bluuebunny/crossref_metadata_2025 huggingface dataset:
Long forgotten perfume bottle nozzle in the uterus: challenges in retrieval in a low resource setting!
Authors: Chhetry Manisha , Yadav Jyotsna , Baniya Aashish
Published: January 2025

Foreign body in the uterus may lead to severe complications and pose significant management dilemmas. We report a 26-year-old lady who presented with foul-smelling discharge, subfertility, and a failed attempt at foreign body removal outside. Pelvic ultrasound revealed an impacted structure in the endocervical canal while a descending pipe was visualized in the endocervical canal per speculum examination. Partial removal vaginally and surgical removal of the nozzle via laparotomy was necessary due to the size, location, and impaction of the object. Posterior uterine incision was used due to easy accessibility. The post-operative stay was uneventful. This case underscores the importance of early detection, imaging, and multidisciplinary management in cases of uterine foreign bodies.
Osteopathic Manipulative Treatment for Postconcussive Symptoms: A Case Report
Authors: Tobon Steven , Bierbower Sonya , Giovanis Athina
Published: January 2025

Concussions are a common form of mild traumatic brain injury characterized by a transient alteration of cerebral function leading to a range of physical, cognitive, and emotional symptoms. Postconcussive symptoms (PCSs) usually resolve in about a week but can persist in 10% to 15% of patients. If left untreated, PCS can profoundly affect a patient’s life. The authors present a case of a previously healthy patient who dealt with residual headaches and anxiety for 10 months after a head injury. She was treated with osteopathic manipulative treatment (OMT), which helped resolve her headaches and her anxiety. The OMT techniques applied during treatment included balanced ligamentous tension, myofascial release, and osteopathy in the cranial field techniques. OMT is a nonpharmacological, noninvasive treatment that can benefit patients suffering with PCS. The authors would like to increase the awareness of clinicians and researchers for OMT’s potential positive outcomes for PCS, as part of a multifactorial approach to care.
methylGrapher: genome-graph-based processing of DNA methylation data from whole genome bisulfite sequencing
Authors: Zhang Wenjin , Macias-Velasco Juan F , Zhuo Xiaoyu , Belter Edward A , Tomlinson Chad , Garza John , Tekkey Nina , Li Daofeng , Wang Ting
Published: January 2025

Genome graphs, including the recently released draft human pangenome graph, can represent the breadth of genetic diversity and thus transcend the limits of traditional linear reference genomes. However, there are no genome-graph-compatible tools for analyzing whole genome bisulfite sequencing (WGBS) data. To close this gap, we introduce methylGrapher, a tool tailored for accurate DNA methylation analysis by mapping WGBS data to a genome graph. Notably, methylGrapher can reconstruct methylation patterns along haplotype paths precisely and efficiently. To demonstrate the utility of methylGrapher, we analyzed the WGBS data derived from five individuals whose genomes were included in the first Human Pangenome draft as well as WGBS data from ENCODE (EN-TEx). Along with standard performance benchmarking, we show that methylGrapher fully recapitulates DNA methylation patterns defined by classic linear genome analysis approaches. Importantly, methylGrapher captures a substantial number of CpG sites that are missed by linear methods, and improves overall genome coverage while reducing alignment reference bias. Thus, methylGrapher is a first step toward unlocking the full potential of Human Pangenome graphs in genomic DNA methylation analysis.
Lack of ST2 aggravates glioma invasiveness, vascular abnormality, and immune suppression
Authors: Wicher Grzegorz , Roy Ananya , Vaccaro Alessandra , Vemuri Kalyani , Ramachandran Mohanraj , Olofsson Tommie , Imbria Rebeca-Noemi , Belting Mattias , Nilsson Gunnar , Dimberg Anna , Forsberg-Nilsson Karin
Published: January 2025

Background

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, characterized by aggressive growth and a dismal prognosis. Interleukin-33 (IL-33) and its receptor ST2 have emerged as regulators of glioma growth, but their exact function in tumorigenesis has not been deciphered. Indeed, previous studies on IL-33 in cancer have yielded somewhat opposing results as to whether it is pro- or anti-tumorigenic.

Methods

IL-33 expression was assessed in a GBM tissue microarray and public databases. As in vivo models we used orthotopic xenografts of patient-derived GBM cells, and syngenic models with grafted mouse glioma cells.

Results

We analyzed the role of IL-33 and its receptor ST2 in nonmalignant cells of the glioma microenvironment and found that IL-33 levels are increased in cells surrounding the tumor. Protein complexes of IL-33 and ST2 are mainly found outside of the tumor core. The IL-33-producing cells consist primarily of oligodendrocytes. To determine the function of IL-33 in the tumor microenvironment, we used mice lacking the ST2 receptor. When glioma cells were grafted to ST2-deficient mouse brains, the resulting tumors exhibited a more invasive growth pattern, and are associated with poorer survival, compared to wild-type mice. Tumors in ST2-deficient hosts are more invasive, with increased expression of extracellular matrix remodeling enzymes and enhanced tumor angiogenesis. Furthermore, the absence of ST2 leads to a more immunosuppressive environment.

Conclusions

Our findings reveal that glia-derived IL-33 and its receptor ST2 participate in modulating tumor invasiveness, tumor vasculature, and immunosuppression in glioma.
The Arabidopsis basic–helix–loop–helix transcription factor LRL1 activates cell wall-related genes during root hair development
Authors: Haghir Shahrzad , Yamada Koh , Kato Mariko , Tsuge Tomohiko , Wada Takuji , Tominaga Rumi , Ohashi Yohei , Aoyama Takashi
Published: January 2025

Lotus japonicus-ROOT HAIR LESS1-LIKE-1 (LRL1) of Arabidopsis thaliana encodes a basic helix–loop–helix (bHLH) transcription factor (TF) involved in root hair development. Root hair development is regulated by an elaborate transcriptional network, in which GLABRA2 (GL2), a key negative regulator, directly represses bHLH TF genes, including LRL1 and ROOT HAIR DEFECTIVE6 (RHD6). Although RHD6 and its paralogous TFs have been shown to connect downstream to genes involved in cell morphological events, such as endomembrane and cell wall modification, the downstream network of LRL1 remains elusive. We found that a mutation of LRL1 causes a short-root hair phenotype and that this phenotype can be partially rescued by a transgene encoding a glucocorticoid receptor (GR) domain-fused LRL1, LRL1-GR, in the presence of glucocorticoids. Using this conditional rescue system, we identified 46 genes that are activated downstream of LRL1. Among these, the cell wall-related genes were significantly enriched and many of them were found to be immediately downstream of LRL1 without de novo protein synthesis in between. We further analyzed three representative genes, PROLINE-RICH PROTEIN1 (PRP1), PRP3, and XYLOGLUCAN ENDOTRANSGLUCOSYLASE/HYDOLASE12 (XTH12). Reporter gene analyses showed that these genes are specifically transcribed in root hair cells including those in the root–hypocotyl junction, and that their proteins were localized to the cell wall of elongating root hairs, root hair bulges, and root hair bulge-expecting loci. A T-DNA insertion mutant of PRP3 showed a moderate short-root hair phenotype. Based on these results, LRL1 is likely to promote root hair development throughout the morphogenetic process by activating cell wall-related genes.
Quantifying behavior-based gender discrimination on collaborative platforms
Authors: Vásárhelyi Orsolya , Vedres Balázs
Published: January 2025

Digital collaborative platforms have become crucial venues of career advancement and individual success in many creative fields, from engineering to the arts. Gender discrimination related to behavioral choices of users is a key component to gendered disadvantage on platforms. Such platforms carried the promise of opening avenues of advancement to previously discriminated groups, such as women, as platforms lack managerial gatekeepers with conventional prejudice. We analyzed the extent of behavior-based gender discrimination on two digital platforms, GitHub and Behance, focused on software development and fine arts and design. We found that the main cause of women’s disadvantage in attention, success, and survival is largely due to the gender typicality of their behavior that varies between 60 and 90% of the total disadvantage of women. Men and women are penalized if they follow highly female-like behavior, while categorical gender is no longer significant. As platforms employ algorithmic tools and AI systems to manage users’ activity and visibility, and recommend new projects to collaborate, stereotypes associated with behavior can have long-lasting consequences.
AI for all: bridging data gaps in machine learning and health
Authors: Wang Monica L , Bertrand Kimberly A
Published: January 2025

Artificial intelligence (AI) and its subset, machine learning, have tremendous potential to transform health care, medicine, and population health through improved diagnoses, treatments, and patient care. However, the effectiveness of these technologies hinges on the quality and diversity of the data used to train them. Many datasets currently used in machine learning are inherently biased and lack diversity, leading to inaccurate predictions that may perpetuate existing health disparities. This commentary highlights the challenges of biased datasets, the impact on marginalized communities, and the critical need for strategies to address these disparities throughout the research continuum. To overcome these challenges, it is essential to adopt more inclusive data collection practices, engage collaboratively with community stakeholders, and leverage innovative approaches like federated learning. These steps can help mitigate bias and enhance the accuracy and fairness of AI-assisted or informed health care solutions. By addressing systemic biases embedded across research phases, we can build a better foundation for AI to enhance diagnostic and treatment capabilities and move society closer to the goal where improved health and health care can be a fundamental right for all, and not just for some.
Bonds without belonging? The genuine link in international, union, and nationality law
Authors: Spieker Luke Dimitrios , Weber Ferdinand
Published: January 2025

What kind of connection should form the basis of nationality? For decades, the ‘genuine link’ has been a central, yet controversial concept in international and European scholarship and practice. The controversy revolves around a simple question: does nationality require a certain degree of belonging? Or put differently, can there be such bonds without belonging? Recently, the debate has been rekindled by the Maltese practice of ‘golden passports’. This contribution traces the state of the debate, anchors the genuine link requirement in international and Union law, develops its contours and conditions, and discusses possible objections. We argue that the genuine link requirement is the result of an interplay of several sources: international law, the prohibition of abuse of law, and the constitutional principles of solidarity and democracy. Together, they form the basis for the genuine link in European Union law.
Peripheral neuropathy: from guidelines to clinical practise
Authors: Jordan Berit , Jahn Franziska , Jordan Karin
Published: January 2025

Purpose of review

Chemotherapy-induced peripheral neuropathy (CIPN) is a substantial adverse effect of anticancer therapy. No effective preventive strategies are established in clinical routine, although some forms of cryotherapy or compression therapy seem to be promising. CIPN is difficult to grade objectively and has mostly relied on a clinician- or patient-based rating that is subjective and not easily reproducible.

Recent findings

Recent preclinical and clinical studies showed an indicative hint of serum neurofilaments for axonal damage as a biomarker and might be introduced in clinical practice in the future. Axonal degeneration in toxic neuropathy is triggered by molecular pathways including SARM1. Presence of certain genotypes predispose for developing severe vincristine neuropathy. Still, treatment of CIPN is focused on treating neuropathic pain primarily based on physicians experience. A positive effect of membrane stabilizers such as gabapentinoids could not be shown in a systematic review mostly due to inconsistent study populations. In the treatment and prevention of functional disability, physical exercise including sensorimotor-training and whole-body vibration seems promising.

More research is needed on quantification of biomarkers indicative for axonal degeneration prior to CIPN symptom expression. All these recent findings should support the health-care team for a patient centred treatment approach.
Immuno-oncology in the daily practice
Authors: Laparra Ariane
Published: January 2025

Purpose of review

Immune checkpoint inhibitors (ICI) have become an integral part of oncology treatment. ICI currently has approval for more than thirty tumor types with proven efficacy. However, ICI can expose patients to inflammatory side effects, such as immuno-related adverse events (irAE). The spectrum of irAE and the time to onset can be very broad, sometimes leading to the patient's death.

Additionally, ICI could be associated with chronic or long-term adverse events that impact quality of life. The expansion of the indications for immunotherapy in the early adjuvant and neoadjuvant stages is altering the benefit-risk balance of these therapies.

Furthermore, the combination of immunotherapies with other oncology treatments makes the interpretation of adverse events difficult.

To date, no predictive factors have been identified in routine practice to identify patients at risk of developing serious toxicity.

Recent findings

This has led us to develop a patient care pathway dedicated to the management of these toxicities, enabling early detection of irAE to improve outcomes.

We have presented a novel care pathway based on a clinical evaluation, encompassing a daily hospital devoted to the management of toxicities, an iTox multidisciplinary board, and a pharmacovigilance database. This pathway involves a translational research program.

The toxicity day hospital allowed us to care for patients at an early stage of an adverse event and to establish whether anticancer treatment was responsible for the onset of symptoms and/or biological abnormalities.

The objective of this pathway is to enhance the quality of life and compliance of oncology treatment, while minimizing the necessity for unscheduled care.
The role of the microbiome in skin cancer development and treatment
Authors: Martin Fuentes Anthony
Published: January 2025

Purpose of review

Recent research underscores the significant influence of the skin and gut microbiota on melanoma and nonmelanoma skin cancer (NMSC) development and treatment outcomes. This review aims to synthesize current findings on how microbiota modulates immune responses, particularly enhancing the efficacy of immunotherapies such as immune checkpoint inhibitors (ICIs).

Recent findings

The microbiota's impact on skin cancer is multifaceted, involving immune modulation, inflammation, and metabolic interactions. Beneficial strains like Bifidobacterium and Lactobacillus have shown potential in supporting anti-PD-1 and anti-CTLA-4 therapies by promoting T-cell activation and immune surveillance. Evidence from preclinical and clinical studies, including fecal microbiota transplantation (FMT), highlights improved response rates in patients with microbiota-rich profiles. Notably, certain bacterial metabolites, such as inosine, contribute to enhanced antitumor activity by stimulating IFN-γ in CD8+ T cells.

Understanding the interplay between microbiota and skin cancer treatment opens promising avenues for adjunctive therapies. Probiotic and prebiotic interventions, FMT, and microbiota modulation are emerging as complementary strategies to improve immunotherapy outcomes and address treatment resistance in melanoma and NMSC.
Robotic surgical techniques and methods for treating renal cell carcinoma with inferior vena cava tumor thrombus
Authors: Luo Jin , Li Zhuoran , Liu Qiwei , Jia Yuqi , Li Jinqiao , Zhao Houming , Chen Zhiqiang , Dong Yujie , Zhang Xu , Ma Xin , Huang Qingbo , Peng Cheng , Wang Baojun
Published: January 2025

Purpose of Review

Renal cell carcinoma with inferior vena cava (IVC) tumor thrombus (RCC-IVCTT) has a high mortality rate, and surgery is the only promising treatment. Open surgery has been the gold standard treatment for several decades. However, with the development of minimally invasive surgical technologies, the advantages of robotic surgery have gradually emerged. The classic Mayo Clinic Classification system has certain limitations in guiding robotic surgery. Therefore, a new classification system that is compatible with robotic surgery is urgently needed. Advancements in robotic surgery must be systematically summarized and evaluated.

Recent Findings

Since Abaza's initial report on robotic surgery, the exploration of robotic radical nephrectomy (RRN) with IVC thrombectomy has resulted in numerous related techniques and approaches, including surgical positions and approaches, control of blood vessels, assisted exposure, step-by-step strategy, and preoperative and intraoperative auxiliary technology and equipment. Our team proposed a new tumor thrombus classification system termed the “301 Classification” based on RRN with venous thrombectomy, which matches each level of tumor thrombus with a distinct robotic surgical strategy.

With advances in technology and accumulated experience, RRN with IVC thrombectomy holds promise as the preferred surgical option for RCC-IVCTT. Although “301 Classification” can provide objective advantages in robotic surgery, more cases are needed to be optimized for guiding surgery accurately. The overview provided in this paper aims to serve as a reference and inspiration for future research and clinical practice regarding RCC-IVCTT.
HELICOBACTER PYLORI ERADICATION TREATMENTS AND RISK OF ALZHEIMER DISEASE: A CASE–CONTROL STUDY NESTED IN THE FINNISH POPULATION
Authors: Keränen Emmi , Rysä Jaana , Tiihonen Miia , Hartikainen Sirpa , Tolppanen Anna-Maija
Published: January 2025

Background:

Helicobacter pylori (H. pylori) has been inconsistently associated with risk of Alzheimer disease. The exposure assessment period has often overlapped with the prodromal time of Alzheimer disease. Cognitive disorders might increase vulnerability to infectious pathogens, complicating the ascertainment of temporal relationship between H. pylori infection and Alzheimer disease.

Methods:

This Finnish nested case–control study included 70,520 persons with incident Alzheimer disease diagnosed between 2005-2011 and 281,233 age-, sex-, and region of residence-matched controls. We obtained information on comorbidities and drug use from the national healthcare registers. We identified dispensed
H. pylori
eradication treatments from the Prescription register. We considered exposure at least 5 years before Alzheimer disease diagnosis in the main analysis. We compared risk of Alzheimer disease between
H. pylori
eradication treatment users and nonusers using confounder-adjusted (comorbidities and other drug use) conditional logistic regression. We assessed cumulative exposure by calculating the number of eradication treatments.

Results:

The prevalence of exposure to H. pylori eradication treatment at least 5 years before the outcome was 4.1% in cases and 3.9% in controls. The odds ratio (95% confidence interval) was 1.06 (1.02–1.11) in the crude and 1.03 (0.99–1.07) in the confounder-adjusted model. We observed no association between cumulative exposure and risk of Alzheimer disease.

Conclusion:

Our results, reflecting diagnosed and treated
H. pylori
infection late in life, do not support the hypothesis of
H. pylori
as an independent risk factor for Alzheimer disease. The previously reported association may be explained by reverse association and confounding.
Construction and demonstrative application of an evaluation indicator system for the distinction of ancient books of traditional chinese medicine based on the delphi method and analytic hierarchy process
Authors: Tong Lin , Zhang Weina , Zhang Lei , Li Meng , Liu Sihong , Chen Guangkun , Li Chen , Zhang Yu , Ye Junze , Su Zhaochen , Li Bing , Li Hongtao , Zhang Huamin
Published: January 2025

Objective:

To construct a scientific and standardized evaluation indicator system for the distinction of ancient books of Traditional Chinese Medicine, aiming to provide a scientific basis for their cascade protection.

Methods:

The Delphi method was applied to establish the evaluation indicator system for the distinction of ancient books of Traditional Chinese Medicine, and the Analytic Hierarchy Process (AHP) was used to determine the weight of each indicator.

Results:

An evaluation indicator system for the distinction of ancient books of Traditional Chinese Medicine was developed, including 4 first-level indicators and 15 second-level indicators. The experts’ enthusiasm, authority, and coordination of opinions were all satisfactory.

Conclusion:

A evaluation indicator system for the distinction of ancient books of Traditional Chinese Medicine was preliminary constructed. The system is targeted, well-structured, and exhibits strong scientific and practical significance.
From the backroom to the boardroom: Health care chief information officers, stereotypes, and strategic leadership in the digital transformation era
Authors: Heath Michele L. , Silvera Geoffrey A. , Porter Tracy H.
Published: January 2025

Issue

The digital transformation of the U.S. health care system is underway, but the role of health care chief information officers (HCIOs) in that transformation has been unclear. As the landscape of health care technology continues to expand, there is an increasing need to understand the influence of HCIOs, who are in a unique position to impact key strategic decisions. We seek to demonstrate the strategic importance of HCIOs in meeting the needs of digital transformation, by managing the emergence and strategic implementation of health care technologies to benefit health care organization performance. We also propose that profession-based stereotypes inhibit HCIOs as they may be viewed as behind-the-scenes technicians rather than strategic leaders.

Critical Theoretical Analysis

Upper echelons (UE) theory demonstrates how HCIOs' unique perspectives gained through education, experience, and the strategic decision-making process also can influence organizational performance. We build on UE to conceptualize the degree to which profession-based stereotypes moderate the decision-making of top management teams).

Theoretical Implications

We present two theoretical contributions. First, we introduce a profession-based stereotype moderated model of UE specific to HCIOs. Second, we offer an analysis of the role of HCIOs as strategic leaders in the digital transformation era.

Practice Implications

We call upon health care scholars and practitioners to examine HCIOs' influence and their roles in health care organization decision-making, top management team interactions, and organizational outcomes as the digital transformation in health care continues.
Pain in very preterm infants—prevalence, causes, assessment, and treatment. A nationwide cohort study
Authors: Graham Hillary , Razaz Neda , Håkansson Stellan , Blomqvist Ylva Thernström , Johansson Kari , Persson Martina , Nyholm Annika , Norman Mikael
Published: January 2025

Studies on pain in preterm infants have usually been confined to observations of painful procedures, and information from extremely preterm infants is limited. Using registry data from a Swedish nationwide cohort, this study explored the epidemiology of pain in very preterm infants, its causes, assessments, and treatment strategies. We included liveborn infants <32 weeks' gestational age (GA) discharged between January 2020 and June 2024. Proportions of infants exposed to potentially painful procedures, experiencing pain, assessed with pain scales, and receiving pharmacological treatment were calculated by each postnatal day. Among 3686 infants (mean birthweight 1176 g, GA 28.2 weeks), 11.6% had a painful condition and 84.1% were exposed to at least 1 potentially painful procedure. In total, 74.6% experienced pain, corresponding to 28,137/185,008 (15.2%) days of neonatal care. For every 2-week increase in GA, significantly lower proportions of infants experienced pain. In infants <28 weeks of GA, proportions with reported pain were approximately half the rate of painful procedures, while in infants born at 28 to 31 weeks, reported pain closely matched exposure to painful procedures. Pain scales were used in 75.0% of the infants. Pharmacological pain treatment was administered to 81.7% of infants, primarily topically or orally. Among infants with pain, proportions treated intravenously were larger at higher GAs. Despite effective analgesia/anesthesia, many very preterm infants experience pain. Visualizing pain epidemiology, procedures, conditions, and treatment by postnatal and gestational age may guide clinical management and generate research hypotheses to reduce short- and long-term adverse effects.
Improving Timely Evaluation of Newborns at Risk for Hemolytic Disease From a Positive Maternal Antibody
Authors: Samaras Athena T. , Sweeney Alison E. , Lewis Emilee C. , Thompson Julie A. , Waldrop Julee
Published: January 2025

Background:

Hemolytic disease of the newborn (HDN) is a rare condition with the potential for high morbidity.

Local Problem:

Practice at a large maternity care center did not align with the American Academy of Pediatrics (AAP) revised hyperbilirubinemia guidelines.

Methods:

A pre/post-implementation design with Plan-Do-Study-Act cycles was used.

Interventions:

A clinical pathway was implemented to improve timely evaluation of newborns at risk for HDN due to a positive maternal antibody using cord blood.

Results:

Cord blood testing increased among the subset of newborns who did not meet collection criteria prior to the practice change (pre: 0% n = 7, post: 39% n = 23). Missed opportunities to test cord blood occurred less frequently post (35 versus 26 days between missed opportunities). Feasibility data identified the need for educational and clinical tools.

Conclusions:

A clinical pathway and tailored tools support the AAP recommendation. Electronic health record supports could bolster future efforts.
Survival Disparity and the Unique Genomic and Microbiome Profiles of Colon Cancer in Appalachian Kentucky
Authors: McDonald Hannah G , Reagan Anna M , Faisal Abu Saleh Mosa , Goettl Ryan , Wang Chi , Hoyd Rebecca , Spakowicz Daniel , Evers B Mark , Kim Joseph , Bhakta Avinash S
Published: January 2025

Background:

Colon cancer is a leading cause of mortality in Appalachian Kentucky. Studies suggest that the microbiome may influence cancer outcomes. We investigate differential gene expression, the tumor microbiome, and the association between the two as potential drivers of disparities in colon cancer outcomes.

Study Design:

This study analyzed patients diagnosed with colon adenocarcinoma between 2010-2023. Demographic data were extracted from Kentucky Cancer Registry. Somatic mutations and significantly mutated genes were identified using Fischer’s exact T-test. RNASeq data was processed for gene expression analysis and Holm-Bonferroni method was used to adjust p-values for multiple comparisons. The STAR aligner, (exotic)v2.1 pipeline, and KrakenUniq database were used to classify microbes in human samples. The R package (exotic) was then used to decontaminate the results.

Results:

The final cohort included 2276 patients, 321 of which had available somatic mutation sequencing data. Demographic differences between Appalachian and non-Appalachian patients included marital status (P = 0.0005), race (P < 0.0001), insurance status, (P = 0.0005), BMI (P = 0.001), type 2 diabetes (P < 0.0001) and Charlson Comorbidity Index (CCI; P = 0.03). There was no difference in gene mutation frequency. There was differential expression of 228 genes. Differential abundance analysis revealed differences in 381 bacterial species. Importantly, 3 microbiota significantly correlated with survival disparities between Appalachian and non-Appalachian patients: C. cadaveris (adjusted P = 0.009), L. salivarius (adjusted P = 0.048), and S. wadsworthensis (adjusted P = 0.009).

Conclusion:

This is the first report of the distinct tumor microbiome in Appalachian Kentucky and its impact on survival. Further studies are needed to better characterize the unique tumor and gut microbiome of Appalachian patients with colon cancer.
Bayesian inference of fitness landscapes via tree-structured branching processes
Authors: Luo Xiang Ge , Kuipers Jack , Rupp Kevin , Takahashi Koichi , Beerenwinkel Niko
Published: January 2025

Motivation: The complex dynamics of cancer evolution, driven by mutation and selection, underlies the molecular heterogeneity observed in tumors. The evolutionary histories of tumors of different patients can be encoded as mutation trees and reconstructed in high resolution from single-cell sequencing data, offering crucial insights for studying fitness effects of and epistasis among mutations. Existing models, however, either fail to separate mutation and selection or neglect the evolutionary histories encoded by the tumor phylogenetic trees. Results: We introduce FiTree, a tree-structured multi-type branching process model with epistatic fitness parameterization and a Bayesian inference scheme to learn fitness landscapes from single-cell tumor mutation trees. Through simulations, we demonstrate that FiTree outperforms state-of-the-art methods in inferring the fitness landscape underlying tumor evolution. Applying FiTree to a single-cell acute myeloid leukemia dataset, we identify epistatic fitness effects consistent with known biological findings and quantify uncertainty in predicting future mutational events, offering a unified framework for understanding tumor progression and potentially for guiding therapeutic strategies.
The receptor-like kinases BIR1 and BIR3 modulate antiviral resistance by different mechanisms
Authors: Robinson Carmen , Guzman-Benito Irene , Sede Ana Rocio , Elvira-Gonzalez Laura , Hua Chenlei , Ciska Malgorzata , Nurnberger Thorsten , Heinlein Manfred , Llave Cesar
Published: January 2025

The BAK1-INTERACTING RECEPTOR-LIKE KINASE (BIR) proteins, including BIR1, are negative regulators of cell death and defense in Arabidopsis. Although BIR1 is upregulated during viral infections, its role in virus defense remains unclear. Here, we demonstrate a conserved role for the BIR family as modulators of antiviral resistance in Arabidopsis. During tobacco rattle virus (TRV) infection, BIR gene expression is regulated by antagonistic interactions between salicylic acid (SA) and jasmonic acid (JA) signaling pathways. Genetic evidence shows that BIR1, BIR2, and BIR3 negatively regulate TRV resistance via distinct mechanisms. The antiviral phenotype in bir1-1 mutants is unaffected by mutations in the receptor-like kinases (RLK) BAK1, SOBIR1, or in the lipase-like PAD4. While BIR1 induction partially suppresses PTI marker gene expression, it does not affect early PTI responses such as reactive oxygen species (ROS) production or ethylene accumulation. BIR1 also inhibits plasmodesmata (PD) callose deposition and facilitates virus spread. Our data suggest that BIR1 modulates antiviral defense through mechanisms that include PTI gene expression, PD callose deposition alongside yet unidentified pathways independent of ROS or BAK1, SOBIR1, or PAD4 signaling components. In contrast, BIR3 suppresses an antiviral resistance pathway against TRV that requires BAK1 and the lipases PAD4 and EDS1. Our results suggest that BIR3 controls an NLR-dependent ETI-like response that restricts virus proliferation without triggering a hypersensitive response. These findings highlight the distinct roles of BIR family members in regulating antiviral defense in Arabidopsis.
The Batch-Resourcing Angiogenesis Tool (BRAT) to enable high-content microscopy screening of microvascular networks
Authors: Krek Harriet , Murphy Ashley R. , McKinnon Ryan , Franco Rose Ann , Allenby Mark C.
Published: January 2025

Vessel forming assays are a valuablein vitrotechnology to evaluate the vasculogenic and angiogenic potential of different cell types, matrix proteins, and soluble factors. Recent advances in high-content microscopy allow for vascular morphogenesis assays to be captured in real-time and in high-throughput screening purposes. Unfortunately, existing microvascular network quantification algorithms are either inaccurate, not user-friendly, or manually analyse one image at a time, unfavourable to high-content screening applications. This manuscript introduces BRAT, the Batch-Resourcing Angiogenesis Tool, a computer algorithm with an open-source graphic user interface to efficiently segment, skeletonize, and analyse large batches of vascular network images with high accuracy. Benchmarked across diverse clinical and cultured microvascular network images, BRAT is the most sensitive vascular network image analysis tool (94.5%) and exhibits leading accuracy (93.3%). BRAT’s multi-threaded processing automatically analysed 886 microscopy images at a speed of 0.17 seconds/image (2:29 minutes) on a performance computer or 2.31 seconds/image (34:04) on a typical laptop. This is 10-to-100 fold more time-efficient than existing tools, which require 12 to 16 seconds of direct user input per image. BRAT is broadly useful to analyse vessel networks of different endothelial cell types cultured on 2D substrates and within 3D biomaterials. BRAT represents a powerful approach for the accurate and high-content screening of vessel forming assays for disease models, regenerative medicines, and therapeutic testing.
Translational activators align mRNAs at the small mitoribosomal subunit for translation initiation
Authors: Bridgers Joseph B. , Carlström Andreas , Sherpa Dawafuti , Couvillion Mary T. , Rovšnik Urška , Gao Jingjing , Wan Bowen , Shao Sichen , Ott Martin , Churchman L. Stirling
Published: January 2025

Mitochondrial gene expression is essential for oxidative phosphorylation. Mitochondrial-encoded mRNAs are translated by dedicated mitochondrial ribosomes (mitoribosomes), whose regulation remains elusive. In the baker’s yeastSaccharomyces cerevisiae, nuclear-encoded mitochondrial translational activators (TAs) facilitate transcript-specific translation by a yet unknown mechanism. Here, we investigated the function of TAs containing RNA-binding pentatricopeptide repeats (PPRs) using selective mitoribosome profiling and cryo-EM structural analysis. These analyses revealed that TAs exhibit strong selectivity for mitoribosomes initiating on their target transcripts. Moreover, TA-mitoribosome footprints indicated that TAs recruit mitoribosomes proximal to the start codon. Two cryo-EM structures of mRNA-TA complexes bound to post-initiation/pre-elongation-stalled mitoribosomes revealed the general mechanism of TA action. Specifically, the TAs bind to structural elements in the 5’ UTR of the client mRNA as well as to the mRNA channel exit to align the mRNA in the small subunit during initiation. Our findings provide a mechanistic basis for understanding how mitochondria achieve transcript-specific translation initiation without relying on general sequence elements to position mitoribosomes at start codons.
Striatal cell-type specific stability and reorganization underlying agency and habit
Authors: Malvaez Melissa , Liang Alvina , Hall Baila S. , Giovanniello Jacqueline R. , Paredes Natalie , Gonzalez Julia Y. , Blair Garrett J. , Sias Ana C. , Murphy Michael D. , Guo Wanyi , Wang Alicia , Singh Malika , Griffin Nicholas K. , Bridges Samuel P. , Wiener Anna , Pimenta Jenna S. , Holley Sandra M. , Cepeda Carlos , Levine Michael S. , Blair H. Tad , Wikenheiser Andrew M. , Wassum Kate M.
Published: January 2025

Adaptive decision making requires agency, knowledge that actions produce particular outcomes. For well- practiced routines, agency is relinquished in favor of habit. Here, we asked how dorsomedial striatum D1+and D2/A2A+neurons contribute to agency and habit. We imaged calcium activity of these neurons as mice learned to lever press with agency and formed habits with overtraining. Whereas many D1+neurons stably encoded actions throughout learning and developed encoding of reward outcomes, A2A+neurons reorganized their encoding of actions from initial action-outcome learning to habit formation. Chemogenetic manipulations indicated that both D1+and A2A+neurons support action-outcome learning, but only D1+neurons enable the use of such agency for adaptive, goal-directed decision making. These data reveal coordinated dorsomedial striatum D1+and A2A+function for the development of agency, cell-type specific stability and reorganization underlying agency and habit, and important insights into the neuronal circuits of how we learn and decide.
Two CTCF motifs impede cohesin-mediated DNA loop extrusion
Authors: Barth Roman , Janissen Richard , Muras Laura , van der Torre Jaco , Litos Gabriele , van der Sluis Eli , van der Graaf Ashmiani , Davidson Iain F. , Peters Jan-Michael , Dekker Cees
Published: January 2025

Cohesin extrudes DNA into loops and is positioned along the genome by stalling at CTCF upon encountering its N-terminal region (NTR). The mechanism underlying this stalling, however, is unresolved. Using single-molecule assays that monitor DNA loop extrusion (LE) in the presence of NTR fragments, we identify two amino acid motifs, YDF and KTYQR, that hinder LE. KTYQR is found to fully impede LE activity, while YDF hinders cohesin to complete LE step cycles and converts cohesin into a unidirectional extruder by strengthening the affinity of STAG1 to DNA. We thus identify two distinct NTR motifs that stall LE via different yet synergistic mechanisms, highlighting the multifaceted ways employed by CTCF to modulate LE to shape and regulate genomes.
Hadron-quark hybrid model, modular transformation, and Roberge-Weiss transition
Authors: Kouno Hiroaki , Oshima Riki , Tachibana Motoi , Kashiwa Kouji
Published: January 2025

In the framework of modular transformations, we reformulate the recently proposed hadron-quark hybrid model when the imaginary baryonic chemical potential is introduced. In this case, the number density of the hybrid model is obtained by the modular transformation of the complex number densities of the baryons (antibaryons) and the quarks (antiquarks). We can regard these number densities as the basis in the complex plane. As a result, we can consider the torus, which is characterized by the basis. Since the complex structure of the torus is invariant under the modular transformation, we can extract the topological property of the hadron-quark system using the untransformed baryon (antibaryon) and the quark (antiquark) number densities. We apply this model to analyze the Roberge-Weiss transition. It is shown that the torus vanishes at the baryonic chemical potential where the Roberge-Weiss transition appears because the number density of baryons (antibaryons) is not linearly independent of the number density of quarks (antiquarks). When the temperature T is lower than the Roberge-Weiss transition temperature TRW, the torus shrinks smoothly to the one-dimensional object at the Roberge-Weiss transition point, but the discontinuity does not appear. On the other hand, the discontinuity of the geometrical object appears when T>TRW. We also calculate the modulus of the torus and transform it into the fundamental region. The transformed moduli are symmetric below TRW, but the symmetry is broken above TRW.

Published by the American Physical Society
2025
Quantum description of wave dark matter
Authors: Cheong Dhong Yeon , Rodd Nicholas L. , Wang Lian-Tao
Published: January 2025

We outline a fundamentally quantum description of bosonic dark matter (DM) from which the conventional classical-wave picture emerges in the limit m≪10  eV. As appropriate for a quantum system, we start from the density matrix, which encodes the full information regarding the possible measurements we could make of DM and their fluctuations. Following fundamental results in quantum optics, we argue that for DM it is most likely that the density matrix takes the explicitly mixed form of a Gaussian over the basis of coherent states. Deviations from this would generate non-Gaussian fluctuations in DM observables, allowing a direct probe of the quantum state of DM. Our quantum optics–inspired approach allows us to rigorously define and interpret various quantities that are often only described heuristically, such as the coherence time or length. The formalism further provides a continuous description of DM through the wave-particle transition, which we exploit to study how density fluctuations over various physical scales evolve between the two limits and to reveal the unique behavior of DM near the boundary of the wave and particle descriptions.

Published by the American Physical Society
2025
Atmospheric Carbon Dioxide Removal: A Physical Science Perspective
Authors: Taylor Washington , Marston Brad , Rosner Robert , Wurtele Jonathan
Published: January 2025

Novel carbon dioxide removal (CDR) technologies are increasingly being considered as potentially useful tools to combat climate change. For specific atmospheric carbon dioxide management targets to be achieved, large-scale CDR strategies may be needed, even with aggressive efforts to reduce carbon dioxide emissions in the coming decades. This American Physical Society report breaks down the physical requirements necessary for large-scale implementation of CDR technologies, demonstrating the challenges inherent to incorporating CDR into any carbon dioxide management portfolio. It also provides a technical overview of new and current CDR approaches and evaluates their fundamental physical constraints. Based on the technical overview, the report makes several recommendations for the U.S. federal government and industry. These include ensuring that the potential for CDR does not compromise ongoing actions to reduce carbon emissions. The report observes, however, that while large-scale CDR technologies require a lot of energy and material resources, they might be needed in combination with emission reduction strategies to achieve specific climate goals. Research and development on CDR should be selectively pursued, despite the many challenges described in the report.

Published by the American Physical Society
2025
The nature of halogen bonding: insights from interacting quantum atoms and source function studies
Authors: Pisati Arianna , Forni Alessandra , Pieraccini Stefano , Sironi Maurizio
Published: January 2025

A detailed study of the X...N (X = I, Br) halogen bonds in complexes formed by an extended set of substituted pyridines with D—X molecules (D = X, CN) is reported here. The nature of these interactions has been investigated at different (MP2 and DFT) levels of theory through Bader's quantum theory of atoms in molecules (QTAIM) and Pendás' interacting quantum atoms (IQA) scheme, focusing on the role of the local environment (i.e. the substituent on the pyridine ring and the halogenated residue) on the halogen bond features. We found that the exchange-correlation energy represents a substantial contribution to the IQA total energy, in some cases comparable to (I2 complexes) or even dominating (ICN complexes) the electrostatic term. Meaningful information is provided by the source function, indicating that the major contribution to the electron density at the bond critical point of the X...N interaction is derived from the halogen atom, while a much lower contribution comes from the nitrogen atom, which acts as either source or sink for electron density. A relevant contribution from distal atoms, including the various electron-donor and electron-withdrawing substituents in different positions of the pyridine ring, is also determined, highlighting the non-local character of the electron density. The existence of possible relationships between binding energies, interaction energies according to IQA, and QTAIM descriptors such as delocalization indices and source function, has been inspected. In general, good correlations are only found when the local environment, external to the directly involved halogen and nitrogen atoms, plays a minor role in the interaction.
How workers construct a sense of positive occupational identity in a contested emerging profession: the case of career coaches
Authors: Felix Bruno , Vieira Ana Patricia Alves
Published: January 2025

Purpose

Using the empirical context of the coaching profession, this study explores how workers in a partially contested and emerging occupation construct a sense of positive occupational identity.

Design/methodology/approach

We adopted a grounded theory method, drawing on interviews with 43 Brazilian career coaches, supplemented by documentary analysis of archival materials related to the profession and non-participant observations conducted during training sessions for these professionals.

Findings

Participants report the ambiguity of their occupational roles as career coaches, with expectations from different groups sometimes aligning and sometimes conflicting. Instead of striving for a homogeneous expectation of how career coaches should be, they suggest finding a sufficient balance between their perceived selves and diverse expectations. This attainable authenticity is reflected in participants' reliance on validation from supportive social groups rather than those who disapprove of career coaching as a vocation. We contend that two combined factors were essential for these professionals in a simultaneously contested and emerging occupation to construct a positive occupational identity. The first involves recognizing that they cannot be entirely authentic in their profession but can be sufficiently authentic. The second is that they should not rely on universal societal approval but instead leverage approval from certain societal groups, accepting that not everyone will approve of them.

Originality/value

This paper represents an original effort to explore how career coaches endeavor to build a positive occupational identity, considering the context of a simultaneously contested and emerging occupation. The simultaneous consideration of these factors, through the specific case of career coaches, was innovative for the literature.
Effects of justice perception on contractor value co-creation behavior in infrastructure megaprojects: the mediating role of psychological ownership
Authors: Tian Bo , Fu Jiaxin , Xu Yongshun , Li Jinjin
Published: January 2025

Purpose

As the complexity and uncertainty of infrastructural megaprojects challenge traditional management models, there is an increasing focus on value co-creation as an organizational strategy to streamline management. However, the role of value co-creation behavior in facilitating the value realization process remains underexplored. This study examines how justice perception (distributive, procedural and interactional justice) improves contractor value co-creation behavior, focusing on the mediating role of psychological ownership.

Design/methodology/approach

Ten hypotheses in the proposed research model were tested through partial least squares structural equation modeling using 199 valid questionnaires from China.

Findings

The results show that contractor value co-creation behavior is directly and positively influenced by procedural, distributive and interactional justice and indirectly influenced by them through the underlying psychological mechanism of psychological ownership.

Originality/value

The findings fill a knowledge gap by examining the effect of justice perception on contractor value co-creation behavior based on social exchange theory. Discovering justice perception will contribute to contractor value co-creation behavior, and psychological ownership mediates this relationship.