, Beta and Delta), as well as 13 wastewater samples collected in London between the 15th and 18th December 2021. We used the fundamental parameters of recall (sensitivity) and precision (specificity) to confirm the presence of mutational profiles defining specific variants across the six variant callers. Our results show that BCFtools, FreeBayes and VarScan found the expected variants with higher precision and recall than GATK or iVar, although the latter identified more expected defining mutations than other callers. LoFreq gave the least reliable results due to the high number of false-positive mutations detected, resulting in lower precision. Similar results were obtained for both the synthetic and wastewater samples.
Colonization and transmission of Staphylococcus aureus in schools: a citizen science project
Authors: van Tonder Andries J. , McCullagh Frances , McKeand Hanan , Thaw Sue , Bellis Katie , Raisen Claire , Lay Liz , Aggarwal Dinesh , Holmes Mark , Parkhill Julian , Harrison Ewan M. , Kucharski Adam , Conlan Andrew
Published: April 2023

Aggregation of children in schools has been established to be a key driver of transmission of infectious diseases. Mathematical models of transmission used to predict the impact of control measures, such as vaccination and testing, commonly depend on self-reported contact data. However, the link between self-reported social contacts and pathogen transmission has not been well described. To address this, we used

Staphylococcus aureus

as a model organism to track transmission within two secondary schools in England and test for associations between self-reported social contacts, test positivity and the bacterial strain collected from the same students. Students filled out a social contact survey and their

S. aureus

colonization status was ascertained through self-administered swabs from which isolates were sequenced. Isolates from the local community were also sequenced to assess the representativeness of school isolates. A low frequency of genome-linked transmission precluded a formal analysis of links between genomic and social networks, suggesting that

S. aureus

transmission within schools is too rare to make it a viable tool for this purpose. Whilst we found no evidence that schools are an important route of transmission, increased colonization rates found within schools imply that school-age children may be an important source of community transmission.
E. coli ST11 (O157:H7) does not encode a functional AcrF efflux pump
Authors: Pugh Hannah L. , Connor Christopher , Siasat Pauline , McNally Alan , Blair Jessica M. A.
Published: April 2023

Escherichia coli

is a facultative anaerobe found in a wide range of environments. Commonly described as the laboratory workhorse,

E. coli

is one of the best characterized bacterial species to date, however much of our understanding comes from studies involving the laboratory strain

E. coli

K-12. Resistance-nodulation-division efflux pumps are found in Gram-negative bacteria and can export a diverse range of substrates, including antibiotics.

E. coli

K-12 has six RND pumps; AcrB, AcrD, AcrF, CusA, MdtBC and MdtF, and it is frequently reported that all

E. coli

strains possess these six pumps. However, this is not true of

E. coli

ST11, a lineage of

E. coli

, which is primarily composed of the highly virulent important human pathogen,

E. coli

O157:H7. Here we show that acrF is absent from the pangenome of ST11 and that this lineage of

E. coli

has a highly conserved insertion within the acrF gene, which when translated encodes 13 amino acids and two stop codons. This insertion was found to be present in 97.59 % of 1787 ST11 genome assemblies. Non-function of AcrF in ST11 was confirmed in the laboratory as complementation with acrF from ST11 was unable to restore AcrF function in

E. coli

K-12 substr. MG1655 ΔacrB ΔacrF. This shows that the complement of RND efflux pumps present in laboratory bacterial strains may not reflect the situation in virulent strains of bacterial pathogens.
The Role of Age and Sex in Non-linear Dilution Adjustment of Spot Urine Arsenic
Authors: Carmine Thomas Clemens
Published: April 2023

Background

Previous research introduced V-PFCRC as an effective spot urinary dilution adjustment method for various metal analytes, including the major environmental toxin arsenic. V-PFCRC normalizes analytes to 1 g/L creatinine (CRN) by adopting more advanced power-functional corrective equations accounting for variation in exposure level. This study expands on previous work by examining the impacts of age and sex on corrective functions.

Methods

Literature review of the effects of sex and age on urinary dilution and the excretion of CRN and arsenic. Data analysis included a Data Set 1 of 5,752 urine samples and a partly overlapping Data Set 2 of 1,154 combined EDTA blood and urine samples. Both sets were classified into age bands, and the means, medians, and interquartile ranges for CRN and TWuAs in uncorrected (UC), conventionally CRN-corrected (CCRC), simple power-functional (S-PFCRC), sex-aggregated (V-PFCRC SA), and sex-differentiated V-PFCRC SD modes were compared. Correlation analyses assessed residual relationships between CRN, TWuAs, and age. V-PFCRC functions were compared across three numerically similar age groups and both sexes. The efficacy of systemic dilution adjustment error compensation was evaluated through power-functional regression analysis of residual CRN and the association between arsenic in blood and all tested urinary result modes.

Results

Significant sex differences in UC and blood were neutralized by CCRC and reduced by V-PFCRC. Age showed a positive association with blood arsenic and TWuAs in all result modes, indicating factual increments in exposure. Sex-differentiated V-PFCRC best matched the sex-age kinetics of blood arsenic. V-PFCRC formulas varied by sex and age and appeared to reflect urinary osmolality sex-age-kinetics reported in previous research.

V-PFCRC minimized residual biases of CRN on TWuAs across all age groups and sexes, demonstrating improved standardization efficacy compared to UC and CCRC arsenic.

Interpretation

Sex differences in UC and CCRC arsenic are primarily attributable to urinary dilution and are effectively compensated by V-PFCRC. While the sex and age influence on V-PFCRC formulas align with sex- and age-specific urinary osmolality and assumed baseline vasopressor activities, their impact on correction validity for entire collectives is minimal.

Conclusion

The V-PFCRC method offers a robust correction for urinary arsenic dilution, significantly reducing systemic dilution adjustment errors. Its application in various demographic contexts enhances the accuracy of urinary biomarker assessments, benefiting clinical and epidemiological research. V-PFCRC effectively compensates for sex differences in urinary arsenic. Age-related increases in TWuAs are exposure-related and should be additionally accounted for by algebraic normalization, covariate models, or standard range adjustments.
Predicting the risk of incident hypertension and increase in blood pressure: A systematic review of existing prediction models for adults
Authors: Bajwa Pravleen K , Levine Natalie A , Bautista Leonelo E
Published: April 2023

Background and aims

Models that can predict the risk of developing essential hypertension or increase in blood pressure (BP) can be used to identify high risk individuals. We aimed to summarize and assess prediction models developed in the general adult population using longitudinal data, as well as any external validation of such models.

Methods

For this systematic review, we searched the literature on Medline and Embase for studies published between database inception and February 5, 2021. We conducted a narrative synthesis of all models and assessed the risk of bias (ROB) in included studies using PROBAST. We also performed a meta-analysis of all external validation studies validating the Framingham hypertension risk model. We excluded models based on cross-sectional data, or those based on specific patient populations.

Results

Our review includes 29 articles which contain 42 prediction models and 11 external validation studies of existing prediction models. Among model development studies, only five models performed both internal and external validation. Among the validation studies, only two existing models were externally validated by researchers other than the ones who developed the model. Most models had low ROB in the predictors and outcomes domains, and half had low ROB in the participants domain. However, all had high ROB in the analysis domain due to inappropriate handling of missing data and/or lack of adequate performance measures, which resulted in high overall ROB for all models.

Conclusions

All current risk prediction models predicting hypertension or increased blood pressure have high ROB and most have not been externally validated. New studies should aim to reduce their ROB using standard reporting guidelines and externally validated existing models.
Infection Risk Shifts of Protests During Pandemics
Authors: Kraft Lennart , Niekamp Michael
Published: April 2023

This research article examines the dual impact of protests on COVID-19 spread, a challenge for policymakers balancing public health and the right to assemble. Using a game theoretical model, it shows that protests can shift infection risks between counties, creating a dilemma for regulators. The empirical study analyzes two German protests in November 2020 using proprietary data from a bus-shuttle service, finding evidence to support the assumption that protests can shift infection risks. The article concludes by discussing the implications of these findings for policymakers, highlighting that regulators’ individually rational strategic decisions may lead to inefficient outcomes.
PRedicting the EVolution of SubjectIvE Cognitive Decline to Alzheimer’s Disease With machine learning: the PREVIEW study protocol
Authors: Mazzeo Salvatore , Lassi Michael , Padiglioni Sonia , Vergani Alberto Arturo , Moschini Valentina , Scarpino Maenia , Giacomucci Giulia , Burali Rachele , Morinelli Carmen , Fabbiani Carlo , Galdo Giulia , Bagnoli Silvia , Emiliani Filippo , Ingannato Assunta , Nacmias Benedetta , Sorbi Sandro , Grippo Antonello , Mazzoni Alberto , Bessi Valentina
Published: April 2023

Background and aims

Subjective Cognitive Decline (SCD) is a condition in which individual complain of cognitive decline with normal performances on neuropsychological evaluation. Many studies demonstrated a higher prevalence of Alzheimer’s pathology in patients diagnosed with SCD as compared to the general population. Consequently, SCD was suggested as an early symptomatic phase of Alzheimer’s disease (AD). We will describe the study protocol of a prospective cohort study (PREVIEW) that aim to identify features and tools to accurately detect SCD patients who will progress to AD.

Methods

We will include patients self-referred to our memory clinic and diagnosed with SCD. Participants will undergo: clinical, neurologic and neuropsychological examination, estimation of cognitive reserve and depression, evaluation of personality traits,APOEandBDNFgenotyping, electroencephalography and event-related potential recording, lumbar puncture for measurement of Aβ42, t-tau, and p-tau concentration and Aβ42/Aβ40ratio. Recruited patients will have follow-up neuropsychological examination every two years. Collected data will be used to train a machine learning algorithm to define the risk of progression from SCD to MCI and AD.

Discussion

There is an urgent need to select cost-effective and easily accessible tools to identify patients at the earliest stages of the disease. Previous studies identified demographic, cognitive, genetic, neurophysiological and brain structure features to stratify SCD patients according to the risk of progression to objective cognitive decline. Nevertheless, only a few studies considered all these features together and applied machine learning approaches on SCD patients.

Conclusions

the PREVIEW study aim to identify new cost-effective disease biomarkers (e.g., EEG-derived biomarkers) and define automated algorithm to detect patients at risk for AD in a very early stage of the disease.
Distinct baseline immune characteristics associated with responses to conjugated and unconjugated pneumococcal polysaccharide vaccines in older adults
Authors: Ravichandran Sathyabaarathi , Erra-Diaz Fernando , Karakaslar Onur E. , Marches Radu , Kenyon-Pesce Lisa , Rossi Robert , Chaussabel Damien , Pascual Virginia , Palucka Karolina , Paust Silke , Nahm Moon H. , Kuchel George A. , Banchereau Jacques , Ucar Duygu
Published: April 2023

Pneumococcal infections cause serious illness and death among older adults. A capsular polysaccharide vaccine PPSV23 (Pneumovax®) and a conjugated polysaccharide vaccine PCV13 (Prevnar®) are used to prevent these infections, yet underlying responses, and baseline predictors remain unknown. We recruited and vaccinated 39 older adults (>60 years) with PPSV23 or PCV13. Both vaccines induced strong antibody responses at day 28 and similar plasmablast transcriptional signatures at day 10, however, their baseline predictors were distinct. Analyses of baseline flow cytometry and RNA-seq data (bulk and single cell) revealed a novel baseline phenotype that is specifically associated with weaker PCV13 responses, characterized by i) increased expression of cytotoxicity-associated genes and increased CD16+NK frequency; ii) increased Th17 and decreased Th1 cell frequency. Men were more likely to display this cytotoxic phenotype and mounted weaker responses to PCV13 than women. Baseline expression levels of a distinct gene set was predictive of PPSV23 responses. This first precision vaccinology study for pneumococcal vaccine responses of older adults uncovered novel and distinct baseline predictors that might transform vaccination strategies and initiate novel interventions.
A Machine Learning Method to Characterize Conformational Changes of Amino Acids in Proteins
Authors: Mollaei Parisa , Farimani Amir Barati
Published: April 2023

Amino acid dynamics are significant in determining the overall function, structure, stability, and activity of proteins. However, atomic-level descriptions of the structural features of proteins are limited by the current resolutions of experimental and computational techniques. In this study, we developed a machine learning (ML) framework for characterizing the individual aminoacids dynamic in a protein and compute its contribution to the overall function of proteins. This framewor identifies specific types of angular features in amino acids, such as bimodal-switch residues. It can assist in the analysis of various protein characteristics and provide valuable insights into the dynamic behavior of individual amino acids within a protein structure. We found that there is a strong correlation between a specific type of bimodal-switch residues and the global features in proteins. This knowledge can help us to identify key residues that are strongly correlated to the overall function of the protein.
Frequency Of pRenatal CAre viSiTs (FORCAST): study protocol to develop a core outcome set for prenatal care schedules
Authors: Turrentine Mark , Nguyen Buu-Hac , Choby Beth , Kendig Susan , King Tekoa L. , Kotelchuck Milton , Simas Tiffany A. Moore , Srinivas Sindhu K. , Zahn Christopher M. , Peahl Alex Friedman
Published: April 2023

Background

Prenatal care, one of the most common preventive care services in the United States, endeavors to improve pregnancy outcomes through evidence-based screenings and interventions. Despite the prevalence of prenatal care and its importance to maternal and infant health, there are several debates about the best methods of prenatal care delivery, including the most appropriate schedule frequency and content of prenatal visits. Current U.S. national guidelines recommend that low-risk individuals receive a standard schedule of 12 to 14 in-office visits, a care delivery model that has remained unchanged for almost a century.

Objectives

In early 2020, to mitigate individuals’ exposure to the SARS-CoV-2 virus, prenatal care providers implemented new paradigms that altered the schedule frequency, interval, and modality (e.g., telemedicine) of how prenatal care services were offered. In this manuscript, we describe development of a core outcome set (COS) that can be used to evaluate the effect of the frequency of prenatal care schedules on maternal and infant outcomes.

Methods

We will systematically review the literature to identify previously reported outcomes important to individuals who receive prenatal care and the people who care for them. Stakeholders with expertise in prenatal care delivery (i.e., patients/family members, healthcare providers, and public health professionals and policymakers) will rate the importance of identified outcomes in an online survey using a three-round Delphi process. A virtual consensus meeting will be held for a group of stakeholder representatives to discuss and vote on the outcomes to include in the final COS.

Results

The Delphi survey was initiated in July 2022 with 71 stakeholders invited. A virtual consensus conference was conducted on October 11, 2022. Data is currently under analysis.

Conclusions

More research about the optimal schedule frequency and modality for prenatal care delivery is needed. Standardizing outcomes that are measured and reported in evaluations of the recommended prenatal care schedules will assist evidence synthesis and results reported in systematic reviews and meta-analyses. Overall, this COS will expand the consistency and patient-centeredness of reported outcomes for various prenatal care delivery schedules and modalities, hopefully improving the overall efficacy of recommended care delivery for pregnant people and their families.

Trial Registration

This study was registered in the Core Outcome Measures for Effectiveness (COMET) database on January 18, 2022, registration #2021http://www.comet-initiative.org/Studies/Details/2021.
Meta-Analysis of Public RNA Sequencing Data of Abscisic Acid-Related Abiotic Stresses inArabidopsis thaliana
Authors: Shintani Mitsuo , Tamura Keita , Bono Hidemasa
Published: April 2023

Abiotic stresses such as drought, salinity, and cold negatively affect plant growth and crop productivity. Understanding the molecular mechanisms underlying plant responses to these stressors is essential for stress tolerance in crops. The plant hormone abscisic acid (ABA) is significantly increased upon abiotic stressors, inducing physiological responses to adapt to stress and regulate gene expression. Although many studies have examined the components of established stress signaling pathways, few have explored other unknown elements. This study aimed to identify novel stress-responsive genes in plants by performing a meta-analysis of public RNA sequencing (RNA-Seq) data onArabidopsis thaliana, focusing on five ABA-related stress conditions (ABA, Salt, Dehydration, Osmotic, and Cold). The meta-analysis of 216 paired datasets from five stress conditions was conducted, and differentially expressed genes were identified by introducing a new metric, called TN (stress-treated (T) and non-treated (N))-score. We revealed that 14 genes were commonly upregulated and 8 genes were commonly downregulated across all five treatments, including some that were not previously associated with these stress responses. On the other hand, some genes regulated by salt, dehydration, and osmotic treatments were not regulated by exogenous ABA or cold stress, suggesting that they may be involved in the plant response to dehydration independent of ABA. Our meta-analysis revealed a list of candidate genes with unknown molecular mechanisms in ABA-dependent and ABA-independent stress responses. These genes could be valuable resources for selecting genome editing targets and potentially contribute to the discovery of novel stress tolerance mechanisms and pathways in plants.
Proteomes Reveal Metabolic Capabilities ofYarrowia lipolyticafor Biological Upcycling of Polyethylene into High-Value Chemicals
Authors: Walker Caleb , Mortensen Max , Poudel Bindica , Cotter Christopher , Okekeogbu Ikenna , Ryu Seunghyun , Khomami Bamin , Giannone Richard J. , Laursen Siris , Trinh Cong T.
Published: April 2023

Polyolefins derived from plastic wastes are recalcitrant for biological upcycling. However, chemical depolymerization of polyolefins can generate depolymerized plastic (DP) oil comprising of a complex mixture of saturated, unsaturated, even and odd hydrocarbons suitable for biological conversion. While DP oil contains a rich carbon and energy source, it is inhibitory to cells. Understanding and harnessing robust metabolic capabilities of microorganisms to upcycle the hydrocarbons in DP oil, both naturally and unnaturally occurring, into high-value chemicals are limited. Here, we discovered that an oleaginous yeastYarrowia lipolyticaundergoing short-term adaptation to DP oil robustly utilized a wide range of hydrocarbons for cell growth and production of citric acid and neutral lipids. When growing on hydrocarbons,Y. lipolyticapartitioned into planktonic and oil-bound cells with each exhibiting distinct proteomes and amino acid distributions invested into establishing these proteomes. Significant proteome reallocation towards energy and lipid metabolism, belonging to two of the 23 KOG (Eukaryotic Orthologous Groups) classes C and I, enabled robust growth ofY. lipolyticaon hydrocarbons, with n-hexadecane as the preferential substrate. This investment was even higher for growth on DP oil where both the KOG classes C and I were the top two, and many associated proteins and pathways were expressed and upregulated including the hydrocarbon degradation pathway, Krebs cycle, glyoxylate shunt and, unexpectedly, propionate metabolism. However, a reduction in proteome allocation for protein biosynthesis, at the expense of the observed increase towards energy and lipid metabolisms, might have caused the inhibitory effect of DP oil on cell growth.

MPORTANCE

Sustainable processes for biological upcycling plastic wastes in a circular bioeconomy are needed to promote decarbonization and reduce environmental pollution due to increased plastic consumption, incineration, and landfill storage. Strain characterization and proteomic analysis revealed the robust metabolic capabilities ofY. lipolyticato upcycle polyethylene into high-value chemicals. Significant proteome reallocation towards energy and lipid metabolisms was required for robust growth on hydrocarbons with n-hexadecane as the preferential substrate. However, an apparent over-investment in these same categories to utilize complex DP oil came at the expense of protein biosynthesis, limiting cell growth. Taken together, this study elucidates howY. lipolyticaactivates its metabolism to utilize DP oil and establishesY. lipolyticaas a promising host for the upcycling of plastic wastes.