bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of Antimicrobial Stewardship Programs Using Therapeutic Drug Monitoring and Pharmacokinetics–Pharmacodynamics Protocols: A Cost-Benefit Review
Authors: Telles João Paulo , Morales Ronaldo , Yamada Carolina Hikari , Marins Tatiana A. , D'Amaro Juodinis Vanessa , Sztajnbok Jaques , Silva Moacyr , Bassetti Bil Randerson , Albiero James , Tuon Felipe Francisco
Published: January 2023

Purpose:

Antimicrobial stewardship programs are important for reducing antimicrobial resistance because they can readjust antibiotic prescriptions to local guidelines, switch intravenous to oral administration, and reduce hospitalization times. Pharmacokinetics–pharmacodynamics (PK-PD) empirically based prescriptions and therapeutic drug monitoring (TDM) programs are essential for antimicrobial stewardship, but there is a need to fit protocols according to cost benefits. The cost benefits can be demonstrated by reducing toxicity and hospital stay, decreasing the amount of drug used per day, and preventing relapses in infection. Our aim was to review the data available on whether PK-PD empirically based prescriptions and TDM could improve the cost benefits of an antimicrobial stewardship program to decrease global hospital expenditures.

Methods:

A narrative review based on PubMed search with the relevant studies of vancomycin, aminoglycosides, beta-lactams, and voriconazole.

Results:

TDM protocols demonstrated important cost benefit for patients treated with vancomycin, aminoglycosides, and voriconazole mainly due to reduce toxicities and decreasing the hospital length of stay. In addition, PK-PD strategies that used infusion modifications to meropenem, piperacillin-tazobactam, ceftazidime, and cefepime, such as extended or continuous infusion, demonstrated important cost benefits, mainly due to reducing daily drug needs and lengths of hospital stays.

Conclusions:

TDM protocols and PK-PD empirically based prescriptions improve the cost-benefits and decrease the global hospital expenditures.
Utilization of a Prenatal Palliative Care Consultation Pathway for Congenital Heart Disease
Authors: Mikal Meggan , Gandhi Rupali , Walsh Susan M.
Published: January 2023

Over 4 decades, short- and long-term survival for children with congenital heart disease (CHD) has significantly increased. Those with complex CHD have a 1-year mortality rate of approximately 25%. Prenatal access to palliative care ensures a comprehensive approach to the infant's physical, emotional, spiritual, and psychosocial well-being and offers enhanced support for parents and families while providing an interprofessional approach to care. Pediatric cardiac provider attitudes, knowledge, patterns of prenatal palliative care, and consultation for fetuses with complex heart disease to guide increased and appropriate prenatal consultation were explored for a quality improvement project completed at a single institution. A retrospective cardiac database review identified that 21.5% of maternal patients seen prenatally and carrying a fetus with complex CHD would have qualified for prenatal palliative care consultation. To increase prenatal palliative care consultation, a pathway for referral was developed. A pre-evaluation of pediatric cardiac provider attitudes regarding palliative care was measured. Survey data informed the intervention phase of prenatal palliative care educational material development, which was presented to pediatric cardiac providers. The number of prenatal palliative care consults was tracked. A postintervention survey completed by pediatric cardiac providers showed increased understanding and utilization of palliative care for comfort and support and not just reserved for death preparation. Greater than 93% agreed or strongly agreed that they gained a better understanding of appropriate use of palliative/supportive care. As pediatric cardiac providers become more knowledgeable about early integration of palliative care, parents and infants will benefit greatly from referrals and initiation of palliative care at the time of prenatal diagnosis.
Automated Detection of Patient Harm: Implementation and Prospective Evaluation of a Real-Time Broad-Spectrum Surveillance Application in a Hospital With Limited Resources
Authors: Saikali Melody , Békarian Gariné , Khabouth José , Mourad Charbel , Saab Antoine
Published: January 2023

Objectives

This study aimed to prospectively validate an application that automates the detection of broad categories of hospital adverse events (AEs) extracted from a basic hospital information system, and to efficiently mobilize resources to reduce the level of acquired patient harm.

Methods

Data were collected from an internally designed software, extracting results from 14 triggers indicative of patient harm, querying clinical and administrative databases including all inpatient admissions (n = 8760) from October 2019 to June 2020. Representative samples of the triggered cases were clinically validated using chart review by a consensus expert panel. The positive predictive value (PPV) of each trigger was evaluated, and the detection sensitivity of the surveillance system was estimated relative to incidence ranges in the literature.

Results

The system identified 394 AEs among 946 triggered cases, associated with 291 patients, yielding an overall PPV of 42%. Variability was observed among the trigger PPVs and among the estimated detection sensitivities across the harm categories, the highest being for the healthcare-associated infections. The median length of stay of patients with an AE showed to be significantly higher than the median for the overall patient population.

Conclusions

This application was able to identify AEs across a broad spectrum of harm categories, in a real-time manner, while reducing the use of resources required by other harm detection methods. Such a system could serve as a promising patient safety tool for AE surveillance, allowing for timely, targeted, and resource-efficient interventions, even for hospitals with limited resources.
Factors Associated With Household Work Limitations in Mexican Patients With Rheumatoid Arthritis
Authors: Ortiz-Haro Ana Belén , Contreras-Yáñez Irazú , Guaracha-Basáñez Guillermo , Pascual-Ramos Virginia
Published: January 2023

Background

Little attention has been given to the impact of rheumatoid arthritis (RA) on domestic work, which remains the domain of women, particularly in the Latin American region. The study identified factors associated with RA-related household work limitations (HOWL) in Mexican for women with long-standing disease.

Methods

This cross-sectional study was performed between September 2020 and April 2022, in patients from the recent-onset RA cohort (initiated in 2004). At study entry, patients had standard rheumatic assessments and were administered the HOWL questionnaire, a survey to assess family responsibilities, household work characteristics, and the patient's economic dependency, and the family APGAR index to assess family function. Multiple logistic regression analysis identified variables associated with RA-related HOWL.

Results

Data from 114 female RA patients were analyzed. Overall, at cohort entry, patients were middle-aged (median, 37.5 years), with 12 years of education, and the minority (n = 42 [39.3%]) were married or living together. Patients were representative of typical patients with recent-onset disease and had significant disease activity. At study entry, the patients had 12 (7–16) years of disease duration, and their disease was under control. The median (interquartile range) HOLW-Q score was 0.67 (0–3.33), and 33 patients (28.9%) had RA-related HOWL. Receiving financial support for family living expenses, requiring assistance for activities of daily living, and DAS28 (Disease Activity Score, 28 joints evaluated) were associated with RA-related HOWL; meanwhile, a better Short-Form 36 score at disease onset was protective.

Conclusions

Domestic work in Mexican RA women might be impacted by social determinants, health-related quality of life at disease onset, and current disease activity status.
Insurance churn after adult traumatic injury: A national evaluation among a large private insurance database
Authors: Fu Sue J. , Arnow Katherine , Barreto Nicolas B. , Aouad Marion , Trickey Amber W. , Spain David A. , Morris Arden M. , Knowlton Lisa M.
Published: January 2023

BACKGROUND

Traumatic injury leads to significant disability, with injured patients often requiring substantial health care resources to return to work and baseline health. Temporary disability or inability to work can result in changes or loss of employer-based private insurance coverage, which may significantly impact health care access and outcomes. Among privately insured patients, we hypothesized increased instability in insurance coverage for patients with higher severity of injury.

METHODS

Adults 18 years and older presenting to a hospital with traumatic injury were evaluated for insurance churn using Clinformatics Data Mart private-payer claims. Insurance churn was defined as cessation of enrollment in the patient's private health insurance plan. Using Injury Severity Score (ISS), we compared insurance churn over the year following injury between patients with mild (ISS, <9), moderate (ISS, 9–15), severe (ISS, 16–24), and very severe (ISS, >24) injuries. Kaplan-Meier analysis was used to compare time with insurance churn by ISS category. Flexible parametric regression was used to estimate hazard ratios for insurance churn.

RESULTS

Among 750,862 privately insured patients suffering from a traumatic injury, 50% experienced insurance churn within 1 year after injury. Compared with patients who remained on their insurance plan, patients who experienced insurance churn were younger and more likely male and non-White. The median time to insurance churn was 7.7 months for those with mild traumatic injury, 7.5 months for moderately or severely injured, and 7.1 months for the very severely injured. In multivariable analysis, increasing injury severity was associated with higher rates of insurance churn compared with mild injury, up to 14% increased risk for the very severely injured.

CONCLUSION

Increasing severity of traumatic injury is associated with higher levels of health coverage churn among the privately insured. Lack of continuous access to health services may prolong recovery and further aggravate the medical and social impact of significant traumatic injury.

LEVEL OF EVIDENCE

Economic and Value Based Evaluations; Level III.
Long-term health-related quality of life and independence among older survivors of serious injury
Authors: Pollack Lauren R. , Liao Joanna , Powelson Elisabeth B. , Gause Emma , Robinson Bryce R. H. , Vavilala Monica S. , Engelberg Ruth A. , Reed May J. , Arbabi Saman , O’Connell Kathleen M.
Published: January 2023

BACKGROUND

Little is known about the recovery experiences of older trauma intensive care unit (TICU) survivors and the relationship between geriatric trauma care and long-term functional ability and health-related quality of life (HRQOL).

METHODS

We conducted a prospective cohort study of 218 patients (age, ≥65 years) admitted to a Level 1 regional trauma center TICU before versus after implementation of a geriatric care bundle with protocolized geriatrics consultations (Geri-T). Survivors or their proxies were interviewed approximately 1 year after hospitalization. Outcomes included the Katz Index of Independence in Activities of Daily Living (ADLs), Lawton Instrumental Activities of Daily Living (IADLs), and EQ-5D-5L HRQOL survey. Two investigator-developed questions regarding recovery experiences were included. Differences in outcomes among survivors admitted before versus after Geri-T were analyzed using multivariable linear regression. Responses to questions about recovery experiences were qualitatively assessed using content analysis.

RESULTS

We reached 67% (146/218) of hospital survivors or their proxies across both groups; 126 patients were still alive and completed the survey. Mean age was 76 (SD, 8), 36% were female, and 90% were independent with ADLs preinjury. At follow-up, independence with ADLs was 76% and IADLs was 63%. The mean EQ-5D-5L index score was 0.78 (SD, 0.18). Most patients (65%) reported having not returned to preinjury functional status. Neither functional ability or HRQOL differed significantly among patients admitted before versus after Geri-T. Content analysis of open-ended questions revealed themes of activity limitations, persistent pain, and cognitive dysfunction.

CONCLUSION

Nearly one-fifth of TICU survivors experienced loss of ADL function 1 year after injury, and most reported having not returned to preinjury functional status. Nonetheless, patient-reported HRQOL was comparable to age-adjusted norms. Geri-T was not associated with differences in HRQOL or functional ability. Survivors reported persistent difficulty with activities beyond those of daily living, pain, and cognition.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic, Level III.
Accuracy of Surgeon and Patient Estimated Cost and Reimbursement for Common General Surgical Operations and Benefit of Centers for Medicare and Medicaid Services Price Transparency Rules
Authors: Frazier Grant D , Turrentine Florence E , Williams Michael D
Published: January 2023

Introduction:

January 1, 2021, the Centers for Medicare and Medicaid Services (CMS) implemented a Hospital Price Transparency Rule. Consumerism as a means of reducing healthcare expenditures is predicated on informed consumers making discrete choices.

Methods:

For 10 months, immediately following an academic medical center preoperative clinic visit, patients and their surgeons were surveyed regarding their estimation of hospital cost and hospital reimbursement for the upcoming surgery. Responses were compared to average FY 2019 institutional Cost for Medicare patients undergoing a laparoscopic approach for each operation. We calculated the difference between actual reimbursements and costs with patients’ estimates and actual reimbursements and costs with surgeons’ estimates.

Results:

66 questionnaires were collected from patients who underwent laparoscopic: cholecystectomy (n=20), inguinal hernia (n=17), umbilical hernia repair (n=6), ventral hernia repair (n=6), incisional hernia (n=6), hiatal hernia repair (n=1), and lipoma or cyst excision (n=10). Patients’ estimates for hospital costs exceeded actual hospital costs by a median of $4502 and were less than hospital reimbursements by a median of $1834. Surgeon estimates for direct costs were $825 less than hospital direct costs and $1659 less than hospital reimbursement.

Conclusion:

Patients as well as their surgeons do not estimate healthcare costs or remuneration accurately and therefore will be ineffective change agents in reducing surgical spending based on price transparency without further education of both parties. Patients consistently overestimated surgical costs while surgeons consistently underestimated surgical costs and reimbursements. Better-informed surgeons and patients are likely necessary prerequisites for CMS Price Transparency Rules to be effective in reducing Medicare expenditures in surgery.
Identification of rare missense mutations in the glutamate ionotropic receptor AMPA type subunit genes in schizophrenia
Authors: Lin Ko-Huan , Hu Tsung-Ming , Hsu Shih-Hsin , Tsai Hsin-Yao , Cheng Min-Chih
Published: January 2023

Objective

The alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors significantly regulate the synaptic transmission and functions of various synaptic receptors. This study aimed to identify single nucleotide mutations in the glutamate receptor, ionotropic, AMPA type (GRIA) gene family, which is associated with schizophrenia.

Methods

The exon regions of four genes (GRIA1, GRIA2, GRIA3, and GRIA4) encoding glutamate ionotropic receptor AMPA type proteins were resequenced in 516 patients with schizophrenia. We analyzed the protein function of the identified rare mutants via immunoblotting.

Results

A total of 24 coding variants were detected in the GRIA gene family, including six missense mutations, 17 synonymous mutations, and one frameshift insertion. Notably, three ultra-rare missense mutations (GRIA1
p.V182A, GRIA2
p.P123Q, and GRIA4
p.Y491H) were not documented in the single nucleotide polymorphism database, gnomAD genomes, and 1517 healthy controls available from Taiwan BioBank. Immunoblotting revealed GRIA4
p.Y491H mutant with altered protein expressions in cultured cells compared with the wild type.

Conclusion

Our findings suggest that, in some patients affected by schizophrenia, the GRIA gene family harbors rare functional mutations, which support rare coding variants that could contribute to the genetic architecture of this illness. The in-vitro impacts of these rare pathological mutations on the pathophysiology of schizophrenia are worthy of future investigation.
Mediating effect of genome-wide DNA methylation on suicidal ideation induced by stressful events
Authors: De Luca Vincenzo , Al-Chalabi Nzaar , Chaudhary Zanib , Qian Jessica , Borlido Carol , Chintoh Araba , Gerretsen Philip , Graff Ariel , Remington Gary , Sanches Marcos , Battaglia Marco
Published: January 2023

Objective

Schizophrenia is a debilitating disease that is associated with higher rates of death by unnatural causes including suicide. Exposure to stressful events is an important risk factor for suicidal ideation (SI); however, the mechanisms that link stress, SI, and suicide remain unclear. Epigenetic processes are involved in both vulnerability to suicidal behavior and stress. Therefore, we sought to study the relationship between epigenetic modifications and suicidal behavior and stress.

Methods

This pilot study was conducted on 39 patients diagnosed with schizophrenia (54% men and age 45.5 ± 12.7). We analyzed the effects of (a) stress exposure and (b) the mediation of DNA methylation [via an epigenetic wide association study (EWAS) of more than 450 000 CpG sites across the genome] on SI severity.

Results

The top CpG site mediating the effect of global stress exposure on SI was cg27660192 located in an intergenic region on chromosome 11, exerting a facilitating effect on worsening SI through DNA hypomethylation.

Conclusion

These preliminary results indicate that DNA methylation in peripheral tissues can shed light on the complex relationship between stress and SI in schizophrenia.
Unusually isolated Staphylococcus arlettae in intra-oral sutures- Case series
Authors: KHERDEKAR RADHIKA SUNIL , DIXIT ASHUTOSH , KOTHARI ASHISH , PANDEY KAMAL PRASAD , ADVANI HOSHANG , GAURAV AMIT , OMAR BALRAM JI
Published: January 2023

Introduction: The human oral cavity comprises various niches such as teeth, gingiva, tongue, soft and hard palate, and various dental prostheses, all inhabited by different bacterial species. Although more than 600 taxa belong to the oral cavity, identifying Staphylococcus arlettae, an incompletely understood bacterium, has been rare.
Methods: Three patients who underwent periodontal flap surgeries were reported with the incidental finding of S. arlettae associated with the intra-oral sutures placed. Environmental sampling was performed, to establish the exact source of this bacterium.
Results: Staphylococcus arlettae was isolated in three patients’ intra-oral sutures. All environmental samples were negative for the presence of the bacterium.
Conclusion: To this date, no studies have identified such an occurrence of Staphylococcus arlettae with intra-oral sutures. Its identification in association with foreign materials, such as sutures, can be considered a potential for surgical site infections and requires further investigation.
Molecular Epidemiology of Antimicrobial Resistance in Central Africa: A Systematic Review
Authors: DIKOUMBA Annicet-Clotaire , ONANGA Richard , MANGOUKA Laurette G. , BOUNDENGA Larson , NGOUNGOU Edgard-Brice , GODREUIL Sylvain
Published: January 2023

Background:  In Central Africa, it is difficult to fight against antibiotic resistance, because of  a  lack of data and information on bacterial resistance, due to the low number of studies carried out in the field. To fill this gap, we carried out a systematic review of the various studies, and devise a molecular epidemiology of antimicrobial resistance from humans, animals and the environmental samples.Method:  A systematic search of all publications from 2005 to 2020 on bacterial resistance in Central Africa was performed on Pubmed, Google scholar and African journals online. All circulating resistance genes, prevalence and genetic carriers of these resistances were collected. The study area was limited to the 9 countries of Central Africa. Results:  Five hundred seventeen studies were identified through a literature search, and sixty studies carried out in 8 countries were included. Among all articles included, 43 articles were from human. Our study revealed not only the circulation of beta-lactamase and carbapenemase genes, but also several other types of resistance genes. To finish, we noticed that some studies reported mobile genetic elements such as integrons, transposons, plasmids, or chromosomes.Conclusion:  The scarcity of data poses difficulties in the implementation of effective strategies in the fight against antibiotic resistance, which requires a health policy in a "One Health" approach.
A genomic blueprint of the healthy human oesophageal microbiome
Authors: Gilroy Rachel , Adam Mina E. , Kumar Bhaskar , Pallen Mark J.
Published: January 2023

Background. The oesophageal microbiome is thought to contribute to the pathogenesis of oesophageal cancer. However, investigations using culture and molecular barcodes have provided only a low-resolution view of this important microbial community. We therefore exploited culturomics and metagenomic binning to generate a catalogue of reference genomes from the healthy human oesophageal microbiome, alongside a comparison set from saliva. 
Results. Twenty-two distinct colonial morphotypes from healthy oesophageal samples were genome-sequenced. These fell into twelve species clusters, eleven of which represented previously defined species. Two isolates belonged to a novel species, which we have named Rothia gullae. We performed metagenomic binning of reads generated from UK samples from this study alongside reads generated from Australian samples in a recent study. Metagenomic binning generated 136 medium or high-quality metagenome-assembled genomes (MAGs). MAGs were assigned to 56 species clusters, eight representing novel Candidatus species, which we have named Ca.Granulicatella gullae, Ca. Streptococcus gullae, Ca. Nanosynbacter quadramensis, Ca. Nanosynbacter gullae, Ca.Nanosynbacter colneyensis, Ca. Nanosynbacter norwichensis, Ca. Nanosynococcus oralis and Ca. Haemophilus gullae. Five of these novel species belong to the recently described phylum Patescibacteria. Although members of the Patescibacteria are known to inhabit the oral cavity, this is the first report of their presence in the oesophagus. Eighteen of the metagenomic species were, until recently, identified only by hard-to-remember alphanumeric placeholder designations. Here we illustrate the utility of a set of recently published arbitrary Latinate species names in providing user-friendly taxonomic labels for microbiome analyses.
Our non-redundant species catalogue contained 63 species derived from cultured isolates or MAGs. Mapping revealed that these species account for around half of the sequences in the oesophageal and saliva metagenomes. Although no species was present in all oesophageal samples, 60 species occurred in at least one oesophageal metagenome from either study, with 50 identified in both cohorts.
Conclusions. Recovery of genomes and discovery of new species represents an important step forward in our understanding of the oesophageal microbiome. The genes and genomes that we have released into the public domain will provide a base line for future comparative, mechanistic and intervention studies
Evaluation of the World Health Organization Global Invasive Bacterial Vaccine-Preventable Disease (IB-VPD) Surveillance Network’s Laboratory External Quality Assessment Programme, 2014–2019
Authors: Litt David , Slack Mary P. E. , Nakamura Tomoka , Gray Steve , Seaton Shila , Fagan Elizabeth J. , Sheppard Carmen , Mwenda Jason M. , Rey-Benito Gloria , Ghoniem Amany , Videbaek Dovile , Tondo Emanuel , Grabovac Varja , Serhan Fatima
Published: January 2023

Introduction. In 2009, the World Health Organization (WHO) established the Global Invasive Bacterial Vaccine Preventable Disease (IB-VPD) Surveillance Network (GISN) to monitor the global burden and aetiology of bacterial meningitis, pneumonia and sepsis caused by

Haemophilus influenzae

(Hi),

Neisseria meningitidis

(Nm) and

Streptococcus pneumoniae

(Sp).

Hypothesis/Gap Statement. The GISN established an external quality assessment (EQA) programme for the characterization of Hi, Nm and Sp by culture and diagnostic PCR.

Aim. To assess the performance of sentinel site laboratories (SSLs), national laboratories (NLs) and regional reference laboratories (RRLs) between 2014 and 2019 in the EQA programme.

Methodology. Test samples consisted of bacterial smears for Gram-staining, viable isolates for identification and serotyping or serogrouping (ST/SG), plus simulated cerebrospinal fluid (CSF) samples for species detection and ST/SG by PCR. SSLs and NLs were only required to analyse the slides for Gram staining and identify the species of the live isolates. RRLs, and any SLs and NLs that had the additional laboratory capacity, were also required to ST/SG the viable isolates and analyse the simulated CSF samples.

Results. Across the period, 69–112 SS/NL labs and eight or nine RRLs participated in the EQA exercise. Most participants correctly identified Nm and Sp in Gram-stained smears but were less successful with Hi and other species. SSLs/NLs identified the Hi, Nm and Sp cultures well and also submitted up to 56 % of Hi, 62 % of Nm and 33 % of Sp optional ST/SG results each year. There was an increasing trend in the proportion of correct results submitted over the 6 years for Nm and Sp. Some SSLs/NLs also performed the optional detection and ST/SG of the three organisms by PCR in simulated CSF from 2015 onwards; 89–100 % of the CSF samples were correctly identified and 76–93 % of Hi-, 90–100 % of Nm- and 75–100 % of Sp-positive samples were also correctly ST/SG across the distributions. The RRLs performed all parts of the EQA to a very high standard, with very few errors across all aspects of the EQA.

Conclusion. The EQA has been an important tool in maintaining high standards of laboratory testing and building of laboratory capacity in the GISN.
Counting Cases and Deaths by Age Tells Us About COVID-19’s Infectious and Lethal Components
Authors: Michaelson James
Published: January 2023

Gauging COVID-19’slethality, and how vaccination can reduce thatlethality, has been challenging. Here, a new method,Gompertzian Analysis, counting cases and deaths, by age, and displaying them on logarithmic graphs, is outlined, and its first findings presented: FIRST, COVID-19Gompertzian Lethality(Deaths/Cases) exhibits an ~10,000-fold exponential increase in the chance of death with age, theGompertzian Force of Mortality, captured by theGompertz Mortality Equation. SECOND, COVID-19Pasteurian Infectivity(Cases/Population) occurs at similar rates across ages. THIRD, the sameGompertzian Force of Mortalitycharacterizes other diseases and all-cause mortality, possibly from loss ofMitotic Dilutionof toxic compounds due to decline in mitosis. FOURTH, resistance to COVID-19infectivityandlethalityappear to be separate processes. FIFTH, Over the past several years,Gompertzian Lethality, has declined, but notPasteurian Infectivity. SIXTH, with each variant,Gompertzian Lethalityhas declined, but notPasteurian Infectivity. SEVENTH, the unvaccinated have seen a decline inGompertzian Lethality, less than the vaccinated, ascribable to infection, at the cost of lives lost. EIGHTH, different vaccines have different reductions inGompertzian LethalityandPasteurian Infectivity. NINTH, vaccination has reducedPasteurian Infectivity, but not enough to suppress the pandemic. TENTH, vaccination has reducedGompertzian Lethality, with sequential vaccination pointing linearly towards zero death after 3 or 4 boosters, without signs of waning. CONCLUSION:Gompertzian Analysisprovides new, practical, actionable, information for understanding, and minimizing, the lethal burden of COVID-19 and other diseases.
Content Analysis of YouTube Videos Related to E-cigarettes and COVID-19
Authors: Lee Juhan , Murthy Dhiraj , Kong Grace
Published: January 2023

INTRODUCTION

E-cigarettes are frequently promoted on social media and portrayed in ways that are attractive to youth. While COVID-19 pandemic significantly affected people’s lives, less known is how the pandemic influenced e-cigarette-related marketing and information on social media. This study identifies how e-cigarettes are portrayed during the COVID-19 pandemic on YouTube, one of the most popular social media platforms.

METHODS

We searched for combinations of search terms related to e-cigarettes (i.e., “electronic cigarette”, “e-cigarette”, “e-cig”, “vape” and “vaping”) and COVID-19 (i.e., “corona”, “COVID”, “lockdown” and “pandemic”). To be included in the analysis, the video must be: uploaded after February 1, 2020, in English, related to e-cigarettes and COVID-19 and less than 30 minutes in length. We assessed video themes related to e-cigarettes and COVID-19, uploader characteristics, and featured e-cigarette products.

RESULTS

We examined N=307 videos and found that N=220 (73.6%) were related to the health effects of e-cigarette use on COVID-19, followed by videos of how COVID-19 affects e-cigarette access/sales (N=40, 12.9%), and face mask-related videos (N=16, 5.1%) which included content regarding masks and e-cigarette use. Instructional videos on how to modify e-cigarettes to use with masks had the highest number of likes (Median=23; IQR=32) and comments (Median=10; IQR=7).

CONCLUSIONS

This study identified various e-cigarette contents on YouTube during the COVID-19 pandemic. Our findings support the need for continuous surveillance on novel vaping-related content in reaction to policies and events such as the global pandemic on social media is needed.
Emotion regulation and cognitive function as mediating factors for the association between lifetime abuse and risky behaviors in women of color
Authors: Villalba Karina , Domenico Lisa H. , Cook Robert L. , O’Connor Julia , Michael-Samaroo Kyndester , Pino Espejo Maria Jose Del , Martin Pilar , Dévieux Jessy G.
Published: January 2023

Background

Lifetime abuse (i.e., childhood abuse, intimate partner violence) has been linked to risky behavioral outcomes (i.e., alcohol use, risky sex). Women who experience lifetime abuse have poor emotion regulation and may have problems with executive functioning, which could help explain the relationship between lifetime abuse and risky behaviors. However, research on executive functioning and emotion regulation as mediators of this relationship has been limited. In the present study, we examined this association. We hypothesized that lifetime abuse would be related to greater difficulty in emotion regulation and executive function, which would also be associated with greater alcohol use and risky sex.

Methods

This cross-sectional study included 150 women with a history of lifetime abuse who were assessed for alcohol use using the AUDIT Score; emotion regulation was measured using the Difficulties with Emotion Regulation Scale (DERS); risky sex was measured using question: “in the last 90 days, how many people did you have anal or vaginal sex without using a condom? Executive function was assessed using the NIH Toolbox.

Results

The mediation model followed the self-regulation theory, which proposes executive function as the higher-order cognitive process. Results showed that executive function deficit and poor emotion regulation significantly mediated the relationship between lifetime abuse and alcohol use severity (indirect effect = .097, SE .031, 95% CI = .035 to .158).

Conclusion

Our findings suggest executive function and emotion regulation as a potential mechanism for alcohol use severity in women who experienced lifetime abuse (i.e., childhood abuse and intimate partner violence).
Westwards expansion of the European catfishSilurus glanisin the Douro River (Portugal)
Authors: Gkenas Christos , Martelo Joana , Ribeiro Diogo , Gago João , Santos Gil , Dias Diogo , Ribeiro Filipe
Published: January 2023

The current study reports the first occurrence and the spread of the European catfishSilurus glanis(Family: Siluridae) in the Portuguese section of the Douro River, suggesting a potential expansion of its distribution in Portugal either via westward dispersal across international rivers and/or human-assisted introductions into new reservoirs and drainages. European catfish has unique features (e.g., opportunistic predator, hunting, and aggregation behaviour) that make it highly suitable for establishing self-sustaining populations in new areas and likely contribute to its invasion success. The species may severely affect native prey communities and modify food web structure and ecosystem functioning. Efficient and sustainable management actions are needed to prevent further introductions in the future.
Tryptophan metabolism determines outcome in tuberculous meningitis: a targeted metabolomic analysis
Authors: Ardiansyah Edwin , Pacheco Julian Avila , Hoang Nhat Le Thanh , Dian Sofiati , Vinh Dao Nguyen , Hai Hoang Thanh , Bullock Kevin , Alisjahbana Bachti , Netea Mihai G , Estiasari Riwanti , Bich Tram Trinh Thi , Donovan Joseph , Heemskerk Dorothee , Hong Chau Tran Thi , Bang Nguyen Duc , Ganiem Ahmad Rizal , Ruslami Rovina , Koeken Valerie ACM , Hamers Raph L , Imran Darma , Maharani Kartika , Kumar Vinod , Clish Clary B. , van Crevel Reinout , Thwaites Guy , van Laarhoven Arjan , Thuong Thuong Nguyen Thuy
Published: January 2023

Background

Cellular metabolism is critical for the host immune function against pathogens, and metabolomic analysis may help understand the characteristic immunopathology of tuberculosis. We performed targeted metabolomic analyses in a large cohort of patients with tuberculous meningitis (TBM), the most severe manifestation of tuberculosis, focusing on tryptophan metabolism.

Methods

We studied 1069 Indonesian and Vietnamese adults with TBM (26.6% HIV-positive), 54 non-infectious controls, 50 with bacterial meningitis, and 60 with cryptococcal meningitis. Tryptophan and downstream metabolites were measured in cerebrospinal fluid (CSF) and plasma using targeted liquid chromatography mass-spectrometry. Individual metabolite levels were associated with survival, clinical parameters, CSF bacterial load and 92 CSF inflammatory proteins.

Results

CSF tryptophan was associated with 60-day mortality from tuberculous meningitis (HR=1.16, 95%CI=1.10-1.24, for each doubling in CSF tryptophan) both in HIV-negative and HIV-positive patients. CSF tryptophan concentrations did not correlate with CSF bacterial load nor CSF inflammation but were negatively correlated with CSF interferon-gamma concentrations. Unlike tryptophan, CSF concentrations of an intercorrelating cluster of downstream kynurenine metabolites did not predict mortality. These CSF kynurenine metabolites did however correlate with CSF inflammation and markers of blood-CSF leakage, and plasma kynurenine predicted death (HR 1.54, 95%CI=1.22-1.93). These findings were mostly specific for TBM, although high CSF tryptophan was also associated with mortality from cryptococcal meningitis.

Conclusion

TBM patients with a high baseline CSF tryptophan or high systemic (plasma) kynurenine are at increased risk of mortality. These findings may reveal new targets for host-directed therapy.

Funding

This study was supported by National Institutes of Health (R01AI145781) and the Wellcome Trust (110179/Z/15/Z and 206724/Z/17/Z).
Detection of circular RNAs and their potential as biomarkers predictive of drug response
Authors: Nguyen Julia , Mammoliti Anthony , Nair Sisira Kadambat , So Emily , Abbas-Aghababazadeh Farnoosh , Eeles Christoper , Smith Ian , Smirnov Petr , He Housheng Hansen , Tsao Ming-Sound , Haibe-Kains Benjamin
Published: January 2023

The introduction of high-throughput sequencing technologies has allowed for comprehensive RNA species detection, both coding and non-coding, which opened new avenues for the discovery of predictive and prognostic biomarkers. However the consistency of the detection of different RNA species depends on the RNA selection protocol used for RNA-sequencing. While preliminary reports indicated that non-coding RNAs, in particular circular RNAs, constitute a rich source of biomarkers predictive of drug response, the reproducibility of this novel class of biomarkers has not been rigorously investigated. To address this issue, we assessed the inter- lab consistency of circular RNA expression in cell lines profiled in large pharmacogenomic datasets. We found that circular RNA expression quantified from rRNA-depleted RNA-seq data is stable and yields robust prognostic markers in cancer. On the other hand, quantification of the expression of circular RNA from poly(A)-selected RNA-seq data yields highly inconsistent results, calling into question results from previous studies reporting their potential as predictive biomarkers in cancer. We have also identified median expression of transcripts and transcript length as potential factors influencing the consistency of RNA detection. Our study provides a framework to quantitatively assess the stability of coding and non-coding RNA expression through the analysis of biological replicates within and across independent studies.
Epileptic seizure suppression: a computational approach for identification and control using real data
Authors: Brogin João A. F. , Faber Jean , Reyes-Garcia Selvin Z. , Cavalheiro Esper A. , Bueno Douglas D.
Published: January 2023

Epilepsy affects millions of people worldwide every year and remains an open subject for research. Current development on this field has focused on obtaining computational models to better understand its triggering mechanisms, attain realistic descriptions and study seizure suppression. Controllers have been successfully applied to mitigate epileptiform activity in dynamic models written in state-space notation, whose applicability is, however, restricted to signatures that are accurately described by them. Alternatively, autoregressive modeling (AR), a typical data-driven tool related to system identification (SI), can be directly applied to signals to generate more realistic models, and since it is inherently convertible into state-space, it can thus be used for the artificial reconstruction and attenuation of seizures as well. Considering this, the first objective of this work is to propose an SI approach using AR models to describe real epileptiform activity. The second objective is to provide a strategy for reconstructing and mitigating such activity artificially, considering non-hybrid and hybrid controllers − designed from ictal and interictal events, respectively. The results show that AR models of relatively low order represent epileptiform activities fairly well and both controllers are effective in attenuating the undesired activity while simultaneously driving the signal to an interictal stage. These findings may lead to customized models based on each signal, brain region or patient, from which it is possible to better define shape, frequency and duration of external stimuli that are necessary to attenuate seizures.

Author summary

Epilepsy is perhaps one of the most studied brain disorders and it is still not sufficiently well understood. The use of computational models is useful in this case since several simulations can be run using them, such that experience and insight about seizures can be gained without necessarily carrying out experiments. These models are usually designed with or without some knowledge about the brain region or phenomenon. Seizure attenuation approaches have been proposed for the first case, but they are limited to the type of seizure correctly described by the model. The present work proposes a similar procedure for the second one (where only the data are available and nothing else is assumed), which is regarded as more realistic due to its direct application on the signals and can lead to customized models for each activity, brain region or patient, defining important information such as the shape, frequency and duration of the external stimuli that must be applied to mitigate a seizure.
ATP-releasing SWELL1 channel in spinal microglia contributes to neuropathic pain
Authors: Chu Jiachen , Yang Junhua , Zhou Yuan , Chen Jianan , Chen Kevin Hong , Zhang Chi , Cheng Henry Yi , Koylass Nicholas , Liu Jun O. , Guan Yun , Qiu Zhaozhu
Published: January 2023

Following peripheral nerve injury, extracellular ATP-mediated purinergic signaling is crucial for spinal cord microglia activation and neuropathic pain. However, the mechanisms of ATP release remain poorly understood. Here, we show that volume-regulated anion channel (VRAC) is an ATP-releasing channel and is activated by inflammatory mediator sphingosine-1-phosphate (S1P) in microglia. Mice with microglia-specific deletion of Swell1 (also known as Lrrc8a), a VRAC essential subunit, had reduced peripheral nerve injury-induced increase in extracellular ATP in spinal cord. The mutant mice also exhibited decreased spinal microgliosis, dorsal horn neuronal hyperactivity, and both evoked and spontaneous neuropathic pain-like behaviors. We further performed high-throughput screens and identified an FDA-approved drug dicumarol as a novel and potent VRAC inhibitor. Intrathecal administration of dicumarol alleviated nerve injury-induced mechanical allodynia in mice. Our findings suggest that ATP-releasing VRAC in microglia is a key spinal cord determinant of neuropathic pain and a potential therapeutic target for this debilitating disease.
Information integration during bioelectric regulation of morphogenesis in the embryonic frog brain
Authors: Manicka Santosh , Pai Vaibhav P. , Levin Michael
Published: January 2023

Spatiotemporal bioelectric states regulate multiple aspects of embryogenesis. A key open question concerns how specific multicellular voltage potential patterns differentially activate distinct downstream genes required for organogenesis. To understand the information processing mechanisms underlying the relationship between spatial bioelectric patterns, genetics, and morphology, we focused on a specific spatiotemporal bioelectric pattern in theXenopusectoderm that regulates embryonic brain patterning. We used machine learning to design a minimal but scalable bioelectric-genetic dynamical network model of embryonic brain morphogenesis that qualitatively recapitulated previous experimental observations. A causal integration analysis of the model revealed a simple higher-order spatiotemporal information integration mechanism relating the spatial bioelectric and gene activity patterns, where the latter is expressed as a function of the causal influence of the voltages of groups of cells. Specific aspects of this mechanism include causal apportioning (certain cell positions are more important for collective decision making), informational asymmetry (depolarized cells are more influential than hyperpolarized cells), long distance influence (genes in a cell are variably sensitive to voltage of faraway cells), and division of labor (different genes are sensitive to different aspects of voltage pattern). The asymmetric information-processing character of the mechanism led the model to predict an unexpected degree of plasticity and robustness in the bioelectric prepattern that regulates normal embryonic brain development. Ourin vivoexperiments verified these predictions via molecular manipulationsin Xenopusembryos. This work shows the power of using a minimalin silicoapproach to drastically reduce the parameter spacein vivo, making hard biological questions tractable. These results provide insight into the collective decision-making process of cells in interpreting bioelectric pattens that guide large-scale morphogenesis, suggesting novel applications for biomedical interventions and new tools for synthetic bioengineering.
Learning cell-specific networks from dynamics and geometry of single cells
Authors: Zhang Stephen Y , Stumpf Michael P H
Published: January 2023

Cell dynamics and biological function are governed by intricate networks of molecular interactions. Inferring these interactions from data is a notoriously difficult inverse problem. The majority of existing network inference methods work at the population level to construct population-averaged representations of gene interaction networks, and thus do not naturally allow us to infer differences in gene regulation activity across heterogeneous cell populations. We introduce locaTE, an information theoretic approach that leverages single cell dynamical information together with geometry of the cell state manifold to infer cell-specific, causal gene interaction networks in a manner that is agnostic to the topology of the underlying biological trajectory. We find that factor analysis can give detailed insights into the inferred cell-specific GRNs. Through extensive simulation studies and applications to three experimental datasets spanning mouse primitive endoderm formation, pancreatic development, and haematopoiesis, we demonstrate superior performance and the generation of additional insights compared to standard static GRN inference methods. We find that locaTE provides a powerful, efficient and scalable network inference method that allows us to distill cell-specific networks from single cell data.

Graphical abstract

Cell-specific network inference from estimated dynamics and geometry

LocaTE takes as input a transition matrixPthat encodes inferred cellular dynamics as a Markov chain on the cell state manifold. By considering the coupling (Xτ,X−τ), locaTE produces an estimate of transfer entropy for each celliand each pair of genes (j, k). Downstream factor analyses can extract coherent patterns of interactions in an unsupervised fashion.
Weakly-supervised Temporal Segmentation of Cell-cycle Stages with Center-cell Focus using Recurrent Neural Networks
Authors: Jose Abin , Roy Rĳo , Stegmaier Johannes
Published: January 2023

Training deep-learning models for biomedical images has always been a problem due to the lack of annotated data. Here we propose using a model and a training approach for the weakly-supervised temporal classification of cell-cycle stages during mitosis. Instead of using annotated data, by using an ordered set of classes called transcript, our proposed approach classifies the cell-cycle stages of cell video sequences. The network design helps to propagate information in time using Recurrent Neural Network and helps to focus the features on the center-cell. The algorithm is evaluated on four datasets from LiveCellMiner and has a performance close to the supervised approaches, which is impressive, considering that annotated data is not used in training.
Fourier transform approach to homogenization of frequency-dependent heat transfer in porous media
Authors: To Quy Dong , Bonnet Guy
Published: January 2023

Purpose

The purpose of this paper is to solve the local problem involving strong contrast heterogeneous conductive material, with application to gas-filled porous media with both perfect and imperfect Kapitza boundary conditions at the bi-material interface. The effective parameters like the dynamic conductivity and the thermal permeability in the acoustics of porous media are also derived from the cell solution.

Design/methodology/approach

The Fourier transform method is used to solve frequency-dependent heat transfer problems. The periodic Lippmann–Schwinger integral equation in Fourier space with source term is first formulated using discrete Green operators and modified wavevectors, which can then be solved by iteration schemes.

Findings

Numerical examples show that the schemes converge fast and yield accurate results when compared with analytical solution for benchmark problems.

Originality/value

The formulation of the method is constructed using static and dynamic Green operators and can be applied to pixelized microstructure issued from tomography images.