bluuebunny/crossref_metadata_2025 huggingface dataset:
Online Screening and Virtual Patient Education for Hereditary Cancer Risk Assessment and Testing
Authors: Waldman Richard N. , DeFrancesco Mark S. , Feltz John P. , Welling Daniel S. , Neiman Wade A. , Pearlstone Melissa M. , Marraccini Christine A. , Karanik Dana , Mielcarski Elaine , Schneider Logan , Lenz Lauren , Smith Edith C. , Taber Katherine Johansen , Adkins Royce T.
Published: December 2024

OBJECTIVE:

To use online screening and virtual patient education tools to improve the provision of hereditary cancer risk assessment.

METHODS:

We conducted a prospective, single-arm study in which clinicians at five U.S. community obstetrics and gynecology practices underwent an 8-week observation followed by 3−4 weeks of training on online patient screening and virtual patient education (prerecorded video with or without a genetic counselor phone call) for genetic testing–eligible patients. After a 4-week practice period, hereditary cancer risk assessment and patient education metrics were collected at 8 weeks and compared with preintervention metrics using univariate conditional logistic regression models stratified by site. The primary outcome was the change in genetic testing completion rate. Clinicians and patients were invited to complete a satisfaction survey.

RESULTS:

A total of 5,795 and 5,135 patients were seen before and after the intervention, respectively. The proportion of screened patients meeting testing guidelines increased from 21.6% before the intervention to 28.2% after the intervention (odds ratio [OR] 1.36, 95% CI, 1.26–1.47, P<.001). Guideline-eligible patients were significantly more likely to be offered genetic testing (59.1% vs 89.1%, OR 2.06, 95% CI, 1.87–2.27, P<.001), to submit a sample (32.9% vs 45.0%, OR 1.49, 95% CI, 1.27–1.74, P<.001), and to complete testing (16.0% vs 34.2%, OR 2.38, 95% CI, 2.00–2.83, P<.001). Most clinicians agreed or strongly agreed that the screening tool improved the identification of patients meeting hereditary cancer risk assessment guidelines (92.1%), saved time (64.9%), and was easy to incorporate (68.4%) and that patient education improved their ability to deliver hereditary cancer risk assessment standard of care (84.2%). Most patients agreed or strongly agreed that virtual education helped them understand the purpose (91.7%) and implications (92.6%) of genetic testing.

CONCLUSION:

A guideline-based online patient screening tool and virtual patient education were well received. The online tool enabled identification of significantly more guideline-eligible candidates for hereditary cancer risk assessment, and education improved patients' genetic literacy. Together, these tools ultimately improved the genetic testing completion rate.
Assessing the value of liver fibrosis scores in hypertension: findings from a cross-sectional study
Authors: Xiong Shengjun , Li Wenhang , Yin Shizhang , Deng Wanshu , Zhao Yuanhui , Wang Pengbo , Guo Xiaofan , Sun Yingxian , Yang Hongmei
Published: December 2024

Background and purpose:

Hypertension is the most significant modifiable risk factor for all-cause morbidity worldwide and is associated with an increased risk of cardiovascular disease. To alleviate the public health burden of hypertension, early identification of risk factors and preventive strategies is vital. Liver fibrosis scores (LFSs), which serve as non-invasive alternatives to liver biopsy, are commonly used to assess liver disease. Growing evidence demonstrated that liver disease may contribute to various systemic adverse effects, such as inflammation and activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system, play a critical role in the pathophysiology of hypertension. This study aims to explore the relationship between LFSs and hypertension.

Methods:

A total of 11,503 participants from the Northeast China Rural Cardiovascular Health Study, which is a large prospective cross-sectional research consisting of a community all coming from rural areas, were included in this study. Four different LFSs were utilized: the aspartate aminotransferase (AST)/platelet ratio index (APRI); the BARD score (incorporating body mass index [BMI], AST/alanine aminotransferase [ALT] ratio, and diabetes status); the BAAT score (BMI, age, ALT, and triglycerides [TGs]); and the fibrosis-4 (FIB-4) index. Logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CI). Subgroup analysis was conducted to examine associations between LFSs and hypertension across different stratifications, while restricted cubic spline analysis demonstrated the linear correlation between LFSs and hypertension risk. The C statistic, net reclassification index (NRI), and integrated discrimination improvement (IDI) were calculated to evaluate the impact of each LFS on hypertension risk prediction.

Results:

Baseline data identified that all four LFSs were higher among participants with hypertension. In multivariate logistic regression analysis, the OR for hypertension was as follows: 2.34 (95% CI: 1.95–2.81) for FIB-4, 1.34 (95% CI: 1.17–1.53) for the BARD score, 1.21 (95% CI: 1.03–1.43) for APRI, and last 1.21 (95% CI: 1.00–1.47) for the BAAT score, comparing high and low levels of each LFS. Adding LFSs to the original risk prediction model improved its predictive accuracy, with higher C-statistics and positive NRI and IDI values, indicating a significant enhancement in risk prediction for hypertension.

Conclusion:

This study demonstrates that LFSs are related to hypertension in individuals aged 35 and older in rural northeastern China.
Prognostic value of red blood cell distribution width-to-albumin ratio in patients with stable coronary artery disease stratified by glucose metabolic status: a prospective cohort study
Authors: Liu Huihui , Guo Yuanlin , Zhu Chenggang , Wu Naqiong , Gao Ying , Xu Ruixia , Dong Qian , Qian Jie , Li Jian-Jun
Published: December 2024

Background and purpose:

The red blood cell distribution width-to-albumin ratio (RAR) has emerged as a prognostic marker in various cardiovascular conditions. This investigated the association between RAR and cardiovascular outcomes in patients with stable coronary artery disease (SCAD), with a focus on variations across glucose metabolism status, a relationship not previously explored.

Methods:

A cohort of 4,266 consecutive SCAD patients was recruited and stratified into quartiles based on RAR levels. All participants were regularly monitored for major adverse cardiovascular events (MACEs), encompassing cardiovascular mortality, non-fatal myocardial infarction, and ischemic stroke. Cox regression analyses and glucose metabolic stratification were employed to assess the correlation between RAR and MACEs.

Results:

Over a mean follow-up of 52.77 ± 20.13 months, 287 MACEs were documented. Multivariate Cox regression analysis revealed a significant association between RAR and MACEs, both as a continuous variable and across quartiles. Patients in the third (Q3) and fourth (Q4) RAR quartiles exhibited a 1.92-fold (95% confidence interval [95% CI]: 1.05–3.52) and 2.01-fold (95% CI: 1.10–3.69) increased risk of MACEs, respectively, compared to those in the first quartile (Q1). Stratified analysis by glucose metabolic status further demonstrated that the correlation between higher RAR and MACEs was primarily observed among individuals with abnormal glucose regulation (AGR), particularly in those with diabetes mellitus.

Conclusions:

RAR served as a robust predictor of MACE risk in SCAD patients, with enhanced prognostic significance in individuals with AGR, especially in those with diabetes mellitus. These findings highlight RAR’s potential as a simple and effective risk stratification tool for high-risk SCAD patients.
In Vivo and Ex Vivo Evaluation of a Novel Method for Topical Delivery of Macromolecules Through the Stratum Corneum for Cosmetic Applications
Authors: Moradi Amir , Bhatia Ashish C. , Behr Kathleen , Napekoski Karl , Foldvari Marianna
Published: December 2024

BACKGROUND

Effective topical delivery of large/charged molecules into skin has always been challenging. Chemical penetration enhancers, organic substances that increase permeability of skin, have been in use for decades with variable success. One application of enhancers involves multilamellar vesicles composed of submicron emulsion droplets and micelles surrounded by concentric phospholipid bilayers.

OBJECTIVE

This report introduces the next generation of multilamellar vesicles, termed Tiered-Release Vesicles (TRVs), as a new platform for topical delivery of macromolecules such as peptides and hyaluronic acid (HA).

METHODS

Fluorescently labeled peptides and HA, diffusion cells, and confocal microscopy were employed to assess the penetration efficiency of macromolecules in TRV formulations using an ex vivo human skin model. Two in vivo studies utilized punch biopsies followed by histochemical staining and analysis.

RESULTS

Based on fluorescent intensity, TRV formulations delivered a large peptide more completely (2–5 fold) into ex vivo human skin than optimized liposomes. The penetration of 2 HA species in TRV formulations was 3- to 13-fold higher than with a simple gel vehicle. In the case studies, reduction of solar elastosis was observed from a topical TRV formulation.

CONCLUSION

Topical delivery of large peptides and HA into human skin using TRV technology has been demonstrated.
A Decadal Exploration of Cutaneous Adverse Effects of FDA-Approved Cardiovascular Medications: Insights From 2013 to 2023
Authors: Jallorina Anika , Vij Kunal , Wan Leo , Thomas Joson , Drum David , Glick Sharon A. , Lee-Wong Mary F.
Published: December 2024

Given the high prevalence of cardiovascular disease in the United States, there is a critical need for new medications to improve the outcomes of these diseases. The US Food and Drug Administration has approved numerous medications that are able to effectively do so. While these drugs have significantly beneficial effects, just like any other medication, they can come with a multitude of unwanted side effects. It has been noted that cardiovascular drugs have been associated with a considerable number of dermatologic reactions. This review examines current literature on the various cutaneous manifestations of these adverse reactions. It focuses on these newly Food and Drug Administration–approved cardiovascular medications from 2013 to 2023, detailing both common and rare effects in the past decade. As more medications continue to enter the market, the necessity for awareness of more systemic side effects will continue to grow. This comprehensive review aims to guide clinicians in identifying drug-induced reactions in patients on these therapies.
Secondary Revision after Breast Reconstruction with Free Abdominal Perforator Flap: Flap Liposuction and Inframammary Fold Reconstruction
Authors: Okumura Seiko , Maruyama Yoko , Nakamura Ryota , Takanari Keisuke , Hyodo Ikuo , Iwata Hiroji , Kamei Yuzuru
Published: December 2024

Background:

In breast reconstruction using the abdominal perforator flap, if the flap capacity is too large, secondary revision procedures can be performed to reduce flap volume and reconstruct the inframammary fold (IMF). We examined the various revision methods and cosmetic results.

Methods:

This study included 28 patients who underwent secondary revision among 216 patients who had breast reconstruction using the abdominal perforator flap between April 2012 and March 2019. The revision method, removal ability, and the inferior breast point (IBP) were analyzed using medical records.

Results:

Revision methods included incision resection in 4 cases, liposuction (LS) in 22 cases, LS and simultaneous IMF reconstruction in 2 cases, and post-LS IMF reconstruction in 1 case. The average LS amount was 317 mL (range, 100 -–700 mL). In 22 patients who underwent LS, the difference in preoperative IBP was 1 cm or more in 19 (86.4%) cases and 1 cm or less in 3 (13.6%) cases. The difference in postoperative IBP was 1 cm or more in 12 (54.5%) cases and 1 cm or less in 10 (45.5%) cases. The receiver operating characteristic curve analysis revealed that the cutoff LS amount for a postoperative IBP difference of 1 cm or less was 375 mL.

Conclusions:

The IBP was increased due to the decrease in flap volume. Revisions were completed with no difference in the LS-only IBP, especially when the LS amount was less than 375 mL. If the removal of 375 mL or more is necessary, removal or reformation of the IMF can be considered. These findings can potentially guide the planning of surgical procedures.
Technical and Analytical Approach for Breast Reconstruction With IMAP Propeller Flap
Authors: Spaggiari Antonio , Morrison Wayne A. , Marra Caterina , Lusetti Irene Laura , Fiocchi Federica , Pinelli Massimo , De Santis Giorgio
Published: December 2024

Background:

The breast-sharing technique uses the lower quadrants discarded from a contralateral symmetrizing reduction mammoplasty to reconstruct the breast after mastectomy. The aim of our study was to revisit this old technique and to improve its vascular predictability by preoperative computed tomography angiography (angio-CT) and intraoperative indocyanine green (ICG) imaging.

Methods:

Twenty-six patients were enrolled and assessed by a preoperative angio-CT to localize and evaluate the internal mammary artery perforator (IMAP). In the selected patients, a Wise skin-pattern reduction was designed to allow elevation of a transversely oriented flap including both inferior poles. The flap was based medially on the IMAP. After elevation, evaluation of its arterial and venous perfusion was assessed with ICG.

Results:

Eight patients were excluded after pre- and intraoperative studies. Sixteen breast-sharing flaps were performed. A distal flap venous compromise appeared in 2 cases, requiring debridement and flap repositioning, and an infection occurred in 1 case. Four patients had detectable firm lumps that resolved. There were no issues with donor site healing, and a repositioning of the areola was necessary in 2 patients.

Conclusions:

Breast-sharing techniques have not gained popularity for many reasons. By combining current understanding of breast cancer behavior, experience with perforator anatomy, and angio-CT and ICG, we believe this study gives a second life to this flap, identifying its weaknesses and improving them. The IMAP propeller flap, simpler and safer in the presence of comorbidities than a free flap, can be a good choice for well-selected candidates.
IDO1 Expression and CD8+ T-Cell Levels Are Useful Prognostic Biomarkers in Preoperative Gastric Cancer Specimens Before Neoadjuvant Chemotherapy
Authors: Chen Hu , Zheng QiaoLin , Jiang Yiting , Lin Lin , Yang Yinghong
Published: December 2024

The tumor immune microenvironment occupies an important position in gastric cancer. In this study, we investigated the relationship between indoleamine 2,3-dioxygenase 1 (IDO1), programmed cell death 1 ligand (PD-L1) expressioon, and CD8+ T-cell levels and their efficacy and prognostic value in preoperative gastric cancer specimens before neoadjuvant chemotherapy (NAC). A total of 162 patients with locally advanced gastric cancer were collected in this study. IDO1, PD-L1 expression, and CD8+ T-cell levels in the biopsy samples was detected by immunohistochemical staining, and the relationship between these indexes and the patients’ clinicopathological parameters, chemotherapeutic efficacy, and prognosis were investigated. The IDO1 positivity rate was 43.2%. High expression of IDO1 was significantly associated with poor chemotherapeutic efficacy, lymph node metastasis (P<0.05). The PD-L1 positivity rate (using the combined positive score) was 38.2%, and was not related to any clinicopathological variable. Higher CD8+ T-cell levels were associated with a lower rate of lymph node metastasis and lower ypTNM stage (P<0.05). Higher CD8+ T-cell levels were negatively correlated with IDO1 expression (r=−0.224, P<0.05) and positively correlated with PD-L1 expression (r=0.254, P<0.05). Cox regression analysis demonstrated that higher CD8+ T-cell levels was an independent risk factor for overall survival (OS) and the expression of IDO1 had a significantly poorer disease-free survival (DFS). Overexpression of IDO1 and lower CD8+ T-cell levels were associated with poor survival in patients with gastric cancer who received neoadjuvant chemotherapy, and overexpression of IDO1 were associated with the poor tumor response. Our data suggest that IDO1 and CD8 testing of biopsy specimens might be a simple and effective prognostic biomarker for gastric cancer, and IDO1 could predict efficacy of neoadjuvant chemotherapy in gastric cancer.
The Value of Whole-Volume Radiomics Machine Learning Model Based on Multiparametric MRI in Predicting Triple-Negative Breast Cancer
Authors: Xu Tingting , Zhang Xueli , Tang Huan , Hua Ting , Xiao Fuxia , Cui Zhijun , Tang Guangyu , Zhang Lin
Published: December 2024

Objective

This study aimed to investigate the value of radiomics analysis in the precise diagnosis of triple-negative breast cancer (TNBC) based on breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and apparent diffusion coefficient (ADC) maps.

Methods

This retrospective study included 326 patients with pathologically proven breast cancer (TNBC: 129, non-TNBC: 197). The lesions were segmented using the ITK-SNAP software, and whole-volume radiomics features were extracted using a radiomics platform. Radiomics features were obtained from DCE-MRI and ADC maps. The least absolute shrinkage and selection operator regression method was employed for feature selection. Three prediction models were constructed using a support vector machine classifier: Model A (based on the selected features of the ADC maps), Model B (based on the selected features of DCE-MRI), and Model C (based on the selected features of both combined). Receiver operating characteristic curves were used to evaluate the diagnostic performance of the conventional MR image model and the 3 radiomics models in predicting TNBC.

Results

In the training dataset, the AUCs for the conventional MR image model and the 3 radiomics models were 0.749, 0.801, 0.847, and 0.896. The AUCs for the conventional MR image model and 3 radiomics models in the validation dataset were 0.693, 0.742, 0.793, and 0.876, respectively.

Conclusions

Radiomics based on the combination of whole volume DCE-MRI and ADC maps is a promising tool for distinguishing between TNBC and non-TNBC.
Candida tropicalis Liver Abscess in an Immunocompromised Patient With Pancreatic Head Cancer on 68Ga-FAPI PET/CT
Authors: Kim Jahae , Kim Seong Eun , Cho Eunae , Choi Kang-Ho
Published: December 2024

Candida infections have become a growing concern to the immunocompromised patients with cancer. We report a case of liver abscess causing Candida tropicalis candidemia in an immunocompromised patient with pancreatic head cancer on 68Ga-FAPI PET/CT. A 77-year-old man had a history of 10-year duration of uncontrolled diabetes, the presence of neutropenia, immunocompromised condition, and the progression of pancreatic cancer despite the 14 cycles of chemotherapy and palliative radiotherapy. After 3 weeks of radiotherapy, he presented with fever and elevated CRP level. 68Ga-FAPI PET/CT scan showed new intense uptake in the liver, and 2 pairs of blood culture revealed C. tropicalis.
Dog Bites With Resultant Periorbital Cellulitis
Authors: Graham Julie-Kathryn , Colio Pedro A.
Published: December 2024

This case study examines the delayed presentation of a facial dog bite, an uncommon occurrence in the periorbital area. Initially perceived as a minor injury, the wound was disregarded in its early stages. However, as the infection progressed, prompting urgent evaluation in the emergency department (ED) as the severity became evident. The patient was diagnosed with an acute facial infection carrying the potential for periorbital cellulitis and abscess formation, necessitating immediate imaging. Prompt evaluation of penetrating animal bites, particularly dog bites, is crucial due to their high infection risk. As emphasized by Hamed-Assam et al., immediate attention and prophylactic antibiotics are advised for such cases, preferably broad-spectrum antibiotics with anaerobic coverage. The patient underwent treatment in the ED approximately a day after the incident, receiving antibiotics and subsequently discharged following advanced diagnostic imaging. This case underscores the importance of recognizing and promptly addressing delayed dog bites, emphasizing the significance of immediate medical intervention post-penetrating animal bites.
Systematic Review of Integration Strategies Across the US Healthcare System: Assessment of Price, Cost, and Quality of Care
Authors: Satiani Bhagwan , Way David P , Hoyt David B , Ellison E Christopher
Published: December 2024

Background.

In the last 30 years, consolidation of healthcare systems in the United States has accelerated through mergers and acquisitions. We completed a systematic literature review on integration to determine if its reputation for enhancing the value of healthcare by reducing price and cost/spending and improving overall quality of care is justified.

Methods.

A systematic review of the literature was completed for articles published in the United States from 1990-2024. Primary inclusion criteria were horizontal integration (joining two or more hospitals) (HI) and vertical integration (merging of physicians and hospitals) (VI) and reporting on at least one measure of value (price, cost/spending, or quality)

Results.

Neither HI nor VI has resulted in consistent and significant improvements in price, cost/spending, or quality associated with healthcare delivery. We screened 1297 articles and identified 37 that met inclusion criteria. Results from any form of integration were mixed. Thirteen of 14 studies (93%) about price reported price increases. Thirteen of 16 studies (81%) about cost/spending showed cost increases or no change. Twenty of 26 studies (77%) about quality showed reductions or no change from integration (HI, VI or both).

Conclusions.

Our review suggests that evidence is lacking to support the theory that integration is an effective strategy for improving the value of healthcare delivery. This finding represents an opportunity for healthcare leaders, including surgeons, to better define value in their efforts to improve quality while balancing the financial stability of the healthcare industry with a focus on benefiting the patient.
Beyond Lectures: Leveraging Competition, Peer Discussion, and Real-World Scenarios in a Digital Card Game to Enhance Learning of Microbiology and Immunology Concepts
Authors: Dillon Michael James , Edwards James , Hughes Alexandra , Stephenson Holly N
Published: December 2024

Teaching the complex interactions between hosts and pathogens is a fundamental yet educationally challenging aspect of life science and healthcare education. The intricate mechanisms of the immune system can pose significant barriers to students’ understanding of infectious disease diagnosis and treatment. To address this, we used a web-based digital whiteboard platform to design a card-based competitive game called Micro-Immune Battles, aimed at more actively engaging students with microbiology and immunology to better develop their knowledge and underlying concepts.
The game facilitates learning through a series of infectious disease scenarios, providing student teams with "immune system response cards" that represent various immune elements. Working in teams, learners must construct sequential card cascades that correctly correspond to the specified pathogen in the scenario. This reinforces the temporal progression of immune responses, whilst encouraging the application of theoretical knowledge to practical cases. Scoring is determined by the accuracy and speed of card placements, incentivising rapid yet correct synthesis of knowledge. Points are deducted for incorrect placements, introducing an element of calculated risk-taking and critical reasoning. Analysis showed statistically significant improvements in microbiology and immunology knowledge after playing the game.
Dynamic modulation of IRE1α-XBP1 signaling by adenovirus
Authors: Jang Yumi , Bunz Fred
Published: December 2024

The abundant production of foreign proteins and nucleic acids during viral infection elicits a variety of stress responses in host cells. Viral proteins that accumulate in the endoplasmic reticulum (ER) can trigger the unfolded protein response (UPR), a coordinated signaling program that culminates in the expression of downstream genes that collectively restore protein homeostasis. The model pathogen adenovirus serotype 5 (HAdV5) activates the UPR via the signaling axis formed by inositol-requiring enzyme type 1 (IRE1α) and the X-box binding protein 1 (XBP1), a transcription factor required for immune function. Recent studies have suggested that IRE1α-XBP1 activity supports adenovirus replication. Here, we show that HAdV5 exerted opposing effects on IRE1α and XBP1. IRE1α was activated in response to HAdV5 but the production of the XBP1 isoform, XBP1s, was post-transcriptionally blocked. The tumor suppressor p53, which is eliminated by HAdV5 after infection, inhibited IRE1α activation. The de-repression of IRE1α following the degradation of p53 conceivably reflects a novel antiviral mechanism, which HAdV5 ultimately evades by suppressing XBP1s. Our findings highlight the defective antiviral defenses in cancer cells and further illustrate the opposing mechanisms used by adenoviruses and their host cells to exert control over the UPR, a critical determinant of cell fate.
Harmonising digitised herbarium data to enhance biodiversity knowledge: creating an updated checklist for the flora of Greenland
Authors: Whitley Brandon Samuel , Abermann Jakob , Alsos Inger Greve , Biersma Elisabeth M. , Gårdman Viktor , Høye Toke Thomas , Jones Laura , Khelidj Nora Meriem , Li Zhao , Losapio Gianalberto , Pape Thomas , Raundrup Katrine , Schmitz Paula , Silva Tiago , Wirta Helena , Roslin Tomas , Ahlstrand Natalie Iwanycki , de Vere Natasha
Published: December 2024

International efforts to digitise herbarium specimens provide the building blocks for a global digital herbarium. However, taxonomic changes and errors can result in inconsistencies when amalgamating specimen metadata, that compromise the assignment of occurrence records to correct taxa, and the subsequent interpretation of patterns in biodiversity. We present a novel workflow to mass-curate digital specimens. By employing existing digital taxonomic backbones, we aggregate specimen names by their accepted name and flag remaining cases for manual review. We then validate names using site-specific floras, balancing automation with taxonomic expert-based curation. Applying our workflow to the vascular plants of Greenland, we harmonised 175,266 digitised herbarium specimens and observations from 92 data providers from the Global Biodiversity Information Facility (GBIF). The harmonised metacollection for the Greenland flora contains 780 plant species. Our workflow increases the number of species known from Greenland compared to other currently available species checklists and increases the mean number of occurrences per species by 42.6. Our workflow illustrates the integration required in order to create a global, universally accessible digital herbarium, and shows how previous obstacles to database curation can be overcome through a combination of automation and expert curation. From the specific perspective of the Greenland flora, our approach arrives at a new checklist of taxa, a new curated metacollection of occurrence data, and revised estimates of plant richness. The list of taxa and their prevalence allow a new basis for biodiversity assessment and conservation planning.

Societal Impact Statement

Digitising plant collections has allowed for data to be aggregated across multiple collections, forming a single harmonised resource of unprecedented scale. This resource is only accurate once the database names are assigned to one accepted name per species. We established a semi-automated workflow for processing plant name data, leveraging taxonomic backbones and employing taxonomic expertise at key stages. Applying our workflow to the flora of Greenland, we developed a curated checklist of 780 species, capturing greater species richness than previously published, while also curating 175,266 plant records. Our findings redefine our knowledge of Greenlandic plant diversity, while harmonising a vast digital collection for further research.
Patient-derived HCC cells recapitulating the transcriptomic landscape of primary HCV-related liver cancer
Authors: Kah Janine , Staffeldt Lisa , Volz Tassilo , Schulze Kornelius , Heumann Asmus , Rövenstrunk Götz , Goebel Meike , Peine Sven , Dandri Maura , Lüth Stefan
Published: December 2024

Background

The hepatocellular carcinoma is one of the leading causes of cancer-related mortality and is characterized by high heterogeneity and subsequently adaptation by developing resistance to current treatments. In this scenario the application of individualized models is crucial to understand the potential of approved therapies. Recently, we established a series of individual cell lines derived from patients who developed HCC on different entities, serving as a platform for individual approaches. In this study, we classified the LC4 cells derived from the center region of a HCC with underlying HIV-HCV co-infection, by using deep analysis on the pathway regulation level.

Methods

We employed DEG analysis, followed by pathway analysis to characterize the preservation level of the LC4 cells and the level of adoption. Next, we classify the model, by employing healthy donor samples, commonly used HCC cell lines and global RNAseq data sets.

Results

We showed that the LC4 cells reflect significant characteristics of the parental region, including the replication of the immuno-suppressive and the proliferative milieu. The LC4 cells exhibit a metabolic reprogramming characterized by the downregulation of drug-metabolizing CYP enzymes compared to healthy individuals, indicating a transition to alternate metabolic pathways. Moreover, we identified common Biomarkers in the parental tissue, global datasets and the LC4 cells.

Conclusion

We showed that the LC4 cell line is applicable as an individual model for pre-clinical testing of treatment regimens in HCC driven research.
A single-cell atlas of transcriptome changes in the intestinal epithelium at the suckling-to-weaning transition
Authors: Malonga Tania , Knudsen Christelle , Lhuillier Emeline , Aymard Patrick , Jones Elisabeth , Lencina Corinne , Despeyroux Manon , Riant Elodie , Cabau Cédric , Ivy Alyssa , Loving Crystal L. , Vialaneix Nathalie , Beaumont Martin
Published: December 2024

The suckling-to-weaning dietary transition is a key step in mammalian intestinal development. However, the relative contributions of genetically wired and nutritional factors in this maturation process remain to be elucidated. Moreover, the cellular diversity of the intestinal epithelium has been overlooked in this context. The aim of our study was to identify the transcriptome changes induced in each cell type of the intestinal epithelium at the onset of solid food ingestion. We compared the single-cell transcriptome of epithelial cells isolated from the caecum of age-matched littermate suckling rabbits ingesting or not solid food. Our dataset provides the first single-cell atlas of the rabbit intestinal epithelium and highlights the interest of the rabbit as a model for studying BEST4+epithelial cells, which are absent in mice. Solid food ingestion induced extensive transcriptome changes in each epithelial cell type, with the most pronounced changes noted in absorptive and BEST4+cells. Some of the effects of solid food introduction were common to most epithelial cell types, such as the upregulation ofALDH1A1, which encodes for a vitamin A processing enzyme. Solid food ingestion remodeled epithelial defenses systems, as observed by the increased expression of interferon-stimulated genes in mature absorptive and BEST4+cells. Solid food also upregulated the gene expression of the immunoglobulin transporterPIGR, specifically in cells located at the base of epithelial crypts and in goblet cells. In addition, solid food triggered epithelial differentiation, which was associated with modification of the expression of genes involved in handling of amino acids, lipids and bile acids, as well as changes in hormone expression by enteroendocrine cells. These cell type-specific transcriptome modifications induced by solid food ingestion coincided with changes in microbiota composition and metabolic activity, which may contribute to epithelial maturation. Overall, our work provides a single-cell atlas of the transcriptome changes induced in the intestinal epithelium at the suckling-to-weaning transition.
Anti-biofilm activity of new low molecular weight compounds produced byLactiplantibacillus plantarumSJ33 againstKlebsiella pneumoniae
Authors: Mohapatra Amrita Ray , Lakshmanan Divya , Jeevaratnam Kadirvelu
Published: December 2024

Community-acquired infections are partly attributed to biofilms formed by drug resistant bacteria signifying major health problems. Hence, there is a critical need for the development of new antibiotics with antibacterial activities. In this study, we investigated the biofilm inhibiting characteristics of antibacterial compounds C1 and C2 confirmed as (3-amino-5-hydroxy-6-(hydroxymethyl)-4-(1-hydroxyprop-2-yn-1-yl)-3,3a,4,5,6,7a-hexahydro-7H-indazol-7-one) and (1-(dimethylamino)-3-hydroxy-3-((2-hydroxypropan-2-yl)oxy)-1 (methylamino)butan-2-one) which were previously characterized and identified by our group. This compound exhibits antibacterial activity against Gram-negative bacteria including activity against clinical isolates ofKlebsiella pnemoniaeandEscherichia coli. Bactericidal activity againstK. pnemoniaewas revealed by scanning electron microscopic (SEM) images that showed cellular leakage by C1 and C2 which is probably the major cause of its antibacterial activity. These findings were supported by antibacterial assays of susceptible as well as resistant pathogens. Biofilm assays also proved anti-biofilm activity of C1 and C2 on biofilm inhibition as well as dispersion of mature biofilms using crystal violet assay and the results were confirmed by fluorescence and SEM observation. In conclusion, our results showed that C1 and C2 exert bactericidal action on target cells by membrane disruption. Biofilm inhibition and dispersion of preformed biofilms was also revealed by microscopic images, making it an interesting alternative for commercial antibiotics for the development of new antibacterial therapies. The bioactive compounds C1 and C2 not only inhibitK. pnemoniaegrowth but also eradicate the biofilm formation thus reducing the virulence ofK. pnemoniaepathogen.
Time is encoded by methylation changes at clustered CpG sites
Authors: Ochana Bracha-Lea , Nudelman Daniel , Cohen Daniel , Peretz Ayelet , Piyanzin Sheina , Gal Ofer , Horn Amit , Loyfer Netanel , Varshavsky Miri , Raisch Ron , Shapiro Ilona , Friedlander Yechiel , Hochner Hagit , Glaser Benjamin , Dor Yuval , Kaplan Tommy , Shemer Ruth
Published: December 2024

Age-dependent changes in DNA methylation allow chronological and biological age inference, but the underlying mechanisms remain unclear. Using ultra-deep sequencing of >300 blood samples from healthy individuals, we show that age-dependent DNA methylation changes are regional and occur at multiple adjacent CpG sites, either stochastically or in a coordinated block-like manner. Deep learning analysis of single-molecule patterns in two genomic loci achieved accurate age prediction with a median error of 1.46-1.7 years on held-out human blood samples, dramatically improving current epigenetic clocks. Factors such as gender, BMI, smoking and other measures of biological aging do not affect chronological age inference. Longitudinal 10-year samples revealed that early deviations from epigenetic age are maintained throughout life and subsequent changes faithfully record time. Lastly, the model inferred chronological age from as few as 50 DNA molecules, suggesting that age is encoded by individual cells. Overall, DNA methylation changes in clustered CpG sites illuminate the principles of time measurement by cells and tissues, and facilitate medical and forensic applications.

Abstract Figure
Pulmonary granuloma formation during latentCryptococcus neoformansinfection in C3HeB/FeJ mice involves progression through three immunological phases
Authors: Betancourt Jovany J. , Ding Minna , Yoder J. Marina , Mutyaba Issa , Atkins Hannah M. , de la Cruz Gabriella , Meya David B. , Nielsen Kirsten
Published: December 2024

Cryptococcus neoformansis a fungal pathogen that can cause lethal disease in immunocompromised patients. Immunocompetent host immune responses, such as formation of pulmonary granulomas, control the infection and prevent disseminated disease. Little is known about the immunological conditions establishing the latent infection granuloma in the lungs. To investigate this, we performed an analysis of pulmonary immune cell populations, cytokine changes, and granuloma formation during infection with a latent disease-causing clinical isolate in C3HeB/FeJ mice over 360 days. We found that latently infected mice progress through three phases of granuloma formation where different immune profiles dominate: an early phase characterized by eosinophilia, high IL-4/IL-13, andC. neoformansproliferation in the lungs; an intermediate phase characterized by multinucleated giant cell formation, high IL-1α/IFNγ, granuloma expansion, and increased blood antigen levels; and a late phase characterized by a significant expansion of T cells, granuloma condensation, and decreases in lung fungal burden and blood antigen levels. These findings highlight a complex series of immune changes that occur during the establishment of granulomas that controlC. neoformansin the lungs and lay the foundation for studies to identify critical beneficial immune responses to Cryptococcus infections.

IMPORTANCE

Cryptococcus neoformansis a fungal pathogen that disseminates from the lungs to the brain to cause fatal disease. Latent C. neoformansinfection in the lungs is controlled by organized collections of immune cells called granulomas. The formation and structure of Cryptococcus granulomas are poorly understood due to inconsistent human pathology results and disagreement between necrotic granuloma-forming rat models and non-necrotic granuloma-forming mouse models. To overcome this, we investigated granuloma formation during latentC. neoformansinfection in the C3HeB/FeJ mouse strain which forms necrotic lung granulomas in response to other pathogens. We found that latentC. neoformansgranuloma formation progresses through phases that we described as early, intermediate, and late with different immune response profiles and granulomatous characteristics. Ultimately, we show that C3HeB/FeJ mice latently infected withC. neoformansform non-necrotic granulomas and could provide a novel mouse model to investigate host immune response profiles.
Prevalence of antimicrobial resistance phenotypes and genes in stable fly- and manure-derived bacterial isolates from clinically relevant taxa in dairy settings
Authors: Sommer Andrew J. , Kettner Julia E. , Worley Travis K. , Petrick Jordan , Haynie Caroline , Coon Kerri L.
Published: December 2024

Aims

This study aimed to characterize and compare the antimicrobial resistance (AMR) profiles of clinically relevant bacterial taxa isolated from biting stable flies (Stomoxysspp.) and bovine manure samples collected at a dairy research facility over the course of an entire fly breeding season. The presence of extended-spectrum beta-lactamase (ESBL) and other antimicrobial resistance genes (ARGs) was also examined.

Methods and results

A total of 606 fly- and 180 manure-derived strains were tested via disk diffusion for susceptibility to commonly administered antibiotics used in veterinary and human medicine. A small percentage of Enterobacterales exhibited resistance to the tested antimicrobials, including ceftiofur and other beta-lactam antibiotics. Extended spectrum beta-lactamase genes (TEM, CTX, OXA, CMY) were detected by PCR amplification in ceftiofur-resistantEscherichia coli,KlebsiellaandEnterobacterspp. isolates. We additionally identified pirlimycin-resistantStaphylococcusandMammaliicoccusspp. isolates encodinglnuA, a lincosamide resistance gene found primarily on small mobilizable plasmids.

Conclusions

These findings highlight the significance of stable flies in the carriage of antimicrobial-resistant bacterial strains and plasmid-associated ARGs on dairy farms.
Rearrangements of viral and human genomes at human papillomavirus integration events and their allele-specific impacts on cancer genome regulation
Authors: Porter Vanessa L. , Ng Michelle , O'Neill Kieran , MacLennan Signe , Corbett Richard D. , Culibrk Luka , Hamadeh Zeid , Iden Marissa , Schmidt Rachel , Tsaih Shirng-Wern , Nakisige Carolyn , Origa Martin , Orem Jackson , Chang Glenn , Fan Jeremy , Nip Ka Ming , Akbari Vahid , Chan Simon K. , Hopkins James , Moore Richard A. , Chuah Eric , Mungall Karen L. , Mungall Andrew J. , Birol Inanc , Jones Steven J.M. , Rader Janet S. , Marra Marco A.
Published: December 2024

Human papillomavirus (HPV) integration has been implicated in transforming HPV infection into cancer. To resolve genome dysregulation associated with HPV integration, we performed Oxford Nanopore long-read sequencing on 72 cervical cancer genomes from an Ugandan dataset that was previously characterized using short-read sequencing. We found recurrent structural rearrangement patterns at HPV integration events, which we categorized as: del(etion)-like, dup(lication)-like, translocation, multibreakpoint, or repeat region integrations. Integrations involving amplified HPV-human concatemers, particularly multibreakpoint events, frequently harbored heterogeneous forms and copy numbers of the viral genome. Transcriptionally active integrants were characterized by unmethylated regions in both the viral and human genomes downstream from the viral transcription start site, resulting in HPV-human fusion transcripts. In contrast, integrants without evidence of expression lacked consistent methylation patterns. Furthermore, whereas transcriptional dysregulation was limited to genes within 200 kilobases of an HPV integrant, dysregulation of the human epigenome in the form of allelic differentially methylated regions affected megabase expanses of the genome, irrespective of the integrant's transcriptional status. By elucidating the structural, epigenetic, and allele-specific impacts of HPV integration, we provide insight into the role of integrated HPV in cervical cancer.
Recovering Quantum Coherence of a Cavity Qubit Coupled to a Noisy Ancilla through Real-Time Feedback
Authors: Goldblatt Uri , Kahn Nitzan , Hazanov Sergey , Milul Ofir , Guttel Barkay , Joshi Lalit M. , Chausovsky Daniel , Lafont Fabien , Rosenblum Serge
Published: December 2024

Decoherence in qubits, caused by their interaction with a noisy environment, poses a significant challenge to the development of reliable quantum processors. A prominent source of errors arises from noise in coupled ancillas, which can quickly spread to qubits. By actively monitoring these noisy ancillas, it is possible to not only identify qubit decoherence events but also to correct these errors in real time. This approach is particularly beneficial for bosonic qubits, where the interaction with ancillas is a dominant source of decoherence. In this work, we uncover the intricate dynamics of decoherence in a superconducting cavity qubit due to its interaction with a noisy transmon ancilla. By tracking the noisy ancilla trajectory and using real-time feedback, we successfully recover the lost coherence of the cavity qubit, achieving a fivefold increase in its pure dephasing time. Additionally, by detecting ancilla errors and converting them into erasures, we improve the pure dephasing time by more than an order of magnitude. These advances are essential for realizing long-lived cavity qubits with high-fidelity gates, and they pave the way for more efficient bosonic quantum error-correction codes.

Published by the American Physical Society
2024
“Unveiling the empowering elixir: exploring the impact of HEXACO traits on leadership and their ripple effect on employee engagement and creative performance”
Authors: Burhan QuratulAin , Khan Muhammad Asif
Published: December 2024

Purpose

The purpose of this study is to find out the role of positive personality traits such as honesty-humility, emotionality, extraversion, agreeableness, conscientiousness and openness to experience (HEXACO) in the development of empowering leadership, and also determine the impact that mastery goal orientation and work engagement play in linking the effects of an empowering leader on the creative performance of their followers.

Design/methodology/approach

The quantitative research design is used along with a deductive approach to achieve the objectives of the study. Data from 337 employees in the telecom sector was collected through self-administered questionnaires using the purposive sampling method. SEM-AMOS methods were used to conduct the analysis, and regression analysis was used to test the formulated hypotheses.

Findings

The study’s findings indicated that each component of HEXACO (honesty-humility beta values = 0.086, p < 0.05, emotionality values as β = 0.275, p < 0.001, extroverts β = 0.217, p < 0.001, consciousness β = 0.277, p < 0.001 and agreeableness β = 0.063) played a significant role in fostering empowered leadership. The results also suggested that there is a sequential mediation of mastery goal orientation and work engagement in the relationship between empowering leadership and creative performance.

Originality/value

This study is unique since it covers the antecedents and outcomes of empowering leadership. For antecedents, the study used the HEXACO personality model with all its elements to identify its role in the development of empowering leadership. Moreover, the study also used mastery goal orientation and work engagement as sequential mediators to check the impact of empowering leadership on the creative performance of employees.
The role of cultural competence in health care to improve communication between immigrant patients and health-care providers in Ottawa, Canada
Authors: Alghazali Idris Shoaeb , Ahmed Rukhsana
Published: December 2024

Purpose

Cultural competence has been recognized as an essential process in reducing racial and ethnic health-care disparities and improving equity in health care. Recent immigrants to Canada encounter a different and unfamiliar health-care system. This study aims to focus on examining the role of cultural competence in improving communication between immigrant patients and their health-care providers.

Design/methodology/approach

Using an exploratory approach, four focus group discussions with a sample of recent immigrants were conducted to gain insights from immigrant patients’ perspectives with regard to communicating with their health-care providers. The focus group discussions were analyzed using a thematic analysis approach. Campinha-Bacote’s Cultural Competence Model was used for this study as its theoretical framework.

Findings

The focus group findings revealed that the lack of cultural competence among health-care providers and language barriers are major issues that impact the health-care experiences of immigrant patients. Health-care organizations may use these findings to better inform their decision-making with regard to effective patient–provider communication.

Originality/value

This study advances the line of research that examines patient–provider communication by adding diverse immigrant patients’ perspectives. The findings can inform the design of cultural competence strategies for health-care organizations.