tbuckley/cabot-search huggingface dataset:
Intergenerational Transmission of Diet‐Induced Obesity, Metabolic Imbalance, and Osteoarthritis in Mice
Authors: Natalia S. Harasymowicz, Yun‐Rak Choi, Chia‐Lung Wu, Leanne Iannucci, Ruhang Tang, Farshid Guilak
Journal: Arthritis & Rheumatology (2019)

Obesity and osteoarthritis (OA) are 2 major public health issues affecting millions of people worldwide. Whereas parental obesity affects the predisposition to diseases such as cancer or diabetes in children, transgenerational influences on musculoskeletal conditions such as OA are poorly understood. This study was undertaken to assess the intergenerational effects of a parental/grandparental high-fat diet on the metabolic and skeletal phenotype, systemic inflammation, and predisposition to OA in 2 generations of offspring in mice.Metabolic phenotype and predisposition to OA were investigated in the first and second (F1 and F2) generations of offspring (n = 10-16 mice per sex per diet) bred from mice fed a high-fat diet (HFD) or a low-fat control diet. OA was induced by destabilizing the medial meniscus. OA, synovitis, and adipose tissue inflammation were determined histologically, while bone changes were measured using micro-computed tomography. Serum and synovial cytokines were measured by multiplex assay.Parental high-fat feeding showed an intergenerational effect, with inheritance of increased weight gain (up to 19% in the F1 generation and 9% in F2), metabolic imbalance, and injury-induced OA in at least 2 generations of mice, despite the fact that the offspring were fed the low-fat diet. Strikingly, both F1 and F2 female mice showed an increased predisposition to injury-induced OA (48% higher predisposition in F1 and 19% in F2 female mice fed the HFD) and developed bone microarchitectural changes that were attributable to parental and grandparental high-fat feeding.The results of this study reveal a detrimental effect of parental HFD and obesity on the musculoskeletal integrity of 2 generations of offspring, indicating the importance of further investigation of these effects. An improved understanding of the mechanisms involved in the transmissibility of diet-induced changes through multiple generations may help in the development of future therapies that would target the effects of obesity on OA and related conditions.
OxyR Is a Convergent Target for Mutations Acquired during Adaptation to Oxidative Stress-Prone Metabolic States
Authors: Amitesh Anand, Ke Chen, Edward Catoiu, Anand V Sastry, Connor A Olson, Troy E Sandberg, Yara Seif, Sibei Xu, Richard Szubin, Laurence Yang, Adam M Feist, Bernhard O Palsson
Journal: Molecular Biology and Evolution (2019)

Oxidative stress is concomitant with aerobic metabolism. Thus, bacterial genomes encode elaborate mechanisms to achieve redox homeostasis. Here we report that the peroxide-sensing transcription factor, oxyR, is a common mutational target using bacterial species belonging to two genera, Escherichia coli and Vibrio natriegens, in separate growth conditions implemented during laboratory evolution. The mutations clustered in the redox active site, dimer interface, and flexible redox loop of the protein. These mutations favor the oxidized conformation of OxyR that results in constitutive expression of the genes it regulates. Independent component analysis of the transcriptome revealed that the constitutive activity of OxyR reduces DNA damage from reactive oxygen species, as inferred from the activity of the SOS response regulator LexA. This adaptation to peroxide stress came at a cost of lower growth, as revealed by calculations of proteome allocation using genome-scale models of metabolism and macromolecular expression. Further, identification of similar sequence changes in natural isolates of E. coli indicates that adaptation to oxidative stress through genetic changes in oxyR can be a common occurrence.
Dislocated jaw is common in patients with Ehlers-Danlos syndromes
Authors: Farzad Borumandi
Journal: BMJ (2019)

Ghali and colleagues give an overview of Ehlers-Danlos syndromes (EDS) and their increasing public awareness owing to the growing number of EDS patient organisations.1

Joint hypermobility is the cardinal characteristic of EDS. Spontaneous dislocation of temporomandibular joints might be one of the first symptoms that patients with EDS present with. Patients with EDS are frequent attenders in …
EP1.03-24 Clinicopathologic Characteristics and Survival Outcome in Chinese Patients with Non-Small Cell Lung Cancer and HGF Mutations
Authors: C. Xu, W. Wang, Q. Zhang, W. Zhuang, Y. Zhu, Y. Huang, G. Chen, M. Fang, T. Lv, Y. Song
Journal: Journal of Thoracic Oncology (2019)
P1.04-53 A High PD-L1 Expression in Non-Small Cell Lung Cancer Correlates with Expression of SPOP and CD8 Tumor-Infiltrating Lymphocytes
Authors: M. Inoue, J. Yoshida, S. Oka, Y. Honda, Y. Chikaishi, D. Yasuda
Journal: Journal of Thoracic Oncology (2019)
P2.14-12 Tyrosine Kinase Inhibitor Resistance Mechanisms in EGFR T790M-Positive Lung Cancer: The University of Chicago Experience
Authors: G. Strohbehn, L. Szeto, B. Beach, K. Edgington, K. Lugtu, J. Segal, L. Ritterhouse, C. Bestvina, E. Vokes, J. Patel
Journal: Journal of Thoracic Oncology (2019)
P1.04-49 Quantitative Computed Tomography (CT) Based Texture Analysis (QTA) Might Identify Responders to Immunotherapy in Non-Small Cell Lung Cancer
Authors: Z. Megyesfalvi, C. Kugler, A. Fülöp, S. Gergely, B. Megyesfalvi, A. Kerpel-Fronius, B. Döme, R. Korn, G. Weiss, Z. Lohinai
Journal: Journal of Thoracic Oncology (2019)
MA04.05 Deciphering the Molecular Mechanisms Underlying the Progression of Bronchial Premalignant Lesions
Authors: E. Denisov, P. Gervas, A. Ponomaryova, A. Schegoleva, T. Gerashchenko, A. Kiselev, G. Demidov, A. Zarubin, L. Lyapunova, S. Kovalenko, O. Cheremisina, S. Tuzikov, O. Pankova, N. Cherdyntseva, V. Perelmuter
Journal: Journal of Thoracic Oncology (2019)
Environmentally Relevant Perinatal Exposures to Bisphenol A Disrupt Postnatal Kiss1/NKB Neuronal Maturation and Puberty Onset in Female Mice
Authors: Francisco Ruiz-Pino, Desiree Miceli, Delphine Franssen, Maria Jesus Vazquez, Alice Farinetti, Juan Manuel Castellano, GianCarlo Panzica, Manuel Tena-Sempere
Journal: Environmental Health Perspectives (2019)

Background: The timing of puberty is highly sensitive to environmental factors, including endocrine disruptors. Among them, bisphenol A (BPA) has been previously analyzed as potential modifier of puberty. Yet, disparate results have been reported, with BPA advancing, delaying, or being neutral in its effects on puberty onset. Likewise, mechanistic analyses addressing the central and peripheral actions/targets of BPA at puberty remain incomplete and conflictive. Objective: We aimed to provide a comprehensive characterization of the impact of early BPA exposures, especially at low, real-life doses, on the postnatal development of hypothalamic Kiss1/NKB neurons, and its functional consequences on female pubertal maturation. Methods: Pregnant CD1 female mice were orally administered BPA at 5, 10, or 40μg/kg body weight (BW)/d from gestational day 11 to postnatal day 8 (PND8). Vaginal opening, as an external marker of puberty onset, was monitored daily from PND19 to PND30 in the female offspring. Blood and brain samples were collected at PND12, 15, 18, 21, and 30 for measuring circulating levels of gonadotropins and analyzing the hypothalamic expression of Kiss1/kisspeptin and NKB. Results: Perinatal exposure to BPA, in a range of doses largely below the no observed adverse effect level (NOAEL; 5mg/kg BW/d, according to the FDA), was associated with pubertal differences in the female progeny compared with those exposed to vehicle alone, with an earlier age of vaginal opening but consistently lower levels of circulating luteinizing hormone. Mice treated with BPA exhibited a persistent, but divergent, impairment of Kiss1 neuronal maturation, with more kisspeptin cells in the rostral (RP3V) hypothalamus but consistently fewer kisspeptin neurons in the arcuate nucleus (ARC). Detailed quantitative analysis of the ARC population, essential for pubertal development, revealed that mice treated with BPA had persistently lower Kiss1 expression during (pre)pubertal maturation, which was associated with lower Tac2 (encoding NKB) levels, even at low doses (5μg/kg BW/d), in the range of the tolerable daily intake (TDI), recently updated by the European Food Safety Authority. Conclusions: Our data attest to the consistent, but divergent, effects of gestational exposures to low concentrations of BPA, via the oral route, on phenotypic and neuroendocrine markers of puberty in female mice, with an unambiguous impact on the developmental maturation not only of Kiss1, but also of the NKB system, both essential regulators of puberty onset. https://doi.org/10.1289/EHP5570
Efficacy of laser capture microdissection plus RT-PCR technique in analyzing gene expression levels of human gastric cancer
Authors: H. Uetake, K. Shitara, K. Sugihara
Journal: Journal of Clinical Oncology (2009)

e15669 Background: We reported the efficacy of laser capture microdissection plus RT-PCR (LCM+RT-PCR) technique in analyzing gene expression levels of human colon cancer (Makino, BMC cancer, 2008). In the present study, gene expression level of angiogenic factors, such as vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP) and cyclooxygenase-2 (COX-2) in human gastric cancer was studies using LCM+RT-PCR methods. Methods: Gene expression level of VEGF, TP and COX-2 were separately quantified in cancer cells and in cancerous stroma of 51 gastric cancers specimen by LCM+RT-PCR methods (Danenberg Tumor Profile). Results: All the gene expressions were successfully estimated separately in cancer cells and cancerous stroma. VEGF and TP gene higher expressed in cancer cell than in cancerous stroma (P&lt;0.0001, Wilcoxon), whereas COX-2 gene expression was higher in cancerous stroma (P=0.0004, Wilcoxon). Only in TP, positive correlation of gene expression was observed between in cancer cells and in cancerous stroma (rs=0.494, P=0.0014, Spearman). And a linear relationship was observed between VEGF and TP gene expression in cancerous stroma (rs=0.768, P&lt;0.0001, Spearman). Conclusions: Gene expression level of angiogenic factor was different between in cancer cells and cancerous stroma. By using LCM+RT-PCR method, gene expression level of angiogenic factors can be separately estimated in cancer cells and cancerous stroma. No significant financial relationships to disclose.
OA04.03 A Randomized Phase 3 Study of Camrelizumab plus Chemotherapy as 1st Line Therapy for Advanced/Metastatic Non-Squamous Non-Small Cell Lung Cancer
Authors: C. Zhou, G. Chen, Y. Huang, J. Zhou, L. Lin, J. Feng, Z. Wang, Y. Shu, J. Shi, Y. Hu, Q. Wang, Y. Cheng, J. Chen, X. Lin, Y. Wang, J. Huang, J. Cui, L. Cao, Y. Liu, Y. Zhang, Y. Pan, J. Zhao, L. Wang, J. Chang, Q. Chen, X. Ren, W. Zhang, Y. Fan, Z. He, J. Fang, K. Gu, X. Dong, F. Jin, H. Gao, G. An, C. Ding, X. Jiang, J. Xiong, X. Zhou, S. Hu, P. Lu, A. Liu, S. Guo, J. Huang, C. Zhu, J. Zhao, B. Gao, Y. Chen, C. Hu, J. Zhang, H. Zhang, H. Zhao, Y. Zhou, Y. Tai
Journal: Journal of Thoracic Oncology (2019)
Simplified monitoring for hepatitis C virus treatment with glecaprevir plus pibrentasvir, a randomised non-inferiority trial
Authors: Gregory J. Dore, Jordan J. Feld, Alex Thompson, Marianne Martinello, Andrew J. Muir, Kosh Agarwal, Beat Müllhaupt, Heiner Wedemeyer, Karine Lacombe, Gail V. Matthews, Michael Schultz, Marina Klein, Christophe Hezode, Gerard Estivill Mercade, Danny Kho, Kathy Petoumenos, Philippa Marks, Fernando Tatsch, Ana Gabriela Pires Dos Santos, Ed Gane
Journal: Journal of Hepatology (2019)
Breast Cancer Imaging With PET Based Radiopharmaceuticals Other Than 18F-FDG
Authors: Rakhee Vatsa, Shashank Shekhar Singh, Abhiram Gopalajois Ashwathanarayana, Rajender Kumar, Nivedita Rana, Jaya Shukla, Bhagwant Rai Mittal
Journal: Clinical Nuclear Medicine (2019)

Abstract Breast cancer is the most common cancer in women with rising incidence worldwide. 18 F-FDG PET/CT imaging has already established itself as a pivotal modality for staging, restating and response assessment in patients with carcinoma breast. The complex biology of this cancer is increasingly being decoded and various molecular targets have been identified and exploited for guiding the treatment at various time points during the course of the disease. We here depict a series of various metabolic and receptor targeting PET radiotracers in breast cancer patients which may help us understand the in vivo biology of this tumor.
Influence of some methylated hepatocarcinogenesis-related genes on the response to antiviral therapy and development of fibrosis in chronic hepatitis C patients
Authors: Waleed Seif Eldin Mohamed Mostafa, Mohammed Hassan Saiem Al-Dahr, Dalia Abdel Hamid Omran, Zeinab Fathy Abdullah, Suzan Hamdy Elmasry, Mohamed Nabil Ibrahim
Journal: Clinical and Molecular Hepatology (2019)

Background and Aim Epigenetics involved in multiple normal cellular processes. Previous research have revealed the role of hepatitis C virus infection in accelerating methylation process and affecting response to treatment in chronic hepatitis patients. This work aimed to elucidate the role of promoter methylation (PM) in response to antiviral therapy, and its contribution to the development of fibrosis through hepatocarcinogenesis-related genes. Methods A total of 159 chronic hepatitis Egyptian patients versus 100 healthy control group were included. The methylation profile of a panel 9 genes (SFRP1, p14, p73, APC, DAPK, RASSF1A, LINE1, O6MGMT, and p16) was detected in patientsâ plasma using methylation-specific polymerase chain reaction (MSP). Results Clinical and laboratory findings were gathered for patients with combined pegylated interferon and ribavirin antiviral therapy. Regarding the patientsâ response to antiviral therapy, the percentage of non-responders for APC, O6MGMT, RASSF1A, SFRP1, and p16 methylated genes were significantly higher versus responders (P<0.05). Of the 159 included patients, the most frequent methylated genes were SFRP1 (102/159), followed by p16 (100/159), RASSF1A (98/159), then LINE1 (81/159), P73 (81/159), APC (78/159), DAPK (66/159), O6MGMT (66/159), and p14 (54/159). A total of 67/98 (68.4%) cases of RASSF1A methylated gene (P=0.0.024), and 62/100 (62%) cases of P16 methylated gene (P=0.03) were associated with mild-degree fibrosis. Conclusions To recapitulate, the PM of SFRP1, APC, RASSF1A, O6MGMT, and p16 genes increases in chronic hepatitis C patients, and can affect patientsâ response to antiviral therapy. The RASSF1A and P16 genes might have a role in the distinction between mild and marked fibrosis. Keywords: Peginterferon alfa-2b; Ribavirin; Fibrosis; Hepatitis C, Chronic
GENE ONTOLOGY ENRICHMENT AND INGENUITY PATHWAY ANALYSIS REVEALS DIFFERENTIALLY IMMUNE REGULATED NETWORKS IN TREATED COMPARED TO UNTREATED CHRONIC HEPATITIS B PATIENTS.
Authors: U S Gill, N Le Bert, K Kunasegaran, N Hansi, D Tan, D Peppa, M K Maini, A Bertoletti, Kennedy Ptf.
Journal: Hepatology (2019)
OA15.01 Combination Olaparib and Temozolomide in Relapsed Small Cell Lung Cancer: Updated Results from Phase 1/2 Clinical Trial
Authors: A. Farago, B. Yeap, R. Heist, J.P. Marcoux, D. Rangachari, D. Barbie, E. Kennedy, M. Mino-Kenudson, A. Shaw
Journal: Journal of Thoracic Oncology (2019)
A proposed new therapy of tumors deficient in methylthioadenosine phosphorylase (MTAP)
Authors: Martin Lubin, Adam Lubin
Journal: Cancer Research (2008)

1531  The MTAP gene lies on 9p21 and is often homozygously deleted, along with p16, in tumors -- especially lung and pancreatic cancer, glioma, mesothelioma, and sarcoma (frequency of deletion is 30-75%). We describe a new, selective therapy of such tumors. MTAP cleaves methylthioadenosine (MTA), a by-product of polyamine synthesis, to adenine and 5-methylthioribose-1-phosphate, which are then converted to adenine nucleotides and methionine. Tumors deficient in MTAP may therefore be sensitive to starvation for purine nucleotides or methionine; thus prior proposals had been to treat such tumors with inhibitors of de novo purine synthesis or by depletion of serum methionine. In our novel therapy, MTA and a toxic adenine analog -- e.g., 2,6-diaminopurine (DAP), 6-methylpurine (MeP), or 2-fluoroadenine -- are co-administered. The abundant adenine generated in normal (MTAP-positive) cells, from the supplied MTA, competitively blocks the adenine analog from conversion, by adenine phosphoribosyltransferase (APRT), to its toxic mononucleotide. In MTAP-negative tumor cells, no adenine is produced; hence conversion of the analog to its mononucleotide is not blocked. As determined by clonogenic assay, this combination therapy (MTA plus adenine analog) rapidly kills MTAP-negative tumor cell lines (human lung, breast, and pancreatic cancers, and leukemias) while MTAP-positive cells (either cell lines or human fibroblasts) proliferate robustly. Selectivity of this method has also been shown with MTAP-negative cells (breast or lung cancer) growing in co-culture with human fibroblasts; there is no sign of metabolic cooperation confounding the treatment. In mice, we have demonstrated that MTA can fully protect from even lethal doses of DAP or MeP. Adding an inhibitor of de novo purine synthesis (methotrexate or L-alanosine) produces synergistic killing of MTAP-negative cells; selectivity is maintained, since the supplied MTA blocks the toxicity of these two drugs, as well, by providing purines to MTAP-positive but not MTAP-negative cells. We have also shown that 5-fluorouracil (FU) and 6-thioguanine (TG) may be used with our method. Though neither FU nor TG is activated by APRT, the adenine produced from supplied MTA in MTAP-positive cells blocks conversion of these drugs to their toxic mononucleotides by competing for their common phosphoribose-donor, 5-phosphoribosyl-1-pyrophosphate. Use of MTA in combination with FU or TG, in the therapy of MTAP-negative tumors, may allow higher clinical doses of these drugs, thus improving therapeutic efficacy. Our method also works well with the toxic methionine analog, ethionine. The reason for selectivity is similar: the metabolic routes of methionine analogs are blocked in MTAP-positive, but not MTAP-negative cells, by the methionine derived from MTAP acting on the supplied MTA. This new selective therapy will now be studied in nude mice bearing MTAP-deficient human tumors.
Novel R41Q- and R46Q-PAR1-Modified Mice Enable Proof-of-Concept Studies for In Vivo Protective Mechanisms of Action for Activated Protein C (APC) in Sepsis and Stroke
Authors: Ranjeet Kumar Sinha, Yaoming Wang, Zhen Zhao, Jose A. Fernandez, Naveen Gupta, Xiao Xu, Greg Martin, Sergey Kupriyanov, Laurent O Mosnier, Berislav Zlokovic, John H. Griffin
Journal: Blood (2016)
P2.04-62 TCR Repertoire Analysis of Peripheral CD8+PD-1+ T Cells Is Effective as a Predictive Biomarker for Response to the Immune Checkpoint Inhibitor
Authors: S. Matsumoto, T. Matsutani, Y. Fujita, K. Kitaura, Y. Nakamura, T. Nakamichi, A. Nakamura, A. Kuroda, M. Hashimoto, N. Kondo, T. Shini, R. Suzuki, S. Hasegawa
Journal: Journal of Thoracic Oncology (2019)
OA02.05 First-In-Human Phase 1/2 Trial of Anti-AXL Antibody–Drug Conjugate (ADC) Enapotamab Vedotin (EnaV) in Advanced NSCLC
Authors: S. Ramalingam, J. Lopez, M. Mau-Sorensen, F. Thistlethwaite, S. Piha-Paul, S. Gadgeel, Y. Drew, P. Jänne, A. Mansfield, G. Chen, U. Forssmann, H. Johannsdottir, N. Pencheva, A. Ervin-Haynes, I. Vergote
Journal: Journal of Thoracic Oncology (2019)
P1.01-30 Non-Small Cell Lung Cancer (NSCLC) Next Generation Sequencing (NGS): Integrating Genomic Sequencing into a Publicly Funded Health Care Model
Authors: K. Perdrizet, T. Stockley, J. Law, M. Shabir, T. Zhang, L. Le, A. Lau, M. Tsao, S. Kamel-Reid, P. Pal, M. Cabanero, J. Schwock, H. Ko, G. Liu, P. Bradbury, A. Sacher, F. Shepherd, N. Leighl
Journal: Journal of Thoracic Oncology (2019)
Prevalence and Prognostic Impact of FLT3-ITD and NPM1 Mutations: A Cohort of Patients with Acute Myeloid Leukemia from the ABC-SP, Brazil
Authors: Carolina Susanna, José Henrique Borducchi, Vitor Mauad, Adriana Del Giglio, Itatiana Rodart, Auro Del Giglio, Davimar Miranda Maciel Borducchi
Journal: Blood (2017)
EP1.03-19 The Frequency and Prognosis of MDM2 Mutations in East Asian Non-Small-Cell Lung Cancer Patients
Authors: B. Wan, C. Xu, W. Wang, X. Zhang, Q. Zhang, W. Zhuang, Y. Zhu, Z. Huang, G. Chen, M. Fang, T. Lv, Y. Song
Journal: Journal of Thoracic Oncology (2019)
Clinical Effect of Genetic Alterations in Pediatric Patients with B-Progenitor Acute Lymphoblastic Leukemia
Authors: Hiroo Ueno, Kenichi Yoshida, Yasuhito Nannya, Yuka Iijima-Yamashita, Yusuke Shiozawa, Yuichi Shiraishi, Tomomi Ishida, Keisuke Kataoka, Tetsuichi Yoshizato, Hideki Makishima, Nobuyuki Kakiuchi, Masafumi Seki, Hiroko Tanaka, Kenichi Chiba, Takao Deguchi, Atsushi Sato, Yoshiko Hashii, Sadao Tokimasa, Junichi Hara, Yoshiyuki Kosaka, Koji Kato, Toshihiko Imamura, Satoru Miyano, Keizo Horibe, Seishi Ogawa, Masashi Sanada
Journal: Blood (2017)
General practice will crumble if politicians impose unrealistic targets, says Stokes-Lampard
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Politicians must not resort to “vote winning gimmicks” in an attempt to reduce waiting times for GP appointments, says Helen Stokes-Lampard, chair of the Royal College of General Practitioners (RCGP).

Speaking at the college’s annual conference in Liverpool on 24 October, she said that GPs must offer what patients need, “not what politicians want,” and warned politicians that, if “unrealistic targets are imposed on our profession, it will crumble.”

A survey of more than 1500 GPs in England, released at the conference, found that 60% of GPs reported …
Risk factors for the development of cutaneous melanoma after allogeneic hematopoietic cell transplantation
Authors: Megan M. Herr, Rochelle E. Curtis, Margaret A. Tucker, Heather R. Tecca, Eric A. Engels, Elizabeth K. Cahoon, Minoo Battiwalla, David Buchbinder, Mary E. Flowers, Ruta Brazauskas, Bronwen E. Shaw, Lindsay M. Morton
Journal: Journal of the American Academy of Dermatology (2019)
Confidentiality Orders and Public Interest in Drug and Medical Device Litigation
Authors: Alexander C. Egilman, Aaron S. Kesselheim, Harlan M. Krumholz, Joseph S. Ross, Jeanie Kim, Amy Kapczynski
Journal: JAMA Internal Medicine (2019)

Litigation involving drug and medical device manufacturers has the potential to reveal important information about product efficacy and safety as well as company marketing. Prevailing legal standards recognize the public's interest in having access to certain types of information in lawsuits. However, in practice, courts and litigants commonly use overly broad or unwarranted confidentiality orders, which can prevent the public from accessing important public health information that emerges during litigation. This Special Communication reviews the rules governing confidentiality orders and discusses the tension between these rules and prevailing legal practices relating to court secrecy in medical product litigation, including competing interests among manufacturers, plaintiffs, and courts. Using examples of successful efforts to challenge confidentiality orders, we describe how these prevailing legal practices can undermine access to information by patients, clinicians, and the US Food and Drug Administration and also obscure patterns of injury and disease associated with the drugs and medical devices at issue. We then discuss several ways to advance access to information important to public health that emerges during litigation, focusing particularly on the role of medical experts engaged in cases.