tbuckley/cabot-search huggingface dataset:
New AHRQ Patient Safety Guidance
Authors: Rita Rubin
Journal: JAMA (2020)

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Covid-19: undocumented migrants are probably at greatest risk
Authors: Raj Bhopal
Journal: BMJ (2020)

Hargreaves and colleagues have pinpointed the challenges in meeting the needs of migrants, particularly those in refugee camps.1 Undocumented migrants, however, have even greater needs. People who are undocumented do not have legal rights to residence in the country they are in; they are also in danger of becoming scapegoats as well as victims of covid-19. For obvious reasons, the numbers of such people are unknown, but immigration authorities estimate that there are hundreds of thousands …
Stepwise Control of Crosslinking in a One‐Pot System for Bioprinting of Low‐Density Bioinks
Authors: Bram G. Soliman, Gabriella C. J. Lindberg, Tomasz Jungst, Gary J. Hooper, Jürgen Groll, Tim B. F. Woodfield, Khoon S. Lim
Journal: Advanced Healthcare Materials (2020)

Extrusion-based 3D bioprinting is hampered by the inability to print materials of low-viscosity. In this study, a single initiating system based on ruthenium (Ru) and sodium persulfate (SPS) is utilized for a sequential dual-step crosslinking approach: 1) primary (partial) crosslinking in absence of light to alter the bioink's rheological profile for print fidelity, and 2) subsequent secondary post-printing crosslinking for shape maintenance. Allyl-functionalized gelatin (Gel-AGE) is used as a bioink, allowing thiol-ene click reaction between allyl moieties and thiolated crosslinkers. A systematic investigation of primary crosslinking reveals that a thiol-persulfate redox reaction facilitates thiol-ene crosslinking, mediating an increase in bioink viscosity that is controllable by tailoring the Ru/SPS, crosslinker, and/or Gel-AGE concentrations. Thereafter, subsequent photoinitiated secondary crosslinking then facilitates maximum conversion of thiol-ene bonds between AGE and thiol groups. The dual-step crosslinking method is applicable to a wide biofabrication window (3-10 wt% Gel-AGE) and is demonstrated to allow printing of low-density (3 wt%) Gel-AGE, normally exhibiting low viscosity (4 mPa s), with high shape fidelity and high cell viability (>80%) over 7 days of culture. The presented approach can therefore be used as a one-pot system for printing low-viscous bioinks without the need for multiple initiating systems, viscosity enhancers, or complex chemical modifications.
Cancer Exacerbates Chemotherapy-Induced Sensory Neuropathy
Authors: Stephen N. Housley, Paul Nardelli, Dario I. Carrasco, Travis M. Rotterman, Emily Pfahl, Lilya V. Matyunina, John F. McDonald, Timothy C. Cope
Journal: Cancer Research (2020)

For the constellation of neurologic disorders known as chemotherapy-induced peripheral neuropathy, mechanistic understanding and treatment remain deficient. Here, we present the first evidence that chronic sensory neuropathy depends on nonlinear interactions between cancer and chemotherapy. Global transcriptional profiling of dorsal root ganglia revealed differential expression, notably in regulators of neuronal excitability, metabolism, and inflammatory responses, all of which were unpredictable from effects observed with either chemotherapy or cancer alone. Systemic interactions between cancer and chemotherapy also determined the extent of deficits in sensory encoding and ion channel protein expression by single mechanosensory neurons, with the potassium ion channel Kv3.3 emerging as one potential contributor to sensory neuron dysfunction. Validated measures of sensorimotor behavior in awake, behaving animals revealed dysfunction after chronic chemotherapy treatment was exacerbated by cancer. Notably, errors in precise forelimb placement emerged as a novel behavioral deficit unpredicted by our previous study of chemotherapy alone. These original findings identify novel contributors to peripheral neuropathy and emphasize the fundamental dependence of neuropathy on the systemic interaction between chemotherapy and cancer. SIGNIFICANCE: These findings highlight the need to account for pathobiological interactions between cancer and chemotherapy as a major contributor to neuropathy and will have significant and immediate impact on future investigations in this field.
Abstract 9970: The Phase of Second Harmonic of Radial Pulse Wave Predicts the Macrovascular and Microvascular Outcomes and Mental Disorder in Asymptomatic Patients With Type 2 Diabetes
Authors: Chi-Wei Chang, Kuomeng Liao, Yi-Ting Chang, Sheng-Hung Wang, Ying-chun Chen, gin-chung wang
Journal: Circulation (2019)

The second harmonic phase of the radial pulse wave (P2) is associated with coronary stenosis and left ventricular dysfunction in patients with type 2 diabetes mellitus (T2DM). We aimed to further v...
COVID-19 pandemic and non invasive respiratory management: Every Goliath needs a David. An evidence based evaluation of problems
Authors: J.C. Winck, N. Ambrosino
Journal: Pulmonology (2020)

The war against Covid-19 is far from won. This narrative review attempts to describe some problems with the management of Covid-19 induced acute respiratory failure (ARF) by pulmonologists. We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and reviewed the references of retrieved articles for additional studies. The search was limited to the terms: Covid-19 AND: acute respiratory distress syndrome (ARDS), SARS, MERS, non invasive ventilation (NIV), high flow nasal cannula (HFNC), pronation (PP), health care workers (HCW). Protection of Health care workers should be paramount, so full Personal Protective Equipment and Negative pressure rooms are warranted. HFNC alone or with PP could be offered for mild cases (PaO2/FiO2 between 200–300); NIV alone or with PP may work in moderate cases (PaO2/FiO2 between 100–200). Rotation and coupled (HFNC/NIV) strategy can be beneficial. A window of opportunity of 1–2 h is advised. If PaO2/FIO2 significantly increases, Respiratory Rate decreases with a relatively low Exhaled Tidal Volume, the non-invasive strategy could be working and intubation delayed. Although there is a role for non-invasive respiratory therapies in the context of COVID-19 ARF, more research is still needed to define the balance of benefits and risks to patients and HCW. Indirectly, non invasive respiratory therapies may be of particular benefit in reducing the risks to healthcare workers by obviating the need for intubation, a potentially highly infectious procedure.
LRRK2 inhibitors induce reversible changes in nonhuman primate lungs without measurable pulmonary deficits
Authors: Marco A. S. Baptista, Kalpana Merchant, Ted Barrett, Sakshi Bhargava, Dianne K. Bryce, J. Michael Ellis, Anthony A. Estrada, Matthew J. Fell, Brian K. Fiske, Reina N. Fuji, Paul Galatsis, Anastasia G. Henry, Sue Hill, Warren Hirst, Christopher Houle, Matthew E. Kennedy, Xingrong Liu, Matthew L. Maddess, Carrie Markgraf, Hong Mei, William A. Meier, Elie Needle, Stephen Ploch, Christopher Royer, Karin Rudolph, Alok K. Sharma, Antonia Stepan, Stefan Steyn, Craig Trost, Zhizhang Yin, Hongshi Yu, Xiang Wang, Todd B. Sherer
Journal: Science Translational Medicine (2020)

Morphological changes in the lungs of macaques induced by several different LRRK2 inhibitors are reversible and do not lead to lung deficits.
Mechanisms of Natural Killer Cell Evasion Through Viral Adaptation
Authors: Mathieu Mancini, Silvia M. Vidal
Journal: Annual Review of Immunology (2020)

The continuous interactions between host and pathogens during their coevolution have shaped both the immune system and the countermeasures used by pathogens. Natural killer (NK) cells are innate lymphocytes that are considered central players in the antiviral response. Not only do they express a variety of inhibitory and activating receptors to discriminate and eliminate target cells but they can also produce immunoregulatory cytokines to alert the immune system. Reciprocally, several unrelated viruses including cytomegalovirus, human immunodeficiency virus, influenza virus, and dengue virus have evolved a multitude of mechanisms to evade NK cell function, such as the targeting of pathways for NK cell receptors and their ligands, apoptosis, and cytokine-mediated signaling. The studies discussed in this article provide further insights into the antiviral function of NK cells and the pathways involved, their constituent proteins, and ways in which they could be manipulated for host benefit.
Crowdsourcing a crisis response for COVID-19 in oncology
Authors: Aakash Desai, Jeremy Warner, Nicole Kuderer, Mike Thompson, Corrie Painter, Gary Lyman, Gilberto Lopes
Journal: Nature Cancer (2020)

Crowdsourcing efforts are currently underway to collect and analyze data from patients with cancer who are affected by the COVID-19 pandemic. These community-led initiatives will fill key knowledge gaps to tackle crucial clinical questions on the complexities of infection with the causative coronavirus SARS-Cov-2 in the large, heterogeneous group of vulnerable patients with cancer.
AMPK Activation by Metformin Promotes Survival of Dormant ER+ Breast Cancer Cells
Authors: Riley A. Hampsch, Jason D. Wells, Nicole A. Traphagen, Charlotte F. McCleery, Jennifer L. Fields, Kevin Shee, Lloye M. Dillon, Darcy B. Pooler, Lionel D. Lewis, Eugene Demidenko, Yina H. Huang, Jonathan D. Marotti, Abigail E. Goen, William B. Kinlaw, Todd W. Miller
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Despite adjuvant endocrine therapy for patients with estrogen receptor alpha (ER)-positive breast cancer, dormant residual disease can persist for years and eventually cause tumor recurrence. We sought to deduce mechanisms underlying the persistence of dormant cancer cells to identify therapeutic strategies. Experimental Design: Mimicking the aromatase inhibitor–induced depletion of estrogen levels used to treat patients, we developed preclinical models of dormancy in ER+ breast cancer induced by estrogen withdrawal in mice. We analyzed tumor xenografts and cultured cancer cells for molecular and cellular responses to estrogen withdrawal and drug treatments. Publicly available clinical breast tumor gene expression datasets were analyzed for responses to neoadjuvant endocrine therapy. Results: Dormant breast cancer cells exhibited upregulated 5′ adenosine monophosphate-activated protein kinase (AMPK) levels and activity, and upregulated fatty acid oxidation. While the antidiabetes AMPK-activating drug metformin slowed the estrogen-driven growth of cells and tumors, metformin promoted the persistence of estrogen-deprived cells and tumors through increased mitochondrial respiration driven by fatty acid oxidation. Pharmacologic or genetic inhibition of AMPK or fatty acid oxidation promoted clearance of dormant residual disease, while dietary fat increased tumor cell survival. Conclusions: AMPK has context-dependent effects in cancer, cautioning against the widespread use of an AMPK activator across disease settings. The development of therapeutics targeting fat metabolism is warranted in ER+ breast cancer.
Reply to Waller et al. Standardizing Surgical Treatment for Mesothelioma
Authors: Joseph S. Friedberg, Melissa J. Culligan, Anne S. Tsao, Valerie Rusch, Prasad S. Adusumilli, Boris Sepesi, Harvey I. Pass, Raphael Bueno, Bryan Burt, David J. Sugarbaker, Marc de Perrot, Alex A. Adjei, Fred R. Hirsch, Shakuntala M. Malik, David J. Harpole
Journal: Journal of Thoracic Oncology (2020)
Is Depression Nature or Nurture? Yes
Authors: Myrna M. Weissman
Journal: American Journal of Psychiatry (2020)

I've increasingly felt that the correct answer to the question "Is depression nature or nurture?" is "yes."In a landmark study in this issue, Kendler and colleagues (1) put substance to this answer.While the answer may still be "yes," through the use of a cleverly designed natural experiment, Kendler et al. have identified a portion of nurture, the rearing environment, that can clearly be defined and even altered with intervention.In brief, they studied 666 high-risk full siblings, with high risk defined as having at least one parent with major depression, and 2,595 high-risk half siblings of which at least one was home-reared and one adopted away.What made this study possible were the large samples from a national registry in Sweden, the parental assessments, and the fact that in Sweden, where adoption is not common, adoptive families are selected to provide high-quality rearing environments, including high educational status, economic security, and a stable environment.It is impressive that this study comes from an investigator group that has done major genetic and twin studies.In both types of studies, the nature of the environment is unclear.Similarly, the adoption studies, another way of studying environmental effects, usually have had insufficient information on the biological parents and their clinical state.As the authors point out, biological parents of adoptees likely have a higher risk of psychopathology, less education, and higher divorce rates.Moreover, the environment in the adopted-away home has not been clearly defined in most studies.In fact, the authors previously carried out an extended adoption study in the same sample and had shown statistically that genetic factors and rearing experiences contributed to an approximately equal extent (2).Both forms of cross-generational transmission act additively on the risk for depression in the offspring.However, the contribution of the rearing environment was only shown statistically.These challenges in this and other previous reports must have led the authors to this study design.The findings confirmed the strong protective effect of a nurturing rearing environment on the child's well-being.However, this protective effect disappeared when an adoptive parent had major depression or the nurturing adoptive home was disrupted by parental death or divorce during the adoptee's childhood or adolescence.The results demonstrate the strong impact of the rearing environment on risk for major depression and support the importance of intervention efforts to improve the rearing environment in highrisk families.
Combined Prebiotic and Microbial Intervention Improves Oral Cholera Vaccination Responses in a Mouse Model of Childhood Undernutrition
Authors: Blanda Di Luccia, Philip P. Ahern, Nicholas W. Griffin, Jiye Cheng, Janaki L. Guruge, Alexandra E. Byrne, Dmitry A. Rodionov, Semen A. Leyn, Andrei L. Osterman, Tahmeed Ahmed, Marco Colonna, Michael J. Barratt, Nicolas F. Delahaye, Jeffrey I. Gordon
Journal: Cell Host & Microbe (2020)
BET Epigenetic Reader Proteins in Cardiovascular Transcriptional Programs
Authors: Patricia Cristine Borck, Lian-Wang Guo, Jorge Plutzky
Journal: Circulation Research (2020)

Epigenetic mechanisms involve the placing (writing) or removal (erasing) of histone modifications that allow heterochromatin to transition to the open, activated euchromatin state necessary for transcription. A third, less studied epigenetic pathway involves the reading of these specific histone marks once placed. The BETs (bromodomain and extraterminal-containing protein family), which includes BRD2, BRD3, and BRD4 and the testis-restricted BRDT, are epigenetic reader proteins that bind to specific acetylated lysine residues on histone tails where they facilitate the assembly of transcription complexes including transcription factors and transcriptional machinery like RNA Polymerase II. As reviewed here, considerable recent data establishes BETs as novel determinants of induced transcriptional programs in vascular cells, like endothelial cells and vascular smooth muscle cells, cardiac myocytes and inflammatory cells, like monocyte/macrophages, cellular settings where these epigenetic reader proteins couple proximal stimuli to chromatin, acting at super-enhancer regulatory regions to direct gene expression. BET inhibition, including the use of specific chemical BET inhibitors like JQ-1, has many reported effects in vivo in the cardiovascular setting, like decreasing atherosclerosis, angiogenesis, intimal hyperplasia, pulmonary arterial hypertension, and cardiac hypertrophy. At the same time, data in endothelial cells, adipocytes, and elsewhere suggest BETs also help regulate gene expression under basal conditions. Studies in the cardiovascular setting have highlighted BET action as a means of controlling gene expression in differentiation, cell identity, and cell state transitions, whether physiological or pathological, adaptive, or maladaptive. While distinct BET inhibitors are being pursued as therapies in oncology, a large prospective clinical cardiovascular outcome study investigating the BET inhibitor RVX-208 (now called apabetalone) has already been completed. Independent of this specific agent and this one trial or the numerous unanswered questions that remain, BETs have emerged as novel epigenetic players involved in the execution of coordinated transcriptional programs in cardiovascular health and disease.
Myofibroblast contraction is essential for generating and regenerating the gas-exchange surface
Authors: Rongbo Li, Xiaoping Li, James Hagood, Min-Sheng Zhu, Xin Sun
Journal: Journal of Clinical Investigation (2020)

A majority (~95%) of the gas-exchange surface area is generated through septa formation during alveologenesis. Disruption of this process leads to alveolar simplification and bronchopulmonary dysplasia (BPD), a prevalent disorder in premature infants. Although several models have been proposed, the mechanism of septa formation remains under debate. Here we show that inactivation of myosin light chain kinase (MLCK), a key factor required for myofibroblast contraction, disrupted septa formation, supporting the myofibroblast contraction model of alveologenesis. The alveoli simplification phenotype was accompanied by decreased yes-associated protein (YAP), a key effector in the Hippo mechanotransduction pathway. Expression of activated YAP in Mlck-mutant lungs led to partial reversal of alveolar simplification. In the adult, although Mlck inactivation did not lead to simplification, it prevented reseptation during compensatory regrowth in the pneumonectomy model. These findings revealed that myofibroblast reactivation and contraction are requisite steps toward regenerating the gas-exchange surface in diseases such as BPD and chronic obstructive pulmonary disease (COPD).
Evaluation of Hidradenitis Suppurativa Disease Course During Pregnancy and Postpartum
Authors: Alexis B. Lyons, Anjelica Peacock, Shanice A. McKenzie, Gordon Jacobsen, Haley B. Naik, Vivian Y. Shi, Iltefat H. Hamzavi, Jennifer L. Hsiao
Journal: JAMA Dermatology (2020)

<h3>Importance</h3> Hidradenitis suppurativa (HS) disproportionately affects women of childbearing potential. There is a paucity of data regarding the HS disease course during pregnancy and in the postpartum period. <h3>Objective</h3> To explore the HS disease course during pregnancy and in the postpartum period. <h3>Design, Setting, and Participants</h3> A retrospective cohort study was conducted on patients in the Henry Ford Health System, Detroit, Michigan—a large, academic, urban referral center. Women with a diagnosis of HS who became pregnant between January 1, 2008, and December 31, 2018, were included.<i>International Classification of Diseases, Ninth Revision</i>, and<i>International Statistical Classification of Diseases and Related Health Problems, Tenth Revision</i>, were used for identification of the diagnosis. <h3>Exposures</h3> Pregnancy in patients with HS. <h3>Main Outcomes and Measures</h3> Hidradenitis suppurativa disease status during pregnancy and the postpartum period. <h3>Results</h3> A total of 127 women with HS were included in this study and accounted for 202 pregnancies. Of the 202 pregnancies, 171 were in black women, 25 in white women, 3 in women of other race/ethnicity, and 3 had unreported data. Mean (SD) age at HS onset was 19.3 (5.6) years; at time of HS diagnosis, 24.4 (5.3) years; and at time of pregnancy, 25.9 (5.0) years. The disease worsened during pregnancy in 70 pregnancies (61.9%), did not change in 34 pregnancies (30.1%), and improved in 9 pregnancies (8.0%). Hidradenitis suppurativa exacerbated in the postpartum period after 82 of 124 pregnancies (66.1%). Dermatologists were involved in managing HS in 28 pregnancies (14.4%) and for a higher proportion of patients with more severe Hurley stage as compared with cases of mild disease (stage 3: 7 of 18 [38.9%] vs stage 1: 10 of 100 [10.0%] or stage 2: 11 of 67 [16.4%];<i>P</i> = .004). In addition, HS medical treatment was administered during 77 pregnancies (38.1%), while HS procedural treatment was administered during 34 pregnancies (16.8%). A significantly higher proportion of patients whose care was managed by dermatologists vs those without dermatologist involvement received any HS medication (22 [78.6%] vs 53 [31.7%],<i>P</i> &lt; .001) or any HS procedure (14 [50%] vs 19 [11.4%],<i>P</i> &lt; .001) during pregnancy. <h3>Conclusions and Relevance</h3> Despite a high rate of HS exacerbation during pregnancy and postpartum, this cohort study found that most of the patients did not receive HS-directed medical treatment or care from a dermatologist during pregnancy. Close monitoring and improved collaborative care between dermatology and obstetrics-gynecology services is warranted.
Infinity hair: a new trichoscopic finding for chemotherapy‐induced alopecia
Authors: A. Patrì, M.C. Annunziata, M. Cantelli, P. Nappa, G. Fabbrocini
Journal: British Journal of Dermatology (2020)

Funding sources: none. Conflicts of interest: The authors declare they have no conflicts of interest. Dear Editor, We retrospectively analysed the trichoscopic images of patients with nonscarring (n = 112) and scarring (n = 30) alopecia. We detected exclusively in three out of 12 cases of chemotherapy‐induced alopecia a trichoscopic feature we termed ‘infinity hair’ (IH). At trichoscopic assessment, the patients had stopped chemotherapy for 5–9 months. IH is a regrowing hair with a tapered end that takes the form of the mathematical sign for ‘infinity’ (Figure 1a, b). This differs from circle hairs, which have the same calibre along the hair shaft (Figure 1c), and pigtail hairs, which taper towards the tip (Figure 1d).1 2 IH may represent a variant of pigtail hair.
Extrastriatal Peri-infarct Accumulation of 99mTc-TRODAT
Authors: S. T. ArunRaj, Madhavi Tripathi, Manjari Tripathi, Hemant Sachani, Roma Singh, Jasim Jaleel, Raja Gulfam Shaikh, Chandrasekhar Bal
Journal: Clinical Nuclear Medicine (2020)

Abstract We describe the extrastriatal accumulation of dopamine transporter imaging agent 99m Tc-TRODAT in the peri-infarct area in a 75-year-old man referred for dopamine transporter SPECT imaging with a suspicion of idiopathic Parkinson disease.