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"Yang, Michelle"
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Hawk of the mind : collected poems
\"The most comprehensive selection of poems by Yang Mu available in English. Translated by noted experts including John Balcom, Steve Bradbury and Andrea Lingenfelter, the volume also contains Yang Mu's prefaces and afterwords to four of his poetry collections, as well as his essay on the origins of Taiwanese poetry. All of this additional material shed light on his poetics. As a member of the first generation of postwar Taiwan, Yang Mu is a modern Taiwanese writer, whose poetry is known for its avant-garde, modernist cosmopolitanism, gracefully combining influences from the best international writing with a reverence for the legacy of classical Chinese poetry. The poems collected in this volume span a wide range of ideas and themes, including Yang Mu's references to music; his comments on social and political reality; his love for nature, and the re-examination of the colonial history of Taiwan. For more than half a century, Yang Mu has been a formative force and the most influential figure on Taiwan's poetry scene. He is widely read in the Chinese-speaking world and has been well received in other parts of the world. Individual volumes of his poetry are available in English, French, German, Japanese, and Swedish\"-- Provided by publisher.
BOOK
Who follows through? Different factors predict initial commitment vs. Following through in a national survey of organ donor registration
Little research has investigated factors that determine whether people falter in the face of an obstacle or successfully follow through on an initial commitment to act. We integrated multiple theories (the Reasoned Action Approach [RAA], Prototype Willingness Model, and anticipated regret theory) to test which factors predict initial commitment to register as an organ donor and to discover whether different factors predict initial commitment vs. following through with registration.
Participants from a nationally representative UK sample (N = 1,008) reported their beliefs about organ donation and indicated their decision to register. An obstacle that participants could not foresee was that they had to complete registration in a second survey 3 days after making their initial commitment.
Findings showed that 14.8% of participants followed through, 19.7% demonstrated initial commitment, and 65.5% declined to register. Linear discriminant function analysis derived two functions that distinguished these registration patterns. The first function discriminated participants who declined to register from the other groups. The declined group had lower scores on RAA variables compared to their counterparts. The second function distinguished participants who made an initial commitment to register from those who followed through. Follow-through was associated with less anticipated negative affect, more favorable descriptive norms, and stronger identification with organ donors.
The present findings indicate that even modest friction leads to a large reduction in follow-through. Moreover, different factors influence initial commitment vs. following through. Whereas RAA variables predicted initial commitment, following through was a function of anticipated negative affect and social processes.
Journal Article
Feminist art activisms and artivisms
The first volume in the new Plural series, this publication seeks to critically dissect the term 'activism,' which today seems to have become a catchword for any woman's empowerment through the arts, and reveal the diversity of practices and realities that it comprises. Presenting a range of critical insights, perspectives, and practices from artists, activists, and academics, it reflects on the role of feminist interventions in the field of contemporary art, the public sphere, and politics. In the process, it touches upon broader questions of cultural difference, history, class, economic standing, ecological issues, and sexual orientation, as well as the ways in which these intersect.
Book
An allosteric pan-TEAD inhibitor blocks oncogenic YAP/TAZ signaling and overcomes KRAS G12C inhibitor resistance
The Hippo pathway is a key growth control pathway that is conserved across species. The downstream effectors of the Hippo pathway, YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif), are frequently activated in cancers to drive proliferation and survival. Based on the premise that sustained interactions between YAP/TAZ and TEADs (transcriptional enhanced associate domain) are central to their transcriptional activities, we discovered a potent small-molecule inhibitor (SMI), GNE-7883, that allosterically blocks the interactions between YAP/TAZ and all human TEAD paralogs through binding to the TEAD lipid pocket. GNE-7883 effectively reduces chromatin accessibility specifically at TEAD motifs, suppresses cell proliferation in a variety of cell line models and achieves strong antitumor efficacy in vivo. Furthermore, we uncovered that GNE-7883 effectively overcomes both intrinsic and acquired resistance to KRAS (Kirsten rat sarcoma viral oncogene homolog) G12C inhibitors in diverse preclinical models through the inhibition of YAP/TAZ activation. Taken together, this work demonstrates the activities of TEAD SMIs in YAP/TAZ-dependent cancers and highlights their potential broad applications in precision oncology and therapy resistance.
Journal Article
Aminoglycoside induces RIPOR2 translocation and phosphatidylserine externalization via distinct mechanisms
Aminoglycosides are widely used to treat severe infections. However, systemically administered AGs preferentially kill cochlear hair cells, resulting in irreversible hearing loss. Recently, we found that AGs induce a rapid translocation of RIPOR2 in hair cells, a process that relies on functional mechanotransduction, subsequently dysregulates the autophagy/mitophagy pathway, and ultimately leads to irreversible hair cell death. Recent studies found that AGs also trigger rapid phosphatidylserine (PS) externalization in hair cells, probably by activating the scramblase activity of TMC1/2, which are the pore-forming subunits of the mechanotransduction channel. To determine whether AG-triggered rapid RIPOR2 translocation and PS externalization are independent, RIPOR2 translocation and PS externalization were extensively investigated in wild-type hair cells treated with AG for different amounts of time. Next, the potential effect of PS externalization on RIPOR2 translocation in hair cells was studied. Finally, we investigated the extent to which cisplatin, a chemotherapy drug that shares several pathological features of ototoxicity with AGs, affects PS externalization and RIPOR2 localization in hair cells. Our results suggest that AG triggers RIPOR2 translocation and PS externalization by independent mechanisms, and that cisplatin and AGs induce hair cell death via distinct molecular pathways.
Journal Article
Left-sided congenital diaphragmatic hernia: can we improve survival while decreasing ECMO?
BackgroundMortality and ECMO rates for congenital diaphragmatic hernia (CDH) remain ~30%. In 2016, we changed our CDH guidelines to minimize stimulation while relying on preductal oxygen saturation, lower mean airway pressures, stricter criteria for nitric oxide (iNO), and inotrope use. We compared rates of ECMO, survival, and survival without ECMO between the two epochs.Design/MethodsRetrospective review of left-sided CDH neonates at the University of Utah/Primary Children’s Hospital NICUs during pre (2003–2015, n = 163) and post (2016–2019, n = 53) epochs was conducted. Regression analysis controlled for defect size and intra-thoracic liver.ResultsFollowing guideline changes, we identified a decrease in ECMO (37 to 13%; p = 0.001) and an increase in survival without ECMO (53 to 79%, p = 0.0001). Overall survival increased from 74 to 89% (p = 0.035).Conclusion(s)CDH management guideline changes focusing on minimizing stimulation, using preductal saturation and less aggressive ventilator/inotrope support were associated with decreased ECMO use and improved survival.
Journal Article
Inflammatory pseudotumor associated with HSV infection of rectal vascular endothelium in a patient with HIV: a case report and literature review
Background
Herpes simplex virus (HSV) typically infects oral or anogenital squamous epithelium and causes blisters and ulcerations. Here we reported an unusual case of HSV induced exuberant rectal inflammatory pseudotumor with vascular endothelial involvement.
Case presentations
A 52-year old man with HIV presented with abdominal pain, rectal drainage and constipation. Proctoscopy and CT scans revealed an 8 × 5 × 4 cm circumferential, mid-lower rectal mass that was concerning for malignancy. PET-CT showed mild to moderate FDG uptake of the rectal mass. Repeated biopsies showed exuberant lymphoplasmacytic inflammation with rich eosinophils and necrosis in the submucosa and scattered single or multi-nucleated viral inclusions in vascular endothelial cells that were positive for HSV by immunostains. There was no evidence of malignancy on histology or by immunostains. The patient started valacyclovir for three weeks and symptoms resolved after the antiviral therapy. Follow-up CT and sigmoidoscopy with biopsy revealed no rectal mass or drainable collection.
Conclusions
HSV may present as proctitis with exuberant inflammatory response and mass-like lesion, and damages vascular endothelial cells in patients with HIV. The HSV-associated mass-like lesion can be effectively treated by 3-week valacyclovir.
Journal Article
PIEZO1 loss-of-function compound heterozygous mutations in the rare congenital human disorder Prune Belly Syndrome
Prune belly syndrome (PBS), also known as Eagle-Barret syndrome, is a rare, multi-system congenital myopathy primarily affecting males. Phenotypically, PBS cases manifest three cardinal pathological features: urinary tract dilation with poorly contractile smooth muscle, wrinkled flaccid ventral abdominal wall with skeletal muscle deficiency, and intra-abdominal undescended testes. Genetically, PBS is poorly understood. After performing whole exome sequencing in PBS patients, we identify one compound heterozygous variant in the PIEZO1 gene. PIEZO1 is a cation-selective channel activated by various mechanical forces and widely expressed throughout the lower urinary tract. Here we conduct an extensive functional analysis of the PIEZO1 PBS variants that reveal loss-of-function characteristics in the pressure-induced normalized open probability (NPo) of the channel, while no change is observed in single-channel currents. Furthermore, Yoda1, a PIEZO1 activator, can rescue the NPo defect of the PBS mutant channels. Thus, PIEZO1 mutations may be causal for PBS and the in vitro cellular pathophysiological phenotype could be rescued by the small molecule, Yoda1. Activation of PIEZO1 might provide a promising means of treating PBS and other related bladder dysfunctional states.
PIEZO1 is a mechanosensitive ion channel. Here, authors identify PIEZO1 human mutations in Prune Belly Syndrome. At a single molecule level these mutations exhibit loss-of-function characteristics.
Journal Article
Significance of Proximal Margin Involvement in Low-Grade Appendiceal Mucinous Neoplasms
Appendiceal adenomas and low-grade appendiceal mucinous neoplasms (LAMNs) confined to the appendix are cured by appendectomy. However, involvement of the proximal margin raises concern for residual disease. Some patients with a positive margin at appendectomy undergo cecal resection to eliminate a perceived risk for tumor recurrence or dissemination, although that likelihood is assumed rather than demonstrated.
To determine whether involvement of the proximal appendiceal resection margin by adenoma or LAMN is a risk factor for local development of recurrence or pseudomyxoma peritonei.
Appendiceal adenomas and LAMNs confined to the appendix were considered for the study if they showed neoplasia or dissecting mucin at the proximal margin. The presence or absence of residual tumor in cecal resections was determined. Follow-up data were obtained from clinical records.
Sixteen patients (14 female, 2 male) with LAMN (n = 15) or adenoma (n = 1) and an involved proximal resection margin were identified, including 9 with neoplastic epithelium within the lumen and 7 with acellular mucin in the appendiceal wall at the margin. Six patients underwent cecal resection and the others were nonsurgically followed. No cecal resection had residual neoplasia. No patient developed recurrence or pseudomyxoma peritonei (mean follow-up, 4.7 years).
In patients with LAMNs confined to the appendix, involvement of the appendectomy margin by neoplastic epithelium or acellular mucin does not predict recurrence of disease, even without further surgery. A conservative approach to managing these patients can be justified.
Journal Article
Crisis leadership behaviors in healthcare: survey validation and influence on staff outcomes in primary care clinics during the COVID-19 pandemic
Background
The COVID-19 pandemic triggered an unprecedented transition from in-person to virtual delivery of primary health care services. Leaders were at the helm of the rapid changes required to make this happen, yet outcomes of leaders’ behaviours were largely unexplored. This study (1) develops and validates the Crisis Leadership and Staff Outcomes (CLSO) Survey and (2) investigates the leadership behaviours exhibited during the transition to virtual care and their influence on select staff outcomes in primary care.
Methods
We tested the CLSO Survey amongst leaders and staff from four Community Health Centres in Ontario, Canada. The CLSO Survey measures a range of crisis leadership behaviors, such as showing empathy and promoting learning and psychological safety, as well as perceived staff outcomes in four areas: innovation, teamwork, feedback, and commitment to change. We conducted an exploratory factor analysis to investigate factor structure and construct validity. We report on the scale’s internal consistency through Cronbach’s alpha, and associations between leadership scales and staff outcomes through odds ratios.
Results
There were 78 staff and 21 middle and senior leaders who completed the survey. A 4-factor model emerged, comprised of the leadership behaviors of (1) “task-oriented leadership” and (2) “person-oriented leadership”, and select staff outcomes of (3) “commitment to sustaining change” and (4) “performance self-evaluation”. Scales exhibited strong construct and internal validity. Task- and person-oriented leadership behaviours positively related to the two staff outcomes.
Conclusion
The CLSO Survey is a reliable measure of leadership behaviours and select staff outcomes. Our results suggest that crisis leadership is multifaceted and both person-oriented and task-oriented leadership behaviours are critical during a crisis to improve perceived staff performance and commitment to change.
Journal Article