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Article ; Online: Robust Heterochiral Strand Displacement Using Leakless Translators.

Mallette, Tracy L / Stojanovic, Milan N / Stefanovic, Darko / Lakin, Matthew R

ACS synthetic biology

2020 Volume 9, Issue 7, Page(s) 1907–1910

Abstract: Molecular computing offers a powerful framework ... ...

Abstract	Molecular computing offers a powerful framework for
MeSH term(s)	Animals ; Base Sequence ; Cattle ; Computers, Molecular ; Culture Media/chemistry ; DNA Fragmentation ; DNA, Single-Stranded/chemistry ; DNA, Single-Stranded/genetics ; Deoxyribonucleases/chemistry ; Nucleic Acid Conformation ; Nucleic Acid Hybridization ; Oligonucleotides/chemistry ; Protein Biosynthesis ; Recombination, Genetic ; Serum Albumin, Bovine
Chemical Substances	Culture Media ; DNA, Single-Stranded ; Oligonucleotides ; Serum Albumin, Bovine (27432CM55Q) ; Deoxyribonucleases (EC 3.1.-)
Language	English
Publishing date	2020-07-01
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2161-5063
ISSN (online)	2161-5063
DOI	10.1021/acssynbio.0c00131
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Article: The effect of cysteamine, cystamine, and the structurally related compounds taurine, N-acetyl-cysteine, and D-penicillamine on plasma prolactin levels in normal and estrogen-primed hyperprolactinemic rats.

Scott, J S / Lakin, C A / Oliver, J R

Endocrinology

1987 Volume 121, Issue 2, Page(s) 812–818

Abstract: ... The structurally related compounds, taurine, N-acetyl-cysteine, and D-penicillamine did not cause any reduction ... Studies were undertaken to evaluate the effects of cysteamine (CSH), cystamine (CS-S), N-acetyl ... cysteine, D-penicillamine, and a major metabolite of CSh, taurine, on plasma PRL levels in normal and ...

Abstract	Studies were undertaken to evaluate the effects of cysteamine (CSH), cystamine (CS-S), N-acetyl-cysteine, D-penicillamine, and a major metabolite of CSh, taurine, on plasma PRL levels in normal and estrogen-primed hyperprolactinemic rats. Both CSH and CS-S caused a marked decrease in plasma PRL concentration in hyperprolactinemic rats. The effects of CSH and CS-S lasted for at least 6 h but returned toward pretreatment levels 24 h later. In normal rats a fall in basal plasma PRL concentration was not readily observed but after stimulation with TRH or metaclopramide, PRL secretion elicited by these stimuli was markedly inhibited by CSH and CS-S. The response to TRH or MCP 24 h after treatment with CSH was variable with CS-S appearing to cause an unexpected increase in PRL release in response to TRH or metaclopramide. The structurally related compounds, taurine, N-acetyl-cysteine, and D-penicillamine did not cause any reduction of plasma PRL levels in hyperprolactinemic rats. This may be due, in the case of taurine, to a loss of the free sulfydryl group, in the case of N-acetyl-cysteine, a change in basicity because of a carboxyl group and derivatization of the amino group and D-penicillamine, again a change in basicity due to a free carboxyl group as well as an altered structural relationship between the free amino and sulfydryl groups. These studies indicate that CSH and CS-S by possible reduction to CSH cause a reversible depletion in plasma PRL in normal and hyperprolactinemic rats. Because both substances inhibit different receptor-mediated stimuli, their mechanism of action is likely to be mediated at a common locus involved with the synthesis and release of PRL.
MeSH term(s)	Acetylcysteine/pharmacology ; Animals ; Cystamine/pharmacology ; Cysteamine/pharmacology ; Estradiol ; Hyperprolactinemia/blood ; Hyperprolactinemia/chemically induced ; Male ; Metoclopramide/pharmacology ; Penicillamine/pharmacology ; Prolactin/blood ; Rats ; Taurine/pharmacology ; Thyrotropin-Releasing Hormone/pharmacology
Chemical Substances	Taurine (1EQV5MLY3D) ; Estradiol (4TI98Z838E) ; Cysteamine (5UX2SD1KE2) ; Thyrotropin-Releasing Hormone (5Y5F15120W) ; Prolactin (9002-62-4) ; Penicillamine (GNN1DV99GX) ; Metoclopramide (L4YEB44I46) ; Cystamine (R110LV8L02) ; Acetylcysteine (WYQ7N0BPYC)
Language	English
Publishing date	1987-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/endo-121-2-812
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Article ; Online: The differences in code status conversation approaches reported by emergency medicine and palliative care clinicians: A mixed-method study.

Ouchi, Kei / Prachanukool, Thidathit / Aaronson, Emily L / Lakin, Joshua R / Higuchi, Masaya / Liu, Shan W / Kennedy, Maura / Revette, Anna C / Chary, Anita N / Kaithamattam, Jenson / Lee, Brandon / Neville, Thanh H / Hasdianda, Mohammad A / Sudore, Rebecca / Schonberg, Mara A / Tulsky, James A / Block, Susan D

Academic emergency medicine : official journal of the Society for Academic Emergency Medicine

2023 Volume 31, Issue 1, Page(s) 18–27

Abstract: Background: During acute health deterioration, emergency medicine and palliative care clinicians routinely discuss code status (e.g., shared decision making about mechanical ventilation) with seriously ill patients. Little is known about their ... ...

Abstract	Background: During acute health deterioration, emergency medicine and palliative care clinicians routinely discuss code status (e.g., shared decision making about mechanical ventilation) with seriously ill patients. Little is known about their approaches. We sought to elucidate how code status conversations are conducted by emergency medicine and palliative care clinicians and why their approaches are different. Methods: We conducted a sequential-explanatory, mixed-method study in three large academic medical centers in the Northeastern United States. Attending physicians and advanced practice providers working in emergency medicine and palliative care were eligible. Among the survey respondents, we purposefully sampled the participants for follow-up interviews. We collected clinicians' self-reported approaches in code status conversations and their rationales. A survey with a 5-point Likert scale ("very unlikely" to "very likely") was used to assess the likelihood of asking about medical procedures (procedure based) and patients' values (value based) during code status conversations, followed by semistructured interviews. Results: Among 272 clinicians approached, 206 completed the survey (a 76% response rate). The reported approaches differed greatly (e.g., 91% of palliative care clinicians reported asking about a patient's acceptable quality of life compared to 59% of emergency medicine clinicians). Of the 206 respondents, 118 (57%) agreed to subsequent interviews; our final number of semistructured interviews included seven emergency medicine clinicians and nine palliative care clinicians. The palliative care clinicians stated that the value-based questions offer insight into patients' goals, which is necessary for formulating a recommendation. In contrast, emergency medicine clinicians stated that while value-based questions are useful, they are vague and necessitate extended discussions, which are inappropriate during emergencies. Conclusions: Emergency medicine and palliative care clinicians reported conducting code status conversations differently. The rationales may be shaped by their clinical practices and experiences.
MeSH term(s)	Humans ; Palliative Care ; Quality of Life ; Communication ; Surveys and Questionnaires ; Emergency Medicine
Language	English
Publishing date	2023-10-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	1329813-6
ISSN	1553-2712 ; 1069-6563
ISSN (online)	1553-2712
ISSN	1069-6563
DOI	10.1111/acem.14818
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Article: A Real-World Effectiveness Study Using a Mobile Application to Evaluate Early Outcomes with Upadacitinib in Rheumatoid Arthritis.

Harrold, Leslie R / Zueger, Patrick / Nowell, W Benjamin / Blachley, Taylor / Schrader, Amy / Lakin, Paul R / Curtis, David / Stradford, Laura / Venkatachalam, Shilpa / Tundia, Namita / Patel, Pankaj A

Rheumatology and therapy

2023 Volume 10, Issue 6, Page(s) 1519–1533

Abstract: Introduction: The impact of upadacitinib on rheumatoid arthritis (RA) symptoms was evaluated during the first 12 weeks of treatment via patient-reported outcomes (PROs) using a mobile health application (app).: Methods: Participating rheumatologists ... ...

Abstract	Introduction: The impact of upadacitinib on rheumatoid arthritis (RA) symptoms was evaluated during the first 12 weeks of treatment via patient-reported outcomes (PROs) using a mobile health application (app). Methods: Participating rheumatologists from the CorEvitas RA Registry (prospective, observational cohort) recruited patients with RA initiating upadacitinib treatment. A modified version of the ArthritisPower® app was used to collect PROs, including the Routine Assessment of Patient Index Data 3 (RAPID3), duration of morning joint stiffness, and the Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue 7a Short Form at baseline and weeks 1-4, 8, and 12. RAPID3 responses over time were assessed using Kaplan-Meier estimation to determine the proportion of patients achieving disease activity improvement and minimal clinically important difference (MCID). Results were analyzed for all patients initiating upadacitinib and a subsample of TNF inhibitor (TNFi)-experienced patients with moderate to severe disease at baseline. Results: A total of 103 patients with RA initiating upadacitinib (62.1% TNFi-experienced) were included. At week 12, 53 patients (51.4%) completed the study and provided PRO data via the app. Among all patients, improvements in RAPID3, pain, morning stiffness, and fatigue were observed at week 1 and were maintained or further improved through week 12. At week 12, 37.5% of patients achieved RAPID3 low disease activity. Starting at week 1, improvements in RAPID3 disease activity category (19.4% of patients) and achievement of MCID (16.3%) were reported, with nearly 50% of patients achieving these outcomes by week 4 (RAPID3 category: 48.8%; MCID: 49.2%) and 60% by week 12 (RAPID3 category: 59.6%; MCID: 59.8%). TNFi-experienced patients generally reported similar outcomes. Patient-reported medication convenience and compliance were generally high. Conclusions: In this real-world cohort of patients with RA, treatment with upadacitinib was associated with early and significant improvement in RAPID3, pain, morning stiffness, and fatigue regardless of prior TNFi experience. Clinically meaningful improvement in RAPID3 patient-reported disease activity was observed as early as week 1, with continued improvement reported through week 12.
Language	English
Publishing date	2023-09-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2783278-8
ISSN	2198-6584 ; 2198-6576
ISSN (online)	2198-6584
ISSN	2198-6576
DOI	10.1007/s40744-023-00594-6
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Article ; Online: Top Ten Tips Palliative Care Clinicians Should Know About Solid Organ Transplantation.

Murakami, Naoka / Baggett, Nathan D / Schwarze, Margaret L / Ladin, Keren / Courtwright, Andrew M / Goldberg, Hilary J / Nolley, Eric P / Jain, Nelia / Landzberg, Michael / Wentlandt, Kirsten / Lai, Jennifer C / Shinall, Myrick C / Ufere, Nneka N / Jones, Christopher A / Lakin, Joshua R

Journal of palliative medicine

2022 Volume 25, Issue 7, Page(s) 1136–1142

Abstract: Solid organ transplantation (SOT) is a life-saving procedure for people with end-stage organ failure. However, patients experience significant symptom burden, complex decision making, morbidity, and mortality during both pre- and post-transplant periods. ...

Abstract	Solid organ transplantation (SOT) is a life-saving procedure for people with end-stage organ failure. However, patients experience significant symptom burden, complex decision making, morbidity, and mortality during both pre- and post-transplant periods. Palliative care (PC) is well suited and historically underdelivered for the transplant population. This article, written by a team of transplant specialists (surgeons, cardiologists, nephrologists, hepatologists, and pulmonologists), PC clinicians, and an ethics specialist, shares 10 high-yield tips for PC clinicians to consider when caring for SOT patients.
MeSH term(s)	Hospice and Palliative Care Nursing ; Humans ; Nephrologists ; Organ Transplantation ; Palliative Care ; Specialization
Language	English
Publishing date	2022-03-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1427361-5
ISSN	1557-7740 ; 1096-6218
ISSN (online)	1557-7740
ISSN	1096-6218
DOI	10.1089/jpm.2022.0013
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Article ; Online: Author Correction: C16orf72/HAPSTR1/TAPR1 functions with BRCA1/Senataxin to modulate replication-associated R-loops and confer resistance to PARP disruption.

Sharma, Abhishek Bharadwaj / Ramlee, Muhammad Khairul / Kosmin, Joel / Higgs, Martin R / Wolstenholme, Amy / Ronson, George E / Jones, Dylan / Ebner, Daniel / Shamkhi, Noor / Sims, David / Wijnhoven, Paul W G / Forment, Josep V / Gibbs-Seymour, Ian / Lakin, Nicholas D

Nature communications

2023 Volume 14, Issue 1, Page(s) 7784

Language	English
Publishing date	2023-11-27
Publishing country	England
Document type	Published Erratum
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-43353-5
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Article ; Online: C16orf72/HAPSTR1/TAPR1 functions with BRCA1/Senataxin to modulate replication-associated R-loops and confer resistance to PARP disruption.

Nature communications

2023 Volume 14, Issue 1, Page(s) 5003

Abstract: While the toxicity of PARP inhibitors to cells with defects in homologous recombination (HR) is well established, other synthetic lethal interactions with PARP1/PARP2 disruption are poorly defined. To inform on these mechanisms we conducted a genome-wide ...

Abstract	While the toxicity of PARP inhibitors to cells with defects in homologous recombination (HR) is well established, other synthetic lethal interactions with PARP1/PARP2 disruption are poorly defined. To inform on these mechanisms we conducted a genome-wide screen for genes that are synthetic lethal with PARP1/2 gene disruption and identified C16orf72/HAPSTR1/TAPR1 as a novel modulator of replication-associated R-loops. C16orf72 is critical to facilitate replication fork restart, suppress DNA damage and maintain genome stability in response to replication stress. Importantly, C16orf72 and PARP1/2 function in parallel pathways to suppress DNA:RNA hybrids that accumulate at stalled replication forks. Mechanistically, this is achieved through an interaction of C16orf72 with BRCA1 and the RNA/DNA helicase Senataxin to facilitate their recruitment to RNA:DNA hybrids and confer resistance to PARP inhibitors. Together, this identifies a C16orf72/Senataxin/BRCA1-dependent pathway to suppress replication-associated R-loop accumulation, maintain genome stability and confer resistance to PARP inhibitors.
MeSH term(s)	DNA Damage ; DNA Helicases/genetics ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; R-Loop Structures/genetics ; RNA ; BRCA1 Protein/genetics ; Intracellular Signaling Peptides and Proteins/genetics
Chemical Substances	DNA Helicases (EC 3.6.4.-) ; Poly(ADP-ribose) Polymerase Inhibitors ; RNA (63231-63-0) ; BRCA1 Protein ; Intracellular Signaling Peptides and Proteins
Language	English
Publishing date	2023-08-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-40779-9
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Article ; Online: Structural Barriers to Well-grounded Advance Care Planning for the Seriously Ill: a Qualitative Study of Clinicians' and Administrators' Experiences During a Pragmatic Trial.

Murray, Genevra F / Lakin, Joshua R / Paasche-Orlow, Michael K / Tulsky, James A / Volandes, Angelo / Davis, Aretha Delight / Zupanc, Sophia N / Carney, Maria T / Burns, Edith / Martins-Welch, Diana / LaVine, Nancy / Itty, Jennifer E / Fix, Gemmae M

Journal of general internal medicine

2023 Volume 38, Issue 16, Page(s) 3558–3565

Abstract: Background: Advance Care Planning (ACP) comprises an iterative communication process aimed at understanding patients' goals, values, and preferences in the context of considering and preparing for future medical treatments and decision making in serious ...

Abstract	Background: Advance Care Planning (ACP) comprises an iterative communication process aimed at understanding patients' goals, values, and preferences in the context of considering and preparing for future medical treatments and decision making in serious illness. The COVID pandemic heightened patients' and clinicians' awareness of the need for ACP. Objective: Our goal was to explore the experiences of clinicians and administrators in the context of an intervention to improve ACP during the COVID pandemic. Design: Qualitative interview study. Participants: Clinicians and administrators across five sites that participated in the ACP-COVID trial. Approach: We conducted semi-structured, qualitative interviews examining the context and approach to ACP. Interviews were analyzed using template analysis to systematically organize the data and facilitate review across the categories and participants. Templates were developed with iterative input and line-by-line review by the analytic team, to reach consensus. Findings were then organized into emergent themes. Key results: Across 20 interviews (4 administrators, 16 clinicians) we identified three themes related to how participants thought about ACP: (1) clinicians have varying views of what constitutes ACP; (2) the health system critically shapes ACP culture and norms; and (3) the centrality of clinicians' affective experience and own needs related to ACP. Varying approaches to ACP include a forms-focused approach; a discussion-based approach; and a parental approach. System features that shape ACP norms are (1) the primacy of clinician productivity measures; (2) the role of the EHR; and (3) the culture of quality improvement. Conclusions: Despite high organizational commitment to ACP, we found that the health system channeled clinicians' ACP efforts narrowly on completion of forms, in tension with the ideal of well-grounded ACP. This resulted in a state of moral distress that risks undermining confidence in the process of ACP and may increase risk of harm for patients, family/caregivers, and providers. Trial registration: ClinicalTrials.gov Identifier: NCT04660422.
MeSH term(s)	Humans ; Advance Care Planning ; Qualitative Research ; Pragmatic Clinical Trials as Topic
Language	English
Publishing date	2023-07-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	639008-0
ISSN	1525-1497 ; 0884-8734
ISSN (online)	1525-1497
ISSN	0884-8734
DOI	10.1007/s11606-023-08320-2
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Article ; Online: Clinical Outcomes of Patients Hospitalized with Coronavirus Disease 2019 (COVID-19) in Boston.

El-Jawahri, Areej / Bohossian, Hacho B / Paasche-Orlow, Michael K / Lakin, Joshua R / Johnson, P Connor / Cooper, Zara / Jagielo, Annemarie D / Brannen, Elise N / Reynolds, Matthew J / Coogan, Kathleen / Vaughn, Dagny / Volandes, Angelo

Journal of general internal medicine

2021 Volume 36, Issue 5, Page(s) 1285–1291

Abstract: ... cardiopulmonary resuscitation, and 25.1% (118/470) died. Among those admitted to the ICU (N=178), the median number of days ...

Abstract	Background: Outcomes of hospitalized patients with COVID-19 have been described in health systems overwhelmed with a surge of cases. However, studies examining outcomes of patients admitted to hospitals not in crisis are lacking. Objective: To describe clinical characteristic and outcomes of all patients with COVID-19 who are admitted to hospitals not in crisis, and factors associated with mortality in this population. Design: A retrospective analysis PARTICIPANTS: In total, 470 consecutive patients with COVID-19 requiring hospitalization in one health system in Boston from January 1, 2020 to April 15, 2020. Main measures: We collected clinical outcomes during hospitalization including intensive care unit (ICU) admission, receipt of mechanical ventilation, and vasopressors. We utilized multivariable logistic regression models to examine factors associated with mortality. Key results: A total of 470 patients (median age 66 [range 23-98], 54.0% male) were included. The most common comorbidities were diabetes (38.5%, 181/470) and obesity (41.3%, 194/470). On admission, 41.9% (197/470) of patients were febrile and 60.6% (285/470) required supplemental oxygen. During hospitalization, 37.9% (178/470) were admitted to the ICU, 33.6% (158/470) received mechanical ventilation, 29.4% (138/470) received vasopressors, 16.4% (77/470) reported limitations on their desire for life-sustaining therapies such as intubation and cardiopulmonary resuscitation, and 25.1% (118/470) died. Among those admitted to the ICU (N=178), the median number of days on the ventilator was 10 days (IQR 1-29), and 58.4% (104/178) were discharged alive. Older age (OR=1.04, P<0.001), male sex (OR=2.14, P=0.007), higher comorbidities (OR=1.20, P=0.001), higher lactate dehydrogenase on admission (2nd tertile: OR=4.07, P<0.001; 3rd tertile: OR=8.04, P<0.001), and the need for supplemental oxygen on admission (OR=2.17, P=0.014) were all associated with higher mortality. Conclusions: The majority of hospitalized patients with COVID-19 and those who received mechanical ventilation survived. These data highlight the need to examine public health and system factors that contribute to improved outcomes for this population.
MeSH term(s)	Aged ; Boston/epidemiology ; COVID-19 ; Female ; Hospitalization ; Humans ; Intensive Care Units ; Male ; Retrospective Studies ; SARS-CoV-2
Language	English
Publishing date	2021-02-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639008-0
ISSN	1525-1497 ; 0884-8734
ISSN (online)	1525-1497
ISSN	0884-8734
DOI	10.1007/s11606-021-06622-x
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Article ; Online: Forms or Free-Text? Measuring Advance Care Planning Activity Using Electronic Health Records.

Zupanc, Sophia N / Lakin, Joshua R / Volandes, Angelo E / Paasche-Orlow, Michael K / Moseley, Edward T / Gundersen, Daniel A / Das, Sophiya / Penumarthy, Akhila / Martins-Welch, Diana / Burns, Edith A / Carney, Maria T / Itty, Jennifer E / Emmert, Kaitlin / Tulsky, James A / Lindvall, Charlotta

Journal of pain and symptom management

2023 Volume 66, Issue 5, Page(s) e615–e624

Abstract: Advance care planning (ACP) discussions seek to guide future serious illness care. These discussions may be recorded in the electronic health record by documentation in clinical notes, structured forms and directives, and physician orders. Yet, most ... ...

Abstract	Advance care planning (ACP) discussions seek to guide future serious illness care. These discussions may be recorded in the electronic health record by documentation in clinical notes, structured forms and directives, and physician orders. Yet, most studies of ACP prevalence have only examined structured electronic health record elements and ignored data existing in notes. We sought to investigate the relative comprehensiveness and accuracy of ACP documentation from structured and unstructured electronic health record data sources. We evaluated structured and unstructured ACP documentation present in the electronic health records of 435 patients with cancer drawn from three separate healthcare systems. We extracted structured ACP documentation by manually annotating written documents and forms scanned into the electronic health record. We coded unstructured ACP documentation using a rule-based natural language processing software that identified ACP keywords within clinical notes and was subsequently reviewed for accuracy. The unstructured approach identified more instances of ACP documentation (238, 54.7% of patients) than the structured ACP approach (187, 42.9% of patients). Additionally, 16.6% of all patients with structured ACP documentation only had documents that were judged as misclassified, incomplete, blank, unavailable, or a duplicate of a previously entered erroneous document. ACP documents scanned into electronic health records represent a limited view of ACP activity. Research and measures of clinical practice with ACP should incorporate information from unstructured data.
Language	English
Publishing date	2023-08-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	639142-4
ISSN	1873-6513 ; 0885-3924
ISSN (online)	1873-6513
ISSN	0885-3924
DOI	10.1016/j.jpainsymman.2023.07.016
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