Publications by authors named "JW Clark"

Article Synopsis
  • Oxford ragwort (Senecio squalidus) is a unique hybrid species that provides insights into genetic changes after hybridization, due to its recent origin and specific genomic traits.
  • The study produced a comprehensive genome assembly, identifying over 30,000 protein-coding genes, with a significant portion of the genome made up of repetitive elements.
  • Key findings include evidence of varied genetic patterns among species, an unequal genetic contribution from the parent species, and the influence of genetic incompatibilities and natural selection on rapid genome stabilization in this hybrid lineage.
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Intrusive memories are a common experience following trauma exposure but can develop into a symptom of posttraumatic stress disorder (PTSD). Recent research has observed a relationship between sleep disturbance and intrusive memory frequency following analog trauma exposure and disruptions in rapid eye movement (REM) sleep are found to contribute to emotional dysregulation and an amplified reaction to negative emotional stimuli. The current study examined the association between REM sleep prior to analog trauma and intrusive memories.

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The nature of the last universal common ancestor (LUCA), its age and its impact on the Earth system have been the subject of vigorous debate across diverse disciplines, often based on disparate data and methods. Age estimates for LUCA are usually based on the fossil record, varying with every reinterpretation. The nature of LUCA's metabolism has proven equally contentious, with some attributing all core metabolisms to LUCA, whereas others reconstruct a simpler life form dependent on geochemistry.

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Objective: The aim of this study was to evaluate the incidence of radiotherapy (RT)-related lymphopenia, its predictors, and association with survival in unresectable intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated-RT (HF-RT).

Methods: Retrospective analysis of 96 patients with unresectable ICC who underwent HF-RT (median 58.05 Gy in 15 fractions) between 2009 and 2022 was performed.

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Neuroendocrine neoplasms (NENs) are rare neoplasms originating from neuroendocrine cells, with increasing incidence due to enhanced detection methods. These tumors display considerable heterogeneity, necessitating diverse management strategies based on factors like organ of origin and tumor size. This article provides a comprehensive overview of therapeutic approaches for NENs, emphasizing the role of imaging in treatment decisions.

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Neuroendocrine neoplasms (NENs) are a diverse group of tumors that express neuroendocrine markers and primarily affect the lungs and digestive system. The incidence of NENs has increased over time due to advancements in imaging and diagnostic techniques. Effective management of NENs requires a multidisciplinary approach, considering factors such as tumor location, grade, stage, symptoms, and imaging findings.

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Purpose: MEK inhibitors (MEKi) lack monotherapy efficacy in most RAS-mutant cancers. BCL-xL is an anti-apoptotic protein identified by a synthetic lethal shRNA screen as a key suppressor of apoptotic response to MEKi.

Patients And Methods: We conducted a dose escalation study (NCT02079740) of the BCL-xL inhibitor navitoclax and MEKi trametinib in patients with RAS-mutant tumors with expansion cohorts for: pancreatic, gynecologic (GYN), non-small cell lung cancer (NSCLC), and other cancers harboring KRAS/NRAS mutations.

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Article Synopsis
  • AbGn-107 is an antibody-drug conjugate targeting the AG-7 antigen, found in various gastrointestinal cancers, which showed promising results in preclinical studies and led to a Phase I trial for GI cancers.
  • The trial used a 3+3 dose escalation design, enrolling 39 patients with advanced, recurrent GI cancers, focusing on safety, maximum tolerated dose, and efficacy with doses ranging from 0.1 to 1.0 mg/kg.
  • Findings indicated that AbGn-107 was generally well-tolerated with some serious side effects; one patient showed a partial response, and nearly half had stable disease, suggesting modest clinical activity and the need for further research on AG-7 as a therapeutic target.
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Land plants are celebrated as one of the three great instances of complex multicellularity, but new phylogenomic and phenotypic analyses are revealing deep evolutionary roots of multicellularity among algal relatives, prompting questions about the causal basis of this major evolutionary transition.

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Article Synopsis
  • - Recent trials indicate that PD-1-directed immunotherapy, specifically pembrolizumab, may help some patients with anal squamous cell carcinoma, but there is a need for reliable biomarkers to predict who will respond to the treatment.
  • - In a phase II clinical trial involving 32 patients, the objective response rate (ORR) to pembrolizumab was low at 9.4%, with a median progression-free survival of only 2.2 months, and most patients showed low levels of beneficial immune cells.
  • - Some patients had long-term responses to pembrolizumab, with one patient lasting over 5 years, particularly those with HPV-positive tumors and no liver metastases, but challenges remain due to ongoing HPV infection
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Polyploidy or whole-genome duplication (WGD) is a major event that drastically reshapes genome architecture and is often assumed to be causally associated with organismal innovations and radiations. The 2R hypothesis suggests that two WGD events (1R and 2R) occurred during early vertebrate evolution. However, the timing of the 2R event relative to the divergence of gnathostomes (jawed vertebrates) and cyclostomes (jawless hagfishes and lampreys) is unresolved and whether these WGD events underlie vertebrate phenotypic diversification remains elusive.

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Substance use disorders are heritable disorders characterized by compulsive drug use, the biological mechanisms for which remain largely unknown. Genetic correlations reveal that predisposing drug-naïve phenotypes, including anxiety, depression, novelty preference and sensation seeking, are predictive of drug-use phenotypes, thereby implicating shared genetic mechanisms. High-throughput behavioral screening in knockout (KO) mice allows efficient discovery of the function of genes.

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Importance: Patient-reported outcomes (PROs), such as quality of life (QOL) and symptoms, are often associated with clinical outcomes in patients with cancer. In practice, oncologists use serum tumor markers (TMs) (ie, carcinoembryonic antigen [CEA] and carbohydrate antigen 19-9 [CA 19-9]) and imaging to monitor clinical outcomes in patients with gastrointestinal cancer.

Objective: To examine associations of 1-month changes in PROs and TMs with treatment response and survival among patients with gastrointestinal cancer.

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Objective: To evaluate the safety and efficacy of neoadjuvant therapy (NAT), followed by surgical resection in patients with pancreatic ductal adenocarcinoma (PDAC) aged ≥75 years.

Background: Whether administration of NAT, followed by surgical resection in elderly patients with PDAC is safe and effective is unknown.

Methods: The present study is a three-part comparison of older (≥75 years) versus younger (<75 years) patients in different settings throughout the continuum of PDAC care.

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The plant kingdom exhibits diverse bodyplans, from single-celled algae to complex multicellular land plants, but it is unclear how this phenotypic disparity was achieved. Here we show that the living divisions comprise discrete clusters within morphospace, separated largely by reproductive innovations, the extinction of evolutionary intermediates and lineage-specific evolution. Phenotypic complexity correlates not with disparity but with ploidy history, reflecting the role of genome duplication in plant macroevolution.

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Plant evolution has been characterised by a series of major novelties in their vegetative and reproductive traits that have led to greater complexity. Underpinning this diversification has been the evolution of the genome. When viewed at the scale of the plant kingdom, plant genome evolution has been punctuated by conspicuous instances of gene and whole-genome duplication, horizontal gene transfer and extensive gene loss.

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Purpose: Portal vein and superior mesenteric vein thrombosis (PVT/SMVT) are potentially morbid complications of radiation dose-escalated local therapy for pancreatic cancer. We retrospectively reviewed records for patients treated with and without intraoperative radiation (IORT) to identify risk factors for PVT/SMVT.

Methods: Ninety-six patients with locally advanced or borderline resectable pancreatic adenocarcinoma received neoadjuvant therapy followed by surgical exploration from 2009 to 2014.

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Substance use disorders (SUDs) are heritable disorders characterized by compulsive drug use, but the biological mechanisms driving addiction remain largely unknown. Genetic correlations reveal that predisposing drug-naïve phenotypes, including anxiety, depression, novelty preference, and sensation seeking, are predictive of drug-use phenotypes, implicating shared genetic mechanisms. Because of this relationship, high-throughput behavioral screening of predictive phenotypes in knockout (KO) mice allows efficient discovery of genes likely to be involved in drug use.

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Article Synopsis
  • Some pancreatic cancers (about 8-10%) don't have a common mutation called KRAS, which makes them different from most cases.
  • In a study of 795 pancreatic cancer patients, 73 were found to have KRAS wild-type (normal) cancer, and many had other mutations that could be targeted for treatment.
  • The research shows that patients with this type of cancer are generally younger and may respond well to specific therapies, especially if they have certain genetic changes.
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.This article describes the care of a young patient with aggressive breast cancer, declining performance status, and multiple hospital admissions who died shortly after being discharged home without essential medications or an adequate plan for follow-up. The patient's death due to her malignancy was unavoidable, but she had inadequate resources before her death, leading to avoidable suffering.

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Article Synopsis
  • GI cancers, particularly from stomach and appendix adenocarcinomas, often lead to hard-to-detect peritoneal metastases that can significantly impact patient outcomes.
  • This study analyzed 13 patients with these conditions, using sensitive ctDNA testing to monitor disease progression over time without altering treatment plans based on the results.
  • Findings showed that ctDNA levels could track changes in disease burden, with some patients prompting early detection of peritoneal disease through baseline ctDNA measurements.
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The medical-legal partnership (MLP) is an innovative and proven-effective approach to addressing health-harming social needs that have legal remedies (e.g., housing concerns, intimate partner violence).

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Background: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are the leading causes of hepatocellular carcinoma (HCC) worldwide. Limited data exist on surgical outcomes for NAFLD/NASH-related HCC compared with other HCC etiologies. We evaluated differences in clinicopathological characteristics and outcomes of patients undergoing surgical resection for NAFLD/NASH-associated HCC compared with other HCC etiologies.

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