bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in Opioid Prescribing and New Persistent Opioid Use After Surgery in the United States
Authors: Luby Alexandra O. , Alessio-Bilowus Dominic , Hu Hsou Mei , Brummett Chad M. , Waljee Jennifer F. , Bicket Mark C.
Published: August 2024

Objective:

To define recent trends in opioid prescribing after surgery and new persistent opioid use in the United States.

Background:

New persistent opioid use after surgery among opioid-naive individuals has emerged as an important postoperative complication. In response, initiatives to promote more appropriate postoperative opioid prescribing have been adopted in recent years. However, current estimates of opioid prescribing and new persistent opioid use following surgery remain unknown.

Methods:

A retrospective cohort study of opioid-naive privately insured adult patients undergoing 17 common surgical procedures between 2013 and 2021 was conducted utilizing multi-payer claims data from the Health Care Cost Institute (HCCI). Initial opioid prescription size in oral morphine equivalents (OMEs) and new persistent opioid use were the outcomes of interest. Trends in opioid prescribing and rates of new persistent opioid use were evaluated across the study period. Mixed effects logistic regression was performed to evaluate independent predictors of new persistent opioid use while adjusting for patient-level factors and year.

Results:

Among 989,354 opioid-naive individuals, the adjusted initial opioid prescription size decreased from 282 mg OME to 164 mg OME, a reduction of 118 mg OME (95% CI: 116–120). The adjusted incidence of new persistent opioid use decreased from 2.7% in 2013 (95% CI: 2.6%–2.8%) to 1.1% in 2021 (95% CI: 1.0%–1.2%). For every 30 OME increase in initial opioid prescription size, new persistent opioid use increased by 3.1%. Other predictors of new persistent opioid use included preoperative nonopioid controlled substances fills [31–365 days: adjusted odds ratio (aOR)=1.78, 95% CI: 1.70–1.86; 0–30 days: aOR=2.71, 95% CI: 2.59–2.84] and undergoing orthopedic procedures [total knee arthroplasty (aOR=3.43, 95% CI: 3.15–3.72); shoulder arthroscopy (aOR=2.39, 95% CI: 2.24–2.56)].

Conclusions:

Both opioid prescription size after surgery and new persistent opioid use decreased over the last decade, suggesting that opioid stewardship practices had favorable effects on the risk of long-term opioid use.
Interobserver Variability in the International Study Group for Pancreatic Surgery (ISGPS)-Defined Complications After Pancreatoduodenectomy
Authors: Hendriks Tessa E. , Balduzzi Alberto , van Dieren Susan , Suurmeijer J. Annelie , Salvia Roberto , Stoop Thomas F. , Del Chiaro Marco , Mieog Sven D. , Nielen Mark , Zani Sabino , Nussbaum Daniel , Hackert Thilo , Izbicki Jakob R. , Javed Ammar A. , Hewitt D. Brock , Koerkamp Bas Groot , de Wilde Roeland F. , Miao Yi , Jiang Kuirong , Nakata Kohei , Nakamura Masafumi , Jang Jin-Young , Lee Mirang , Ferrone Cristina R. , Shrikhande Shailesh V. , Chaudhari Vikram A. , Busch Olivier R. , Siriwardena Ajith K. , Strobel Oliver , Werner Jens , Bonsing Bert A. , Marchegiani Giovanni , Besselink Marc G. ,   for the International Study Group for Pancreatic Surgery (ISGPS)
Published: August 2024

Objective:

To determine the interobserver variability for complications of pancreatoduodenectomy as defined by the International Study Group for Pancreatic Surgery (ISGPS) and others.

Background:

Good interobserver variability for the definitions of surgical complications is of major importance in comparing surgical outcomes between and within centers. However, data on interobserver variability for pancreatoduodenectomy-specific complications are lacking.

Methods:

International cross-sectional multicenter study including 52 raters from 13 high-volume pancreatic centers in 8 countries on 3 continents. Per center, 4 experienced raters scored 30 randomly selected patients after pancreatoduodenectomy. In addition, all raters scored 6 standardized case vignettes. This variability and the “within centers” variability were calculated for 2-fold scoring (no complication/grade A vs grade B/C) and 3-fold scoring (no complication/grade A vs grade B vs grade C) of postoperative pancreatic fistula, postpancreatoduodenectomy hemorrhage, chyle leak, bile leak, and delayed gastric emptying. Interobserver variability is presented with Gwet AC-1 measure for agreement.

Results:

Overall, 390 patients after pancreatoduodenectomy were included. The overall agreement rate for the standardized cases vignettes for 2-fold scoring was 68% (95% CI: 55%–81%, AC1 score: moderate agreement), and for 3-fold scoring 55% (49%–62%, AC1 score: fair agreement). The mean “within centers” agreement for 2-fold scoring was 84% (80%–87%, AC1 score; substantial agreement).

Conclusions:

The interobserver variability for the ISGPS-defined complications of pancreatoduodenectomy was too high even though the “within centers” agreement was acceptable. Since these findings will decrease the quality and validity of clinical studies, ISGPS has started efforts aimed at reducing the interobserver variability.
Optical Coherence Tomography Angiography Retinal Imaging Associations With Burden of Small Vessel Disease and Amyloid Positivity in the Brain
Authors: Bermudez Camilo , Lesnick Timothy G. , More Swati S. , Ramanan Vijay K. , Knopman David S. , Rabinstein Alejandro A. , Cogswell Petrice M. , Jack Clifford R. , Vemuri Prashanthi , Petersen Ronald C. , Graff-Radford Jonathan , Chen John J.
Published: August 2024

Background:

Alzheimer disease (AD) and other dementias are associated with vascular changes and amyloid deposition, which may be reflected as density changes in the retinal capillaries. These changes may can be directly visualized and quantified with optical coherence tomography angiography (OCTA), making OCTA a potential noninvasive preclinical biomarker of small vessel disease and amyloid positivity. Our objective was to investigate the feasibility of retinal imaging metrics as noninvasive biomarkers of small vessel disease and amyloid positivity in the brain.

Methods:

We investigated associations between OCTA and neuroimaging and cognitive metrics in 41 participants without dementia from the Mayo Clinic Study of Aging and Alzheimer’s Disease Research Center. OCTA metrics included superficial, deep, and full retina capillary density of the fovea, parafovea, and macula as well as the area of the foveal avascular zone (FAZ). Neuroimaging metrics included a high burden of white matter hyperintensity (WMH), presence of cerebral microbleeds (CMB), lacunar infarcts, and amyloid positivity as evidenced on positron emission tomography (PET), whereas cognitive metrics included mini-mental status examination (MMSE) score. We performed generalized estimating equations to account for measurements in each eye while controlling for age and sex to estimate associations between OCTA metrics and neuroimaging and cognitive scores.

Results:

Associations between OCTA and neuroimaging metrics were restricted to the fovea. OCTA showed decreased capillary density with high burden of WMH in both the superficial (P = 0.003), deep (P = 0.004), and full retina (P = 0.01) in the fovea but not the parafovea or whole macula. Similarly, participants with amyloid PET positivity had significantly decreased capillary density in the superficial fovea (P = 0.027) and deep fovea (P = 0.03) but higher density in the superficial parafovea (P = 0.038). Participants with amyloid PET positivity also had a significantly larger FAZ (P = 0.031), whereas in those with high WMH burden the difference did not reach statistical significance (P = 0.075). There was also a positive association between MMSE and capillary density of the full retina within the fovea (P = 0.037) and in the superficial parafovea (P = 0.046). No associations were found between OCTA metrics and presence of CMB or presence of lacunar infarcts.

Conclusions:

The associations of lower foveal capillary density with cerebral WMH and amyloid positivity suggest that further research is warranted to evaluate for shared mechanisms of disease between small vessel disease and AD pathologies.
Advancing Surgical Research for Immigrant Patients: A Call to Action
Authors: Desai Priya J , Chugh Priyanka V , Sanchez Sabrina E , Allee Lisa
Published: August 2024

Immigrants in the US face unique challenges in accessing healthcare. There have been several studies highlighting some of the barriers that this population faces; however, there is still a lack of robust research on this patient population in the context of surgical access and outcomes. Immigration status is a protected variable that is not documented in patient charts for a myriad of reasons. This makes it incredibly difficult to identify this population in the first place, resulting in a decreased ability to study this group retrospectively and, therefore, restricting the quantity and quality of research into these vulnerable patients. This article aims to provide a call to action for medical professionals to develop ways to accurately document immigration status in medical records while assuaging the concerns related to this documentation and its implications on patient care and confidentiality.
Novel Gammapapillomavirus type in the nasal cavity of a wild red colobus (Piliocolobus tephrosceles)
Authors: Weary Taylor E. , Mehta Kavi P.M. , Goldberg Tony L.
Published: August 2024

Papillomaviruses (PVs) are double-stranded, circular, epitheliotropic DNA viruses causing benign warts (papillomas) or inducing dysplasia that can progress to cancer. Although they have been identified in all vertebrate taxa, most classified types are human PVs (HPVs); relatively little is known about PVs in other species. Here we characterize a novel Gammapapillomavirus type, PtepPV1, from a nasal swab of a wild red colobus (Piliocolobus tephrosceles) in Kibale National Park, Uganda. The virus has a genome of 6,576 bases, encoding the seven canonical early (E) ORFs (E6, E7, E1, E2, E4, E1^E4, and E8^E2) and two late (L) ORFs (L1 and L2) of the gammapapillomaviruses, and is 81.0% similar to HPV-mSK_118, detected in a cutaneous wart from an immunocompromised human patient, in the L1 gene at the amino acid level.  Alphapapillomaviruses (genus Alphapapillomavirus) cause anogenital carcinomas such as cervical cancer and have been described previously in several nonhuman primates. However, the first gammapapillomavirus (genus Gammapapillomavirus), which cause transient cutaneous infections, was not described until 2019 in a healthy rhesus macaque (Macaca mulatta) genital swab. The new virus from red colobus, PtepPV1, has many genomic features encoded by high-risk oncogenic PVs, such as the E7 gene LXSXE and CXXC motifs, suggesting potential for pRb and zinc-finger binding, respectively. To our knowledge, PtepPV1 is also the first reported nonhuman primate PV found in the nasal cavity. PtepPV1 expands the known host range, geographic distribution, tissue tropism, and biological characteristics of nonhuman primate PVs.
The Energetics of Maintaining the Lateral Balance Are Terrain-Specific; a Normal Lookahead Significantly Reduces Active Balance Maintenance Work
Authors: Hosseini-Yazdi Seyed-Saleh
Published: August 2024

Humans must actively control their lateral balance through frontal plane work or adjusting lateral foot placement. With constant muscle efficiency and considering the energetic consequences of Center of Mass (COM) work variability, we estimated the metabolic cost of lateral balance maintenance and compared it with the Workman model. Like the Workman model, we found that lateral balance energetics were mainly associated with terrain amplitude. Increased walking speed’s effect on step transition work might be offset by reduced step width. A significant rise in lateral work magnitude (+157.1%) with restricted lookahead was potentially linked to wider steps. Comparing mechanical work with the Workman model, we found significant differences in magnitudes, suggesting that the Workman model included additional costs such as force rate generation, muscle coactivation, or posture maintenance not reflected in the COM lateral work and its variability.

Practitioner Summary

Lateral balance maintenance during walking requires active regulation, yet it is not studied mechanically. Our study found that lateral control costs are terrain-specific and increase with restricted lookahead. With age, only variability increases. We assume associated energetics rise with both work and variability.
Lipoprotein retention and inflammation due to regurgitant blood flow as part of the natural history of degenerative ascending aortic aneurysms
Authors: Freiholtz David , Lång Karin , Bergman Otto , Olsson Christian , Granbom Koski Malin , Dismorr Michael , Österholm Cecilia , Caidahl Kenneth , Franco-Cereceda Anders , Eriksson Per , Gisterå Anton , Björck Hanna M
Published: August 2024

BACKGROUND

An abnormal accumulation of immune cells and a disrupted lipoprotein metabolism has previously been described as part of the pathogenesis of ascending aortic aneurysm in patients with tricuspid aortic valves. The factor driving the accumulation of immune cells remains unclear; however, it may be considered in light of the observation that proximal aortic dilatation often occurs alongside aortic regurgitation but rarely with aortic stenosis. In the present study we aim to investigate the natural history of ascending aortic aneurysm in patients with tricuspid aortic valves by assessing the association between aortic regurgitation and vascular deterioration.

MATERIAL AND METHODS

Patients tricuspid aortic valves undergoing elective open- heart surgery for ascending aortic- and/or aortic valve replacement were included. Aortic specimens from organ donors were obtained through the University of Miami Tissue Bank, USA. Protein expression/localization and differences in aortic intima-media gene expression were assessed using immunohistochemistry and transcriptomics, respectively. Ten-year aortic growth was measured using echocardiography. In total 142 patients were included across experiments (mRNA expression n=44, immunohistochemistry n=49, 10-year follow-up n=49).

RESULTS

Aortic regurgitation was associated with the presence of oxidized apolipoprotein B-containing lipoproteins and infiltrating CD68+ cells in the non-dilated ascending aortic media, which was not observed in aortas of patients with aortic stenosis. Assessing factors influencing lipoprotein retention showed increased levels of genes encoding core proteins of proteoglycans (HSPG2, CSPG4, ACAN, andBGN) in patients with regurgitant valves, compared with aortas from patients with stenotic valves. Moreover, dilated aortas of patients with aortic regurgitation exhibited higher levels of the receptor for oxidized low-density lipoprotein,OLR1, which correlated positively with inflammatory markers in both dilated and non-dilated aortas. Surgical replacement of regurgitant aortic valves mitigated long-term aortic growth, in contrast to replacement of stenotic valves, which was associated with continuous aortic dilation.

CONCLUSIONS

The natural history of ascending aortic aneurysm in patients with tricuspid aortic valves involves medial lipoprotein retention and oxidation with subsequentOLR1-driven pathological inflammation, and can be mitigated by replacement of the regurgitant aortic valve.
Emergency Department Discharge Center Program Evaluation from a “Learning Organization” lens: Methods, Lessons Learned, and Future Directions
Authors: Razack Bibi S. , Mahabir Naya , Iyeke Lisa , Jordan Lindsay , Hope Roland , Diaz Emily , Barcia Lyze , Fuzailov Diana , Willis Helena , Gizzi-Murphy Marina , Davis Frederick , Berman Adam , Richman Mark , Kwon Nancy
Published: August 2024

Our ED’s Discharge Center (EDDC) facilitates appointments and paper-based social determinants of health (SDoH) screening. No criteria guide EDDC utilization. The ED’s provider-administrator-run, patient-satisfying follow-up call program contacts only ∼25% of discharges. We describe Learning Organization-principle-guided evaluation of EDDC efficiency, aiming to create EDDC time to expand the follow-up program.

We reviewed appointment-making, SDoH-screening, and follow-up program data. We surveyed patients to determine whether adopting SHOUT tool criteria (no home, no primary care physician, or insurance) might yield more-judicious EDDC utilization.

EDDC staff’s 20 minutes/patient yielded fewer ED returns and admissions. Most patients improved post-discharge and made appointments themselves; 6% met SHOUT criteria for EDDC assistance; 4.5% would benefit from SDoH screening.

Adopting SHOUT criteria would create significant time for EDDC-staffed follow-up program expansion. QR-code-accessible SDoH surveys would screen thousands more patients, minimizing EDDC staff involvement, saving 95% of the effort while retaining 100% of the benefit.
Genomic epidemiology reveals 2022 mpox epidemic in New York City governed by heavy-tailed sexual contact networks
Authors: Pekar Jonathan E. , Wang Yu , Wang Jade C. , Shao Yucai , Taki Faten , Forgione Lisa A. , Amin Helly , Clabby Tyler , Johnson Kimberly , Torian Lucia V. , Braunstein Sarah L. , Pathela Preeti , Omoregie Enoma , Hughes Scott , Suchard Marc A. , Vasylyeva Tetyana I. , Lemey Philippe , Wertheim Joel O.
Published: August 2024

The global mpox epidemic in 2022 was likely caused by transmission of mpox virus (MPXV) through sexual contact networks, with New York City (NYC) experiencing the first and largest outbreak in the United States. By performing a phylogeographic and epidemiological analysis of MPXV, we identify at least 200 introductions of MPXV into NYC and 84 leading to onward transmission. Through a comparative analysis with human immunodeficiency virus (HIV) in NYC, we find that both MPXV and HIV genomic cluster sizes are best fit by scale-free distributions and that people in MPXV clusters are more likely to have previously received an HIV diagnosis (odds ratio=1.58;p=0.012) and be a member of a recently growing HIV transmission cluster, indicating overlapping sexual contact networks. We then model the transmission of MPXV through sexual contact networks and show that highly connected individuals would be disproportionately infected at the start of an epidemic, thereby likely resulting in the exhaustion of the most densely connected parts of the sexual network. This dynamic explains the rapid expansion and decline of the NYC outbreak, as well as the estimated cumulative incidence of less than 2% within high-risk populations. By synthesizing the genomic epidemiology of MPXV and HIV with epidemic modeling, we demonstrate that MPXV transmission dynamics can be understood by general principles of sexually transmitted pathogens.
An Interpretable Machine Learning Tool for In-Home Screening of Agitation Episodes in People Living with Dementia
Authors: Bafaloukou Marirena , Schalkamp Ann-Kathrin , Fletcher-Lloyd Nan , Capstick Alex , Walsh Chloe , Sandor Cynthia , Kouchaki Samaneh ,   CR&T Group, Nilforooshan Ramin , Barnaghi Payam
Published: August 2024

Background

Agitation affects around 30% of people living with dementia (PLwD), increasing carer burden and straining care services. Agitation screening typically relies on subjective clinical scales and direct patient observation, which are resource-intensive and challenging to incorporate into routine care. Clinical applicability of data-driven methods for agitation screening is limited by constraints such as short observational periods, data granularity, and lack of interpretability and generalisability. Current interventions for agitation are primarily medication-based, which may lead to severe side effects and lack personalisation. Understanding how real-world factors affect agitation within home settings offers a promising avenue towards identifying potential personalised non-pharmacological interventions.

Methods

We used longitudinal data (32,896 person-days from n=63 PLwD) collected using in-home monitoring devices. Employing machine learning techniques, we developed a screening tool to determine the weekly risk of agitation. We incorporated a traffic-light system for risk stratification to aid clinical decision-making and employed the SHapley Additive exPlanations (SHAP) framework to increase interpretability. We designed an interactive tool that enables the exploration of personalised non-pharmacological interventions, such as modifying ambient light and temperature.

Results

Light Gradient-boosting Machine (LightGBM) achieved the highest performance in identifying agitation with a sensitivity of 71.32±7.38% and specificity of 75.28%. Implementing the traffic-light system for risk stratification increased specificity by 15% and improved all metrics. Significant contributors to agitation included low nocturnal respiratory rate, heightened alertness during sleep, and increased indoor illuminance, as revealed by statistical and feature importance analysis. Using our interactive tool, we identified that adjusting indoor lighting levels and temperature were promising and feasible interventions within our cohort.

Conclusions

Our interpretable framework for agitation screening, developed using data from a dementia care study, showcases significant clinical value. The accompanying interactive interface allows for thein-silicosimulation of non-pharmacological interventions, facilitating the design of personalised interventions that can improve in-home dementia care.
Association of METS-IR Index with Type 2 Diabetes: A Cross-sectional Analysis of National Health and Nutrition Examination Survey Data from 2009 to 2018
Authors: Hou Yisen , Li Rui , Xu Zhen , Chen Wenhao , Li Zhiwen , Jiang Weirong , Meng Yong , Han Jianli
Published: August 2024

Background

With rising global diabetes prevalence, precise early identification and management of diabetes risk are critical research areas. The METS-IR, a novel non-insulin-based tool, is gaining attention for quantifying insulin resistance using multiple metabolic parameters. Despite its potential in predicting diabetes and its precursors, evidence on its specific relationship with diabetes is limited, especially in large-scale population validation and mechanistic exploration.

Objective

This study aims to analyze the association between METS-IR and type 2 diabetes (T2DM) in American adults.

Methods

We conducted a cross-sectional analysis of NHANES data from 2009 to 2018. Participants aged 20 years and above were included, excluding individuals with missing data on BMI, fasting blood glucose (FBG), high-density lipoprotein cholesterol (HDL-C), glycated hemoglobin (HbA1c) and diabetes status. Logistic regression analysis, subgroup analysis, and restricted cubic spline analysis were used to assess the association between METS-IR and T2DM, controlling for potential confounding factors.

Results

After adjusting for age, gender, race, education level, smoking status, drinking habits, depression, physical activity, hypertension, and hyperlipidemia, we found a positive association between METS-IR and the risk of T2DM. Specifically, each unit increase in METS-IR was associated with a 7% increase in the risk of T2DM (OR=1.07, 95% CI: 1.06, 1.08). Subgroup analysis showed that the association between METS-IR and T2DM incidence was significantly positive in the highest quartile group, particularly among Mexican Americans over 40 years old and those diagnosed with depression, hypertension, or hyperlipidemia.

Conclusion

Our study revealed a significant positive association between METS-IR and the prevalence of T2DM, indicating that this relationship persists even after controlling for various confounding factors. Therefore, monitoring METS-IR may provide a valuable tool for the early identification of individuals at risk of glucose metabolism disorders. Further research should focus on the applicability of METS-IR in different populations and its potential impact on clinical practice.
Topical Probiotics Decrease the Severity of Atopic Dermatitis. A Systematic Review and Meta-Analysis of Double-Blind, Randomized, Placebo Control Trials
Authors: Flint Elliot , Ahmad Nabeel , Rowland Kevin , Hildebolt Charles , Raskin David
Published: August 2024

Atopic Dermatitis (AD) is a chronic skin disease that commonly appears during childhood but can present at any age. There are many reports showing that probiotics relieve AD symptoms in children. This systematic review and meta-analysis sought to determine the efficacy of topical probiotic treatment for AD in adult populations. A database search was conducted of peer-reviewed, double-blind clinical trials, and studies underwent a systematic exclusion and inclusion process, yielding four that met the criteria. Disease severity, as measured by a standardized scoring tool (SCORAD), was collected, and compared to placebo at two-week and four-week time points. All studies showed improvement in SCORAD in the treatment groups compared to baseline at all time points. Two showed significant decreases in SCORAD after two weeks of treatment, and three studies showed long-lasting improvement after four weeks of treatment. Interestingly, while each study showed a reduction in severity of AD at the two- and four-week time points, a pooled meta-analysis did not show a statistically significant difference between treatment and control at four weeks of treatment. Clinically, there may be benefits to topical probiotic usage as evidenced by the individual studies, more studies need to be performed including adults to show statistical significance.
Explaining the Variance in Cardiovascular Health Indicators among Asian Americans: A Comparison of Demographic, Socioeconomic, and Ethnicity
Authors: Sevillano Lalaine , Bacong Adrian Matias , Maglalang Dale Dagar
Published: August 2024

BACKGROUND

The Asian American (AA) population is the fastest-growing major racial or ethnic group in the U.S. Typically treated as a monolith in research, disaggregated data show disproportionate cardiovascular disease (CVD) burden among certain AA ethnic groups. This analysis aimed to identify which factors explain variance in cardiovascular health among AA ethnic groups.

METHODS

We analyzed pooled 2010-2018 National Health Interview Survey cross-sectional data from Chinese, Asian Indian, Filipino, and Other Asian adults in the U.S. Coronary heart disease, heart attack, and stroke were the CVD outcomes of interest. Covariates included sociodemographic characteristics, CVD-related health behaviors (e.g., smoking tobacco, physical inactivity), and health conditions (e.g., diabetes, hypertension). The distribution of self-reported CVD outcomes and covariates were examined among the full AA sample and disaggregated ethnic groups. Variance explained by sociodemographic, health behaviors, and health conditions were calculated based on the adjusted R-squared from a series of five models for each CVD health outcome.

RESULTS

Of the 10,353 AAs in the sample, 53% identified as female and 86% between the ages of 18-64 years old. Compared to the aggregate AA sample and the other ethnic groups, Filipinos had a higher burden of any CVD outcome (5.9%), particularly for coronary heart disease (4.0%) and heart attack (2.5%).The combination of all predictors explained at most 13% of variance, with sociodemographic characteristics accounting for at least half of the variance explained among all participants. Health behaviors explained a greater amount of additional variance for all CVD outcomes among Asian Indians, including an additional 3.1% for stroke. Inversely, existing health conditions were significant predictors of CVD for all AA ethnic groups compared to Asian Indians.

CONCLUSIONS

There is heterogeneity in CVD outcomes and related risk factors in AA ethnic groups, emphasizing the need for culturally-tailored prevention and intervention strategies.
Preparation of inexpensive, pre-stained molecular weight marker using proteins isolated from chicken egg for SDS PAGE and Western blot application
Authors: Balaji Karthika KB , Jain Vini VJ , Rangasamy Sundarraj SR , Rajendran Gokila GR , Kittappa Vinothkumar VK , Muruganandam Arumugam AM
Published: August 2024

Molecular weight markers, which are utilized in protein chemistry applications, including gel filtration chromatography, SDS-PAGE, and Western blotting, determine the molecular weight of distinct proteins that have been separated. These markers act as standards and are made of a variety of differently sized proteins that lie within a wide range of sizes corresponding to known molecular weights. They are indispensable tools in techniques such as protein analysis and characterization, as they may be used to estimate the approximate molecular weight of unknown proteins by comparing their movement pattern on the gel to established standards. Molecular weight markers can be obtained from multiple sources. There are many ways to obtain molecular weight markers, such as recombinant expression from organisms such asE. colior mammalian cells as well as purification of proteins from organisms such asE. coli, bovine plasma, porcine muscle, and bovine milk. Moreover, the chicken egg white and egg yolk consist of proteins of varying molecular weights. This study aims to employ cost effective natural products such as chicken egg to create easily developed, reasonably priced protein markers with molecular weights that range from 250 to 14 kDa.
Non-physical Intimate Partner Violence and Long-term Public Healthcare Costs in a Representative Sample of Canadian Women
Authors: Metheny Nicholas , Dusing Gabriel John , Essue Beverley M. , O’Campo Patricia
Published: August 2024

This study investigated the impact of non-physical intimate partner violence (IPV), including emotional and verbal abuse, and coercive/controlling behaviors, on Ontario Health Insurance Plan costs, the universal healthcare provider in the province of Ontario, Canada. Women exposed to non-physical IPV alone had 17% higher healthcare costs over 10 years compared to those not exposed, translating to CA$686 million in additional annual costs, challenging the perception that non-physical IPV is less harmful than physical forms. We argue for prevention of non-physical IPV and improved screening in healthcare settings is vital to mitigate its long-term impacts on individuals and healthcare systems.
Resource Quality Differentially Impacts Daphnia Interactions with Two Parasites
Authors: Fearon Michelle L , Sanchez Kristel F , Sun Syuan-Jyun , Calhoun Siobhan K , Monell Kira J , Ravichandran Varun , Duffy Meghan A
Published: August 2024

Resource quality can have conflicting effects on host-parasite interactions; for example, higher resource quality might increase host investment in immune function, or conversely, might permit greater parasite reproduction. Thus, anticipating the impact of changing resource quality on host-parasite interactions is challenging, especially because we often lack a mechanistic understanding of how resource quality influences host physiology and fitness to alter infection outcomes. We investigated whether there are generalizations in how resource quality affects multiple host clones' interactions with different parasites. We used the Daphnia freshwater zooplankton model system to experimentally investigate how a resource quality gradient from high-quality green algae to poor-quality cyanobacteria diets influences host fitness, physiology, and infection by two parasites: a bacterium, Pasteuria ramosa, and a fungus, Metschnikowia bicuspidata. We ran a separate experiment for each parasite using a factorial design with four diets, two Daphnia dentifera host clones, and parasite-inoculated and uninoculated treatments (16 treatments per experiment). Diet strongly influenced infection by the fungus but not the bacterium. These relationships between diet and infection cannot be explained by changes in feeding rate (and, therefore, parasite exposure). Instead, the impact of diet on fungal infection was associated with impacts of diet on the earliest stage of infection: hosts that fed on poor quality diets had very few attacking spores in their guts. Diet did not significantly influence host immune responses. Diet influenced spore production differently for the two parasites, with reduced resource quality limiting the number of fungal spores and the size (but not number) of bacterial spores. Diet, host clone, and infection all affected host fitness. Interestingly, diet influenced the impact of the bacterium, a parasitic castrator that induces gigantism; for one clone, infected hosts fed high quality diets still produced a substantial number of offspring, whereas resource limitation hindered gigantism. Finally, there were often costs of resisting infection, though these generally were not affected by diet. Overall, we show that resource quality differentially impacts the exposure, infection, and proliferation processes for different parasites and host clones, which highlights the need to use multi-genotype and multi-parasite studies to better understand these complex interactions.
Comparative analysis of the treatment-naïve microbiome across rheumatic diseases to predict MTX treatment response
Authors: Amend Lena , Huang Kun D. , Sivapornnukul Pavaret , Rabenow Miriam , Bielecka Agata Anna , Wang Xiao-yu , Neumann-Schaal Meina , Witte Torsten , Strowig Till
Published: August 2024

The human gut microbiota is recognized as a modulator of inflammatory diseases and has been linked to interindividual differences in therapy responsiveness. However, the robustness of disease-specific microbiome signatures across closely related diseases is rarely compared. Here, we compared treatment-naïve microbiota composition and functional potential across rheumatic diseases, including rheumatoid arthritis (RA) and spondyloarthritis subforms, to identify disease-specific biomarkers. While we failed to define robust disease-specific microbiota signatures, we identified microbial signatures linked to methotrexate (MTX) responsiveness for the two rheumatic diseases RA and psoriatic arthritis (PsA), for which MTX is the first-line treatment. Notably, the signatures were distinct, i.e., we could define a signature based on the relative abundance of microbial species for RA, yet the signature for PsA was based on the relative abundance of microbial pathways. Together this supports the previously recognized value of microbiota to predict treatment responses to MTX in RA and identifies distinct signatures predicting MTX responsiveness for PsA.
Quantitative Label-Free Single-Cell Proteomics on the Orbitrap Astral MS
Authors: Petrosius Valdemaras , Aragon-Fernandez Pedro , Arrey Tabiwang N. , Woessman Jakob , Üresin Nil , de Boer Bauke , Su Jinyu , Furtwängler Benjamin , Stewart Hamish , Denisov Eduard , Petzoldt Johannes , Peterson Amelia C. , Hock Christian , Damoc Eugen , Makarov Alexander , Zabrouskov Vlad , Porse Bo T. , Schoof Erwin M.
Published: August 2024

Single-cell proteomics by mass spectrometry (scp-MS) holds the potential to provide unprecedented insights into molecular features directly linked to the cellular phenotype, while deconvoluting complex organisms into their basic building blocks. Tailored sample preparation that maximizes the extracted amount of material that is introduced into the mass spectrometer has rapidly propelled the field forward. However, the measured signal is still at the lower edge of detection approaching the sensitivity boundary of current instrumentation. Here, we investigate the capacity of the enhanced sensitivity of the Orbitrap Astral mass spectrometer to facilitate deeper proteome profiles from low-input to single-cell samples. We carry out a comprehensive data acquisition method survey to pinpoint which parameters provide most sensitivity. Furthermore, we explore the quantitative accuracy of the obtained measurements to ensure that the obtained abundances are in line with expected ground truth values. We culminate our technical exploration by generating small datasets from two cultured cell lines and a primary bone marrow sample, to showcase obtainable proteome coverage differences from different source materials. Finally, as a proof of concept we explore protein covariation to showcase how information on known protein complexes is captured inherently in our scp-MS data.
UsingSAFEPATHto Uncover a Novel Mechanism of Hepatotoxicity for Gefitinib
Authors: Hosseini-Gerami Layla , Masarone Sara , Lane Jordan
Published: August 2024

This white paper details the research conducted by Ignota Labs using their advanced causal and explainable AI technology,SAFEPATH, to analyse the mechanisms of hepatotoxicity for two EGFR-TKI inhibitors, Erlotinib and Gefitinib, the latter having an as yet unknown mechanism of toxicity. The known mechanism of UGT1A1-mediated toxicity of Erlotinib was recovered, and a novel sphingolipid metabolism mechansim of toxicity of Gefitinib was hypothesised and subsequently experimentally validated. Crucially, we were also able to suggest the reason for the observed heterogeneous toxicity response to Gefitinib. This study exemplifies the potential of integrating AI tools with comprehensive datasets to improve drug safety and patient management.
Proteome-wide quantification of inositol pyrophosphate-protein interactions
Authors: Richter Annika , Ruwolt Max , Lampe Sarah , Liu Fan , Furkert David , Fiedler Dorothea
Published: August 2024

Inositol polyphosphates (InsPs) and inositol pyrophosphates (PP-InsPs) constitute a group of highly phosphorylated molecules that are involved in many cellular signaling processes. To characterize discrete signaling events of these structurally closely related molecules, a mass spectrometry approach was developed to derive apparent binding constants for these ligands on a proteome-wide scale. The method employed a series of chemically synthesized, biotinylated affinity reagents for inositol hexakisphosphate (InsP6), and the inositol pyrophosphates 1PP-InsP5, 5PP-InsP5and 1,5(PP)2-InsP4(also termed InsP8). Application of these affinity reagents at different concentrations, in combination with tandem mass tag (TMT) labeling, provided binding data for thousands of proteins from a mammalian cell lysate. Investigation of different enrichment conditions, where Mg2+ions were either available or not, showcased a strong influence of Mg2+on the protein binding capacities of PP-InsPs. Gene ontology analysis closely linked PP-InsP-interacting proteins to RNA processing in the nucleus and nucleolus. Subsequent data analysis enabled a targeted search for protein pyrophosphorylation among PP-InsP interactors, and identified four new pyrophosphorylated proteins. The data presented here constitute a valuable resource for the community, and application of the method reported here to other biological contexts will enable the exploration of PP-InsP dependent signaling pathways across species.
Obtaining super-resolved images at the mesoscale through Super-Resolution Radial Fluctuations
Authors: Brown Mollie , Foylan Shannan , Rooney Liam M. , Gould Gwyn W. , McConnell Gail
Published: August 2024

Super-resolution microscopy overcomes the diffraction limit of light to achieve higher spatial resolutions than are typically available when using light microscopy techniques. However, these methods are usually restricted to imaging a very small field of view (FOV). Here, we have applied one of these super-resolution techniques, Super-Resolution Radial Fluctuations (SRRF) in conjunction with the Mesolens, which has the unusual combination of a low-magnification and high numerical aperture, to obtain super-resolved images over a FOV of 4.4 mm x 3.0 mm. We assessed the accuracy of these SRRF images through error maps calculated using a secondary analysis method, Super-resolution Quantitative Image Rating and Reporting of Error Locations (SQUIRREL). We demonstrate it is possible to achieve images with a resolution of 446.3 ± 10.9 nm, providing a ∼1.6-fold improvement in spatial resolution over a uniquely large field, with consistent structural agreement between raw data and SRRF processed images.

Motivation

Current super-resolution imaging techniques allow for a greater understanding of cellular structures however they are often complex or only have the ability to image a few cells at once. This small field of view may not represent the behaviour across the entire sample and the manual selection of which restricted ROI to use may introduce bias. Currently, this is often circumvented by stitching and tiling methods which stitch many small ROI together, however this can result in artefacts across an image which poses an issue when analysing data. To combat this, we have used the Mesolens alongside Super-Resolution Radial Fluctuations analysis, to obtain super-resolved images over a field of view of 4.4 mm x 3.0 mm with minimal error.
Silk-Ovarioids: Establishment and characterization of human ovarian primary cells 3D-model system
Authors: Di Nisio Valentina , Li Tianyi , Xiao Zhijie , Papaikonomou Kiriaki , Damdimopoulos Anastasios , Végvári Ákos , Lebre Filipa , Alfaro-Moreno Ernesto , Pedersen Mikael , Svingen Terje , Zubarev Roman , Acharya Ganesh , Damdimopoulou Pauliina , Salumets Andres
Published: August 2024

In vitromodels that mimic ovaries are crucial for elucidating the biological mechanisms underlying follicle activation and growth. Three-dimensional (3D) systems are particularly relevant because they can replicate the heterogeneity and cell-cell communication between different ovarian cell types. However, complex models using human ovarian primary cells have not yet been established. In this study, we developed and characterized long-term cultured 3D models of primary ovarian somatic cells isolated from adult tissues, using Biosilk as a scaffold. We successfully established both ovarian cortex- and medulla-derived 3D systems, termed Silk-Ovarioids. The presence of key ovarian somatic cell types – including granulosa, stromal, endothelial, and perivascular cells – was confirmed by transcriptomics, proteomics, and immunostaining. Notably, Silk-Ovarioids exhibited the formation of a pro-angiogenic hypoxic core, as evidenced by the development of vessel-like structures after six weeks of culture. The Silk-Ovarioids demonstrated low intra-batch variability and long-term culture stability, underscoring their potential as a robust step towards creating a bioengineered, patient-specific artificial ovary.
A Subset of Cortical Areas Exhibit Adult-like Functional Network Patterns in Early Childhood
Authors: Tu Jiaxin Cindy , Wang Yu , Wang Xintian , Dierker Donna , Sobolewski Chloe M. , Day Trevor K. M. , Kardan Omid , Miranda-Domínguez Óscar , Moore Lucille A. , Feczko Eric , Fair Damien A. , Elison Jed T. , Gordon Evan M. , Laumann Timothy O. , Eggebrecht Adam T. , Wheelock Muriah D.
Published: August 2024

The human cerebral cortex contains groups of areas that support sensory, motor, cognitive, and affective functions, often categorized into functional networks. These networks show stronger internal and weaker external functional connectivity (FC), with FC profiles more similar within the same network. Previous studies have shown these networks develop from nascent forms before birth to their mature, adult-like structures in childhood. However, these analyses often rely on adult functional network definitions. This study assesses the potential misidentification of infant functional networks when using adult models and explores the consequences and possible solutions to this problem.

Our findings suggest that although adult networks only marginally describe infant FC organization better than chance, misidentification is primarily driven by specific areas. Restricting functional networks to areas with adult-like network clustering revealed consistent within-network FC across scans and throughout development. These areas are also near locations with low network identity variability. Our results highlight the implications of using adult networks for infants and offer guidance for selecting and utilizing functional network models based on research questions and scenarios.

Highlights

Previous studies primarily investigated age-specific networks in infants, with limited focus on how well adult networks describe infant functional connectivity (FC).

ur analysis identified a subset of areas in infants showing adult-like network organization, where within-network FC shows less age-related variation and higher scan-to-scan reliability.

These areas are positioned near locations with low variability in functional network identity in adults, indicating a potential link between developmental sequence and interindividual variability in functional network organization.
Dietary fiber content in clinical ketogenic diets modifies the gut microbiome and seizure resistance in mice
Authors: Özcan Ezgi , Yu Kristie B. , Dinh Lyna , Lum Gregory R. , Lau Katie , Hsu Jessie , Arino Mariana , Paramo Jorge , Lopez-Romero Arlene , Hsiao Elaine Y.
Published: August 2024

The gut microbiome is emerging as an important modulator of the anti-seizure effects of the classic ketogenic diet. However, many variations of the ketogenic diet are used clinically to treat refractory epilepsy, and how different dietary formulations differentially modify the gut microbiome in ways that impact seizure outcome is poorly understood. We find that clinically prescribed ketogenic infant formulas vary in macronutrient ratio, fat source, and fiber content and also in their ability to promote resistance to 6-Hz psychomotor seizures in mice. By screening specific dietary variables for their effects on a model human infant microbial community, we observe that dietary fiber, rather than fat ratio or source, drives substantial metagenomic shifts. Addition of dietary fiber to a fiber-deficient ketogenic formula restores seizure resistance, and supplementing protective ketogenic formulas with excess dietary fiber further potentiates seizure resistance. By screening 13 fiber sources and types, we identify distinct subsets of metagenomic responses in the model human infant microbial community that correspond with increased seizure resistance in mice. In particular, supplementation with seizure-protective fibers enriches microbial representation of genes related to queuosine biosynthesis and preQ0biosynthesis and decreases representation of microbial genes related to sucrose degradation, which is also seen in seizure-protected mice that are fed fiber-containing ketogenic infant formulas. Overall, this study reveals that different formulations of clinical ketogenic diets, and dietary fiber content in particular, differentially impact seizure outcome in mice, likely through modification of the gut microbiome. Understanding interactions between dietary components of the ketogenic diet, the gut microbiome, and host susceptibility to seizures could inform novel microbiome-guided approaches to treat refractory epilepsy.
Src promotes tumor cell invasion by hijacking the translation machinery
Authors: Bonnard Benjamin , Chatefau Anouk , Dourthe Cyril , Tommaso Sylvaine Di , Dupuy Jean-William , Mahouche Isabelle , Solorzano Jacobo , Bras Morgane Le , Raymond Anne-Aurélie , Moreau Violaine , Jabouille Arnaud , Blangy Anne , Martineau Yvan , Saltel Frédéric
Published: August 2024

The Src oncogene controls cancer cell invasiveness by promoting invadosome formation and extracellular matrix degradation (ECM). Invadosomes are enriched in the eukaryotic translation initiation factor 3 (eIF3) complex associated with a local mRNA translation activity mandatory for their maintenance. Here, we show that Src regulates mRNA translation by controlling the expression of eIF3 subunits. Among them, eIF3h/e/d are essential for invadosome formation and ECM degradation. We demonstrate that Src controls the canonical mTOR/eIF4E and the non-canonical eIF3d cap-dependent translation initiation pathways. We show that both pathways are necessary for invadosome formation and their ECM degradation function. Finally, we highlighted a correlation betweenSrcandeIF3h/e/doverexpression, which is associated with poor prognosis in hepatocellular carcinoma (HCC) patients and controls the ECM degradation and invasive properties of HCC cells. These findings identify Src as a major regulator of translation initiation pathways, which leads to invadosome formation, ECM degradation and tumor cell invasion.

Abstract Figure

Graphical abstract