Challenges

@book{medawar1967mathematical1,
    author = "Medawar, P",
    title = "Mathematical Challenges to the Neo-Darwinian Interpretation of Evolution",
    year = "1967",
    publisher = "Philadelphia, Wistar Institute Press",
    note = "talkorigins\_source = {true}; raw\_reference = {Medawar, P., 1967, Mathematical Challenges to the Neo-Darwinian Interpretation of Evolution: Philadelphia, Wistar Institute Press.}"
}

@techreport{wright1967comments2,
    author = "Wright, S",
    title = "Comments on the Preliminary Working Papers of Eden and Waddington, in Moorehead, P. S., and Kaplan, M. M., eds., Mathematical Challenges to the Neo-Darwinian Theory of Evolution, 5 of Wistar Institute Symposium",
    year = "1967",
    howpublished = "Philadelphia, Wistar Institute, p. 117-120",
    note = "talkorigins\_source = {true}; raw\_reference = {Wright, S., 1967, Comments on the Preliminary Working Papers of Eden and Waddington, in Moorehead, P. S., and Kaplan, M. M., eds., Mathematical Challenges to the Neo-Darwinian Theory of Evolution, 5 of Wistar Institute Symposium: Philadelphia, Wistar Institute, p. 117-120.}"
}

NonDarwinian evolution of protein and DNA, comparing expectations of evolution models for protein and amino acid changes

@article{doi101126science1643881788,
    author = "King, Jack Lester and Jukes, Thomas H.",
    title = "Non-Darwinian Evolution",
    year = "1969",
    journal = "Science",
    abstract = "NonDarwinian evolution of protein and DNA, comparing expectations of evolution models for protein and amino acid changes",
    url = "https://doi.org/10.1126/science.164.3881.788",
    doi = "10.1126/science.164.3881.788",
    openalex = "W1983519005",
    references = "doi101007bf02984069, doi101016s0021925818643212, doi101017s0016672300011459, doi101017s0305004100015644, doi101038217624a0, doi101073pnas581142, doi101093genetics5011, doi101126science14636511535, doi101126science1613841529, doi1023073211856"
}

@incollection{crow1972darwinian,
    author = "Crow, James F.",
    title = "DARWINIAN AND NON-DARWINIAN EVOLUTION",
    year = "1972",
    booktitle = "Darwinian, Neo-Darwinian, and Non-Darwinian Evolution, April 9–12, 1971",
    url = "https://doi.org/10.1525/9780520313897-001",
    doi = "10.1525/9780520313897-001",
    openalex = "W1827579558",
    pages = "1-22",
    references = "doi1010160040580972900354, doi101038217624a0, doi101073pnas4211855, doi101093genetics163290, doi101093genetics494725, doi101093genetics614893, doi101126science1643881788, doi1023072341823, openalexw2171582839"
}

@incollection{schuster1983appendix,
    author = "Schuster, P.",
    title = {Appendix: Comments on "Non-DARWiNian"-Phase of Evolution and Hypercycles},
    year = "1983",
    booktitle = "Darwin today",
    url = "https://doi.org/10.1515/9783112542309-016",
    doi = "10.1515/9783112542309-016",
    openalex = "W4211133938",
    pages = "166-170"
}

@incollection{rechenberg1984the,
    author = "Rechenberg, Ingo",
    title = "The Evolution Strategy. A Mathematical Model of Darwinian Evolution",
    year = "1984",
    booktitle = "Springer Series in Synergetics",
    url = "https://doi.org/10.1007/978-3-642-69540-7\_13",
    doi = "10.1007/978-3-642-69540-7\_13",
    openalex = "W23797105",
    pages = "122-132",
    references = "doi101002fedr4910860506, doi1010160378475482901173, doi1023072581158, openalexw1514875444"
}

Darwinian Evolution. Anthony Flew. New Brunswick, NJ: Transaction Publishers, 1997.150 pp.

@article{bowler1998darwinian,
    author = "Bowler, Peter J.",
    title = "Darwinian Evolution",
    year = "1998",
    journal = "American Anthropologist",
    abstract = "Darwinian Evolution. Anthony Flew. New Brunswick, NJ: Transaction Publishers, 1997.150 pp.",
    url = "https://doi.org/10.1525/aa.1998.100.3.806",
    doi = "10.1525/aa.1998.100.3.806",
    number = "3",
    openalex = "W4230133078",
    pages = "806-807",
    volume = "100"
}

@incollection{crossref2008challenges,
    title = "Challenges",
    year = "2008",
    booktitle = "Quests",
    url = "https://doi.org/10.1201/b10929-10",
    doi = "10.1201/b10929-10",
    pages = "119-156"
}

BACKGROUND: The year 2009 is the 200th anniversary of the publication of Jean-Bapteste Lamarck's Philosophie Zoologique and the 150th anniversary of Charles Darwin's On the Origin of Species. Lamarck believed that evolution is driven primarily by non-randomly acquired, beneficial phenotypic changes, in particular, those directly affected by the use of organs, which Lamarck believed to be inheritable. In contrast, Darwin assigned a greater importance to random, undirected change that provided material for natural selection. THE CONCEPT: The classic Lamarckian scheme appears untenable owing to the non-existence of mechanisms for direct reverse engineering of adaptive phenotypic characters acquired by an individual during its life span into the genome. However, various evolutionary phenomena that came to fore in the last few years, seem to fit a more broadly interpreted (quasi)Lamarckian paradigm. The prokaryotic CRISPR-Cas system of defense against mobile elements seems to function via a bona fide Lamarckian mechanism, namely, by integrating small segments of viral or plasmid DNA into specific loci in the host prokaryote genome and then utilizing the respective transcripts to destroy the cognate mobile element DNA (or RNA). A similar principle seems to be employed in the piRNA branch of RNA interference which is involved in defense against transposable elements in the animal germ line. Horizontal gene transfer (HGT), a dominant evolutionary process, at least, in prokaryotes, appears to be a form of (quasi)Lamarckian inheritance. The rate of HGT and the nature of acquired genes depend on the environment of the recipient organism and, in some cases, the transferred genes confer a selective advantage for growth in that environment, meeting the Lamarckian criteria. Various forms of stress-induced mutagenesis are tightly regulated and comprise a universal adaptive response to environmental stress in cellular life forms. Stress-induced mutagenesis can be construed as a quasi-Lamarckian phenomenon because the induced genomic changes, although random, are triggered by environmental factors and are beneficial to the organism. CONCLUSION: Both Darwinian and Lamarckian modalities of evolution appear to be important, and reflect different aspects of the interaction between populations and the environment.

@article{doi10118617456150442,
    author = "Koonin, Eugene V. and Wolf, Yuri I.",
    title = "Is evolution Darwinian or/and Lamarckian?",
    year = "2009",
    journal = "Biology Direct",
    abstract = "BACKGROUND: The year 2009 is the 200th anniversary of the publication of Jean-Bapteste Lamarck's Philosophie Zoologique and the 150th anniversary of Charles Darwin's On the Origin of Species. Lamarck believed that evolution is driven primarily by non-randomly acquired, beneficial phenotypic changes, in particular, those directly affected by the use of organs, which Lamarck believed to be inheritable. In contrast, Darwin assigned a greater importance to random, undirected change that provided material for natural selection. THE CONCEPT: The classic Lamarckian scheme appears untenable owing to the non-existence of mechanisms for direct reverse engineering of adaptive phenotypic characters acquired by an individual during its life span into the genome. However, various evolutionary phenomena that came to fore in the last few years, seem to fit a more broadly interpreted (quasi)Lamarckian paradigm. The prokaryotic CRISPR-Cas system of defense against mobile elements seems to function via a bona fide Lamarckian mechanism, namely, by integrating small segments of viral or plasmid DNA into specific loci in the host prokaryote genome and then utilizing the respective transcripts to destroy the cognate mobile element DNA (or RNA). A similar principle seems to be employed in the piRNA branch of RNA interference which is involved in defense against transposable elements in the animal germ line. Horizontal gene transfer (HGT), a dominant evolutionary process, at least, in prokaryotes, appears to be a form of (quasi)Lamarckian inheritance. The rate of HGT and the nature of acquired genes depend on the environment of the recipient organism and, in some cases, the transferred genes confer a selective advantage for growth in that environment, meeting the Lamarckian criteria. Various forms of stress-induced mutagenesis are tightly regulated and comprise a universal adaptive response to environmental stress in cellular life forms. Stress-induced mutagenesis can be construed as a quasi-Lamarckian phenomenon because the induced genomic changes, although random, are triggered by environmental factors and are beneficial to the organism. CONCLUSION: Both Darwinian and Lamarckian modalities of evolution appear to be important, and reflect different aspects of the interaction between populations and the environment.",
    url = "https://doi.org/10.1186/1745-6150-4-42",
    doi = "10.1186/1745-6150-4-42",
    openalex = "W2159322112",
    references = "doi101007s0023900400463, doi101016jcell200901035, doi101016jcell200901046, doi101017s0094837300004310, doi101038227561a0, doi101126science1138140, doi101126science1159689, doi101126science15739260, doi1023071852361, doi105860choice396411, openalexw2624262714"
}

@incollection{crossref2011darwinian,
    title = "Darwinian Evolution",
    year = "2011",
    booktitle = "Encyclopedia of Astrobiology",
    url = "https://doi.org/10.1007/978-3-642-11274-4\_2318",
    doi = "10.1007/978-3-642-11274-4\_2318",
    openalex = "W4250848644",
    pages = "409-409"
}

Information theoretic approaches and model averaging are increasing in popularity, but this approach can be difficult to apply to the realistic, complex models that typify many ecological and evolutionary analyses. This is especially true for those researchers without a formal background in information theory. Here, we highlight a number of practical obstacles to model averaging complex models. Although not meant to be an exhaustive review, we identify several important issues with tentative solutions where they exist (e.g. dealing with collinearity amongst predictors; how to compute model-averaged parameters) and highlight areas for future research where solutions are not clear (e.g. when to use random intercepts or slopes; which information criteria to use when random factors are involved). We also provide a worked example of a mixed model analysis of inbreeding depression in a wild population. By providing an overview of these issues, we hope that this approach will become more accessible to those investigating any process where multiple variables impact an evolutionary or ecological response.

@article{doi101111j14209101201002210x,
    author = "Grueber, Catherine E. and Nakagawa, Shinichi and Laws, Rebecca and Jamieson, Ian G.",
    title = "Multimodel inference in ecology and evolution: challenges and solutions",
    year = "2011",
    journal = "Journal of Evolutionary Biology",
    abstract = "Information theoretic approaches and model averaging are increasing in popularity, but this approach can be difficult to apply to the realistic, complex models that typify many ecological and evolutionary analyses. This is especially true for those researchers without a formal background in information theory. Here, we highlight a number of practical obstacles to model averaging complex models. Although not meant to be an exhaustive review, we identify several important issues with tentative solutions where they exist (e.g. dealing with collinearity amongst predictors; how to compute model-averaged parameters) and highlight areas for future research where solutions are not clear (e.g. when to use random intercepts or slopes; which information criteria to use when random factors are involved). We also provide a worked example of a mixed model analysis of inbreeding depression in a wild population. By providing an overview of these issues, we hope that this approach will become more accessible to those investigating any process where multiple variables impact an evolutionary or ecological response.",
    url = "https://doi.org/10.1111/j.1420-9101.2010.02210.x",
    doi = "10.1111/j.1420-9101.2010.02210.x",
    openalex = "W1584343945",
    references = "doi101002sim3107, doi1010079781475729177, doi101016jtree200310013, doi101016s0169534702024898, doi101017s0305004100015644, doi101073pnas4211855, doi101093biomet762297, doi101111j2041210x200900001x, doi1023073803199, doi105962bhltitle110800"
}

@article{doi101016jenvsoft201409013,
    author = "Maier, Holger R. and Kapelan, Zoran and Kasprzyk, Joseph and Kollat, Joshua B. and Matott, L. Shawn and da Conceição Cunha, Maria and Dandy, Graeme C. and Gibbs, Matthew S. and Keedwell, Edward and Marchi, Angela and Ostfeld, Avi and Savić, Dragan and Solomatine, Dimitri and Vrugt, Jasper A. and Zecchin, Aaron C. and Minsker, Barbara and Barbour, Emily and Kuczera, G. and Pasha, Fayzul and Castelletti, Andrea and Giuliani, Matteo and Reed, Patrick M.",
    title = "Evolutionary algorithms and other metaheuristics in water resources: Current status, research challenges and future directions",
    year = "2014",
    journal = "Environmental Modelling \& Software",
    url = "https://doi.org/10.1016/j.envsoft.2014.09.013",
    doi = "10.1016/j.envsoft.2014.09.013",
    openalex = "W2108750696",
    references = "doi101016jpaerosci200502001, doi1010292011wr011527, doi101061ascewr194354520000053, doi10108003052159508941193"
}

The prevailing view that the evolution of cells in a tumor is driven by Darwinian selection has never been rigorously tested. Because selection greatly affects the level of intratumor genetic diversity, it is important to assess whether intratumor evolution follows the Darwinian or the non-Darwinian mode of evolution. To provide the statistical power, many regions in a single tumor need to be sampled and analyzed much more extensively than has been attempted in previous intratumor studies. Here, from a hepatocellular carcinoma (HCC) tumor, we evaluated multiregional samples from the tumor, using either whole-exome sequencing (WES) (n = 23 samples) or genotyping (n = 286) under both the infinite-site and infinite-allele models of population genetics. In addition to the many single-nucleotide variations (SNVs) present in all samples, there were 35 "polymorphic" SNVs among samples. High genetic diversity was evident as the 23 WES samples defined 20 unique cell clones. With all 286 samples genotyped, clonal diversity agreed well with the non-Darwinian model with no evidence of positive Darwinian selection. Under the non-Darwinian model, MALL (the number of coding region mutations in the entire tumor) was estimated to be greater than 100 million in this tumor. DNA sequences reveal local diversities in small patches of cells and validate the estimation. In contrast, the genetic diversity under a Darwinian model would generally be orders of magnitude smaller. Because the level of genetic diversity will have implications on therapeutic resistance, non-Darwinian evolution should be heeded in cancer treatments even for microscopic tumors.

@article{doi101073pnas1519556112,
    author = "Ling, Shaoping and Hu, Zheng and Yang, Zuyu and Yang, Fang and Li, Yawei and Lin, Pei and Chen, Ke and Dong, Lili and Cao, Lihua and Tao, Yong and Hao, Lingtong and Chen, Qingjian and Gong, Qiang and Wu, Dafei and Li, Wenjie and Zhao, Wenming and Tian, Xiuyun and Hao, Chunyi and Hungate, Eric A. and Catenacci, Daniel V.T. and Hudson, Richard R. and Li, Wen‐Hsiung and Lu, Xuemei and Wu, Chung‐I",
    title = "Extremely high genetic diversity in a single tumor points to prevalence of non-Darwinian cell evolution",
    year = "2015",
    journal = "Proceedings of the National Academy of Sciences",
    abstract = {The prevailing view that the evolution of cells in a tumor is driven by Darwinian selection has never been rigorously tested. Because selection greatly affects the level of intratumor genetic diversity, it is important to assess whether intratumor evolution follows the Darwinian or the non-Darwinian mode of evolution. To provide the statistical power, many regions in a single tumor need to be sampled and analyzed much more extensively than has been attempted in previous intratumor studies. Here, from a hepatocellular carcinoma (HCC) tumor, we evaluated multiregional samples from the tumor, using either whole-exome sequencing (WES) (n = 23 samples) or genotyping (n = 286) under both the infinite-site and infinite-allele models of population genetics. In addition to the many single-nucleotide variations (SNVs) present in all samples, there were 35 "polymorphic" SNVs among samples. High genetic diversity was evident as the 23 WES samples defined 20 unique cell clones. With all 286 samples genotyped, clonal diversity agreed well with the non-Darwinian model with no evidence of positive Darwinian selection. Under the non-Darwinian model, MALL (the number of coding region mutations in the entire tumor) was estimated to be greater than 100 million in this tumor. DNA sequences reveal local diversities in small patches of cells and validate the estimation. In contrast, the genetic diversity under a Darwinian model would generally be orders of magnitude smaller. Because the level of genetic diversity will have implications on therapeutic resistance, non-Darwinian evolution should be heeded in cancer treatments even for microscopic tumors.},
    url = "https://doi.org/10.1073/pnas.1519556112",
    doi = "10.1073/pnas.1519556112",
    openalex = "W2177689130",
    references = "doi101038nature12213, doi101038scientificamerican117998, doi101056nejmoa1113205, doi101093bioinformaticsbtg412, doi101093bioinformaticsbtp324, doi101093bioinformaticsbtp352, doi101093oxfordjournalsmolbeva040454, doi101126science1235122, doi101126science959840, doi101146annurevgenom082908150129, doi105962bhltitle27468"
}

The article is devoted to the relevance of the training of executive personnel in Uzbekistan, the problems and tasks that need to be addressed. At the same time, it analyzes the activities of organizations that are directly involved in the development of managerial skills of leading personnel in Uzbekistan, how effectively they perform their tasks, outlines problems and shortcomings in their work and in the activities of leading personnel

@article{andberdiev2020leadership,
    author = "Berdiev, Bektosh",
    title = "LEADERSHIP TRAINING: CHALLENGES AND CHALLENGES",
    year = "2020",
    journal = "INTERNATIONAL JOURNAL OF CONSENSUS",
    abstract = "The article is devoted to the relevance of the training of executive personnel in Uzbekistan, the problems and tasks that need to be addressed. At the same time, it analyzes the activities of organizations that are directly involved in the development of managerial skills of leading personnel in Uzbekistan, how effectively they perform their tasks, outlines problems and shortcomings in their work and in the activities of leading personnel",
    url = "https://doi.org/10.26739/2181-0788-2020-3-14",
    doi = "10.26739/2181-0788-2020-3-14",
    number = "1",
    pages = "122-129",
    volume = "3"
}

@incollection{crossref2020darwinian,
    title = "Darwinian Evolution",
    year = "2020",
    booktitle = "History of Particle Theory",
    url = "https://doi.org/10.1142/9789811224669\_0005",
    doi = "10.1142/9789811224669\_0005",
    openalex = "W4241003487",
    pages = "71-95"
}

@article{carreira2021challenges,
    author = "Carreira, Erick M. and Chiu, Pauline",
    title = "Challenges and More Challenges",
    year = "2021",
    journal = "Organic Letters",
    url = "https://doi.org/10.1021/acs.orglett.0c03811",
    doi = "10.1021/acs.orglett.0c03811",
    number = "1",
    pages = "1-1",
    volume = "23"
}

@incollection{crossref2021darwinian,
    title = "Darwinian Evolution",
    year = "2021",
    booktitle = "A Philosopher Looks at Human Beings",
    url = "https://doi.org/10.1017/9781108907057.004",
    doi = "10.1017/9781108907057.004",
    openalex = "W4249678390",
    pages = "48-74"
}

Stem cell-based approaches are rapidly expanding the therapeutic repertoire against cancer by combining targeted delivery, immune modulation, and cellular engineering. This review synthesizes current knowledge across four interconnected domains: hematopoietic stem cells (HSCs), which serve as mediators of graft-derived antitumor immunity and as platforms for lineage-engineered immune effectors; mesenchymal stromal/stem cells (MSCs), which exhibit tumor-tropic homing and can function as context-dependent modulators or carriers within the tumor microenvironment (TME); induced pluripotent stem cells (iPSCs), which provide a scalable source for generating autologous or allogeneic immune effector cells and designer cell therapies; and cancer stem cells (CSCs), which underlie therapeutic resistance, minimal residual disease, and relapse. We evaluate promising translational strategies including chimeric antigen receptors (CAR)-engineered HSC and iPSC-derived effectors, MSC-mediated targeted delivery of therapeutics, and extracellular vesicles (EVs) engineering alongside critical biological and manufacturing barriers. Principal challenges include the context-dependent pro- versus antitumor activities of MSCs, the tumorigenic risk associated with pluripotent-derived products, immunological compatibility and durability of responses, and product heterogeneity that complicates reproducibility and regulatory assessment. To accelerate safe clinical translation, we recommend standardized functional characterization assays, rigorous in vivo safety and efficacy testing across tumor models, adoption of robust potency and identity metrics, and strategic combinations of molecular engineering with controllable safety switches and immune-modulating adjuncts. By aligning mechanistic insight with translational priorities, the field can prioritize approaches most likely to deliver durable, safe, and broadly applicable cell-based cancer therapies.

@article{doi101016jintimp2026116738,
    author = "Ebrahimi, Seyed Ahmad and Pourkheiri, Forough and Sherafat, Negar Sadat and Moradi, Seyedeh Mahshad and Hormozi, Ghazal and Zaheri, Pardis and Asadirad, Ali",
    title = "Stem cells at the tumor frontier: Mechanistic insights, therapeutic challenges, and emerging horizons.",
    year = "2026",
    journal = "International immunopharmacology",
    abstract = "Stem cell-based approaches are rapidly expanding the therapeutic repertoire against cancer by combining targeted delivery, immune modulation, and cellular engineering. This review synthesizes current knowledge across four interconnected domains: hematopoietic stem cells (HSCs), which serve as mediators of graft-derived antitumor immunity and as platforms for lineage-engineered immune effectors; mesenchymal stromal/stem cells (MSCs), which exhibit tumor-tropic homing and can function as context-dependent modulators or carriers within the tumor microenvironment (TME); induced pluripotent stem cells (iPSCs), which provide a scalable source for generating autologous or allogeneic immune effector cells and designer cell therapies; and cancer stem cells (CSCs), which underlie therapeutic resistance, minimal residual disease, and relapse. We evaluate promising translational strategies including chimeric antigen receptors (CAR)-engineered HSC and iPSC-derived effectors, MSC-mediated targeted delivery of therapeutics, and extracellular vesicles (EVs) engineering alongside critical biological and manufacturing barriers. Principal challenges include the context-dependent pro- versus antitumor activities of MSCs, the tumorigenic risk associated with pluripotent-derived products, immunological compatibility and durability of responses, and product heterogeneity that complicates reproducibility and regulatory assessment. To accelerate safe clinical translation, we recommend standardized functional characterization assays, rigorous in vivo safety and efficacy testing across tumor models, adoption of robust potency and identity metrics, and strategic combinations of molecular engineering with controllable safety switches and immune-modulating adjuncts. By aligning mechanistic insight with translational priorities, the field can prioritize approaches most likely to deliver durable, safe, and broadly applicable cell-based cancer therapies.",
    url = "https://pubmed.ncbi.nlm.nih.gov/42044579/",
    doi = "10.1016/j.intimp.2026.116738",
    pmid = "42044579"
}

BACKGROUND: Intracerebral hemorrhage (ICH) in cancer patients may reflect hypertension, vascular malformations, coagulopathy, or hemorrhagic metastases. Differentiating atypical hemorrhages from brain metastases is diagnostically challenging, particularly in patients with prior breast cancer. OBSERVATIONS: The authors describe the case of a 67-year-old female with a history of breast cancer who presented with a first generalized seizure and bifrontal headache. Imaging revealed atypical bilateral ICHs in the right frontal and left occipital lobes, without trauma or anticoagulation. CT and MRI findings favored subacute hemorrhage without enhancement. Given the patient's oncological history, surgery with biopsy was performed to exclude metastasis. Histopathological analysis revealed only organized hemorrhage, with no tumor cells or vascular malformation. The patient recovered well after craniotomy. The authors are not aware of previous reports of 2 atypical ICHs in the frontal and occipital lobes in a patient with a history of cancer, without trauma, and without blood-thinning drugs. LESSONS: Atypical bilateral ICH in a breast cancer patient may mimic metastases. In such cases, biopsy and histological analysis are mandatory to guide treatment. Correct differentiation avoids overtreatment and enables tailored management. https//thejns.org/doi/10.3171/CASE251001.

@article{doi103171case251001,
    author = "Adam, Mosab Ahmed Abker and Senger, Sebastian and Camal Ruggieri, Iván Nadir and Kuzmin, Dzmitry",
    title = "Intracerebral atypical hemorrhages mimicking metastases in a patient with breast cancer history: diagnostic challenges and key insights. Illustrative case.",
    year = "2026",
    journal = "Journal of neurosurgery. Case lessons",
    abstract = "BACKGROUND: Intracerebral hemorrhage (ICH) in cancer patients may reflect hypertension, vascular malformations, coagulopathy, or hemorrhagic metastases. Differentiating atypical hemorrhages from brain metastases is diagnostically challenging, particularly in patients with prior breast cancer. OBSERVATIONS: The authors describe the case of a 67-year-old female with a history of breast cancer who presented with a first generalized seizure and bifrontal headache. Imaging revealed atypical bilateral ICHs in the right frontal and left occipital lobes, without trauma or anticoagulation. CT and MRI findings favored subacute hemorrhage without enhancement. Given the patient's oncological history, surgery with biopsy was performed to exclude metastasis. Histopathological analysis revealed only organized hemorrhage, with no tumor cells or vascular malformation. The patient recovered well after craniotomy. The authors are not aware of previous reports of 2 atypical ICHs in the frontal and occipital lobes in a patient with a history of cancer, without trauma, and without blood-thinning drugs. LESSONS: Atypical bilateral ICH in a breast cancer patient may mimic metastases. In such cases, biopsy and histological analysis are mandatory to guide treatment. Correct differentiation avoids overtreatment and enables tailored management. https//thejns.org/doi/10.3171/CASE251001.",
    url = "https://pubmed.ncbi.nlm.nih.gov/42044532/",
    doi = "10.3171/CASE251001",
    pmid = "42044532"
}