bluuebunny/crossref_metadata_2025 huggingface dataset:
Volumetric Effect and Patient Satisfaction after Facial Fat Grafting
Authors: Tuin A. Jorien , Schepers Rutger H. , Spijkervet Frederik K. L. , Vissink Arjan , Jansma Johan
Published: June 2022

Background:

Facial fat grafts decrease in volume after transplantation. This observation is based on overall facial three-dimensional analyses, because there is sparse information on volume changes in well-defined aesthetic areas. The authors aimed to assess the overall and, more specifically, the local volumetric effects of facial fat grafting and relate these effects to patient satisfaction up to 1 year after treatment.

Methods:

All consecutive adult female patients who were scheduled for facial fat grafting without additional surgical procedures were asked to participate. All patients underwent the same fat grafting method. An algorithm-based personalized aesthetic template was applied to define specific aesthetic areas on the preoperative three-dimensional image. Objective outcome parameters [i.e., three-dimensional volume differences, patient satisfaction (FACE-Q questionnaire)] were measured at baseline and at 6 weeks, 6 months, and 12 months after fat grafting.

Results:

Of 33 female patients who underwent a facial fat graft procedure, 23 patients had complete three-dimensional data and were eligible for analysis. The highest volume gain was observed 6 weeks after grafting and was followed by a gradual loss thereafter. Overall and in the zygomatic area, a substantial gain in volume was still present 1 year after grafting, whereas this effect was lost in the lip area. FACE-Q scales Satisfaction with Facial Appearance Overall and Satisfaction with Cheeks improved too, whereas scores for Lines: Lips returned to baseline levels. The improvement in FACE-Q scales was in agreement with the objective change in volume.

Conclusion:

Gain in overall and local volumetric effects is accompanied by comparable changes in patient satisfaction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Evolution of the Coleman Technique
Authors: Egro Francesco M. , Roy Eva , Rubin J. Peter , Coleman Sydney R.
Published: June 2022

Fat grafting is one of the most revolutionary surgical techniques of our century, and it has changed the field of plastic surgery and regenerative medicine. Early reports of fat grafting date back to the late nineteenth century, but the results were unsatisfactory because of minimal graft retention. It was not until Sydney R. Coleman challenged the dogma and introduced a standardized approach to fat grafting after years of research and learning from experts across the world. The Coleman technique represents an evolutionary approach to fat grafting, with three main components: harvesting, refinement, and placement. The Coleman technique has been adopted and modified by surgeons around the world because it has allowed a reliable increase in fat graft survival through a standardized process. This article discusses the influencing factors and milestones that led to this world-known technique, in addition to Dr. Coleman’s current practices, pearls, pitfalls, and lessons learned over the years. The knowledge of the true potential and usefulness of fat is in its infancy, with its regenerative potential becoming increasingly recognized. Current and future research will likely prove that autologous fat has many clinical applications beyond its well-known aesthetic and reconstructive benefits and extending beyond the regenerative realm.
Variation in Heart Failure Risk by HIV Severity and Sex in People With HIV Infection
Authors: Lam Jennifer O. , Leyden Wendy A. , Leong Thomas K. , Horberg Michael A. , Reynolds Kristi , Ambrosy Andrew P. , Avula Harshith R. , Hechter Rulin C. , Towner William J. , Vupputuri Suma , Go Alan S. , Silverberg Michael J.
Published: June 2022

Background:

HIV is an independent risk factor for heart failure (HF). However, the association of HIV severity with incident HF and the potential interaction with sex are incompletely understood.

Setting:

Integrated health care system.

Methods:

We conducted a cohort study of people with HIV (PWH) and matched people without HIV (PWoH), all aged ≥ 21 years and with no previous HF. Poisson regression was used to compare incident HF by HIV status, with PWH stratified by severity of HIV infection [defined by recent (<6 months) CD4 count, nadir CD4 count, or recent HIV RNA level]. Models were adjusted for sociodemographic characteristics, substance use, and HF risk factors. Analyses were conducted for men and women combined, then by sex.

Results:

The study included 38,868 PWH and 386,569 PWoH (mean baseline age = 41.0 ± 10.8 years; 88% men). Compared with PWoH, incident HF risk was higher among PWH with lower recent CD4 [200–499 cells/µL, adjusted rate ratio (aRR) = 1.82, 95% confidence interval (CI) = 1.50 to 2.21 and <200 cells/µL, aRR = 3.26 (2.47 to 4.30)] and a low nadir CD4 [<200 cells/µL, aRR = 1.56 (1.37 to 1.79)] but not among PWH with normal CD4 [≥500 cells/µL, aRR = 1.14 (0.90 to 1.44)]. Higher incident HF risk was observed among PWH at all HIV RNA levels, with greater HF risk at higher HIV RNA levels. The excess HF risk associated with low CD4 (recent or nadir) and high HIV RNA was stronger among women than men (P interactions=0.05, 0.08, and 0.01, respectively).

Conclusions:

Given the association of HIV severity with HF, optimizing HIV treatment and management may be important for HF prevention among PWH.
The microbiota in respiratory tract infections: from association to intervention
Authors: Koenen Mischa H. , de Steenhuijsen Piters Wouter A.A. , Bogaert Debby , Verhagen Lilly M.
Published: June 2022

Purpose of review

The respiratory microbiota has a role in respiratory tract infection (RTI) pathogenesis. On the mucosa, the respiratory microbiota interacts with potential pathogenic viruses, bacteria and the host immune system, including secretory IgA (sIgA). This review discusses the role of the respiratory microbiota and its interaction with the (mucosal) immune system in RTI susceptibility, as well as the potential to exploit the microbiota to promote health and prevent RTIs.

Recent findings

Recent studies confirm that specific microbiota profiles are associated with RTI susceptibility and during susceptibility and found accompanying RTIs, although clear associations have not yet been found for SARS-CoV-2 infection. sIgA plays a central role in RTI pathogenesis: it stands under control of the local microbiota, while at the same time influencing bacterial gene expression, metabolism and defense mechanisms. Respiratory microbiota interventions are still newly emerging but promising candidates for probiotics to prevent RTIs, such as Corynebacterium and Dolosigranulum species, have been identified.

Improved understanding of the respiratory microbiota in RTIs and its interplay with the immune system is of importance for early identification and follow-up of individuals at risk of infection. It also opens doors for future microbiota interventions by altering the microbiota towards a healthier state to prevent and/or adjunctively treat RTIs.
Updates in central nervous system malaria: literature review and considerations
Authors: Marino Andrea , Bivona Dalida Angela , Bonacci Paolo
Published: June 2022

Purpose of review

Cerebral malaria (CM) represents one of the most common and severe complications of Plasmodium falciparum infection, leading to high morbidity and mortality along with challenging sequelae, especially in children.

Recent findings

Although CM pathogenesis remains unclear due to the few studies made and the difficulty to analyze affected patients, there are valid theories involving P. falciparum endothelium interactions, and clinical manifestations have been better investigated and differentiated between adults and children.

At the time of writing, diagnostic management is based on fast severe malaria identification by blood smear (thin and thick). However, newer techniques involving molecular testing (such as PCR or LAMP) and biomarkers identification are now available. It is also important to check patients’ cerebral functions. As regards therapeutic management, although we could rely on several options, artesunate represents the gold standard treatment. Cerebral complications such as seizures and coma need to be managed as well.
Neurocysticercosis: an update on diagnosis, treatment, and prevention
Authors: Pineda-Reyes Roberto , White A. Clinton
Published: June 2022

Neurocysticercosis (NCC) is an important cause of neurological disease worldwide, including imported cases in nonendemic countries.

Purpose of review

The purpose of this review is to update information on diagnosis, management, and prevention of neurocysticercosis

Recent findings

WHO and Infectious Diseases Society of America/American Society of Tropical Medicine and Hygiene guidelines emphasize the importance of corticosteroids and antiparasitic drugs for viable parenchymal disease and single enhancing lesions. Subarachnoid NCC is associated with a high fatality rate unless optimally treated. Advances in subarachnoid NCC include use of prolonged antiparasitic and anti-inflammatory courses and the increasing use of antigen-detection and quantitative PCR assays in diagnosis and follow-up. Emerging data support the safety and efficacy of minimally invasive surgery in ventricular cases. Calcified neurocysticercosis continues to be associated with a high burden of disease. Field studies are demonstrating the feasibility of eradication using a combination of mass chemotherapy for human tapeworms and vaccination/treatment of porcine cysticercosis.

NCC remains an important and challenging cause of neurological disease with significant morbidity despite advances in treatment and prevention.
Diagnostic approach and update on encephalitis
Authors: Bhimraj Adarsh , Hasbun Rodrigo
Published: June 2022

Purpose of review

The present article gives an update and outlines the fundamental principles of clinical reasoning and a diagnostic approach to a patient suspected to have acute encephalitis.

Recent findings

Encephalitis remains to be associated with significant mortality and neurological morbidity. Unfortunately, the etiologic diagnosis remains elusive for the majority of the patients with encephalitis preventing targeted therapies. Clinicians could utilize clues such as duration of symptoms, exposure history, cerebrospinal fluid profile, neuroimaging findings and locations, and entertain certain opportunistic infections in immunosuppressed individuals. A comprehensive diagnostic for the most common viral and autoimmune etiologies should be systematically done and prompt empiric antiviral therapy should be started. Evaluation and therapy for autoimmune etiologies should be done for patients with a negative viral work up. Brain biopsy and metagenomic sequencing should be considered for patients with unknown etiologies that are clinically worsening.

Encephalitis remains with unacceptable mortality and morbidity with the most common etiologies being idiopathic. A comprehensive diagnostic work up and prompt antiviral and autoimmune therapies are of paramount importance to improve the outcomes of this devastating disease.
Escherichia coli 0157:H7 virulence factors and the ruminant reservoir
Authors: Kolodziejek Anna M. , Minnich Scott A. , Hovde Carolyn J.
Published: June 2022

Purpose of review

This review updates recent findings about Escherichia coli O157:H7 virulence factors and its bovine reservoir. This Shiga toxin (Stx)-producing E. coli belongs to the
E
nterohemorrhagic
E
.
c

oli (EHEC) pathotype causing hemorrhagic colitis. Its low infectious dose makes it an efficient, severe, foodborne pathogen. Although EHEC remains in the intestine, Stx can translocate systemically and is cytotoxic to microvascular endothelial cells, especially in the kidney and brain. Disease can progress to life-threatening hemolytic uremic syndrome (HUS) with hemolytic anemia, acute kidney failure, and thrombocytopenia. Young children, the immunocompromised, and the elderly are at the highest risk for HUS. Healthy ruminants are the major reservoir of EHEC and cattle are the primary source of human exposure.

Recent findings

Advances in understanding E. coli O157:H7 pathogenesis include molecular mechanisms of virulence, bacterial adherence, type three secretion effectors, intestinal microbiome, inflammation, and reservoir maintenance

Many aspects of E. coli O157:H7 disease remain unclear and include the role of the human and bovine intestinal microbiomes in infection. Therapeutic strategies involve controlling inflammatory responses and/or intestinal barrier function. Finally, elimination/reduction of E. coli O157:H7 in cattle using CRISPR-engineered conjugative bacterial plasmids and/or on-farm management likely hold solutions to reduce infections and increase food safety/security.
Successful clozapine rechallenge after myopericarditis: a case report
Authors: Boscutti Andrea , Cereda Guido , Lazzaretti Matteo , Enrico Paolo , Fiorentini Alessio , Prunas Cecilia , Callari Antonio , Fontana Elisa , Delvecchio Giuseppe , Brambilla Paolo
Published: June 2022

Clozapine-induced myocarditis and pericarditis are uncommon adverse effects of clozapine treatment. However, in most cases, they lead to clozapine discontinuation. Here, we describe a case of successful clozapine rechallenge after clozapine-induced myopericarditis. The patient, a 31-year-old male with treatment-resistant schizophrenia (TRS), developed dyspnea on exertion and chest pain on day 19 after the start of clozapine titration. An electrocardiogram (ECG) showed widespread, mild, convex ST interval elevation. While troponin levels were mildly elevated, the echocardiogram was unremarkable. A myopericarditis diagnosis was formulated, and clozapine was stopped, with a progressive resolution of clinical, laboratory and ECG abnormalities. After 6 months, a rechallenge with clozapine was attempted. A very slow titration scheme was adopted, along with close monitoring of clinical, laboratory and ECG parameters. Clozapine target dose was reached without the occurrence of any abnormality. Given the unique role of clozapine in the management of TRS, clozapine rechallenge may be considered after pericarditis, even with troponin levels elevation. Further studies are needed to update current clinical guidelines.
The role of personality traits in following quarantine orders during the COVID-19 pandemic
Authors: Eslamzadeh Mahboubeh , Fayyazi Bordbar Mohammad Reza , Moodi Ghalibaf AmirAli , Modaresi Farzaneh , Emadzadeh Maryam , Farhoudi Fateme
Published: June 2022

Patients’ personalities seem to affect their response to the COVID-19 pandemic. This study examined the association of personality traits and characteristics of Iranian COVID-19 outpatients with their compliance to nonmandatory quarantine orders. This cross-sectional study was conducted in 2020-2021 on 97 COVID-19 outpatients. The temperament and character inventory-revised short version (TCI-RS) and a self-report checklist assessing compliance with quarantine orders were used to collect data. SPSS was used to analyze the data and P < 0.05 was considered statistically significant. Of 142 patients who were contacted, 97 participated in the study (68% response rate). The mean age of patients was 39.21 ± 10.27 years and 54 (55.7%) of them were men. Compliance with quarantine orders was correlated with cooperativeness (r = 0.33; P = 0.001), persistence (r = 0.23, P = 0.020), self-transcendence (r = 0.27, P = 0.006) and harm avoidance (r = -0.26, P = 0.008). Linear regression analysis demonstrated persistence (P = 0.034), cooperativeness (P = 0.008) and being married (P = 0.002) as predictors for following the quarantine orders. Lower levels of cooperativeness, persistence, self-transcendence, and higher levels of harm avoidance are associated with noncompliance with quarantine orders. These traits should be considered while persuasive communication to the public is formulated to recognize the target population and increase compliance with nonmandatory quarantine orders.
COVID-19 pandemic dynamics in India, the SARS-CoV-2 Delta variant and implications for vaccination
Authors: Yang Wan , Shaman Jeffrey
Published: June 2022

The Delta variant is a major SARS-CoV-2 variant of concern first identified in India. To better understand COVID-19 pandemic dynamics and Delta, we use multiple datasets and model-inference to reconstruct COVID-19 pandemic dynamics in India during March 2020–June 2021. We further use the large discrepancy in one- and two-dose vaccination coverage in India (53% versus 23% by end of October 2021) to examine the impact of vaccination and whether prior non-Delta infection can boost vaccine effectiveness (VE). We estimate that Delta escaped immunity in 34.6% (95% CI: 0–64.2%) of individuals with prior wild-type infection and was 57.0% (95% CI: 37.9–75.6%) more infectious than wild-type SARS-CoV-2. Models assuming higher VE among non-Delta infection recoverees, particularly after the first dose, generated more accurate predictions than those assuming no such increases (best-performing VE setting: 90/95% versus 30/67% baseline for the first/second dose). Counterfactual modelling indicates that high vaccination coverage for first vaccine dose in India combined with the boosting of VE among recoverees averted around 60% of infections during July–mid-October 2021. These findings provide support to prioritizing first-dose vaccination in regions with high underlying infection rates, given continued vaccine shortages and new variant emergence.
Towards an advanced neurotechnological system: colorimetric sensing with a novel grism-based spectrometer, functionalized gold nanoparticles and a heterogeneous embedded system
Authors: Lachance Gabriel P. , Boisselier Élodie , Boukadoum Mounir , Miled Amine
Published: June 2022

Neurotransmitter sensing in the brain is crucial for the understanding of neuro-degenerative diseases. Most modern methods for the purpose rely on bulky instruments or are disruptive to the neurotransmitter medium. In this work, we describe and evaluate the design of a novel, compact and non-invasive instrument for neurotransmitter detection based on the colorimetric sensing method. The instrument includes a grism-based spectrometer that measures the wavelength shift of gold nanoparticles that are functionalized with aptamers to act as neurotransmitter-specific markers. It also includes microfluidic and electronic subsystems for sample preparation and control, and processing of the obtained signal. The instrument is tested with gold nanoparticles and its performance is compared to that of a commercial instrument, showing that the designed prototype matches the commercial instrument in performance while being much smaller, and it can surpass it with further improvements.

This article is part of the theme issue ‘Advanced neurotechnologies: translating innovation for health and well-being’.
Full-hand electrotactile feedback using electronic skin and matrix electrodes for high-bandwidth human–machine interfacing
Authors: Abbass Yahya , Dosen Strahinja , Seminara Lucia , Valle Maurizio
Published: June 2022

Tactile feedback is relevant in a broad range of human–machine interaction systems (e.g. teleoperation, virtual reality and prosthetics). The available tactile feedback interfaces comprise few sensing and stimulation units, which limits the amount of information conveyed to the user. The present study describes a novel technology that relies on distributed sensing and stimulation to convey comprehensive tactile feedback to the user of a robotic end effector. The system comprises six flexible sensing arrays (57 sensors) integrated on the fingers and palm of a robotic hand, embedded electronics (64 recording channels), a multichannel stimulator and seven flexible electrodes (64 stimulation pads) placed on the volar side of the subject’s hand. The system was tested in seven subjects asked to recognize contact positions and identify contact sliding on the electronic skin, using distributed anode configuration (DAC) and single dedicated anode configuration. The experiments demonstrated that DAC resulted in substantially better performance. Using DAC, the system successfully translated the contact patterns into electrotactile profiles that the subjects could recognize with satisfactory accuracy (i.e. median{IQR} of 88.6{11}%for static and93.3{5}%for dynamic patterns). The proposed system is an important step towards the development of a high-density human–machine interfacing between the user and a robotic hand.

This article is part of the theme issue ‘Advanced neurotechnologies: translating innovation for health and well-being’.
Life-history diversity in lakes is associated with ecosystem size
Authors: Rypel Andrew L.
Published: June 2022

In this study, I inspect how ecosystem size drives fish life-history strategies in north temperate lakes. Species were classified as equilibrium, periodic, or opportunistic strategists according to Winemiller and Rose (1992), and species-area curves assembled and compared among strategy types. The smallest lakes were often dominated by only one species, usually an opportunistic strategist. Overall, species richness rose with ecosystem size, but larger ecosystems tended to be dominated by more periodic and equilibrium strategists. Richness of periodic species increased with ecosystem size at a faster rate compared to opportunistic species. Similarly, life-history niche space increased with ecosystem size in accord with species-area relationships, but showed saturation behavior (i.e., life-history niche space became increasingly ‘packed’ in large lakes). As predicted by theory, relative abundances of opportunistic strategists were extremely variable over space and time, whereas abundances of equilibrium and periodic strategists were more stable. Integration of species-area relationships with life-history theory provides insights into community assembly at multiple scales, and has broad conservation applications.
Habitat protection and restoration: win-win opportunities for migratory birds in the Northern Andes
Authors: Gonzalez Ana M. , Espejo Nestor , Armenteras Dolors , Hobson Keith A. , Kardynal Kevin J. , Mitchell Greg W. , Mahony Nancy , Bishop Christine A. , Negret Pablo J. , Wilson Scott
Published: June 2022

Identifying strategies that offer co-benefits for biodiversity protection, forest restoration and human well-being are important for successful conservation outcomes. In this study, we identified opportunities where forest restoration and rehabilitation programs in Colombia also align with priority areas for the conservation of Neotropical migratory birds. We used citizen science eBird-based abundance estimates to define regions with the highest richness of Neotropical migratory birds of conservation concern at montane elevations in Colombia and aligned these high richness areas with domestic initiatives for forest protection (Forest Areas), restoration (Restoration Areas) and rehabilitation (Rehabilitation Areas). We quantified the location and amounts of these three areas as well as the type of land protection and designation within them, specifically, National Protected Areas, Indigenous Reserves, Afro-descendent territories, and regions affected by poverty and violence that are prioritized for rural development by the Colombian government in Post-conflict Territorially Focused Development Programs (PDET). Almost half of Forest Areas overlapped with PDETs where goals for economic development present a risk of forest loss if not done sustainably. There was a 20% overlap between Forest Areas and Afro-descendant territories and indigenous reserves; most of this overlap was outside of established protected areas thus presenting an opportunity for community forest conservation that benefits migratory birds. We found an alignment of less than 6% between migrant bird focal areas and the priority Restoration and Rehabilitation Planning Areas identified by the Colombian National Restoration Plan indicating less opportunity for these programs to simultaneously benefit Neotropical migrant species. Our approach highlights that timely and efficient conservation of declining migrants depends on identifying the regions and strategies that incorporate local communities as part of the solution to forest loss and degradation in Colombia.

Highlights

Colombia covers over half of key wintering areas for migratory birds in South America

Most of the migrants’ overwinter range overlaps with working landscapes

Priority national restoration/rehabilitation areas are ineffective to benefit migrants

Forest conservation needs actions involving vulnerable and minority groups
Intracranial Aneurysm Wall Displacement Predicts Instability
Authors: Pionteck A. , Abderezaei J. , Fillingham P. , Chuang Y.-C. , Sakai Y. , Belani P. , Rigney B. , De Leacy R. , Fifi J. , Chien A. , Villablanca P. , Colby G. , Jahan R. , Duckwiler G. , Sayre J. , Holdsworth S. , Levitt M. , Mocco J. , Kurt M. , Nael K.
Published: June 2022

Ruptured intracranial aneurysms (IAs) are catastrophic events associated with a high mortality rate. An estimation of 6 million people in the United States have reported IAs, raising a pressing need for diagnostic tools to assess IAs rupture risks. Current population-based guidelines are imperfect, hence the need for new quantifiable variables and imaging markers. Aneurysm wall motion has been identified as a potential marker of high risk aneurysms, but conventional imaging techniques are challenged by small IAs sizes and limited spatial resolution. Recently, amplified Flow (aFlow) has been introduced as an algorithm which allows visualization and quantification of aneurysm wall motion based on amplification of 4D flow MRI data. In this work, we used aFlow to assess IAs wall motion in patients with growing aneurysms. The results were compared with a patient cohort with stable aneurysms. Among 118 patients with unruptured IAs who underwent sequential surveillance imaging, 10 patients with growing IAs who had baseline 3D TOF-MRA and 4D flow MR imaging were identified and matched with another cohort of patients with stable IAs based on IAs size and location. aFlow was then applied to the 4D flow MR data to amplify the aneurysm wall displacement. Voxel-based values of displacement were extracted for each aneurysm and normalized with respect to the reference parent artery. Following histogram analysis, the highest and lowest IAs displacements were calculated, together with their standard deviation and interquartile ranges. A paired-wise analysis was adopted to assess the differences among clinical variables, demographic data, morphological features, and aFlow parameters between patients with stable versus growing aneurysm. Results demonstrated higher wall motion and higher variability of deformation for the growing aneurysms, possibly due to inhomogeneities of the mechanical characteristics of the vessels walls or to underlying hemodynamics. Computational Fluid Dynamic simulation was also conducted for a subset of 6 stable and 6 growing aneurysms to examine the correlation between hemodynamic parameters, wall motion, and aneurysm stability. The magnitude and variance of directional wall shear stress gradient, in addition to area of colocation of elevated oscillatory shear stress and high variance in pressure, were highly correlated with both wall motion and aneurysm stability. We demonstrated here that the measurement and amplification of the aneurysm wall motion achieved with our method has the potential to differentiate stable from growing aneurysms, and potentially act as a substitute for in depth computational fluid dynamic analysis.
CREWdb 1.0: Optimizing Chromatin Readers, Erasers, and Writers Database using Machine Learning-Based Approach
Authors: Natesan Maya , Ghag Reetika , Kong Mitchell , Shi Min , Mollah Shamim
Published: June 2022

Aberration in heterochromatin and euchromatin states contributes to various disease phenotypes. The transcriptional regulation between these two states is significantly governed by post-translational modifications made by three functional types of chromatin regulators: readers, writers, and erasers. Writers introduce a chemical modification to DNA and histone tails, readers bind the modification to histone tails using specialized domains, and erasers remove the modification introduced by writers. Altered regulation of these chromatin regulators results in complex diseases such as cancer, neurodevelopmental diseases, myocardial diseases, kidney diseases, and embryonic development. Due to the reversible nature of chromatin modifications, we can develop therapeutic approaches targeting these chromatin regulators. However, a limited number of chromatin regulators have been identified thus far, and a subset of them are ambiguously classified as multiple chromatin regulator functional types. Thus, we have developed machine learning-based approaches to predict and classify the functional roles of chromatin regulator proteins, thereby optimizing the accuracy of the first comprehensive database of chromatin regulators known asCREWdb.

GitHub URL

CREWdb source code is available athttps://github.com/smollahlab/CREWdb

Database URL

CREWdb webtool is available athttp://mollahlab.wustl.edu/crewdb
Spectral performance evaluation of a second-generation spectral detector CT
Authors: Liu Leening P. , Shapira Nadav , Halliburton Sandra S. , Meyer Sebastian , Perkins Amy , Litt Harold I. , Kauczor Hans Ulrich , Leiner Tim , Stiller Wolfram , Noël Peter B.
Published: June 2022

Objective

To characterize a second-generation wide-detector dual-layer spectral computed tomography system for material quantification accuracy, acquisition parameter and patient size dependencies, and tissue characterization capabilities.

Methods

A phantom with multiple tissue-mimicking and material inserts was scanned with a dual-layer spectral detector CT using different tube voltages, collimation widths, radiation dose levels, and size configurations. Accuracy of iodine density maps and virtual monoenergetic images (MonoE) were investigated. Additionally, differences between conventional and MonoE 70 keV images were calculated to evaluate acquisition parameter and patient size dependencies. To demonstrate material quantification and differentiation, liver-mimicking inserts with adipose and iron were analyzed with a two-base decomposition utilizing MonoE 50 and 150 keV, and root mean square error (RMSE) for adipose and iron content was reported.

Results

Spectral accuracy was high for the measured inserts across a wide range of MonoE levels. MonoE 70 keV demonstrated reduced dependence compared to conventional image for phantom size (3 vs. 29 HU) and acquisition parameters, particularly tube voltage (5 vs. 43 HU) and noise-dose (9 vs. 11 HU). Iodine density quantification was successful with errors ranging from 0.25 to 0.5 mg/mL. Similarly, inserts with different amounts of adipose and iron were easily differentiated, and the small deviation in values within inserts corresponded to a RMSE of 1.78 ± 0.37% and 0.87 ± 0.37 mg/mL for adipose and iron content, respectively.

Conclusion

The second-generation dual-layer CT enables acquisition of quantitatively accurate spectral data without compromises from differences in patient size and acquisition parameters.

Key Points

-

With second-generation wide-detector dual-layer computed tomography, spectral quantification is further improved.

-

Spectral performance is independent of acquisition parameters such as tube voltage (100 kVp versus 120 kVp) and z-coverage (10 versus 80 mm).

-

Spectral performance is not significantly impacted by patient habitus.
Protein profiling of breast carcinomas reveals expression of immune-suppressive factors and signatures relevant to patient outcome
Authors: Ruoff Felix , Kersten Nicolas , Anderle Nicole , Jerbi Sandra , Stahl Aaron , Koch André , Staebler Anette , Hartkopf Andreas , Brucker Sara Y. , Hahn Markus , Schenke-Layland Katja , Schmees Christian , Templin Markus F.
Published: June 2022

Background

In cancerous tissue, a complex interplay of tumour cells with different cell types from the tumour microenvironment is causing modulations in signalling processes. By directly assessing expression of a multitude of proteins and protein variants, extensive information on signalling pathways, their activation status and the effect of the immunological landscape can be obtained providing viable information for treatment response.

Methods

Protein extracted from archived breast cancer tissue from patients without adjuvant therapy was subjected to high-throughput Western blotting using the DigiWest technology. Expression of 150 proteins and protein variants covering cell cycle control, apoptosis, Jak/Stat, MAPK-, Pi3K/Akt-, Wnt-, and, autophagic signalling as well as general tumour markers was monitored in a cohort of 84 patient samples. The degree of immune cell infiltration was investigated and set against treatment outcome by integrating patient specific follow-up data.

Results

Characterization of the tumour microenvironment by monitoring CD8α, CD11c, CD16 and CD68 expression revealed a strong correlation of event-free patient survival with immune cell infiltration. Furthermore, the presence of tumour infiltrating lymphocytes was linked to a pronounced activation of the Jak/Stat signalling pathway and apoptotic processes. Elevated phosphorylation of peroxisome proliferator-activated receptor gamma (PPARγ, pS112) in non-immune infiltrated tumour tissue suggests a novel immune evasion mechanism in breast cancer characterized by increased PPARγ activation.

Conclusion

Multiplexed immune cell marker assessment and protein profiling of tumour tissue provides functional signalling data facilitating breast cancer patient stratification.
A Multi-scale, Multiomic Atlas of Human Normal and Follicular Lymphoma Lymph Nodes
Authors: Radtke Andrea J. , Postovalova Ekaterina , Varlamova Arina , Bagaev Alexander , Sorokina Maria , Kudryashova Olga , Meerson Mark , Polyakova Margarita , Galkin Ilia , Svekolkin Viktor , Isaev Sergey , Perelman Grigory , Lozinsky Yaroslav , Yaniv Ziv , Lowekamp Bradley C. , Speranza Emily , Yao Li , Pittaluga Stefania , Shaffer Arthur L. , Jonigk Danny , Phelan James D. , Davies-Hill Theresa , Huang Da Wei , Ovcharov Pavel , Nomie Krystle , Nuzhdina Ekaterina , Kotlov Nikita , Ataullakhanov Ravshan , Fowler Nathan , Kelly Michael , Muppidi Jagan , Davis Jeremy , Hernandez Jonathan M. , Wilson Wyndham H. , Jaffe Elaine S. , Staudt Louis M. , Roschewski Mark , Germain Ronald N.
Published: June 2022

Reference atlases, molecular and spatial maps of mammalian tissues, are critical resources for discovery efforts and translational research. Their utility is dependent on operationalizing the resulting data by identifying cell types, histological patterns, and predictive biomarkers underlying health and disease. The human lymph node (LN) offers a compelling use case because of its importance in immunity, structural and cellular diversity, and neoplastic involvement. One hematological malignancy, follicular lymphoma (FL), evolves from developmentally blocked germinal center B cells residing in and trafficking through these tissues. To promote survival and immune escape, tumor B cells undergo significant genetic changes and extensively remodel the lymphoid microenvironment. Here, we present an integrated portrait of healthy and FL LNs using multiple genomic and advanced imaging technologies. By leveraging the strengths of each platform, we identified several tumor-specific features and microenvironmental patterns enriched in individuals who experience early relapse, the most high-risk of FL patients.
Epigenome-wide association study analysis of calorie restriction in humans, CALERIE™ Trial analysis
Authors: Ramaker Megan E. , Corcoran David L. , Apsley Abner T. , Kobor Michael S. , Kraus Virginia B. , Kraus William E. , Lin David T. S. , Orenduff Melissa C. , Pieper Carl F. , Waziry Reem , Huffman Kim M. , Belsky Daniel W.
Published: June 2022

BACKGROUND

Calorie restriction (CR) increases healthy lifespan and is accompanied by slowing or reversal of aging-associated DNA methylation (DNAm) changes in animal models. In the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) human trial we evaluated associations of CR and changes in whole-blood DNAm.

METHODS

CALERIE™ randomized 220 healthy, non-obese adults in a 2:1 allocation to two years of CR or ad libitum (AL) diet. The average CR in the treatment group through 24-months of follow-up was 12%. Whole blood (baseline, 12 and 24 month) DNAm profiles were measured. Epigenome-wide association study (EWAS) analysis tested CR-induced changes from baseline to 12- and 24-months in the n=197 participants with available DNAm data.

RESULTS

No CpG-site-specific changes with CR reached epigenome-wide significance (FDR<0.05). Secondary analyses of CpG sites identified in published EWAS suggest, we found that CR induced DNAm changes opposite those associated with body mass index (BMI) and smoking (p<0.003 at 12- and 24-month follow-ups). In contrast, CR altered DNAm at chronological-age associated CpG sites in the direction of older age (p<0.003 at 12- and 24-month follow-ups).

CONCLUSION

Although individual CpG site DNAm changes in response to CR were not identified, analyses of sets CpGs identified in prior EWAS revealed CR-induced changes to blood DNAm. Altered CpG sets were enriched for insulin-production, glucose-tolerance, inflammation, and DNA-binding and -regulation pathways, several of which are known to be modified by CR. DNAm changes may contribute to CR effects on aging.
Increasing information gain in animal research by improving statistical model accuracy
Authors: Waterkamp Christoph , von Kortzfleisch Vanessa Tabea , Neu Christoph , Kitanovski Simo , Richter S. Helene , Hoffmann Daniel
Published: June 2022

Reduction of the numbers of laboratory animals is one of the three pillars of ethical animal research. Equivalently, information gain per animal should be maximized. A road towards this goal that is barely taken in current animal research is the more accurate statistical modeling of experiments. Here we show for a typical experiment (“open field test”) with outcomes that are non-normally distributed count data, how this can be implemented and what information gain is achieved. We contrast the state of the art – the use of confidence intervals based on null-hypothesis significance testing (NHST) –, with a Bayesian approach with the same underlying normal model, and a Bayesian approach with a more accurate negative binomial model. We find that the more accurate model leads to a marked improvement of knowledge gained with the experiment, especially for small sample sizes. As experimental data that violate assumptions of simple, conventional models are frequent, our findings have wider implications.
Multi-task learning for single-cell multi-modality biology
Authors: Tang Xin , Zhang Jiawei , He Yichun , Zhang Xinhe , Lin Zuwan , Partarrieu Sebastian , Hanna Emma Bou , Ren Zhaolin , Yang Yuhong , Wang Xiao , Li Na , Ding Jie , Liu Jia
Published: June 2022

Current biotechnologies can simultaneously measure multi-modality high-dimensional information from the same cell and tissue samples. To analyze the multi-modality data, common tasks such as joint data analysis and cross-modal prediction have been developed. However, current analytical methods are generally designed to process multi-modality data for one specific task without considering the underlying connections between tasks. Here, we present UnitedNet, a multi-task deep neural network that integrates the tasks of joint group identification and cross-modal prediction to analyze multi-modality data. We have found that multi-task learning for joint group identification and cross-modal prediction significantly improves the performance of each task. When applied to various single-cell multi-modality datasets, UnitedNet shows superior performance in each task, achieving better unsupervised and supervised joint group identification and cross-modal prediction performances compared with state-of-the-art methods. Furthermore, by considering the spatial information of cells as one modality, UnitedNet substantially improves the accuracy of tissue region identification and enables spatially resolved cross-modal prediction.
Bayesian Optimization for Ternary Complex Prediction (BOTCP)
Authors: Rao Arjun , Tunjic Tin M. , Brunsteiner Michael , Müller Michael , Fooladi Hosein , Weber Noah
Published: June 2022

Proximity-inducing compounds (PICs) are an emergent drug technology through which a protein of interest (POI), often a drug target, is brought into the vicinity of a second protein which modifies the POI’s function, abundance or localisation, giving rise to a therapeutic effect. One of the best-known examples for such compounds are heterobifunctional molecules known as proteolysis targeting chimeras (PROTACs). PROTACs reduce the abundance of the target protein by establishing proximity to an E3 ligase which targets the protein towards degradation via the ubiquitin-proteasomal pathway. Design of PROTACs in silico requires the computational prediction of the ternary complex consisting of POI, PROTAC molecule, and the E3 ligase.

Here, we present a novel machine learning-based method for predicting PROTAC-mediated ternary complex structures using Bayesian optimization. We show how a fitness score combining an estimation of protein-protein interactions with PROTAC binding energy calculations enables the sample-efficient exploration of candidate structures. Furthermore, our method presents two novel scores for filtering and reranking which take PROTAC stability (Autodock-Vina based PROTAC stability score) and protein interaction restraints (the TCP-AIR score) into account. We evaluate our method using DockQ scores and demonstrate, that even with a clustering that require members to have a high similarity, i.e. with smaller clusters, we can assign high ranks to those clusters that contain poses close to the experimentally determined native structure of the ternary complexes. We also demonstrate the resultant improved yeild of near-native poses in these clusters.
DeepTracer ID: De Novo Protein Identification from Cryo-EM Maps
Authors: Chang Luca , Wang Fengbin , Connolly Kiernan , Meng Hanze , Su Zhangli , Cvirkaite-Krupovic Virginija , Krupovic Mart , Egelman Edward H. , Si Dong
Published: June 2022

The recent revolution in cryo-electron microscopy has made it possible to determine macromolecular structures directly from cell extracts. However, identifying the correct protein from the cryo-EM map is still challenging and often needs additional sequence information from other techniques, such as tandem mass spectrometry and/or bioinformatics. Here, we present DeepTracer-ID, a server-based approach to identify the candidate protein in a user-provided organism de novo from a cryo-EM map, without the need for additional information. Our method first uses DeepTracer to generate a protein backbone model that best represents the cryo-EM map, and this model is then searched against the library of AlphaFold2 predictions for all proteins in the given organism. This method is highly accurate and robust: in all 13 experimental maps tested blindly, DeepTracer-ID identified the correct proteins as the top candidates. Eight of the maps were of known structures, while the other five unpublished maps were validated by prior protein annotation and careful inspection of the model refined into the map. The program also showed promising results for both homomeric and heteromeric protein complexes. This platform is possible because of the recent breakthroughs in large-scale protein 3D structure prediction.

Statement of Significance

While it has now become routine for cryo-EM maps of proteins to reach a near-atomic resolution, potentially allowing for reliable atomic models to be built, there are a growing number of instances where the protein identity may not be known. Without knowing the protein sequence, it is impossible to build an atomic model. DeepTracer-ID is a server-based approach to surmount this problem by identifying the proteins in a given organism that are found in the cryo-EM map. A free web service for global academic access is provided.
Pontine waves accompanied by short hippocampal sharp wave-ripples during non-rapid eye movement sleep
Authors: Tsunematsu Tomomi , Matsumoto Sumire , Merkler Mirna , Sakata Shuzo
Published: June 2022

Ponto-geniculo-occipital (PGO) or pontine (P) waves have long been recognized as an electrophysiological signature of rapid eye movement (REM) sleep. However, P-waves can be observed not just during REM sleep, but also during non-REM (NREM) sleep. Recent studies have uncovered that P-waves are functionally coupled with hippocampal sharp wave-ripples (SWRs) during NREM sleep. However, it remains unclear to what extent P-waves during NREM sleep share their characteristics with P-waves during REM sleep and how the functional coupling to P-waves modulates SWRs. Here, we address these issues by performing multiple types of electrophysiological recordings and fiber photometry in both sexes of mice. P-waves during NREM sleep share their waveform shapes and local neural ensemble dynamics at a short (∼100 ms) timescale with their REM sleep counterparts. However, the dynamics of mesopontine cholinergic neurons are distinct at a longer (∼10 s) timescale: although P-waves are accompanied by cholinergic transients, the cholinergic tone gradually reduces before P-wave genesis during NREM sleep. While P-waves are coupled to hippocampal theta rhythms during REM sleep, P-waves during NREM sleep are accompanied by a rapid reduction in hippocampal ripple power. SWRs coupled with P-waves are short-lived and hippocampal neural firing is also reduced after P-waves. These results demonstrate that P-waves are part of coordinated sleep-related activity by functionally coupling with hippocampal ensembles in a state-dependent manner.
Distributed information encoding and decoding using self-organized spatial patterns
Authors: Lu Jia , Tsoi Ryan , Luo Nan , Ha Yuanchi , Wang Shangying , Kwak Minjun , Baig Yasa , Moiseyev Nicole , Tian Shari , Zhang Alison , Gong Neil Zhenqiang , You Lingchong
Published: June 2022

Dynamical systems often generate distinct outputs according to different initial conditions, and one can infer the corresponding input configuration given an output. This property captures the essence of information encoding and decoding. Here, we demonstrate the use of self-organized patterns, combined with machine learning, to achieve distributed information encoding and decoding. Our approach exploits a critical property of many natural pattern-formation systems: in repeated realizations, each initial configuration generates similar but not identical output patterns due to randomness in the patterning process. However, for sufficiently small randomness, different groups of patterns that arise from different initial configurations can be distinguished from one another. Modulating the pattern generation and machine learning model training can tune the tradeoff between encoding capacity and security. We further show that this strategy is applicable to non-biological dynamical systems and scalable by implementing the encoding and decoding of all characters of the standard English keyboard.

Significance Statement

Self-organized patterns are ubiquitous in biology. They arise from interactions in and between cells, and with the environment. These patterns are often used as a composite phenotype to distinguish cell states and environment conditions. Conceptually, pattern generation under an initial condition is encoding; discerning the initial condition from the pattern represents decoding. Inspired by these examples, we develop a scheme, integrating mathematical modeling and machine learning, to use self-organization for secure and accurate information encoding and decoding. We show that this strategy is applicable to non-biological dynamical systems. We further demonstrate the scalability of the scheme by generating a complete mapping of the standard English keyboard, allowing encoding of English text. Our work serves as an example of nature-inspired computation.