bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcutaneous sentinel lymph node detection in skin melanoma with near-infrared fluorescence imaging using indocyanine green
Authors: Zweedijk Bo E. , Schurink Antonius W. , van Dalen Thijs , van Ginhoven Tessa M. , Verhoef Cornelis , Kremer Bernd , Hilling Denise E. , Keereweer Stijn , Grünhagen Dirk J.
Published: August 2024

The aim of the study is to assess whether indocyanine green (ICG) fluorescence can replace technetium in the preoperative detection of sentinel lymph nodes (SLN) from cutaneous melanoma. The current golden standard for SLN detection is the radioisotope technetium. A promising alternative is fluorescence imaging (FLI) using ICG. In this study, we enrolled patients undergoing sentinel lymph node biopsy (SLNB) for skin melanoma at the Erasmus Medical Center between November 2022 and July 2023. The SLNB procedure was performed as a standard of care. After general anesthesia, ICG was injected intradermally around the primary tumor site. Both the patient and the surgeon were not blinded for the location of the SLN. FLI was performed before incision, in vivo after incision, and ex vivo. Fluorescent SLNs were confirmed using the gamma probe in all cases. Thirty-two patients were included in this study, and a total of 39 SLNs were harvested. The transcutaneous detection rate of ICG was 21.9%. The combined ex vivo ICG fluorescence and technetium uptake was 94.9%. One SLN contained only ICG (2.6%) and one SLN contained only technetium-uptake (2.6%). FLI using ICG resulted in a relatively low transcutaneous detection, which means that exclusive use of this technique in its present form is not feasible. However, we did find a high accumulation of ICG in the SLN, indicating the potential of ICG in combination with other imaging techniques.
Bayesian Kernel Machine Regression for Social Epidemiologic Research
Authors: Bather Jemar R. , Robinson Taylor J. , Goodman Melody S.
Published: August 2024

Background:

Little attention has been devoted to framing multiple continuous social variables as a “mixture” for social epidemiologic analysis. We propose using the Bayesian kernel machine regression analytic framework that yields univariate, bivariate, and overall exposure mixture effects.

Methods:

Using data from the 2023 Survey of Racism and Public Health, we conducted a Bayesian kernel machine regression analysis to study several individual, social, and structural factors as an exposure mixture and their relationships with psychological distress among individuals with at least one police arrest. Factors included racial and economic polarization, neighborhood deprivation, perceived discrimination, police perception, subjective social status, and substance use. We complemented this analysis with a series of unadjusted and adjusted models for each exposure mixture variable.

Results:

We found that more self-reported discrimination experiences in the past year (posterior inclusion probability = 1.00) and greater substance use (posterior inclusion probability = 1.00) correlated with higher psychological distress. These associations were consistent with the findings from the unadjusted and adjusted linear regression analyses: past year perceived discrimination (unadjusted b = 2.58, 95% confidence interval [CI]: 1.86, 3.30; adjusted b = 2.20, 95% CI: 1.45, 2.94) and substance use (unadjusted b = 2.92, 95% CI: 2.21, 3.62; adjusted b = 2.59, 95% CI: 1.87, 3.31).

Conclusion:

With the rise of big data and the expansion of variables in long-standing cohort and census studies, novel applications of methods from adjacent disciplines are a step forward in identifying exposure mixture associations in social epidemiology and addressing the health needs of socially vulnerable populations.
Sacral Ulcer after Carbon Ion Radiotherapy Reconstructed with a Superior Gluteal Artery Perforator Flap
Authors: Kuwahara Masamitsu , Okazaki Hideaki , Nashihara Sakuka , Kanagawa Saori , Sasaki Chikako
Published: August 2024

As carbon ion radiotherapy (CIRT) was developed only recently, reports of CIRT-induced ulcers requiring plastic surgery are still rare, but the number of such cases is expected to increase. Here, we describe a case of a CIRT-induced ulcer to aid the treatment of such ulcers. An 82-year-old man had a sacral chordoma (12 × 7.5 × 7.5 cm), which extended from the fourth to fifth sacral vertebrae. He underwent CIRT (70.4 Gy). An ulcer developed 30 months after the treatment. The ulcer enlarged to 13 cm × 7 cm. Debridement, negative-pressure wound therapy, and antibiotics were used. We tried to avoid injuring the rectum and sciatic nerve, and covered the ulcer with a delayed superior gluteal artery perforator flap. Wound healing was difficult to achieve in the lower half of the flap. Further debridement was appropriate, but we considered that it was likely to cause complications. Once a post-CIRT ulcer develops, its progression and the required extent of debridement can be roughly predicted based on the radiotherapy treatment plan. In this case, the rectum and sciatic nerve were irradiated, but there were no related symptoms. Therefore, we performed surgery to preserve these structures. However, there was very thick scar tissue surrounding these structures, making debridement difficult, and the wound was slow to heal. It is desirable to use a flap with good blood flow, such as a myocutaneous flap, for covering post-CIRT ulcers.
Evaluation of the Inner Macula Layers, Circumpapillary Retinal Nerve Fiber Layer, and Minimum Rim Width Thickness in Patients With Pseudoexfoliation Syndrome Without Glaucoma Compared With Controls
Authors: Azimi Ali , Bostanian Pardis , Jalalpour Mohammad Hassan , Hassanipour Hamid Reza , Chhablani Jay , Sadeghi Elham
Published: August 2024

Précis:

Minimum rim width (MRW) is thinner in patients with non-glaucomatous pseudoexfoliation syndrome (XFS) and may be the first parameter affected in these patients due to the vascular nature of this disease.

Objective:

To evaluate the macular inner layers, circumpapillary retinal nerve fiber layer (cp-RNFL), and MRW in non-glaucomatous XFS compared with healthy patients.

Patients and Methods:

In this prospective study, using Heidelberg Spectralis optical coherence tomography with Glaucoma Module Premium Edition, 8×8 grids of macular inner layers were exported, and the global, superior, and inferior thicknesses were used. Also, on the deviation map, the elliptical annulus around the fovea, which was 4.8×4 mm in size, was analyzed. Moreover, both groups calculated cp-RNFL and MRW values in 3 superior and 3 inferior sectors.

Results:

Thirty-two eyes of 32 patients with clinically detected non-glaucomatous XFS and 30 right eyes of age-sex–matched healthy controls were included. No significant difference was found between the case and control groups concerning the intraocular pressure (14.94 ± 2.09 vs 15.27 ± 2.27 mm Hg, respectively, P = 0.556). The MRW of the superotemporal segment (MRW–temporal superior) was significantly thinner in the XFS group compared with the control ones (303.69 ± 60.49 vs 341.43 ± 56.19 µm, P = 0.014). No significant differences were found in the other sectors of MRW, macular inner layers, and cp-RNFL thickness between the groups.

Conclusion:

These findings indicate that the MRW, especially in the superotemporal sector, may show early eye damage in patients with non-glaucomatous XFS, and it may be used to detect the early stage of glaucoma in XFS.
Guide to Muscular Injuries and Common Ligamentous Injuries Among Soccer Players
Authors: Ravi Sreeram , Dopke Kelly , Richardson Micah , Vatsia Sohrab , Lynch Scott
Published: August 2024

With over 250 million players worldwide, soccer is the most popular sport in the world. The overall number of players at professional, amateur, and recreational levels has increased along with an increase in player diversity, including age and sex. These increases in player numbers, as well as a variety of demographics, have resulted in an increase in soccer-related injuries. Injury in the professional setting can lead to time off the field and an effect on team results and earnings. Injury at the amateur and recreational levels can lead to time off work, away from other activities, and change in activities of daily living. We provide an extensive list of common injuries sustained by soccer players, their pathophysiology, diagnosis, treatment, and general guidelines on return to play.
A Randomized Control Trial Comparing the Yield of Bronchoalveolar Lavage Using Three Different Techniques in Patients Undergoing Flexible Bronchoscopy (BAL-3T)
Authors: Sehgal Inderpaul Singh , Kaur Gurkirat , Gupta Nalini , Dhooria Sahajal , Prasad Kuruswamy Thurai , Bal Amanjit , Gupta Parikshaa , Aggarwal Ashutosh Nath , Muthu Valliappan , Agarwal Ritesh
Published: August 2024

Background:

Three techniques have been described for aspirating the bronchoalveolar lavage (BAL) fluid, namely the wall mount suction (WMS), manual suction (MS), and manual suction with tubing (MST). However, there is no direct comparison among the 3 methods.

Methods:

We randomized patients undergoing flexible bronchoscopy and BAL in a 1:1:1 ratio to one of the 3 arms. The primary outcome was to compare the optimal yield, defined as at least 30% return of volume instilled and <5% bronchial cells. The key secondary outcomes were the percentage of volume and total amount (in millimeters) return of BAL, as well as complications (hypoxemia, airway bleeding, and others).

Results:

We randomized 942 patients [MST (n = 314), MS (n = 314), WMS (n = 314)]. The mean age of the study population [58.7% (n = 553) males] was 46.9 years. The most common indication for BAL was suspected pulmonary infection. Right upper lobes and middle lobes were the commonest sampled lobes. The optimal yield was similar in all the groups [MST (35.6%) vs MS (42.2%) vs WMS (36.5%); P = 0.27]. A significantly higher proportion of patients had BALF return >30% (P = 0.005) in the WMS (54.2%) and MS (54%) than in the MST arm (42.9%). The absolute and the percentage volume of BALF was also higher in WMS and MS than in the MST arm. There was no difference in the complication rate or other secondary outcomes across the groups.

Conclusion:

We found no difference in the optimal yield of BAL or complications using any one of the 3 methods for BAL fluid retrieval.
TakeMeHome: A Novel Method for Reaching Previously Untested People Through Online Ordering and Self-Collect HIV and STI Testing
Authors: Hecht Jennifer , Facente Shelley N. , Cohen Stephanie , Menza Tim , Trainor Nikole , Heumann Christine , Juhasz Marta , Sullivan Patrick
Published: August 2024

Background

Despite national testing guidelines, rates of testing for HIV, sexually transmitted infections (STIs), and hepatitis C remain lower than recommended for men who have sex with men in the United States. To help address this, the TakeMeHome (TMH) program was started in March 2020 by Building Healthy Online Communities, a consortium of public health organizations and dating apps, to work with health departments to increase access to HIV testing for men who have sex with men on dating apps.

Methods

Users of participating dating apps were sent messages about opportunities for testing with self-collected specimens through TMH. Program users were eligible to receive test kits if they lived in a participating zip code and were aged at least 18 years. Users who were interested in testing could order kits to be mailed to them for laboratory-based testing of HIV, hepatitis C, chlamydia, gonorrhea, and/or syphilis, depending on risk and availability in their zip code. Orders were sent via application programming interface to Molecular Testing Labs for fulfillment; kits were provided at no cost to the program user. Within approximately 24 hours of order receipt, Molecular Testing Labs mailed program users a kit with required collection supplies, directions, and a link to a video instruction for self-collection. Program users received an automated email after testing was complete with a link to access results through their online account. Individuals with positive results on any of the relevant tests were directed to additional information and to local providers for linkage to additional testing or treatment, depending on local protocols.

Results

The positivity rate of specimens processed through TMH was 1.4% for HIV, 0.6% for hepatitis C, and 2.9% for all STIs combined. The per-person positivity rate was 15.3% across all STIs.

Conclusions

The TMH program demonstrates that self-collected laboratory-processed testing is feasible and effective at identifying new HIV and STI cases.
Photon-Counting Detector CT Applications in Musculoskeletal Radiology
Authors: Grunz Jan-Peter , Huflage Henner
Published: August 2024

Photon-counting detectors (PCDs) have emerged as one of the most influential technical developments for medical imaging in recent memory. Surpassing conventional systems with energy-integrating detector technology in many aspects, PCD-CT scanners provide superior spatial resolution and dose efficiency for all radiological subspecialities. Demanding detailed display of trabecular microarchitecture and extensive anatomical coverage frequently within the same scan, musculoskeletal (MSK) imaging in particular can be a beneficiary of PCD-CT's remarkable performance. Since PCD-CT provides users with a plethora of customization options for both image acquisition and reconstruction, however, MSK radiologists need to be familiar with the scanner to unlock its full potential. From filter-based spectral shaping for artifact reduction over full field-of-view ultra-high-resolution scans to postprocessing of single- or dual-source multienergy data, almost every imaging task can be met with an optimized approach in PCD-CT. The objectives of this review were to give an overview of the most promising applications of PCD-CT in MSK imaging to date, to state current limitations, and to highlight directions for future research and developments.
FDG PET/CT in Staging of α-Fetoprotein–Producing Hepatoid Adenocarcinoma of the Pancreas
Authors: Ji Xia , Dong Aisheng , Wang Yang
Published: August 2024

Hepatoid adenocarcinoma of the pancreas is a rare aggressive tumor with poor prognosis. We describe contrast-enhanced CT and FDG PET/CT findings in a case of pancreatic hepatoid adenocarcinoma with significantly elevated α-fetoprotein level presenting as acute pancreatitis. The primary pancreatic tumor diffusely involved the pancreas and showed heterogeneous enhancement mimicking acute necrotizing pancreatitis on contrast-enhanced CT. FDG PET/CT showed intense FDG uptake (SUVmax, 24.5) of the left supraclavicular and retroperitoneal lymph node metastases, suggesting FDG PET/CT may be useful for staging of this aggressive tumor.
Detection of novel orthoparamyxoviruses, orthonairoviruses and an orthohepevirus in European white-toothed shrews
Authors: Haring Viola C. , Litz Benedikt , Jacob Jens , Brecht Michael , Bauswein Markus , Sehl-Ewert Julia , Heroldova Marta , Wylezich Claudia , Hoffmann Donata , Ulrich Rainer G. , Beer Martin , Pfaff Florian
Published: August 2024

Graphical Abstract
ClinGen Hereditary Cardiovascular Disease Gene Curation Expert Panel: Reappraisal of Genes associated with Hypertrophic Cardiomyopathy
Authors: Hespe Sophie , Waddell Amber , Asatryan Babken , Owens Emma , Thaxton Courtney , Adduru Mhy-lanie , Anderson Kailyn , Brown Emily , Hoffman-Andrews Lily , Jordan Elizabeth , Josephs Katherine , Mayers Megan , Peters Stacey , Stafford Fergus , Bagnall Richard Douglas , Bronicki Lucas , Callewaert Bert , Chahal C. Anwar , James Cynthia A. , Jarinova Olga , Landstrom Andrew P , McNally Elizabeth M. , Murray Brittney , Muiño-Mosquera Laura , Parikh Victoria N. , Reuter Chloe , Walsh Roddy , Wayburn Bess , Ware James , Ingles Jodie
Published: August 2024

Background: Hypertrophic cardiomyopathy (HCM) is an inherited cardiac condition affecting ~1 in 500 and exhibits marked genetic heterogeneity. Previously published in 2019, 57 HCM-associated genes were curated providing the first systematic evaluation of gene-disease validity. Here we report work by the ClinGen Hereditary Cardiovascular Disorders Gene Curation Expert Panel (HCVD-GCEP) to reappraise the clinical validity of previously curated and new putative HCM genes. Methods: The ClinGen systematic gene curation framework was used to re-classify the gene-disease relationships for HCM and related syndromic entities involving left ventricular hypertrophy. Genes previously curated were included if their classification was not definitive, and if the time since curation was >2-3 years. New genes with literature assertions for HCM were included for initial evaluation. Existing genes were curated for new inheritance patterns where evidence existed. Curations were presented on twice monthly calls, with the HCVD-GCEP composed of 29 individuals from 21 institutions across 6 countries. Results: Thirty-one genes were re-curated and an additional 5 new potential HCM-associated genes were curated. Among the re-curated genes, 17 (55%) genes changed classification: 1 limited and 4 disputed (from no known disease relationship), 9 disputed (from limited), and 3 definitive (from moderate). Among these, 3 (10%) genes had a clinically relevant upgrade, including TNNC1, a 9th sarcomere gene with definitive HCM association. With new evidence, two genes were curated for multiple inheritance patterns (TRIM63, disputed for autosomal dominant but moderate for autosomal recessive; ALPK3, strong for autosomal dominant and definitive for recessive). CSRP3 was curated for a semi-dominant mode of inheritance (definitive). Nine (29%) genes were downgraded to disputed, further discouraging clinical reporting of variants in these genes. Five genes recently reported to cause HCM were curated: RPS6KB1 and RBM20 (limited), KLHL24 and MT-TI (moderate), and FHOD3 (definitive). Conclusions: We report 29 genes with definitive, strong or moderate evidence of causation for HCM or isolated LVH, including sarcomere, sarcomere-associated and syndromic conditions.
Applications of ICG in Breast Cancer for Sentinel Lymph Node Mapping: A Scoping Review Protocol
Authors: Kurdi Feryal N. , Kurdi Yahya N. , Reshetov Igor V.
Published: August 2024

Objective

The objective of this scoping review is to evaluate the current literature on the use of Indocyanine Green (ICG) in sentinel lymph node (SLN) mapping for breast cancer patients. This review aims to assess the accuracy, efficacy, and safety of ICG in this context and to identify gaps in the existing research. The outcomes will contribute to the development of further research as part of a PhD project.

Introduction

Breast cancer is the leading cause of morbidity and mortality worldwide. Accurate SLN mapping is crucial for staging and treatment planning in early-stage breast cancer. ICG has emerged as a promising agent for fluorescence imaging in SLN mapping. However, comprehensive assessment of its clinical utility, including accuracy and adverse effects, remains limited. This scoping review aims to consolidate evidence on the use of ICG in breast cancer SLN mapping.

Inclusion criteria

Patients with early-stage breast cancer (T1, T2), selected T3 cases where sentinel lymph node biopsy is accurate, and clinically node-negative breast cancer. The intervention includes studies using ICG for SLN mapping and assessment of fluorescence imaging cameras.

Methods

Five electronic databases will be searched (PubMed, EMBASE, MEDLINE, Web of Science, and SCOPUS) using search strategies developed in consultation with the academic supervisor. The search strategy is set to human studies published in English within the last 11 years. All retrieved citations will be imported to Zotero and then uploaded to Covidence for screening of titles, abstracts, and full text according to pre-specified inclusion criteria. Citations meeting the inclusion criteria for full-text review will have their data extracted by two independent reviewers, with disagreements resolved by discussion. A data extraction tool will be developed to capture full details about the participants, concept, and context, and findings relevant to the scoping review will be summarized.
Helping Breast Cancer Diagnosis on Mammographies using Convolutional Neural Networks
Authors: García-Mojón Rocío , Martín-Rodríguez Fernando , Fernández-Barciela Mónica
Published: August 2024

In this paper a study about breast cancer detection is presented. Mammography images in DICOM format are processed using Convolutional Neural Networks (CNN’s) to get a pre-diagnosis. Of course, this preliminary result needs to be checked by a trained radiologist. CNN’s are trained and checked using a big database that is publicly available. Standard measurements for success are computed (accuracy, precision, recall) obtaining outstanding results better than other examples from the literature.
Study on the Situation of Growth and Development of Kindergarten Children and the Relationship between Vitamin D and Body Composition, Chengdu, Sichuan Province, China
Authors: Wang Yanli , Ren Ying , Xing Fenglin , Liu Dan , Hu Mengjuan , Tongyong Luo
Published: August 2024

Vitamin D plays a critical role in bone health, mineral metabolism, and overall well-being, including immune function and muscle strength. Its potential impact on body composition in children, particularly in relation to obesity and undernutrition, is an area of growing interest. However, existing literature presents inconsistent findings regarding the correlation between Vitamin D levels and body composition parameters in pediatric populations. The aim of this study was to explore the relationship between Vitamin D levels and body composition among kindergarten-aged children in Chengdu, Sichuan Province, China, providing insights that could contribute to health promotion strategies for this demographic.A cross-sectional study was conducted among children aged 3 to 6 years across 47 kindergartens in Chengdu. Participants were selected via stratified random sampling to ensure representativeness. Data collection took place during April to June to minimize seasonal effects on Vitamin D levels. Body composition was assessed using bio-electrical impedance analysis (BIA). Vitamin D status was determined through blood tests, and the distribution of Vitamin D levels by sex and age groups was analyzed. The study included 1239 children, with 75.54% having insufficient Vitamin D levels and 24.46% having sufficient levels. There was no statistically significant difference in Vitamin D status between sexes (χ2=0.676, p=0.411) or age groups (χ2=4.700, p=0.095). Correlation analysis revealed that BMI had a weak negative correlation with Vitamin D (−0.028, p=0.320) but no significant correlation with Vitamin A (−0.007, p=0.799). Similar results were observed for other body composition components. This study suggests that a majority of kindergarten children in Chengdu have insufficient Vitamin D levels, regardless of sex or age. While some correlations between Vitamin D levels and body composition were observed, they were weak and not clinically significant. Further research is needed to elucidate the complex interplay between Vitamin D, body composition, and other influencing factors in this age group. Our findings contribute to the ongoing debate about the role of Vitamin D in pediatric health and may guide future interventions aimed at improving Vitamin D status and overall body composition in children.
Determinants of sexual and reproductive empowerment: a cross-national analysis in five Sub-Saharan African countries
Authors: Moreau Caroline , Karp Celia , Wood Shannon N. , Guiella Georges , Gichangi Peter , Makumbi Frederick , Mosso Rosine , Oumarou Sani , Zimmerman Linnea
Published: August 2024

Research has shown inconsistent associations between women’s empowerment and sexual and reproductive health (SRH) in sub-Saharan Africa (SSA), pointing to a lack of salient measures in this context. A novel measure provides an opportunity to explore different facets of SRH empowerment in SSA.

Methods

We used five national surveys among women 15-49 years conducted between 2019-2020 in Kenya (n=5,504), Uganda (n=2,273), Cote d’Ivoire (n=2,329), Burkina Faso (n=4,135), and Niger (n=2,228). Two measures of contraceptive and sexual empowerment were combined into a four-category SRH empowerment measure to identify the opportunity structures associated with SRH empowerment using multinomial logistic regression modeling.

Results

SRH empowerment was lowest in Niger and highest in Kenya. Between 15.0% and 21.7% of participants had more sexual but less contraceptive empowerment than their peers, while the opposite was true for 15.4% to 20.4% of participants. Education increased overall SRH empowerment or sexual empowerment alone in all sites and contraceptive empowerment alone in Kenya. Wealth increased overall SRH empowerment or sexual empowerment alone in three sites. Parity increased overall empowerment or contraceptive empowerment alone in all sites but decreased sexual empowerment alone in Uganda. Finally, healthcare provider contact increased overall and contraceptive empowerment in four sites while family planning media messages increased overall empowerment in two sites.

Conclusion

This study confirms the multidimensional nature of SRH empowerment, which varies by country, domain, and by women’s parity and social capital. Longitudinal research is needed to comprehend how women gain or lose SRH empowerment and how empowerment predicts SRH outcomes.
Citizen science informs demand-driven breeding of opportunity crops
Authors: Voss Rachel C. , de Sousa Kauê , N’Danikou Sognigbé , Shango Abdul , Aglinglo Lys Amavi , Laporte Marie-Angélique , Legba Eric C. , Houdegbe Aristide Carlos , Diarra Danfing dit Youssouf , Dolo Aminata , Sidibe Amadou , Ouedraogo Colette , Coulibaly Harouna , Achigan-Dako Enoch G. , Kileo Aishi , Malulu Dickson , Matumbo Zamira , Dinssa Fekadu , van Heerwaarden Joost , van Etten Jacob , Riar Amritbir , van Zonneveld Maarten
Published: August 2024

CONTEXT

Opportunity crops, also known as neglected and underutilized species (NUS), offer benefits to diversify food systems with nutritious and climate-resilient foods. A major limitation to incorporate these crops in farming systems is the lack of improved varieties impedes farmers accessing quality planting material of these crops.

OBJECTIVES

The study explored how citizen science methods can support demand-driven breeding and seed production of opportunity crops using leafy amaranth – a nutritious and hardy vegetable- as a case study. The study identified farmer preferences and market segments, with particular attention to gender and social differentiation.

METHODS

We used the tricot approach to conduct participatory on-farm trials of 14 varieties with 2,063 farmers from Benin, Mali, and Tanzania. We then analyzed farmer trait and varietal preferences in aggregate and among segments of farmers, generated using cluster analysis.

RESULTS

Farmers’ overall preferences for amaranth varieties was driven principally by plant survival, yield, leaf size, taste, and marketability. Distinct farmer segments (older women generalists, young women specialists, older men generalists, and young men specialists) preferred different varieties depending on gender, business-orientation.

DISCUSSION AND CONCLUSION

The farmer segments identified here, along with their unique variety preferences provide valuable information for breeders and seed enterprises, and support demand-driven amaranth breeding and seed system development. We specifically noted the need for breeding programs to understand the preferences of young amaranth specialists, both men and women, and to explore organoleptic and market-related properties of amaranth.

SIGNIFICANCE

Our findings on differentiated producer preferences will support scaling seed supply of amaranth in Africa to diversify farming systems with a climate-resilient and nutritious crop. The methods used and lessons learned from our citizen science exercise can be applied to enhance breeding and seed supply of other opportunity crops that are underutilized in Africa or other continents.

Highlights

Farmer citizen science methods reveal seed market insights for opportunity crops

Amaranth variety preferences vary widely across gender, age, and countries

Young amaranth producers focus on market and sensory traits compared to old producers

Large-scale farmer feedback guides opportunity crop breeding for diverse segments
Beta-arrestin 1 mediated Src activation via Src SH3 domain revealed by cryo-electron microscopy
Authors: Pakharukova Natalia , Thomas Brittany N. , Bansia Harsh , Li Linus , Abzalimov Rinat R. , Kim Jihee , Kahsai Alem W. , Pani Biswaranjan , Bassford Dana K. , Liu Shibo , Zhang Xingdong , des Georges Amedee , Lefkowitz Robert J.
Published: August 2024

Beta-arrestins (βarrs) are key regulators and transducers of G-protein coupled receptor signaling; however, little is known of how βarrs communicate with their downstream effectors. Here, we use cryo-electron microscopy to elucidate how βarr1 recruits and activates non-receptor tyrosine kinase Src. βarr1 binds Src SH3 domain via two distinct sites: a polyproline site in the N-domain and a non-proline site in the central crest region. At both sites βarr1 interacts with the aromatic surface of SH3 which is critical for Src autoinhibition, suggesting that βarr1 activates Src by SH3 domain displacement. Binding of SH3 to the central crest region induces structural rearrangements in the β-strand V, finger, and middle loops of βarr1 and interferes with βarr1 coupling to the receptor core potentially impacting receptor desensitization and downstream signaling.

One-Sentence Summary

Beta-arrestin 1 uses two distinct sites to bind the SH3 domain of Src and drive relief of Src autoinhibition.
Contributions of genetic variation in astrocytes to cell and molecular mechanisms of risk and resilience to late onset Alzheimer’s disease
Authors: Lee Hyo , Pearse Richard V. , Lish Alexandra M. , Pan Cheryl , Augur Zachary M. , Terzioglu Gizem , Gaur Pallavi , Liao Meichen , Fujita Masashi , Tio Earvin S. , Duong Duc M. , Felsky Daniel , Seyfried Nicholas T. , Menon Vilas , Bennett David A. , De Jager Philip L. , Young-Pearse Tracy L.
Published: August 2024

Reactive astrocytes are associated with Alzheimer’s disease (AD), and several AD genetic risk variants are associated with genes highly expressed in astrocytes. However, the contribution of genetic risk within astrocytes to cellular processes relevant to the pathogenesis of AD remains ill-defined. Here we present a resource for studying AD genetic risk in astrocytes using a large collection of induced pluripotent stem cell (iPSC) lines from deeply phenotyped individuals with a range of neuropathological and cognitive outcomes. IPSC lines from forty-four individuals were differentiated into astrocytes followed by unbiased molecular profiling using RNA sequencing and tandem mass tag-mass spectrometry. We demonstrate the utility of this resource in examining gene- and pathway-level associations with clinical and neuropathological traits, as well as in analyzing genetic risk and resilience factors through parallel analyses of iPSC-astrocytes and brain tissue from the same individuals. Our analyses reveal that genes and pathways altered in iPSC-derived astrocytes from AD individuals are concordantly dysregulated in AD brain tissue. This includes increased prefoldin proteins, extracellular matrix factors, COPI-mediated trafficking components and reduced proteins involved in cellular respiration and fatty acid oxidation. Additionally, iPSC-derived astrocytes from individuals resilient to high AD neuropathology show elevated basal levels of interferon response proteins and increased secretion of interferon gamma. Correspondingly, higher polygenic risk scores for AD are associated with lower levels of interferon response proteins. This study establishes an experimental system that integrates genetic information with a heterogeneous set of iPSCs to identify genetic contributions to molecular pathways affecting AD risk and resilience.
HMCES corrupts replication fork stability during base excision repair in homologous recombination deficient cells
Authors: Peña-Gómez María José , Rodríguez-Martin Yaiza , Oliva Marta del Rio , Masson Jean Yves , Reyes José Carlos , Rosado Iván V.
Published: August 2024

Apurinic/apyrimidinic (AP) sites and single-strand breaks (SSB) arising from base excision repair (BER) during misincorporation of damaged nucleobases may hinder replication fork stability in homologous recombination-deficient (HRD) cells. At templated AP-sites, HMCES DNA-protein crosslinks (DPC) regulate replication fork speed while avoiding APE1-mediated cytotoxic double-strand breaks (DSB). Whereas the role of HMCES at template DNA strand is well studied, its consequences on nascent DNA are less understood. Here, we provide evidence that HMCES play detrimental roles during removal of 5- hydroxymethyl-2’-deoxycytidine (5hmdC)-derived 5-hydroxymethyl-2’-deoxyuridine (5hmdU) by BER at replication forks. HRD cells display heightened HMCES chromatin levels, which increase upon 5hmdC exposure, suggesting that HMCES binds both spontaneous and 5hmdC-induced AP-sites. HMCES depletion largely suppresses 5hmdC- mediatedFancd2-/-replication fork defects, chromosomal aberrations and cell lethality, suggesting that HMCES is responsible for the replication fork impairment and lethality observed in HRD cells. Therefore, HMCES-DPCs are a novel source of BER-initiated PRIMPOL-mediated ssDNA gaps, implying endogenous DPCs as a source of DNA damage in HRD tumours.

Teaser

Covalent binding of HMCES to nascent DNA blocks replication progression and kills homologous recombination deficient cancer cells
Modelling Protein-Glycan Interactions with HADDOCK
Authors: Ranaudo Anna , Giulini Marco , Ayuso Angela Pelissou , Bonvin Alexandre M. J. J.
Published: August 2024

The term glycan refers to a broad category of molecules composed of monosaccharides units linked to each other in a variety of ways, whose structural diversity is related to different functions in living organisms. Among others, glycans are recognized by proteins with the aim of carrying information and for signalling purposes. Determining the three-dimensional structures of protein-protein-glycan complexes is essential both for the understanding of the mechanisms glycans are involved in, and for applications such as drug design. In this context, molecular docking approaches are of undoubted importance as complementary approaches to experiments. In this study, we show how HADDOCK can be efficiently used for the prediction of protein-glycan complexes. Using a benchmark of 89 complexes, starting from their bound or unbound forms, and assuming some knowledge of the binding site on the protein, our protocol reaches a 70% and 40% top 5 success rate on bound and unbound datasets, respectively. We show that the main limiting factor is related to the complexity of the glycan to be modelled and the associated conformational flexibility.
Sex-chromosome-dependent aging in female heterogametic methylomes
Authors: Tangili Marianthi , Sudyka Joanna , Furni Fabricio , Palsbøll Per J. , Verhulst Simon
Published: August 2024

DNA methylation-based indices predict mortality and provide insights into aging mechanisms. Even though sex chromosomes are thought to play an important role in sex-specific aging, they have been largely ignored in epigenetic aging studies. We identified age-related CpG (AR-CpG) sites in the full methylomes of two avian species (zebra finch and jackdaw), including for the first time the avian sex chromosomes (Z and the female-specific, haploid W). In both species, we find a high concentration of AR-CpG sites on the W chromosome, with DNA methylation levels predominantly decreasing with age. Our results highlight distinct age-related changes in sex chromosome DNA methylation compared to the rest of the genome, suggesting that this feature of sex chromosomes may contribute to sex-dependent aging.
PRMT7 mediated PTEN activation promotes bone formation in female mice
Authors: Zhang Yingfei , Qing Jia , Li Yang , Gao Xin , Lu Dazhuang , Wang Yiyang , Gu Lanxin , Zhang Hui , Li Zechuan , Wang Xu , Zhou Yongsheng , Zhang Ping
Published: August 2024

Although the epigenetic mechanisms underlying bone formation are recognized, their specific roles and regulatory pathways remain largely unexplored. In this study, we unveil PRMT7 as a novel epigenetic modulator of MSCs’ osteogenic commitment. The conditional knockout ofPrmt7in mice reveals significantly impaired osteogenesis and bone regeneration exclusively in females, affecting both long bones and craniofacial structures, with no discernible impact in males. Our findings demonstrate that PRMT7 orchestrates osteogenic differentiation through a methyltransferase-dependent manner. Mechanistically, PRMT7 modulates MSCs’ osteogenic differentiation through the activation of PTEN. Specifically, PRMT7 augmentsPTENtranscription by increasing H3R2me1 levels at thePTENpromoter. Furthermore, PRMT7 interacts with the PTEN protein, and its deficiency leads to the ubiquitination and subsequent degradation of nuclear PTEN, revealing an unprecedented pathway. Crucially, PTEN overexpression ameliorates the osteogenic deficits observed inPrmt7-deficient mice. Our research positions PRMT7 as a potential therapeutic target to enhance bone formation and offers novel molecular insights into the PRMT7-PTEN regulatory axis, underscoring its significance in bone biology and regenerative medicine.

Subject CategoriesDevelopmental Biology, Musculoskeletal System, Epigenetics, Post-translational Modifications
Model-driven engineering ofYarrowia lipolyticafor improved microbial oil production
Authors: Duman-Özdamar Zeynep Efsun , Julsing Mattijs K. , Martins dos Santos Vitor A.P. , Hugenholtz Jeroen , Suarez-Diez Maria
Published: August 2024

Extensive usage of plant-based oils, especially palm oil, has led to environmental and social issues, such as deforestation and loss of biodiversity, thus sustainable alternatives are required. Microbial oils, especially fromYarrowia lipolytica, offer a promising solution due to their similar composition to palm oil, low carbon footprint, and ability to utilize low-cost substrates. In this study, we employed the Design-Build-Test-Learn (DBTL) approach to enhance lipid production inY. lipolytica. We systematically evaluated predictions from the genome-scale metabolic model to identify and overcome bottlenecks in lipid biosynthesis. We tested the effect of predicted medium supplements and genetic intervention targets, including the overexpression of ATP-citrate lyase (ACL), acetyl-CoA carboxylase (ACC), threonine synthase (TS), diacylglycerol acyltransferase(DGA1), the deletion of citrate exporter gene (CEX1) and disruption of β-oxidation pathway (MFE1). CombiningTSandDGA1overexpression in theΔmfe_Δcexbackground achieved a remarkable 200% increase in lipid content (56 % w/w) and a 230% increase in lipid yield on glycerol. These findings underscore the potential ofY. lipolyticaas an efficient microbial cell factory for fatty acid production. Our study advances the understanding of lipid metabolism inY. lipolyticaand demonstrates a viable approach for developing sustainable and economically feasible alternatives to palm oil.

Graphical Abstract

We followed the Design-Build-Test-Learn approach to identify and overcome bottlenecks in lipid biosynthesis inY. lipolytica. DBTL intertwined the predictions from the metabolic model with addressed bottlenecks, investigated the effect of genetic interventions and medium supplements on lipid content, and ultimately defined an efficient strain design strategy.
Comparative lifespan and healthspan of nonhuman primate species common to biomedical research
Authors: Huber Hillary F , Ainsworth Hannah C , Quillen Ellen E , Salmon Adam , Ross Corinna , Azhar Adinda D , Bales Karen , Basso Michele A , Coleman Kristine , Colman Ricki , Darusman Huda S , Hopkins William , Hotchkiss Charlotte E , Jorgensen Matthew J , Kavanagh Kylie , Li Cun , Mattison Julie A , Nathanielsz Peter W , Saputro Suryo , Scorpio Diana G , Sosa Paul-Michael , Vallender Eric J , Wang Yaomin , Zeiss Caroline J , Shively Carol A , Cox Laura A
Published: August 2024

There is a critical need to generate age- and sex-specific survival curves to characterize chronological aging consistently across nonhuman primates (NHP) used in biomedical research. Sex-specific Kaplan-Meier survival curves were computed in 12 translational aging models: baboon, bonnet macaque, chimpanzee, common marmoset, coppery titi monkey, cotton-top tamarin, cynomolgus macaque, Japanese macaque, pigtail macaque, rhesus macaque, squirrel monkey, and vervet/African green. After employing strict inclusion criteria, primary results are based on 12,269 NHP that survived to adulthood and died of natural/health-related causes. A secondary analysis was completed for 32,616 NHP that died of any cause. Results show a pattern of reduced male survival among catarrhines (African and Asian primates), especially macaques, but not platyrrhines (Central and South American primates). For many species, median lifespans were lower than previously reported. An important consideration is that these analyses may offer a better reflection of healthspan than lifespan since research NHP are typically euthanized for humane welfare reasons before their natural end of life. This resource represents the most comprehensive characterization of sex-specific lifespan and age-at-death distributions for 12 biomedically relevant species, to date. These results clarify relationships among NHP ages and provide a valuable resource for the aging research community, improving human-NHP age equivalencies, informing investigators of expected survival rates, providing a metric for comparisons in future studies, and contributing to understanding of factors driving lifespan differences within and among species.
Impact of aging on the GABAB receptor-mediated connectome
Authors: Vásquez Elena , Oresti Gerardo M. , Paez María D. , Callegari Eduardo A. , Masone Diego , Muñoz Estela M.
Published: August 2024

GABA B receptors (GABABRs) are heterodimeric seven-transmembrane receptors that interact with a range of proteins and form large protein complexes on cholesterol-rich membrane microdomains. As the brain ages, membrane cholesterol levels exhibit alterations, although it remains unclear how these changes impact protein-protein interactions and downstream signaling. Herein, we studied the structural bases for the interaction between GABABR and the KCC2 transporter, including their protein expression and distribution, and we compared data between young and aged rat cerebella. Also, we analyzed lipid profiles for both groups, and we used molecular dynamics simulations on three plasma membrane systems with different cholesterol concentrations, to further explore the GABABR-transporter interaction. Based on our results, we report that a significant decrease in GABAB2 subunit expression occurs in the aged rat cerebella. After performing a comparative co-immunoprecipitation analysis, we confirm that GABABR and KCC2 form a protein complex in adult and aged rat cerebella, although their interaction levels are reduced substantially as the cerebellum ages. On the other hand, our lipid analyses reveal a significant increase in cholesterol and sphingomyelin levels of the aged cerebella. Finally, we used the Martini coarse-grained model to conduct molecular dynamics simulations, from which we observed that membrane cholesterol concentrations can dictate whether the GABABR tail domains physically establish G protein-independent contacts with a transporter, and the timing when those associations eventually occur. Taken together, our findings illustrate how age-related alterations in membrane cholesterol levels affect protein-protein interactions, and how they could play a crucial role in regulating GABABR's interactome-mediated signaling.
Autophagy-mediated CTR1 turnover orchestrates the reciprocal interaction between autophagy and ethylene signaling
Authors: Park Hye Lin , Zhang Weiwei , Chien Yuan-Chi , Park Chanung , Yoon Gyeong Mee
Published: August 2024

The phytohormone ethylene and autophagy are crucial for plant adaptation to various environmental stresses, yet the integration of these signaling networks into stress responses is not fully understood. Here, we report that ethylene signaling and autophagy reciprocally regulate each other through Constitutive Triple Response 1 (CTR1), a negative regulator of ethylene signaling. Autophagy facilitates the turnover of the CTR1 protein, which interacts with the key autophagy-related protein ATG8 as autophagic cargo. Impaired autophagy attenuates ethylene responses. Conversely, ethylene-insensitive mutants exhibit enhanced autophagic flux, while a constitutive ethylene response mutant is hypersensitive to carbon starvation stress, which induces autophagy. This suggests that ethylene suppresses autophagy during carbon limitation. We further elucidated that ethylene receptors with a receiver domain play a primary role in modulating autophagy, while receptor kinase activity is not essential. Our findings uncover that the autophagic control of CTR1 degradation allows reciprocal cross-regulation between autophagy and ethylene transduction cascades, optimizing stress responses and resilience.
Interferon-induced activation state of circulating dendritic cells and monocytes triggered by yellow fever vaccination correlates with early protective antibody responses
Authors: Winheim Elena , Santos-Peral Antonio , Ehm Tamara , Rinke Linus , Riemer Sandra , Zaucha Magdalena , Goresch Sebastian , Lehmann Lisa , Eisenächer Katharina , Pritsch Michael , Barba-Spaeth Giovanna , Straub Tobias , Rothenfusser Simon , Krug Anne B.
Published: August 2024

Yellow fever vaccination provides long-lasting protection and is a unique model for studying the immune response to an acute RNA virus infection in humans. To elucidate the early innate immune events preceding the rapid generation of protective immunity, we performed transcriptome analysis of human blood dendritic cell (DC) and monocyte subpopulations before and 3, 7, 14 and 28 days after vaccination. We detected temporary upregulation of IFN-stimulated genes (ISG) in all DC and monocyte subsets on day 3 and 7 after vaccination as well as cell type specific responses and temporal dynamics. Single cell RNA sequencing revealed rapid appearance of activated DC and monocyte clusters dominated by ISGs, inflammatory chemokines and genes involved in antigen processing and presentation. This was confirmed by flow cytometric analysis in a large cohort of vaccinees. We identified SIGLEC1/CD169 upregulation as a sensitive indicator of the transient IFN-induced activation state elicited in DCs and monocytes by YF17D vaccination correlating with early protective IgM antibody responses.