Take a deeper look into all the publications produced by researchers at The Dartmouth Institute.

Diffenbaugh NS, Singh D, Mankin JS

2018 Feb;4(2):eaao3354doi: 10.1126/sciadv.aao3354

The United Nations Paris Agreement creates a specific need to compare consequences of cumulative emissions for pledged national commitments and aspirational targets of 1.5° to 2°C global warming. We find that humans have already increased the probability of historically unprecedented hot, warm, wet, and dry extremes, including over 50 to 90% of North America, Europe, and East Asia. Emissions consistent with national commitments are likely to cause substantial and widespread additional increases, including more than fivefold for warmest night over ~50% of Europe and >25% of East Asia and more than threefold for wettest days over >35% of North America, Europe, and East Asia. In contrast, meeting aspirational targets to keep global warming below 2°C reduces the area experiencing more than threefold increases to <10% of most regions studied. However, large areas-including >90% of North America, Europe, East Asia, and much of the tropics-still exhibit sizable increases in the probability of record-setting hot, wet, and/or dry events.

Sci Adv|2018 Feb

Weeks WB, Goertz CM, Long CR, Meeker WC, Marchiori DM

2018 Feb 15;pii: S0161-4754(17)30293-2. doi: 10.1016/j.jmpt.2017.12.003

The purpose of this study was to explore the relationship between self-reported use of opioids by patients with neck and back pain and their demographics, pain characteristics, treatment preferences, and recollections of their physicians' opinions regarding treatment options.

J Manipulative Physiol Ther|2018 Feb 15

Rodriguez-Garcia M, Fortier JM, Barr FD, Wira CR

2018 Feb 18;doi: 10.1111/acel.12733

As women age, susceptibility to systemic and genital infections increases. Tissue-resident memory T cells (TRMs) are CD103CD8long-lived lymphocytes that provide critical mucosal immune protection. Mucosal dendritic cells (DCs) are known to induce CD103 expression on CD8T cells. While CD103CD8T cells are found throughout the female reproductive tract (FRT), the extent to which aging impacts their presence and induction by DCs remains unknown. Using hysterectomy tissues, we found that endometrial CD103CD8T cells were increased in postmenopausal compared to premenopausal women. Endometrial DCs from postmenopausal women were significantly more effective at inducing CD103 expression on allogeneic naïve CD8T cells than DCs from premenopausal women; CD103 upregulation was mediated through membrane-bound TGFβ signaling. In contrast, cervical CD103T cells and DC numbers declined in postmenopausal women with age. Decreases in DCs correlated with decreased CD103T cells in endocervix, but not ectocervix. Our findings demonstrate a previously unrecognized compartmentalization of TRMs in the FRT of postmenopausal women, with loss of TRMs and DCs in the cervix with aging, and increased TRMs and DC induction capacity in the endometrium. These findings are relevant to understanding immune protection in the FRT and to the design of vaccines for women of all ages.

Aging Cell|2018 Feb 18

Shajani-Yi Z, de Abreu FB, Peterson JD, Tsongalis GJ

2018 Feb 13;20(3):256-262doi: 10.1016/j.neo.2017.12.005

The tumor suppressor gene TP53 is the most frequently mutated gene in human cancer. It encodes p53, a DNA-binding transcription factor that regulates multiple genes involved in DNA repair, metabolism, cell cycle arrest, apoptosis, and senescence. TP53 is associated with human cancer by mutations that lead to a loss of wild-type p53 function as well as mutations that confer alternate oncogenic functions that enable them to promote invasion, metastasis, proliferation, and cell survival. Identifying the discrete TP53 mutations in tumor cells may help direct therapies that are more effective. In this study, we identified the frequency of individual TP53 mutations in patients with colon adenocarcinoma (48%), non-small cell lung carcinoma (NSCLC) (36%), and glioma/glioblastoma (28%) at our institution using next-generation sequencing. We also identified the occurrence of somatic mutations in numerous actionable genes including BRAF, EGFR, KRAS, IDH1, and PIK3CA that occurred concurrently with these TP53 mutations. Of the 480 tumors examined that contained one or more mutations in the TP53 gene, 219 were colon adenocarcinomas, 215 were NSCLCs, and 46 were gliomas/glioblastomas. Among the patients positive for TP53 mutations diagnosed with colon adenocarcinoma, 50% also showed at least one mutation in pathogenic genes of which 14% were BRAF, 33% were KRAS, and 3% were NRAS. Forty-seven percent of NSCLC patients harboring TP53 mutations also had a mutation in at least one actionable pathogenic variant with the following frequencies: BRAF: 4%, EGFR: 10%, KRAS: 28%, and PIK3CA: 4%. Fifty-two percent of patients diagnosed with glioma/glioblastoma with a positive TP53 mutation had at least one concurrent mutation in a known pathogenic gene of which 9% were CDKN2A, 41% were IDH1, and 11% were PIK3CA.

Neoplasia|2018 Feb 13

Tillmann S, Awwad HM, Eskelund AR, Treccani G, Geisel J, Wegener G, Obeid R

2018 Feb 17;doi: 10.1002/mnfr.201701070

Probiotics may influence one-carbon (C1) metabolism, neurotransmitters, liver function markers, or behavior.

Mol Nutr Food Res|2018 Feb 17

Gacerez AT, Hua CK, Ackerman ME, Sentman CL

2018 Feb 16;doi: 10.1007/s00262-018-2124-1

B7H6 is emerging as a promising tumor antigen that is known to be expressed on a wide array of tumors and is reported to stimulate anti-tumor responses from the immune system. As such, B7H6 presents a good target for tumor-specific immunotherapies. B7H6-specific chimeric antigen receptors (CAR) based on a murine antibody showed successful targeting and elimination of tumors expressing B7H6. However, mouse single chain variable fragments (scFvs) have the potential to induce host anti-CAR responses that may limit efficacy, so human scFvs specific for B7H6 were selected by yeast surface display. In this study, we validate the functionality of these human scFvs when formatted into chimeric antigen receptors. The data indicate that T cells expressing these B7H6-specific human scFvs as CARs induced potent anti-tumor activity in vitro and in vivo against tumors expressing high amounts of B7H6. Importantly, these human scFv-based CARs are sensitive to changes in B7H6 expression which may potentially spare non-tumor cells that express B7H6 and provides the foundation for future clinical development.

Cancer Immunol Immunother|2018 Feb 16

Leyenaar JK, Rizzo PA, O'Brien ER, Lindenauer PK

2018 Feb 16;pii: bmjqs-2017-007442. doi: 10.1136/bmjqs-2017-007442

Hospital admission, like hospital discharge, represents a transition of care associated with changes in setting, healthcare providers and clinical management. While considerable efforts have focused on improving the quality and safety of hospital-to-home transitions, there has been little focus on transitionshospital.

BMJ Qual Saf|2018 Feb 16

Young-Xu Y, Van Aalst R, Mahmud SM, Rothman KJ, Thornton Snider J, Westreich D, Mor V, Gravenstein S, Lee JKH, Thommes EW, Decker MD, Chit A

2018 Feb 14;doi: 10.1093/infdis/jiy088

To examine whether a high-dose inactivated influenza vaccine was more efficacious in preventing hospitalizations than a standard-dose vaccine in the Veterans Health Administration (VHA) senior population.

J Infect Dis|2018 Feb 14

Szczepiorkowski ZM, Burnett CA, Dumont LJ, Abhyankar SH

2018 Feb 16;doi: 10.1111/trf.14532

Extracorporeal photopheresis (ECP) has been approved for the treatment of advanced cutaneous T-cell lymphoma since 1988. While the precise mechanisms resulting in clinical effects are not fully understood, the photoactivation of mononuclear cells (MNCs) using ultraviolet A (UVA) light and methoxsalen is believed to be the predominant initiating process. The effects of MNC passage through the instrument without photoactivation are unknown. The objective of this study was to evaluate the effect of cell processing through the photopheresis instruments on MNCs.

Transfusion|2018 Feb 16

Maguen S, Madden E, Patterson OV, DuVall SL, Goldstein LA, Burkman K, Shiner B

2018 Feb 15;doi: 10.1007/s10488-018-0850-5

To derive a method of identifying use of evidence-based psychotherapy (EBP) for post-traumatic stress disorder (PTSD), we used clinical note text from national Veterans Health Administration (VHA) medical records. Using natural language processing, we developed machine-learning algorithms to classify note text on a large scale in an observational study of Iraq and Afghanistan veterans with PTSD and one post-deployment psychotherapy visit by 8/5/15 (N = 255,968). PTSD visits were linked to 8.1 million psychotherapy notes. Annotators labeled 3467 randomly-selected psychotherapy notes (kappa = 0.88) to indicate receipt of EBP. We met our performance targets of overall classification accuracy (0.92); 20.2% of veterans received ≥ one session of EBP over the study period. Our method can assist with identifying EBP use and studying EBP-associated outcomes in routine clinical practice.

Adm Policy Ment Health|2018 Feb 15


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