Search

Abstract The transcriptional and phenotypic characteristics that define alveolar monocyte and macrophage subsets in acute hypoxemic respiratory failure (AHRF) are poorly understood. Here, we apply CITE-seq (single-cell RNA-sequencing and cell-surface protein quantification) to bronchoalveolar lavage and blood specimens longitudinally collected from participants with AHRF to identify alveolar myeloid subsets, and then validate their identity in an external cohort using flow cytometry. We identify alveolar myeloid subsets with transcriptional profiles that differ from other lung diseases as well as several subsets with similar transcriptional profiles as reported in healthy participants (Metallothionein) or patients with COVID-19 (CD163/LGMN). We use information from CITE-seq to determine cell-surface proteins that distinguish transcriptional subsets (CD14, CD163, CD123, CD71, CD48, CD86 and CD44). In the external cohort, we find a higher proportion of CD163/LGMN alveolar macrophages are associated with mortality in AHRF. We report a parsimonious set of cell-surface proteins that distinguish alveolar myeloid subsets using scalable approaches that can be applied to clinical cohorts.

Abstract Oesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic and methylation data from 115 oesophageal adenocarcinoma patients mostly from the DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN12609000665235), with exploratory analysis pre-specified in the study protocol of the trial. We report genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures. We also show that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. Transcriptomic analysis categorises patients into four immune clusters correlated with survival. The immune suppressed cluster is associated with worse survival, enriched with myeloid-derived cells, and an epithelial-mesenchymal transition signature. The immune hot cluster is associated with better survival, enriched with lymphocytes, myeloid-derived cells, and an immune signature including CCL5, CD8A, and NKG7. The immune clusters highlight patients who may respond to immunotherapy and thus may guide future clinical trials.

Misinformation regarding vaccine science decreased the receptiveness to COVID-19 vaccines, exacerbating the negative effects of the COVID-19 pandemic on society. To mitigate the negative societal impact of the COVID-19 pandemic, impactful and creative science communication was needed, yet little research has explored how to encourage COVID-19 vaccine acceptance and address misconceptions held by non-Science, Technology, Engineering and Mathematics majors (referred to as non-majors). We have previously demonstrated that including expert guest lectures in the vaccine module in the non-major introductory biology course helps combat students' vaccine hesitancy. In the present study, we further address how learning about vaccines impacts student knowledge and impressions of the COVID-19 vaccines through a podcast assignment. As a part of this assignment, non-majors created podcasts to address COVID-19 vaccine misconceptions of their choice. We coded pre and post, open-ended essay reflections (n = 40) to assess non-majors' knowledge and impressions of the COVID-19 vaccines. Non-majors' impressions of the vaccines improved following the podcast assignment with more than three times as many students reporting a positive view of the assignment than negative views. Notably, eight of the nine interviewed students still ended the course with misconceptions about the COVID-19 vaccines, such as the vaccines being unnecessary or causing fertility issues. In a post semi-structured interview following this assignment, students (n = 7) discussed the impact of looking into the specific misconceptions related to COVID-19 vaccines themselves, including improved science communication skills and understanding of different perspectives. Thus, podcasts can provide opportunities for students to improve engagement in valuable societal topics like vaccine literacy in the non-majors classroom.

IMPORTANCE:. Kidney and lung injury are closely inter-related during acute respiratory illness, but the molecular risk factors that these organ injuries share are not well defined. OBJECTIVES:. We identified plasma biomarkers associated with severe acute kidney injury (AKI) during acute respiratory illness, and compared them to biomarkers associated with severe acute respiratory failure (ARF). DESIGN, SETTINGS, AND PARTICIPANTS:. Prospective observational cohort study enrolling March 2020 through May 2021, at three hospitals in a large academic health system. We analyzed 301 patients admitted to an ICU with acute respiratory illness. MAIN OUTCOMES AND MEASURES:. Outcomes were ascertained between ICU admission and day 14, and included: 1) severe AKI, defined as doubling of serum creatinine or new dialysis and 2) severe ARF, which included new or persistent need for high-flow oxygen or mechanical ventilation. We measured biomarkers of immune response and endothelial function, pathways related to adverse kidney and lung outcomes, in plasma collected within 24 hours of ICU admission. Severe AKI occurred in 48 (16%), severe ARF occurred in 147 (49%), and 40 (13%) patients experienced both. Two-fold higher concentrations of soluble tumor necrosis factor receptor-1 (sTNFR-1) (adjusted relative risk [aRR], 1.56; 95% CI, 1.24–1.96) and soluble triggering receptor on myeloid cells-1 (sTREM-1) (aRR, 1.85; 95% CI, 1.42–2.41), biomarkers of innate immune activation, were associated with higher risk for severe AKI after adjustment for age, sex, COVID-19, and Acute Physiology and Chronic Health Evaluation-III. These biomarkers were not significantly associated with severe ARF. Soluble programmed cell death receptor-1 (sPDL-1), a checkpoint pathway molecule, as well as soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1), molecules involved with endothelial-vascular leukocyte adhesion, were associated with both severe AKI and ARF. CONCLUSIONS AND RELEVANCE:. sTNFR-1 and sTREM-1 were linked strongly to severe AKI during respiratory illness, while sPDL-1, sICAM-1 and sVCAM-1 were associated with both severe AKI and ARF. These biomarker signatures may shed light on pathophysiology of lung-kidney interactions, and inform precision medicine strategies for identifying patients at high risk for these organ injuries.

Plain English summary The term presbyopia describes the difficulty to focus the eyes on things nearby, due to stiffening of the eye lens. The condition often considered something which worsens with increasing age. Many people cope with presbyopia by wearing reading glasses or bifocals, but alternative treatments are being developed. This publication reports from a moderated discussion among people with presbyopia and healthcare professionals specialising in eye health. People with presbyopia strongly felt that it should not be seen as an inevitable effect of middle age, but as something which may be treated medically. They felt that reading glasses, bifocals and monovision lenses were a daily burden and did not fit with how they wanted to live their lives. When discussing possible medical treatments, the option to use drops instead of glasses to improve eye sight appealed to the participants, particularly if the drops acted on the mechanism behind the stiffened lens with effect over many weeks or months. Convenience was the key benefit the participants would look for when considering a new treatment. Importantly, drops must not have any undesirable effects such as burning. The roundtable discussion showed the need for both healthcare professionals and those living with presbyopia to take the condition seriously with an an action-oriented view towards better therapies in the future.

Objective To determine the effect of continuous wound infusion of local anaesthetic drug (bupivacaine) on total amount of systemic opioid use in the first 72 hours in newborn infants undergoing laparotomy.Design A two-arm parallel, open-label randomised controlled trial.Setting A quaternary newborn intensive care unit.Patients Infants>37 weeks of gestation undergoing laparotomy for congenital or acquired abdominal conditions.Interventions Continuous wound infusion of local anaesthetic (bupivacaine) for the first 72 hours along with systemic opioid analgesia (catheter group) or only systemic opioid analgesia (opioid group).Main outcome Total amount of systemic opioid used within the first 72 hours post laparotomy.Results The study was underpowered as only 30 of the expected sample size of 70 infants were enrolled. 16 were randomised to catheter group and 14 to opioid group. The two groups were similar at baseline. There was no significant difference between the groups for the primary outcome of median total systemic opioid use in the first 72 hours post laparotomy (catheter 431.5 µg/kg vs opioid 771 µg/kg, difference −339.5 µg/kg, 90% CIhigh 109, p value 0.28). There was no significant difference between the groups for any of the secondary outcomes including pain scores, duration of mechanical ventilation, time to reach full feeds and duration of hospital stay. There were no adverse events noted.Conclusion Continuous wound infusion of local anaesthetic along with systemic opioid analgesia is feasible. The lack of a difference in total systemic opioid use in the first 72 hours cannot be reliably interpreted as the study was underpowered.Trial registration number ACTRN12610000633088.

Research experiences are an integral part of training future scientists and fostering diversity in science. Providing culturally responsive research mentorship, defined as mentorship that incorporates cultural knowledge to improve learning experiences for a particular group, is a critical step in this endeavor. While culturally responsive mentoring is most commonly associated with mentoring students with underrepresented races and ethnicities in the sciences, it can also be helpful for mentees with a diversity of abilities, sexualities, economic backgrounds, and religions. In this essay, we discuss how mentors can provide more culturally responsive mentoring of Muslim research mentees in the sciences. Muslims are a stigmatized minority group in the United States who participate in a religious culture that often differs from the secular culture of science. Notably, there are few resources for how to engage in culturally responsive mentoring of Muslim research mentees. To address this gap, we drew from the extant literature on the challenges that Muslims encounter in the United States, which likely extends to the context of scientific research, and identified potential culturally responsive accommodations in research.

Abstract Background Analyses of blood biomarkers involved in the host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection can reveal distinct biological pathways and inform development and testing of therapeutics for COVID-19. Our objective was to evaluate host endothelial, epithelial and inflammatory biomarkers in COVID-19. Methods We prospectively enrolled 171 ICU patients, including 78 (46%) patients positive and 93 (54%) negative for SARS-CoV-2 infection from April to September, 2020. We compared 22 plasma biomarkers in blood collected within 24 h and 3 days after ICU admission. Results In critically ill COVID-19 and non-COVID-19 patients, the most common ICU admission diagnoses were respiratory failure or pneumonia, followed by sepsis and other diagnoses. Similar proportions of patients in both groups received invasive mechanical ventilation at the time of study enrollment. COVID-19 and non-COVID-19 patients had similar rates of acute respiratory distress syndrome, severe acute kidney injury, and in-hospital mortality. While concentrations of interleukin 6 and 8 were not different between groups, markers of epithelial cell injury (soluble receptor for advanced glycation end products, sRAGE) and acute phase proteins (serum amyloid A, SAA) were significantly higher in COVID-19 compared to non-COVID-19, adjusting for demographics and APACHE III scores. In contrast, angiopoietin 2:1 (Ang-2:1 ratio) and soluble tumor necrosis factor receptor 1 (sTNFR-1), markers of endothelial dysfunction and inflammation, were significantly lower in COVID-19 (p

Abstract Purpose To compare CTVHR and OAR dimensions and inter-rater agreement between magnetic resonance (MR) and trans-rectal ultrasound (TRUS) images in IB cervical cancer patients. Methods IB cervical cancer patients treated with (chemo)radiotherapy plus MR-guided brachytherapy (BT) were prospectively enrolled in this study. Radiation oncologists contoured CTVHR and OARs in pre-BT MR images (MRI) and intra-operative TRUS images. These contours were subsequently compared in regard to volume and dimension. Contour inter-rater agreement analysis was also investigated using kappa index (KI). Stata 15.0 was used for statistical analysis and a p-value

Background In this study, we assessed the activity of durvalumab, an antibody to programmed death ligand-1, in two cohorts of women with advanced endometrial cancers (AEC)—mismatch repair proficient (pMMR) and mismatch repair deficient (dMMR).Methods A multicenter phase two study was performed in women with AEC with pMMR tumor progressing after one to three lines of chemotherapy and women with AEC with dMMR tumor progressing after zero to three lines of chemotherapy. Mismatch repair status was based on immunohistochemistry expression. All women received durvalumab 1500 mg given every 4 weeks until progression or unacceptable toxicity. The primary endpoint was objective tumor response by RECIST V.1.1 modified for immune-based therapeutics.Results Seventy-one women were recruited: 35 dMMR and 36 pMMR. Median follow-up was 19 vs 21 months in dMMR versus pMMR, respectively. Median age was 67 years. Histology in dMMR versus pMMR included endometrioid (94% vs 57%) and serous (0% vs 31%) and was high grade in 26% vs 74%. The objective tumor response rate (OTRR) in the dMMR cohort was 47% (17/36, 95% CI 32 to 63), including 6 complete responses and 11 partial responses (PRs)) vs 3% in the pMMR cohort (1/35, 95% CI 1 to 15, PR). In the dMMR cohort, durvalumab was the first-line therapy in 58% (OTRR 57%) and the second-line therapy in 39% (OTRR 38%). Median progression-free survival was 8.3 months in the dMMR cohort vs 1.8 months in the pMMR cohort. The 12-month overall survival (OS) rate was 71% in dMMR vs 51% in pMMR, with median OS not reached for dMMR vs 12 months for pMMR. Immune-related adverse events occurred in 14 women, mostly grades 1–2.Conclusion Durvalumab monotherapy showed promising activity and acceptable safety in AEC with dMMR regardless of prior lines of chemotherapy, but activity was limited in AEC with pMMR.Trial registration numbers ANZGOG1601, ACTRN12617000106336, and NCT03015129.

Abstract Atmospheric rivers (ARs) play a vital role in shaping the hydroclimate of many regions globally, and can substantially impact water resource management, emergency response planning, and other socioeconomic entities. The second International Atmospheric Rivers Conference took place at the Scripps Institution of Oceanography, University of California, San Diego, during 25–28 June, 2018, in La Jolla, California, USA. It was sponsored by the Center for Western Weather and Water Extremes (CW3E). A total of 120 people attended the Conference with 94 abstracts submitted and 30 participating students. In addition to the conference, the Student Forecasting Workshop was organised in the same week. During this workshop, students were exposed to AR forecasting tools, and learned examples of how these tools could be used to make decisions for various applications. The main goals of this conference were to bring together experts from across the fields of hydrology, atmospheric, oceanic, and polar sciences, as well as water management, civil engineering, and ecology to advance the state of AR science and to explore the future directions for the field. The conference was organised into traditional oral and poster presentations, along with panel discussions and Breakout Groups. This format allowed enhanced interaction between participants, driving progress within the scientific community and the enhanced communication of societal needs by various stakeholders. Several emerging topics of research were highlighted, including subseasonal‐to‐seasonal (S2S) prediction of ARs and an overview of the AR Reconnaissance campaign. In addition to providing a forum to disseminate and debate new results from scientific talks and posters, the conference was equally effective and useful in linking scientists to users and decision‐makers that require improved knowledge on ARs to manage resources and prepare for hazards. The third International Atmospheric Rivers Conference will be held in Chile in 2020, and hosted by the University of Chile, Santiago.

The tension between religion and science as a long-standing barrier to science education has led researchers to explore ways of improving the experiences of Christian students in biology who can experience their Christianity as stigmatized in academic biology environments. As undergraduate science classes become student-centered, interactions among students increase, and Christians may feel a need to conceal their religious identities during peer discussions. In this interview study, we used the social psychology framework of concealable stigmatized identities to explore 30 Christian students' experiences during peer interactions in undergraduate biology courses to find potential ways to improve those experiences. We found that students felt their religious identity was salient during peer interactions in biology, and students thought revealing their religious identity to peers in their biology courses could be beneficial, yet few actually did so. Additionally, though most students "anticipated" stigma, comparatively few had "experienced" stigma from other students in their biology courses, despite the prior documented cultural stigma against Christians in biology. These results indicate a need for future studies exploring the impact of learning environments in which students are given the opportunity to share their religious identities with one another, which could reduce their anticipated and perceived stigma.

To increase participation of students of color in science graduate programs, research has focused on illuminating student experiences to inform ways to improve them. In biology, Black students are vastly underrepresented, and while religion has been shown to be a particularly important form of cultural wealth for Black students, Christianity is stigmatized in biology. Very few studies have explored the intersection of race/ethnicity and Christianity for Black students in biology where there is high documented tension between religion and science. Since graduate school is important for socialization and Black students are likely to experience stigmatization of their racial and religious identity, it is important to understand their experiences and how we might be able to improve them. Thus, we interviewed 13 Black Christian students enrolled in biology graduate programs and explored their experiences using the theoretical lens of stigmatized identities. Through thematic content analysis, we revealed that students negotiated experiences of cultural isolation, devaluation of intelligence, and acts of bias like other racially minoritized students in science. However, by examining these experiences at the intersection of race/ethnicity and religion, we shed light on interactions students have had with faculty and peers within the biology community that cultivated perceptions of mistrust, conflict, and stigma. Our study also revealed ways in which students' religious/spiritual capital has positively supported their navigation through biology graduate school. These results contribute to a deeper understanding of why Black Christian graduate students are more likely to leave or not pursue advanced degrees in biology with implications for research and practice that help facilitate their success.

Merkel cell carcinoma of the head and neck (MCCHN) presents a clinical challenge due to its aggressive natural history, unpredictable lymphatic drainage, and high degree of treatment related morbidity. Histological examination of the regional lymph nodes is very important in determining the optimal treatment and is usually achieved by sentinel lymph node biopsy. Radiotherapy plays a critical role in the treatment of most patients with MCCHN. Surgery with adjuvant radiotherapy to the primary tumour site is associated with high local control rates. If lymph nodes are clinically or microscopically positive, adjuvant radiotherapy is indicated to decrease the risk of regional recurrence. The majority of locoregional recurrences occur at the edge or just outside of the radiation field, reflecting both the inherent radiosensitivity of MCC and the importance of relatively large volumes to include “in-transit” dermal lymphatic pathways. When surgical excision of the primary or nodal disease is not feasible, primary radiotherapy alone should be considered as a potentially curative modality and confers good loco-regional control. Concurrent chemoradiotherapy is well tolerated and may further improve outcomes.

Effective communication about science is a core skill undergraduates should learn, but little research has explored how students communicate about culturally controversial science topics. In this study, we explored how Black undergraduate science students took on the role of science communicators in their communities during the COVID-19 pandemic. We interviewed 23 Black students about their experiences learning about COVID-19 vaccines and communicating about COVID-19 vaccines to their communities. We found that students' racial/ethnic and science backgrounds made them feel a responsibility to be effective communicators about COVID-19 vaccines as potential trusted messengers within their communities. However, students were using limited strategies when communicating and were unsure how to communicate about COVID-19 topics effectively to those who were vaccine-hesitant or doubted the severity of the pandemic. Finally, students described ways that their biology instructors could have helped them be more confident when communicating about COVID-19 vaccines with their communities. Findings suggest that biology instructors could teach science communication principles in addition to content knowledge about culturally controversial science topics in their undergraduate classes to build on students' developing science communication skills.

Researchers who study student acceptance of evolution rely on surveys that are designed to measure evolution acceptance. It is important for these surveys to measure evolution acceptance accurately and in isolation from other constructs, so that researchers can accurately determine what leads to low acceptance. The Inventory of Student Evolution Acceptance (I-SEA) and the Generalized Acceptance of EvolutioN Evaluation (GAENE) are two surveys that were developed to improve upon the limitations of earlier surveys. Yet neither survey has been extensively tested for response process validity, which can assess the extent to which students use constructs other than their acceptance of evolution to answer survey items. In this study, we examined the response-process validity of the I-SEA and GAENE by conducting cognitive interviews with 60 undergraduate students. Interviews revealed that both surveys retain certain response-process issues. The I-SEA conflated knowledge about and acceptance of evolution for a subset of students. The GAENE measured evolution acceptance inconsistently because students interpreted "evolution" in different ways; it also measured willingness to advocate for evolution in addition to acceptance. Researchers can use these findings to better inform their survey choice when designing future studies, and to further improve the measurement of evolution acceptance.