bluuebunny/crossref_metadata_2025 huggingface dataset:
Type 2 diabetes and bone mineral density: A meta-analysis and systematic review
Authors: Li Minghan , Sun Hanqiao , Chen Honggu , Ma Weiwei , Li Ying
Published: November 2024

Background:

Type 2 diabetes (T2D), a widespread chronic metabolic disorder, presents frequently in clinical settings. The relationship between T2D and bone mineral density (BMD) has been subject to ongoing investigation, yielding inconclusive results.

Methods:

A systematic literature search was conducted across several databases, including CNKI, VIP, CBM, Wanfang, PubMed, Cochrane Library, and Embase, targeting observational studies that explored the impact of microangiopathy associated with T2D on BMD or bone metabolism. The search spanned from the inception of each database to July 1, 2023. The Newcastle–Ottawa Scale was employed for quality assessment, and RevMan 5.3 software was utilized for data analysis. Stata 14.0 was used for the quantitative evaluation of publication bias regarding outcome measures.

Results:

The inclusion criteria were met by 30 observational studies, comprising 6470 participants—3121 with diabetes and 3349 without. The meta-analysis revealed no significant difference in overall BMD between the nondiabetic and T2D groups (mean difference [MD] = −0.07, 95% confidence interval [CI] [−0.17, 0.03], Z = 1.45, P = .15). However, BMD at the lumbar vertebrae was significantly higher in nondiabetic individuals compared with those with T2D (MD = −0.14, 95% CI [−0.22, −0.06], Z = 3.32, P = 0.0009), as was the case with femoral neck BMD (MD = −0.11, 95% CI [−0.18, −0.04], Z = 3.08, P = .002). A difference in femoral neck BMD between nondiabetics and individuals with T2D approached but did not reach statistical significance (MD = −0.14, 95% CI [−0.27, 0.00], Z = 1.94, P = .05). An inverted funnel plot analysis suggested possible publication bias, as evidenced by an asymmetrical distribution of studies around the axis of symmetry, with overlap observed in several cases.

Conclusion:

The findings indicate a significant association between T2D and reduced BMD at critical sites such as the lumbar vertebrae and femoral neck, highlighting an increased risk of osteoporosis or osteoporotic fractures in these regions.
Osteosarcopenia in patients with cancer: A systematic review and meta-analysis
Authors: Wang Chien-Chieh , Liu Hsuan-Chih , Lin Wen-Li , Wu Li-Min , Guo How-Ran , Huang Soon-Cen , Huang Wen-Tsung , Lin Cheng-Yao , Nguyen Thi-Hoang-Yen
Published: November 2024

Background:

Osteosarcopenia is frequent, and the relative risk of fracture is higher among patients with sarcopenia. It is a strong predictor of poor outcomes in older adults undergoing cancer treatment, suggesting that osteosarcopenia is important in an aging society. This study aimed to evaluate the overall survival (OS) and disease-free survival (DFS) of patients with cancer with and without osteosarcopenia.

Methods:

Five electronic databases—Embase, PubMed, Web of Science, Scopus, and CINAHL—were searched for relevant articles published before February 2024. Studies that met the criteria were used to evaluate the OS and DFS of patients with cancer with and without osteosarcopenia. From the 603 initially identified articles, 8 involving 1608 participants were included in the meta-analysis.

Results:

We observed that patients with cancer diagnosed with osteopenia, sarcopenia, or osteosarcopenia had worse DFS than those without these conditions. Specifically, osteopenia (pooled hazard ratio [HR] = 1.70, P = .01) and osteosarcopenia (pooled HR = 2.17, P = .0001) emerged as independent predictors of DFS. However, sarcopenia was significantly associated with DFS. The quality of the included studies was generally good, and no publication bias was detected among them for either OS or DFS.

Conclusion:

These meta-analysis results suggest that osteopenia and osteosarcopenia are associated with worse DFS among patients with cancer. The use of different case definitions appeared to be a major source of heterogeneity among studies. Further studies are warranted to confirm our findings, especially those regarding OS and DFS.
Experience of physical activity in patients with stroke: A qualitative meta-synthesis
Authors: Li Xingru , Yang Xinchen , Fan Yifan , Tang Yun , Shu Yue
Published: November 2024

Background:

Inadequate physical activity (PA) is increasingly common among stroke patients, we aim to comprehensively analyze the experience of stroke patients delivering physical activity, understand the obstacles and promoting factors of physical activity, and summarize clinical management strategies.

Methods:

An electronic search of PubMed, Web of Science, Cochrane Library, ProQuest, SinoMed, CNKI, and WanFang Database was conducted for qualitative studies on the experience of PA in stroke patients. The review was appraised using the Joanna Briggs Institute methodology, the subsequent findings were synthesized via the Thomas and Harden approach and the credibility of the research results was evaluated by the CERqual tool.

Results:

Six thousand five hundred forty-nine findings were yielded through the search, ultimately 11 studies were included through screening, a total of 194 stroke patients participated in the study, and 3 synthesized themes that emerged were identified: barriers to PA, facilitators to PA, and strategies to improve compliance with physical activity in stroke patients. All selected articles were of medium quality and all themes were of medium or high quality.

Conclusion:

The experience of PA among stroke patients should be given more attention. Healthcare professionals should provide physical activity-related knowledge education, social support, personalized care, improved environments, and create more opportunities for PA. In the future, more tailored interventions should be carried out to develop PA habits and improve compliance.
Utilization of Computer-Assisted Navigation Technology Within Craniomaxillofacial Fracture Surgery
Authors: Thuman Jenna , Andrade Erika , Brantley Rebecca , Herrera Fernando A. , Scomacao Isis Raulino
Published: November 2024

Background

Use of intraoperative computer-assisted navigation (iCAN) has been well-established in otolaryngology and neurosurgery; however, its use in surgical management of facial fractures is yet to be reported on a large scale. This study aimed to review the existing literature to determine the outcomes, limitations, risks, and benefits of iCAN use in facial fracture management.

Methods

A systematic review of iCAN use in craniomaxillofacial fracture surgery was performed by 2 authors in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search was conducted on 3 databases, PubMed, Cochrane Library, and Embase, using the search terms “navigation,” “intraoperative,” and “brain lab” in combination with “facial fractures” or “facial reconstruction.” Study type, demographics, fracture characteristics, surgery characteristics, iCAN devices, intraoperative fracture fixation accuracy, postoperative outcomes, complications, navigation limitations, and risks and benefits were analyzed.

Results

There were 909 studies identified in the initial search, of which 42 were chosen for final use. iCAN use was most commonly reported in unilateral (57.1%) and complex (50%) facial fracture cases. Surgical accuracy ranged from 0.7 to 4 mm and postoperative discrepancy ranged from 0.05 to 8 mm. Benefits included improved intraoperative surgical accuracy (95.2%), improved postoperative surgical discrepancy (52.4%), and decreased total surgical time (35.7%). Limitations reported with iCAN device use included operative technical difficulties (23.8%) and persistent systematic errors during device registration (21.4%). None of the studies discussed cost analysis or risks compared to conventional fixation methods.

Conclusions

Advancements in and increasing familiarity with iCAN technology have preliminarily shown favorable surgical outcomes in facial fracture fixation, which include improved operative accuracy and discrepancy and decreased surgical time.
Intraocular Pressure Changes After Combined Orbital Decompression and Glucocorticoid Treatment for Graves Orbitopathy
Authors: Wang Mingyang , Li Dongmei
Published: November 2024

Objective:

To evaluate the change in the intraocular pressure (IOP) in subjects with Graves orbitopathy (GO) after orbital decompression (OD) with glucocorticoids (GCs).

Methods:

Ninety-nine orbits of 76 patients with GO were retrospectively reviewed, with either OD (Group A), OD with intravenous glucocorticoids (i.v.GC) (Group B) or parabulbar GC (Group C) administration. The main outcome measures included pre-and post-operative IOP in the primary and upward gazes.

Results:

Mean postoperative IOPs in the primary gaze were lower than the preoperative values for groups A and C (P < 0.05). The IOPs during the upward gaze were higher than those in the primary gaze before and after OD (all groups, P < 0.05). The mean postoperative and preoperative IOPs during upward gaze were similar in all groups except group C (P = 0.001). The mean decrease in IOP in the primary gaze was 1.57 ± 6.00 mm Hg and 2.22 ± 2.62 mm Hg in groups A and C, respectively (P < 0.05). Only in group C, the mean IOPs during upward gaze decrease by 5.29 ± 4.89 mm Hg (active GO before OD), and the mean gaze-related IOP decreased from 7.75 ± 6.02 to 2.57 ± 4.21 mm Hg (P < 0.05).

Conclusions:

A pbGC treatment before OD can effectively reduce the primary and upward gaze IOPs and lead to a greater postoperative reduction in the upward gaze IOP to approximate that in the primary gaze. A pbGC treatment may be preferred for patients with GO in the active or congestive phase before OD considering the IOP.
Understanding Hemodynamic Incoherence: Mechanisms, Phenotypes, and Implications for Treatment
Authors: Huang Lin , Huang Qiaobin , Ma Weiquan , Yang Hong
Published: November 2024

The reversal of microcirculation dysfunction is crucial for assessing the success of shock resuscitation and significantly influences patient prognosis. However hemodynamic incoherence is observed when microcirculatory dysfunction persists despite the restoration of macrocirculatory function post-resuscitation. Recent advancements in technology have enabled bedside assessment of microcirculation in shock patients, allowing for direct visualization of microcirculatory morphology and quantitative evaluation of its functional status. This article reviews the pathophysiological mechanisms that lead to hemodynamic incoherence. It also introduces the current understanding and classification framework for the different phenotypes of hemodynamic incoherence. Existing evidence indicates that the diverse mechanisms leading to microcirculatory disorders result in varied manifestations among patients experiencing hemodynamic incoherence, highlighting the heterogeneity of this population. Some classification frameworks have been proposed to enhance our understanding of these phenotypes. By integrating pathophysiological mechanisms, clinical symptoms, indicators of macrocirculation, microcirculation, tissue metabolism, and biomarkers, we can summarize certain clinical features of phenotypes in hemodynamic incoherence to form a conceptual framework. Additionally, strategies for creating targeted treatments based on different phenotypes require further validation.
Implementing a Digital Platform for Recurrent Urinary Tract Infections
Authors: Arya Lily A. , Agrawal Surbhi , Ikpeama Ngozi , Harvie Heidi , Feldman Rebecca Hamm , Dutcher Lauren
Published: November 2024

Importance

A patient-centered care model is needed for recurrent urinary tract infection (UTI) management.

Objective

The aim of this study was to develop a conceptual model for a digital platform to implement evidence-based guidelines for recurrent UTI management.

Study Design

This was a qualitative, 3-stage mixed methods study that included (1) developing an evidence-based prototype texting platform; (2) qualitative feedback from recurrent UTI patients using the platform; and (3) quantitative data on acceptability (proportion of patients engaging with the platform), accuracy (proportion of patient messages interpreted accurately by the platform), and usability (score 0–100).

Results

Thirty-one women with recurrent UTI (median age, 71 years; range, 60–74 years) participated in testing over 4 months. The prototype platform was modified through iterative rounds of qualitative and quantitative analysis until engagement ≥85%, accuracy ≥90%, and usability score of ≥80 were achieved in 10 patients. Qualitative feedback indicated that patients valued rapid access to treatment through fewest possible health encounters during an acute episode, evidence-based education about prevention, and ability to participate in self-management with support from health care providers. Based on this feedback, a conceptual model consisting of 3 main components was developed: (1) an algorithm to triage acute symptoms, (2) educational videos emphasizing prevention strategies, and (3) supportive messages. Patient feedback identified 4 key implementation outcomes—usability, acceptability (engagement), fidelity (accuracy), and cost—and 3 clinical outcomes—self-efficacy, health care utilization, and rate of unnecessary antibiotics for testing the model.

Conclusion

The proposed model can be used to implement and test a patient-centered evidence-based digital platform for the management of recurrent UTI.
Investigating the Role of Management Decisions in Subspecies Hybridization Across the Wild Turkey’s Range
Authors: Beckman Amanda K. , Hamer Sarah A. , Rosenthal Gil G. , Brennan Leonard A. , Hancock Zach B.
Published: November 2024

The expanded geographic range and recovery to millions of wild turkeys across the country would not have been possible without management actions that included introducing and translocating individuals. However, the range-wide genetic impact of management decisions on one of North America’s greatest conservation success stories remains unknown despite the potential economic impact as hunters seek out easily identifiable subspecies for grand slams. In this study, we used DNA extracted from hunter-collected feathers from 29 states and Ontario to investigate genetic differences among turkeys in their historic and introduced ranges. Additionally, we compiled state-level management data to investigate how different management decisions are associated with the amount of admixture among subspecies. We found no difference in the amount of admixture in the turkey’s historic range compared to the introduced range. However, management decisions like as the number of subspecies introduced and the number of unique source states resulted in an increased level of admixture detected, but there was no relationship in admixture and the number of unique relocated counties. This first investigation into the hybridization among subspecies of wild turkey provides evidence that individual state’s management actions have influenced the genetic makeup of subspecies in that state.
Disease-Linked Regulatory DNA Variants and Homeostatic Transcription Factors in Epidermis
Authors: Porter Douglas F. , Meyers Robin M. , Miao Weili , Reynolds David L. , Hong Audrey W. , Yang Xue , Mondal Smarajit , Siprashvili Zurab , Srinivasan Suhas , Ducoli Luca , Meyers Jordan M. , Nguyen Duy T. , Ko Lisa A. , Kellman Laura , Elfaki Ibtihal , Guo Margaret , Winge Mårten CG , Lopez-Pajares Vanessa , Porter Imani E. , Tao Shiying , Khavari Paul A.
Published: November 2024

Identifying noncoding single nucleotide variants (SNVs) in regulatory DNA linked to polygenic disease risk, the transcription factors (TFs) they bind, and the target genes they dysregulate is a goal in polygenic disease research. Massively parallel reporter gene analysis (MPRA) of 3,451 SNVs linked to risk for polygenic skin diseases characterized by disrupted epidermal homeostasis identified 355 differentially active SNVs (daSNVs). daSNV target gene analysis, combined with daSNV editing, underscored dysregulated epidermal differentiation as a pathomechanism shared across common polygenic skin diseases. CRISPR knockout screens of 1772 human TFs revealed 108 TFs essential for epidermal progenitor differentiation, uncovering novel roles for ZNF217, CXXC1, FOXJ2, IRX2 and NRF1. Population sampling CUT&RUN of 27 homeostatic TFs identified allele-specific DNA binding (ASB) differences at daSNVs enriched near epidermal homeostasis and monogenic skin disease genes, with notable representation of SP/KLF and AP-1/2 TFs. This resource implicates dysregulated differentiation in risk for diverse polygenic skin diseases.
Fear, Stigma and Uncertainty: The short and long-term effects of Ebola on survivors, affected families, and community in Bundibugyo, Western Uganda
Authors: Namusisi Shamilah , Waila Jacinta Mukulu , Hoffman Sarah J. , Roberston Cheryl , Pelican Katey , Mahero Michael
Published: November 2024

In 2014, Uganda was identified as a high-risk country for Ebola Virus Disease (EVD), with a series of outbreaks recorded since 2000. In 2007, the second outbreak in Bundibugyo district resulted in 149 reported cases and 37 confirmed Ebola deaths. Through the outbreak response, a new strain of the Ebola virus (Bundibugyo ebolavirus)was discovered. Although much is known about the nature of Ebola, including disease signs and symptoms, transmission and management, there is limited understanding of the short and long-term sociocultural impacts of the disease in communities. The study team conducted a focused ethnography in Bundibugyo District 10 years after the 2007 outbreak. Data collection included a review of archival data, participant observation, field notes and 19 in-depth interviews with survivors and affected families. Results underscored time-limited social, cultural and economic disruptions caused by the outbreak. We interpreted findings through an Eco-health framework with an emphasis on ways that underlying stigma accentuated detrimental long-term effects of the outbreak. Affected women, particularly widows, experienced social exclusion, and economic strain, and acknowledged loss of opportunity for a better life for their orphaned children. Deepening fear of the possible recurrence of Ebola resulted in ethnic tension driven by speculations on the 2007 outbreak source. Survivors reported varying persistent health effects including impaired vision and general body weakness. Community members reported positive changes in health seeking behaviors. Health care workers described high levels of alert for early clinical signs of Ebola, a critical factor for early outbreak detection at the community level. Our findings can inform future Ebola response and recovery interventions, particularly those targeting community re-integration and a mitigation of the fear and stigma associated with survivorship.
GPT-4 Improves Readability of Institutional Heart Failure Patient Education Materials: An Observational Study
Authors: King Ryan C. , Samaan Jamil S. , Haquang Joseph , Bharani Vishnu , Margolis Samuel , Srinivasan Nitin , Peng Yuxin , Yeo Yee Hui , Ghashghaei Roxana
Published: November 2024

Introduction

Heart failure management involves comprehensive lifestyle modifications such as daily weights, fluid and sodium restriction, and blood pressure monitoring placing additional responsibility on patients and caregivers with successful adherence often requiring extensive counseling and understandable patient education materials (PEMs). Prior research has shown PEMs related to cardiovascular disease often exceed the American Medical Association’s 5th-6thgrade recommended reading level. The large language model (LLM) Chat Generative Pre-trained Transformer (ChatGPT) may be a useful tool for improving PEM readability.

Materials and Methods

A total of 143 heart failure PEMs were collected from the websites of the top 10 institutions listed on the 2022-2023 US News & World Report for “Best Hospitals for Cardiology, Heart & Vascular Surgery”. PEMs were individually entered into GPT-4 (Version updated 20 July 2023) preceded by the prompt “please explain the following in simpler terms”. The readability of the institutional PEM and ChatGPT revised PEM were both assessed usingTextstatlibrary in Python and theTextstat readabilitypackage in R software. The accuracy and comprehensiveness of revised GPT-4 PEMs were assessed by a board-certified cardiologist.

Results

The Flesch-Kincaid grade reading level ranged from 8th grade to college freshman with a median of 10th grade vs 6thto 8thgrade with a median of 7thgrade for institutional PEMs and GPT-4 PEMs (p< 0.001), respectively. There were 13/143 (9.1%) institutional PEMs below the 6thgrade reading level which improved to 33/143 (23.1%) after revision by GPT-4 (p<0.001). No GPT-4 revised PEMs were graded as less accurate or less comprehensive compared to institutional PEMs. A total of 33/143 (23.1%) GPT-4 PEMs were graded as more comprehensive.

Conclusions

GPT-4 significantly improved the readability of institutional heart failure PEMs. The model may be a promising adjunct resource in addition to care provided by a licensed healthcare professional for patients living with heart failure. Further rigorous testing and validation is needed to investigate its safety, efficacy and impact on patient health literacy.
Hydrocarbon effects on cell survival and antioxidant system of breast tumorigenic and non-tumorigenic cells
Authors: Mardirosian Mariana , Lasagna Marianela , Núñez Mariel , Galarza Tamara , Espert Nuria , Venturino Andrés , Cocca Claudia
Published: November 2024

Over the last decades, environmental pollution with polycyclic aromatic hydrocarbons (PAH) has risen due to human development and industrial activities. The consequences of potential contamination with oil or any of its components must be evaluated. Here, we faced the effects on cell growth and detoxification that might arise from the exposure to hydrocarbons sourced from contaminated waters. MCF-7 and MDA-MB-231 human breast cancer cells and/or MCF-10A epithelial non-tumorigenic cells were exposed to water-accommodated oil fraction (WAF) or anthracene as a PAH currently found in the environment to evaluate clonogenicity, viability, GST and CAT activities. WAF decreased MDA-MB-231 cells clonogenicity and MDA-MB-231 and MCF-7 cells viability. Anthracene significantly reduced non-tumorigenic cells’ viability and clonogenicity, without affecting the survival of tumorigenic cells. Both tumorigenic cells responded mainly by activating the antioxidant system through the increment of CAT when exposed to low concentrations of WAF. In both cell lines, WAF also increased GST. Anthracene exposure significantly decreased CAT activity of the three cell lines evaluated. GST activity decreased 38% after 28 µM anthracene exposure in MDA-MB-231 cells (p<0.05) and 15, 17 and 21% after 7 (p<0.05), 14 and 28 µM (p<0.01) in MCF-10A cells, while in MCF-7 cells 28 µM anthracene increased GST activity by 75% (p<0.001). We conclude that the sensitivity of cells to the different contaminants evaluated is affected by the degree of cellular tumorigenicity and exposure to WAF or anthracene may exacerbate malignant conditions. The integration of multiple parameters, analyzed through multivariate methods, offers a comprehensive evaluation of toxicant effects.

HIGHLIGHTS

WAF and anthracene affect tumorigenic mammary cells viability and clonogenicity

Non tumorigenic mammary cells show more sensitivity to anthracene exposure

WAF activates antioxidant and detoxicant system in tumorigenic mammary cells

Anthracene decreased CAT activity of tumorigenic and non-tumorigenic mammary cells

Anthracene affected GST activity of tumorigenic and non-tumorigenic mammary cells
Physical vitrification and nanowarming at human organ scale to enable cryopreservation
Authors: Gangwar Lakshya , Han Zonghu , Scheithauer Cameron , Namsrai Bat-Erdene , Kantesaria Saurin , Goldstein Rob , Etheridge Michael L. , Finger Erik B. , Bischof John C.
Published: November 2024

Organ banking by vitrification could revolutionize transplant medicine. However, vitrification and rewarming have never been demonstrated at the human organ scale. Using modeling and experimentation, we tested the ability to vitrify and rewarm 0.5 – 3 L volumes of three common cryoprotective agent (CPA) solutions: M22, VS55, and 40% EG+0.6M Sucrose. We first demonstrated our ability to avoid ice formation by convectively cooling faster than the critical cooling rates of these CPAs while also maintaining adequate uniformity to avoid cracking. Vitrification success was then verified by visual, thermometry, and x-ray μCT inspection. M22 and EG+sucrose were successfully vitrified in 0.5 L bags, but only M22 was vitrified at 3 L. VS55 did not vitrify at any tested volumes. As additional proof of principle, we successfully vitrified a porcine liver (∼1L) after perfusion loading with 40% EG+0.6M Sucrose. Uniform volumetric rewarming was then achieved in up to 2 L volumes (M22 with ∼5 mgFe/mL iron-oxide nanoparticles) using nanowarming, reaching a rate of ∼88 °C/min with a newly developed 120 kW radiofrequency (RF) coil operating at 35kA/m and 360kHz. This work demonstrates that human organ scale vitrification and rewarming is physically achievable, thereby contributing to technology that enables human organ banking.
Distilling Structural Representations into Protein Sequence Models
Authors: Ouyang-Zhang Jeffrey , Gong Chengyue , Zhao Yue , Krähenbühl Philipp , Klivans Adam R. , Diaz Daniel J.
Published: November 2024

Protein language models, like the popular ESM2, are widely used tools for extracting evolution-based protein representations and have achieved significant success on downstream biological tasks. Representations based on sequence and structure models, however, show significant performance differences depending on the downstream task. A major open problem is to obtain representations that best capture both the evolutionary and structural properties of proteins in general. Here we introduceImplicitStructureModel(ISM), a sequence-only input model with structurally-enriched representations that outperforms state-of-the-art sequence models on several well-studied benchmarks including mutation stability assessment and structure prediction. Our key innovations are a microenvironment-based autoencoder for generating structure tokens and a self-supervised training objective that distills these tokens into ESM2’s pre-trained model. We have madeISM’s structure-enriched weights easily available: integrating ISM into any application using ESM2 requires changing only a single line of code. Our code is available athttps://github.com/jozhang97/ISM.
Accurate prediction of CRISPR editing outcomes in somatic cell lines and zygote with few-shot learning
Authors: Zheng Weizhong , Yu Lu , Wang Guoliang , Cao Shaoxian , Ho Kenso , Song Jun , Cheng Chen , Ho Joshua W.K. , Liu Xueqing , Wu Meng , Liu Zhonghua , Wang Huili , Liu Pentao , Lan Guocheng , Huang Yuanhua
Published: November 2024

The CRISPR-Cas system has revolutionized gene editing, while its outcome prediction remains unsatisfactory, especially in new cell states due to their distinct DNA repair preferences. In this study, we introduce inDecay, a flexible system for predicting CRISPR editing outcomes from target sequence, returning probabilities of nearly the full spectrum of indel events. Uniquely, inDecay utilizes informative and parameter-efficient features for each indel event and incorporates cell-type-specific repair preferences through a multi-stage design. While both inDecay and existing methods achieve accurate results for prediction within cell lines, only inDecay with transfer learning can retain the high performance for cross-cell line prediction. We then applied inDecay to mouse embryo editing using our newly generated data and observed remarkable accuracy by including as few as 30 fine-tuning embryonic samples. Notably, inDecay is the first software to predict embryonic editing. Therefore, our few-shot learning-supported system may accelerate guide RNA prioritization in mouse model generation, mammal embryonic gene editing, and cellular therapeutics.
Video tracking of single cells to identify clustering behaviour
Authors: Korsnes Mónica Suárez , Ramberg Håkon André , Taskén Kristin Austlid , Korsnes Reinert
Published: November 2024

Cancer cell clustering is a critical factor in metastasis, with cells often believed to migrate in groups as they establish themselves in new environments. This study presents preliminary findings from anin vitroexperiment, suggesting that co-culturing cells provides an effective method for observing this phenomenon, even though the cells are grown as monolayers. We introduce a novel single-cell tracking approach based on graph theory to identify clusters in PC3 cells cultivated in both monoculture and co-culture with PC12 cells, using 66-hour time-lapse recordings. The initial step consists of defining ‘linked’ pairs of PC3 cells, laying the foundation for the application of graph theory. We propose two alternative definitions for cell pairings. The first method,Method 1, defines cells as ‘linked’ at a given timetif they are close together within a defined time period before and aftert. A second potential alternative method,Method 2, pairs cells if there is an overlap between the convex hulls of their respective tracks during this time period. Pairing cells enables the application of graph theory for subsequent analysis. This framework represents a cell as a vertex (node) and a relation between two cells as an edge. An interconnected set of high-degree nodes (nodes with many connections or edges) forms a subgraph, or backbone, that defines a patch (cluster) of cells. All nodes connected to this backbone are part of the subgraph. The backbone of high-degree nodes functions as a partition (or cut) of the initial graph. Two consecutive clusters in the video are considered to share the same identity if the following cluster contains at leastp= 75 % of the cells from the preceding cluster, and the mean positions of their cells are within △r= 75 µm. PC3 cells grown in co-culture appear to form persistent clusters exceeding 10 cells after 40 to 50 h incubation following seeding. In contrast, PC3 cells cultured alone (mono-culture) did not exhibit this behaviour. This approach is experimental and requires further validation with a broader dataset.
Small proteins from prokaryotes in marine water column at full ocean depth
Authors: Li Qing-Mei , He Li-Sheng , Wang Yong
Published: November 2024

Small proteins (SPs,≤50 amino acids) are usually ignored by automated bioinformatic algorithms and difficult to be detected by traditional protein purification. In this study, 193,281 prokaryotic SP clusters were generated using 433,311 small open reading frames (sORFs) predicted in assemblies of 71 full-ocean-depth marine water metagenomes from the western pacific. Further filtration with at least 5 copies per million reads resulted in 75,581 prevalent SP clusters, among which 4,307 clusters have coding capacity as predicted by RNAcode. For these RNAcode-filtered SP (RfSP) clusters hosted largely by Proteobacteria, Thaumarchaeota and Marinimicrobia, 29.16% of them show homology () in all prokaryotic genomes. About 2% of the RfSP clusters were estimated as potential antimicrobial peptides and were distributed across all depth zones. Transcription of 7.96% of the RfSP clusters was verified in 12 deep-sea metatranscriptomes, and translation of 34 prevalent SP clusters was detected in 14 metaproteomes. The transcribed RfSP clusters are involved in processes such as DNA stability under stress condition, betaine transport and cell division regulation for a rapid response to varying deep-sea environments. This study uncovers a vast reservoir of SPs with pivotal functions in potential antibiotic activities, hyperoxide detoxification and pressure resistance for fitness of marine prokaryotes in deep ocean.
Inferring the demographic history of aye-ayes (Daubentonia madagascariensis) from high-quality, whole-genome, population-level data
Authors: Terbot John W. , Soni Vivak , Versoza Cyril J. , Pfeifer Susanne P. , Jensen Jeffrey D.
Published: November 2024

The nocturnal aye-aye,Daubentonia madagascariensis, is one of the most elusive lemurs on the island of Madagascar. The timing of its activity and arboreal lifestyle has generally made it difficult to obtain accurate assessments of population size using traditional census methods. Therefore, alternative estimates provided by population genetic inference are essential for yielding much needed information for conservation measures and for enabling ecological and evolutionary studies of this species. Here, we utilize genomic data from 17 unrelated individuals — including 5 newly sequenced, high-coverage genomes — to estimate this history. Essential to this estimation are recently published annotations of the aye-aye genome which allow for variation at putatively neutral genomic regions to be included in the estimation procedures, and regions subject to selective constraints, or in linkage to such sites, to be excluded owing to the biasing effects of selection on demographic inference. By comparing a variety of demographic estimation tools to develop a well-supported model of population history, we find strong support for the species to consist of two demes, separating northern Madagascar from the rest of the island. Additionally, we find that the aye-aye has experienced two severe reductions in population size. The first occurred rapidly, approximately 3,000 to 5,000 years ago, and likely corresponded with the arrival of humans to Madagascar. The second occurred over the past few decades and is likely related to substantial habitat loss, suggesting that the species is still undergoing population decline and remains at great risk for extinction.
A pedigree-based map of crossovers and non-crossovers in aye-ayes (Daubentonia madagascariensis)
Authors: Versoza Cyril J. , Lloret-Villas Audald , Jensen Jeffrey D. , Pfeifer Susanne P.
Published: November 2024

Gaining a better understanding of rates and patterns of meiotic recombination is crucial for improving evolutionary genomic modelling, with applications ranging from demographic to selective inference. Although previous research has provided important insights into the landscape of crossovers in humans and other haplorrhines, our understanding of both the considerably more common outcome of recombination (i.e., non-crossovers) as well as the landscapes in more distantly-related primates (i.e., strepsirrhines) remains limited owing to difficulties associated with both the identification of non-crossover tracts as well as species sampling. Thus, in order to elucidate recombination patterns in this under-studied branch of the primate clade, we here characterize crossover and non-crossover landscapes in aye-ayes utilizing whole-genome sequencing data from six three-generation pedigrees as well as three two-generation multi-sibling families, and in so doing provide novel insights into this important evolutionary process shaping genomic diversity in one of the world’s most critically endangered primate species.
Rapid Caspian sea level decline requires dynamic spatio-temporal conservation planning to keep biodiversity protection measures relevant
Authors: Court Rebecca , Lattuada Matteo , Shumeyko Nataliya , Baimukanov Mirgaliy , Eybatov Tariel , Kaidarova Altynay , Mamedov Elchin V. , Rustamov Eldar , Tasmagambetova Aselle , Prange Matthias , Wilke Thomas , Hassall Christopher , Goodman Simon J.
Published: November 2024

The Caspian Sea is the world’s largest landlocked waterbody, providing habitat for hundreds of endemic and migratory species, along with ecosystem services that sustain millions of people. Global warming is projected to drive declines in water levels of up to 21 m by 2100. Using geospatial analyses, we assessed the impact of sea level decline on habitats, protected areas, and human infrastructure. We show that a water level decline of just 5–10 m will critically disrupt key ecosystems, reduce existing marine protected area coverage by up to 94%, and render billions of dollars of civil and industrial infrastructure obsolete. Urgent action is needed to replace traditional static conservation planning with a pre-emptive, dynamic approach that allows protected areas to track shifting ecosystems. This will be essential to help the Caspian Sea’s endemic biodiversity adapt to these changes, and avoid conflicts with mitigation efforts directed at protecting human activity.

Russian abstract

Абстракт

Каспийское море – крупнейший в мире внутренний водоем, обеспечивающий среду обитания для сотен эндемичных и мигрирующих видов, а также экосистемные услуги, обеспечивающие жизнедеятельность миллионов людей. Согласно прогнозам, глобальное потепление приведет к снижению уровня воды до 21 м к 2100 году. С помощью геопространственного анализа проведена оценка влияния снижения уровня моря на места обитания, охраняемые территории и объекты инфраструктуры. Мы показываем, что снижение уровня воды всего на 5–10 м приведет к критическим нарушениям в ключевых экосистемах, сократит охват существующих морских охраняемых районов до 94% и приведет к выводу из эксплуатации гражданской и промышленной инфраструктуры стоимостью в миллиарды долларов. Необходимы безотлагательные меры по замене традиционного статичного планирования природоохранной деятельности упреждающим, динамичным подходом, который позволит корректировать границы охраняемых районов вслед за смещением экосистем. Это необходимо для адаптации эндемичного биоразнообразия Каспийского моря к изменениям, а также для того, чтобы усилия по его сохранению не вступали в конфликт с мерами по защите деятельности человека.
Maternal inheritance of primary sex ratios in the dark-winged fungus gnatLycoriella ingenua
Authors: Shlyakonova Maria , Monteith Katy M. , Ross Laura , Baird Robert B.
Published: November 2024

Sex determination mechanisms in insects are extraordinarily diverse, although most species have zygotic genotypic sex determination where sex is established by sex chromosomes upon fertilisation. Dark-winged fungus gnats (Diptera: Sciaridae) are a large and speciose family of flies where sex determination is a result of an unusual interplay of zygotic, maternal, and environmental factors. This causes some species to produce clutches of offspring that deviate considerably from the standard 1:1 Fisherian sex ratio. An early study suggested that these primary sex ratios may be heritable from mother to daughter, but this observation has not been corroborated and the genetic basis for this trait remains unknown. Other studies have found that in some species, there is an additional temperature effect on the primary sex ratio, but again the mechanism is unknown. Here, we perform sibling crosses and temperature-shift experiments in a recently isolated line of the speciesLycoriella ingenuaand find evidence for highly variable and heritable primary sex ratios, but no significant environmental effect. We discuss the consequences of our findings for understanding the mechanisms that produce these unusual sex ratios, and the evolution of sex determination more broadly in this clade.
CelLink: integrating single-cell multi-omics data with weak feature linkage and imbalanced cell populations
Authors: Luo Xin , Huang Yuanhao , Tao Yicheng , Feng Fan , Hopkirk Alexander , Bate Thomas S.R. , Saunders Diane C. , Orchard Peter , Robertson Catherine , Shrestha Shristi , Cartailler Jean-Philippe , Parker Stephen C. J. , Brissova Marcela , Liu Jie
Published: November 2024

Single-cell multi-omics technologies capture complementary molecular layers, enabling a comprehensive view of cellular states and functions. However, integrating these data types poses significant challenges when their features are weakly linked and cell population sizes are imbalanced. Currently, no method efficiently addresses these two issues simultaneously. Therefore, we developed CelLink, a novel single-cell multi-omics data integration method designed to overcome these challenges. CelLink normalizes and smooths feature profiles to align scales across datasets and integrates them through a multi-phase pipeline that iteratively employs the optimal transport algorithm. It dynamically refines cell-cell correspondences, identifying and excluding cells that cannot be reliably matched, thus avoiding performance degradation caused by erroneous imputations. This approach effectively adapts to weak feature linkage and imbalanced cell populations between datasets. Benchmarking CelLink on scRNA-seq and spatial proteomics datasets, as well as paired CITE-seq data, demonstrates its superior performance across various evaluation metrics, including data mixing, cell manifold structure preservation, and feature imputation accuracy. Compared to state-of-the-art methods, CelLink significantly outperforms others in imbalanced cell populations while consistently achieving better performance for balanced datasets. Moreover, CelLink uniquely enables cell subtype annotation, correction of mislabelled cells, and spatial transcriptomic analyses by imputing transcriptomic profiles for spatial proteomics data. CelLink sets a new milestone for multi-omics data integration. Its great ability to impute large-scale paired single-cell multi-omics profiles positions it as a pivotal tool for building single-cell multi-modal foundation models and advancing spatial cellular biology.
Leveraging genetic ancestry continuum information to interpolate PRS for admixed populations
Authors: Ruan Yunfeng , Bhukar Rohan , Patel Aniruddh , Koyama Satoshi , Hull Leland , Truong Buu , Hornsby Whitney , Zhang Haoyu , Chatterjee Nilanjan , Natarajan Pradeep
Published: November 2024

The relatively low representation of admixed populations in both discovery and fine-tuning individual-level datasets limits polygenic risk score (PRS) development and equitable clinical translation for admixed populations. Under the assumption that the most informative PRS weight for a homogeneous sample varies linearly in an ancestry continuum space, we introduce a GeneticDistance-assisted PRSCombination Pipeline forDiverse GeneticAncestries(DiscoDivas) to interpolate a harmonized PRS for diverse, especially admixed, ancestries, leveraging multiple PRS weights fine-tuned within single-ancestry samples and genetic distance. DiscoDivas treats ancestry as a continuous variable and does not require shifting between different models when calculating PRS for different ancestries. We generated PRS with DiscoDivas and the current conventional method, i.e. fine-tuning multiple GWAS PRS using the matched or similar ancestry samples. DiscoDivas generated a harmonized PRS of the accuracy comparable to or higher than the conventional approach, with the greatest advantage exhibited in admixed individuals.
Eye features and retinal photoreceptors of the nocturnal aardvark (Orycteropus afer, Tubulidentata)
Authors: Peichl Leo , Meimann Sonja , Solovei Irina , Gügel Irene L. , Geiger Christina , Schauerte Nicole , Goździewska-Harłajczuk Karolina , Klećkowska-Nawrot Joanna E. , Wibbelt Gudrun , Haverkamp Silke
Published: November 2024

The nocturnal aardvarkOrycteropus aferis the only extant species in the mammalian order Tubulidentata. Previous studies have claimed that it has an all-rod retina. In the retina of one aardvark, we found rod densities ranging from 124,000/mm² in peripheral retina to 214,000/mm² in central retina; the retina of another aardvark had 182,000 – 245,000 rods/mm². This is moderate in comparison to other nocturnal mammals. With opsin immunolabelling we found that the aardvark also has a small population of cone photoreceptors. Cone densities ranged from 300 to 1,300/mm² in one animal, and from 1,100 to 1,600/mm² in the other animal, with large local variations and no large central-peripheral density gradient. Overall, cones comprised 0.25-0.9% of the photoreceptors. Both typical mammalian cone opsins, longwave-sensitive (L) and shortwave-sensitive (S), were present. However, there was colocalization of the two opsins in many cones across the retina (35 – 96% dual pigment cones). Pure L cones and S cones formed smaller populations. This probably results in poor colour discrimination. Thyroid hormones, important regulators of cone opsin expression, showed normal blood serum levels. The relatively low rod density and hence a relatively thin retina may be related to the fact that the aardvark retina is avascular and its oxygen and nutrient supply have to come from the choriocapillaris by diffusion. In contrast to some previous studies, we found that the aardvark eye has a reflective tapetum lucidum with features of a choroidal tapetum fibrosum, in front of which the retinal pigment epithelium is unpigmented. The discussion considers these findings from a comparative perspective.
Heterogeneous Effects of Src Inhibition on Determinants of Metastasis in Preclinical Models of Human Bladder Cancer
Authors: Aragaki Kai , Wehrenberg Bryan , Hayashi Yujiro , McConkey David J.
Published: November 2024

Background

Past work in preclinical models of solid tumors have implicated SRC in invasion and metastasis, but also demonstrated it inhibited bladder cancer metastasis.

Objective

Determine if the role of SRC in metastasis is dependent on bladder cancer molecular subtype membership.

Methods

We analyzed large public datasets, performedin vitroinvasion and migration assays using small-molecule and doxycycline inducible SRC knock-down constructs, andin vivoexperimental metastasis assays.

Results

Looking at large public datasets, we found SRC is upregulated in luminal papillary muscle invasive bladder cancer. Using the consensus classifier on RNA expression from 30 cell lines, we demonstrated that chemical SRC antagonists inhibited migration in luminal papillary cells but had little effect in basal/squamous lines. Conditional SRC knockdown inhibited migration in luminal papillary RT112 cells, whereas it increased migration and reduced proliferation in luminal papillary UM-UC6 cells. Regardless, these effects did not affect levels or sites of experimental metastasisin vivo.

Conclusions

The results support the conclusion that SRC’s biological effects in bladder cancer are not primarily involved in promoting invasion and metastasis. Further work is required to define SRC’s roles in luminal papillary bladder cancers.