The tuatara genome reveals ancient features of amniote evolution.

The tuatara (Sphenodon punctatus)-the only living member of the reptilian order Rhynchocephalia (Sphenodontia), once widespread across Gondwana1,2-is an iconic species that is endemic to New Zealand2,3. A key link to the now-extinct stem reptiles (from which dinosaurs, modern reptiles, birds and mammals evolved), the tuatara provides key insights into the ancestral amniotes2,4. Here we analyse the genome of the tuatara, which-at approximately 5 Gb-is among the largest of the vertebrate genomes yet assembled. Our analyses of this genome, along with comparisons with other vertebrate genomes, reinforce the uniqueness of the tuatara. Phylogenetic analyses indicate that the tuatara lineage diverged from that of snakes and lizards around 250 million years ago. This lineage also shows moderate rates of molecular evolution, with instances of punctuated evolution. Our genome sequence analysis identifies expansions of proteins, non-protein-coding RNA families and repeat elements, the latter of which show an amalgam of reptilian and mammalian features. The sequencing of the tuatara genome provides a valuable resource for deep comparative analyses of tetrapods, as well as for tuatara biology and conservation. Our study also provides important insights into both the technical challenges and the cultural obligations that are associated with genome sequencing.

Publisher Correction: The tuatara genome reveals ancient features of amniote evolution.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Group Coping Intervention in Patients With Chronic Graft-Versus-Host Disease: A Pilot Randomized Clinical Trial.

BACKGROUND: More than half the long-term survivors of allogeneic hematopoietic cell transplantation develop chronic graft-versus-host disease (GVHD), a debilitating inflammatory syndrome. Supportive interventions to assist survivors in coping with chronic GVHD are critically needed. PATIENTS AND METHODS: We conducted a pilot randomized clinical trial of a multidisciplinary group intervention (Horizons Program; n=39) versus minimally enhanced usual care (n=41) for patients with moderate or severe chronic GVHD. Horizons participants received 8 weekly sessions about GVHD and coping co-led by a transplant clinician and a behavioral health expert via a secure videoconferencing platform. Participants completed the following surveys before randomization, at 10 weeks, and at 18 weeks: Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT) for quality of life (QoL), Lee Symptom Scale for symptom burden, and Hospital Anxiety and Depression Scale-Depression Symptoms (HADS) for mood. The primary endpoint was feasibility (≥50% enrollment, ≥80% attendance in half the sessions for the Horizons arm only, and ≥80% retention). We also explored preliminary efficacy of the Horizons intervention on changes in patient-reported outcomes with linear mixed effects models and estimates of effect size at 10 weeks. RESULTS: We enrolled and registered 80 (67.2%) of 119 eligible patients (mean age, 62 years; 48.8% female). Of the participants in the Horizons Program, 84.6% attended at least half the sessions. Of registered participants, 91.3% completed assessment follow-ups (Horizons, 35/39 [89.7%]; minimally enhanced usual care, 38/41 [92.7%]). Horizons participants reported improvements in QoL (b = 2.24; d=0.53), anxiety symptoms (b = -0.10; d=0.34), and depression symptoms (b = -0.71; d=0.44) compared with participants who received minimally enhanced usual care. CONCLUSIONS: Participation in a multidisciplinary group intervention study was feasible for patients with chronic GVHD, with promising signals for improving QoL and mood. A full-scale efficacy trial is needed to confirm effects on patient-reported outcomes.

Pilot Randomized Controlled Trial of an Educational Video for CAR T-Cell Therapy Recipients.

BACKGROUND: CAR T-cell therapy has transformed the treatment of hematologic malignancies, but it is complex and challenging to convey to patients. Educational video interventions are efficacious for improving patient knowledge about cancer therapeutics and informing their care preferences, yet no educational videos have been evaluated in CAR T-cell therapy. METHODS: We conducted a randomized controlled trial comparing an educational video versus usual care in adults (age ≥18 years) with hematologic malignancies receiving CAR T-cell therapy at Massachusetts General Hospital. Intervention participants watched a 13-minute video depicting how CAR T-cell therapy works, logistics, toxicities, prognosis, recovery, and approaches for dealing with prognostic uncertainty. The primary outcome was feasibility (≥60% enrollment rate). Secondary outcomes included acceptability (≥80% reporting comfort with the video), patients' knowledge about CAR T-cell therapy (10-item test), and self-efficacy (Communication and Attitudinal Self-Efficacy Scale-Cancer), decision satisfaction (Decision Conflict Scale), psychological distress (Hospital Anxiety and Depression Scale), and preference for CAR T-cell therapy. RESULTS: We enrolled 79% (80/101) of eligible patients. Of that group, 91% (30/33) reported being very or somewhat comfortable watching the video, and 94% (31/33) would definitely or probably recommend the video. At 1 month, participants in the video arm reported higher self-efficacy (mean difference [MD], 9.2 [95% CI, -4.0 to 22.3]; Cohen's d, 0.32), decision satisfaction (MD, 2.5 [95% CI, 0.7-4.2]; Cohen's d, 0.67), and lower anxiety (MD, -0.8 [95% CI, -2.5 to 0.7]; Cohen's d, 0.26) compared with participants in the usual care arm. At 1 week, both arms reported high preferences for CAR T-cell therapy (video arm, 94% [33/35]; usual care, 84% [27/32]). CONCLUSIONS: We found that an educational video for patients receiving CAR T-cell therapy was feasible and acceptable. The educational video demonstrated promising preliminary effects on patient self-efficacy and decision satisfaction and warrants further study.

Gratitude, optimism, and satisfaction with life and patient-reported outcomes in patients undergoing hematopoietic stem cell transplantation.

OBJECTIVE: Associations between positive psychological well-being (PPWB) and patient-reported outcomes (PROs, e.g., quality of life [QOL]) have yet to be studied extensively in patients with hematologic malignancies who are allogeneic hematopoietic stem cell transplant (HSCT) survivors, despite substantial evidence that PPWB impacts PROs of other medical populations. METHODS: We conducted a secondary analysis of cross-sectional data examining the association of PPWB and PROs at day 100 post-transplant among 158 allogeneic HSCT recipients. Optimism, gratitude, life satisfaction, and PROs (i.e., QOL, anxiety, depression, and PTSD symptoms) were assessed using the Life Orientation Test-Revised, Gratitude Questionnaire, Satisfaction with Life Scale, Functional Assessment of Cancer Therapy-Bone Marrow Transplant, Hospital Anxiety and Depression Scale, and Post-Traumatic Stress Disorder (PTSD) Checklist-Civilian Version, respectively. We used linear and multivariate regressions for all analyses and controlled for patient factors. RESULTS: Optimism was associated with better QOL (ß = 1.46; p < 0.001) and lower levels of anxiety (ß = -0.28; p < 0.001), depression (ß = -0.31; p < 0.001), and PTSD (ß = -0.58; p < 0.001). Gratitude was associated with better QOL (ß = 1.11; p < 0.001) and lower levels of anxiety (ß = -0.21; p = 0.001), depression (ß = -0.14; p = 0.021), and PTSD (ß = -0.32; p = 0.032). Finally, satisfaction with life was associated with better QOL (ß = 1.26; p < 0.001) and lower levels of anxiety (ß = -0.18; p < 0.001), depression (ß = -0.21; p < 0.001), and PTSD (ß = -0.49; p < 0.001). CONCLUSION: Optimism, gratitude, and satisfaction with life were all associated with better QOL and lower levels of psychological distress in allogeneic HSCT survivors. These data support studies to harness PPWB as a therapeutic intervention for this population throughout HSCT recovery.

Psychological mobile app for patients with acute myeloid leukemia: A pilot randomized clinical trial.

BACKGROUND: Patients with acute myeloid leukemia (AML) experience a substantial decline in quality of life (QoL) and mood during their hospitalization for intensive chemotherapy, yet few interventions have been developed to enhance patient-reported outcomes during treatment. METHODS: We conducted a pilot randomized trial (ClinicalTrials.gov identifier NCT03372291) of DREAMLAND, a psychological mobile application for patients with a new diagnosis of AML who are receiving intensive chemotherapy. Patients were randomly assigned to DREAMLAND or usual care. DREAMLAND included four required modules focused on: (1) supportive psychotherapy to help patients deal with the initial shock of diagnosis, (2) psychoeducation to manage illness expectations, (3) psychosocial skill-building to promote effective coping, and (4) self-care. The primary end point was feasibility, which was defined as ≥60% of eligible patients enrolling and 60% of those enrolled completing ≥60% of the required modules. We assessed patient QoL (the Functional Assessment of Cancer Therapy-Leukemia), psychological distress (the Hospital Anxiety and Depression Scale and the Patient Health Questionnaire-9), symptom burden (the Edmonton Symptom Assessment Scale), and self-efficacy (the Cancer Self-Efficacy Scale) at baseline and at day 20 after postchemotherapy. RESULTS: We enrolled 60 of 90 eligible patients (66.7%), and 62.1% completed ≥75% of the intervention modules. At day 20 after chemotherapy, patients who were randomized to DREAMLAND reported improved QoL scores (132.06 vs. 110.72; p =.001), lower anxiety symptoms (3.54 vs. 5.64; p = .010) and depression symptoms (Hospital Anxiety and Depression Scale: 4.76 vs. 6.29; p = .121; Patient Health Questionnaire-9: 4.62 vs. 8.35; p < .001), and improved symptom burden (24.89 vs. 40.60; p = .007) and self-efficacy (151.84 vs. 135.43; p = .004) compared with the usual care group. CONCLUSIONS: A psychological mobile application for patients with newly diagnosed AML is feasible to integrate during hospitalization for intensive chemotherapy and may improve QoL, mood, symptom burden, and self-efficacy.

Coping and Perception of Prognosis in Patients With Indolent Non-Hodgkin's Lymphoma.

BACKGROUND: Indolent non-Hodgkin's lymphomas (iNHL) are a heterogenous group of mostly incurable diseases with prolonged illness courses and prognostic uncertainty. Yet, studies evaluating coping and perception of prognosis are limited. METHODS: We conducted a cross-sectional study of adults newly diagnosed with iNHL in the past 3 months at a single academic center. We assessed quality of life (QOL: Functional Assessment of Cancer Therapy-General), psychological symptoms (Hospital Anxiety and Depression Scale), coping (Brief-COPE), and perception of prognosis (Prognosis Awareness Impact Scale). RESULTS: We enrolled 70.6% (48/68) of eligible patients. Patients had older age (mean = 66.9,sd = 10.5), were female (60.4%), predominantly identified as White (85.4%), and had at least received a college degree (75%). Chronic lymphocytic leukemia (39.6%) and follicular lymphoma (33.3%) were the most common diagnoses. Overall, 27.1% and 14.6% of patients reported clinically significant anxiety and PTSD symptoms, respectively. Patients highly utilized acceptance (56.2%), seeking emotional support (47.9%), and denial (47.9%) as coping strategies at diagnosis. While 66.7% of patients recalled their oncologist assessment of illness as incurable, only 35.4% reported that the illness is unlikely to be cured. Overall, 45.8% indicated that they were worried about prognosis and 31.2% reported perseverating on their prognosis. Higher emotional coping with prognosis was associated with fewer anxiety (B = -0.6, SE = 0.2, P < .001), depression (B = -0.3, SE = .1, P = .005), and PTSD (B = -1.3, SE = 0.4, P < .001) symptoms and better QOL (B = 1.7, SE = 0.4, P < .001). DISCUSSION: Patients with iNHL report substantial psychological distress, a diversity of coping strategies, and complex cognitive understanding of their prognosis. Interventions, which address prognostic uncertainty and promote positive emotional coping with prognosis, may ameliorate psychological distress in this population.

Relationship Between Longitudinal Coping Strategies and Outcomes in Patients With Acute Myeloid Leukemia.

BACKGROUND: Patients with acute myeloid leukemia (AML) face an abrupt life-threatening illness and experience immense physical and psychological symptoms. However, no data describe how patients with AML cope longitudinally with their illness or the relationship between longitudinal coping and outcomes. METHODS: We conducted a secondary analysis of longitudinal data from 160 patients with high-risk AML enrolled in a supportive care intervention trial to describe coping strategies longitudinally across the illness course. We used the Brief COPE questionnaire, the Hospital Anxiety and Depression Scale, the Post-Traumatic Stress Disorder (PTSD) Checklist-Civilian Version, and the Functional Assessment of Cancer Therapy-Leukemia to measure coping strategies, psychological distress, and quality of life (QoL) at baseline and at weeks 2, 4, 12, and 24 after diagnosis. Electronic health records were used to assess healthcare utilization and end-of-life (EoL) outcomes, and multivariate analyses were used to assess the relationship between coping and outcomes. RESULTS: Longitudinal utilization of approach-oriented coping strategies was significantly associated with less distress (anxiety: ß, -0.18; P<.001; depression symptoms: ß, -0.42; P<.001; PTSD symptoms: ß, -0.60; P<.001) and better QoL (ß, 2.00; P<.001). Longitudinal utilization of avoidant coping strategies was significantly associated with greater distress (anxiety: ß, 0.64; depression symptoms: ß, 0.54; PTSD symptoms: ß, 2.13; P<.001 for all) and worse QoL (ß, -4.27; P<.001). Although the use of approach-oriented and avoidant coping strategies was not significantly associated with hospitalization, chemotherapy administration, or hospice use in the last 30 days of life, approach-oriented coping was associated with lower odds of ICU admissions (odds ratio, 0.92; P=.049). CONCLUSIONS: Longitudinal use of approach-oriented coping strategies was associated with less psychological distress, better QoL, and a lower likelihood of ICU admission, suggesting a possible target for supportive oncology interventions. Coping strategies did not impact EoL outcomes, and further research is needed to elucidate which patient factors impact EoL decision-making.

Associations of patient-reported care satisfaction with symptom burden and healthcare use in hospitalized patients with cancer.

BACKGROUND: Hospitalized patients with cancer often experience a high symptom burden, which may impact care satisfaction and healthcare utilization. METHODS: We prospectively enrolled patients with cancer and unplanned hospitalizations from September 2014 to April 2017. Upon admission, we assessed patients' care satisfaction (FAMCARE items: satisfaction with care coordination and speed with which symptoms are treated) and physical (Edmonton Symptom Assessment System [ESAS]) and psychological (Patient Health Questionnaire-4 [PHQ-4]) symptoms. We used regression models to identify factors associated with care satisfaction and associations of satisfaction with symptom burden and hospital length of stay (LOS). RESULTS: Among 1,576 participants, most reported being "satisfied"/ "very satisfied" with care coordination (90%) and speed with which symptoms are treated (89%). Older age (coordination: B < 0.01, P = 0.02, speed: B = 0.01, P < 0.01) and admission to a dedicated oncology service (B = 0.20, P < 0.01 for each) were associated with higher satisfaction. Higher satisfaction with care coordination was associated with lower ESAS-physical (B = - 1.28, P < 0.01), ESAS-total (B = - 2.73, P < 0.01), PHQ4-depression (B = - 0.14, P = 0.02), and PHQ4-anxiety (B = - 0.16, P < 0.01) symptoms. Higher satisfaction with speed with which symptoms are treated was associated with lower ESAS-physical (B = - 1.32, P < 0.01), ESAS-total (B = - 2.46, P < 0.01), PHQ4-depression (B = - 0.14, P = 0.01), and PHQ4-anxiety (B = - 0.17, P < 0.01) symptoms. Satisfaction with care coordination (B = - 0.48, P = 0.04) and speed with which symptoms are treated (B = - 0.44, P = 0.04) correlated with shorter LOS. CONCLUSIONS: Hospitalized patients with cancer report high care satisfaction, which correlates with older age and admission to a dedicated oncology service. Significant associations among higher care satisfaction, lower symptom burden, and shorter hospital LOS highlight the importance of improving symptom management and care coordination in this population.

Flexibility of the petunia strigolactone receptor DAD2 promotes its interaction with signaling partners.

Strigolactones (SLs) are terpenoid-derived plant hormones that regulate various developmental processes, particularly shoot branching, root development, and leaf senescence. The SL receptor has an unusual mode of action. Upon binding SL, it hydrolyzes the hormone, and then covalently binds one of the hydrolytic products. These initial events enable the SL receptor DAD2 (in petunia) to interact with the F-box protein PhMAX2A of the Skp-Cullin-F-box (SCF) complex and/or a repressor of SL signaling, PhD53A. However, it remains unclear how binding and hydrolysis structurally alters the SL receptor to enable its engagement with signaling partners. Here, we used mutagenesis to alter DAD2 and affect SL hydrolysis or DAD2's ability to interact with its signaling partners. We identified three DAD2 variants whose hydrolytic activity had been separated from the receptor's interactions with PhMAX2A or PhD53A. Two variants, DAD2N242I and DAD2F135A, having substitutions in the core α/ß hydrolase-fold domain and the hairpin, exhibited hormone-independent interactions with PhMAX2A and PhD53A, respectively. Conversely, the DAD2D166A variant could not interact with PhMAX2A in the presence of SL, but its interaction with PhD53A remained unaffected. Structural analyses of DAD2N242I and DAD2D166A revealed only small differences compared with the structure of the WT receptor. Results of molecular dynamics simulations of the DAD2N242I structure suggested that increased flexibility is a likely cause for its SL-independent interaction with PhMAX2A. Our results suggest that PhMAX2A and PhD53A have distinct binding sites on the SL receptor and that its flexibility is a major determinant of its interactions with these two downstream regulators.

Clinical Outcomes, Treatment Toxicity, and Health Care Utilization in Older Adults with Aggressive Non-Hodgkin Lymphoma.

BACKGROUND: Although balancing treatment efficacy with risks of complications is critical for older adults with aggressive non-Hodgkin lymphoma (NHL), few studies have described these patients' clinical outcomes, rates of toxicities, and health care utilization. METHODS: We conducted a retrospective analysis of adults ≥65 years diagnosed with aggressive NHL and receiving systemic therapy at Massachusetts General Hospital from April 2000 to July 2020. We abstracted patient characteristics, clinical outcomes, treatment toxicity, unplanned hospitalizations, and intensive care unit (ICU) admissions within 6 months of treatment initiation from the medical record. Using multivariable logistic regression, we examined factors associated with rates of grade 3+ nonhematologic toxicity and unplanned hospitalization. RESULTS: Among 295 patients (median age, 73 years; 39.0% female), 5-year overall survival (OS) was 74.2%. Five-year OS by age group (65-69, 70-74, 75-79, and 80+ years) was 82.2%, 72.0%, 73.6%, and 66.4%, respectively. Overall, 42.4% experienced grade 3+ toxicity, with 8.1% experiencing grades 4-5. The rates of unplanned hospitalization and ICU admission were 41.0% and 6.1%, respectively. In multivariable analysis, hypoalbuminemia (odds ratio [OR], 4.29; p < .001) and high comorbidity score (OR, 4.22; p < .001) were associated with likelihood of grade 3+ toxicity. Hypoalbuminemia (OR, 2.83; p = .003), high comorbidity score (OR, 3.93; p = .001), and receipt of EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin; OR, 5.45; p = .012) were associated with likelihood of unplanned hospitalization. CONCLUSIONS: The majority of older adults receiving upfront therapy for aggressive NHL survive beyond 5 years, yet nearly half experience substantial treatment toxicities and unplanned hospitalizations. Our findings underscore the need for supportive care interventions to enhance the care experience of this population. IMPLICATIONS FOR PRACTICE: The results of this study highlight the potential benefits of intensive chemoimmunotherapy for the majority of older adults with aggressive non-Hodgkin lymphoma, even at advanced ages. Nearly half of older adults experienced substantial treatment toxicities and unplanned hospitalizations, emphasizing the unmet need for supportive care interventions in this population. The present study also identified hypoalbuminemia and patient comorbidity score as factors associated with grade 3+ nonhematologic toxicity and unplanned hospitalization. These findings may guide the development and implementation of targeted supportive care interventions in high-risk older adults with aggressive non-Hodgkin lymphoma.

Associations of Skeletal Muscle With Symptom Burden and Clinical Outcomes in Hospitalized Patients With Advanced Cancer.

BACKGROUND: Low muscle mass (quantity) is common in patients with advanced cancer, but little is known about muscle radiodensity (quality). We sought to describe the associations of muscle mass and radiodensity with symptom burden, healthcare use, and survival in hospitalized patients with advanced cancer. METHODS: We prospectively enrolled hospitalized patients with advanced cancer from September 2014 through May 2016. Upon admission, patients reported their physical (Edmonton Symptom Assessment System [ESAS]) and psychological (Patient Health Questionnaire-4 [PHQ-4]) symptoms. We used CT scans performed per routine care within 45 days before enrollment to evaluate muscle mass and radiodensity. We used regression models to examine associations of muscle mass and radiodensity with patients' symptom burden, healthcare use (hospital length of stay and readmissions), and survival. RESULTS: Of 1,121 patients enrolled, 677 had evaluable muscle data on CT (mean age, 62.86 ± 12.95 years; 51.1% female). Older age and female sex were associated with lower muscle mass (age: B, -0.16; P<.001; female: B, -6.89; P<.001) and radiodensity (age: B, -0.33; P<.001; female: B, -1.66; P=.014), and higher BMI was associated with higher muscle mass (B, 0.58; P<.001) and lower radiodensity (B, -0.61; P<.001). Higher muscle mass was significantly associated with improved survival (hazard ratio, 0.97; P<.001). Notably, higher muscle radiodensity was significantly associated with lower ESAS-Physical (B, -0.17; P=.016), ESAS-Total (B, -0.29; P=.002), PHQ-4-Depression (B, -0.03; P=.006), and PHQ-4-Anxiety (B, -0.03; P=.008) symptoms, as well as decreased hospital length of stay (B, -0.07; P=.005), risk of readmission or death in 90 days (odds ratio, 0.97; P<.001), and improved survival (hazard ratio, 0.97; P<.001). CONCLUSIONS: Although muscle mass (quantity) only correlated with survival, we found that muscle radiodensity (quality) was associated with patients' symptoms, healthcare use, and survival. These findings underscore the added importance of assessing muscle quality when seeking to address adverse muscle changes in oncology.

Determinants of Latent Tuberculosis Treatment Acceptance and Completion in Healthcare Personnel.

BACKGROUND: US public health strategy for eliminating tuberculosis (TB) prioritizes treatment of latent TB infection (LTBI). Healthcare personnel (HCP) are less willing to accept treatment than other populations. Little is known about factors associated with HCP LTBI therapy acceptance and completion. METHODS: We conducted a retrospective chart review to identify all employees with LTBI at time of hire at a large academic medical center during a 10-year period. Personal demographics, occupational factors, and clinic visit variables were correlated with LTBI treatment acceptance and completion rates using multivariate logistic regression. RESULTS: Of 470 HCP with LTBI for whom treatment was recommended, 193 (41.1%) accepted treatment, while 137 (29.1%) completed treatment. Treatment adherence was better with 4 months of rifampin than 9 months of isoniazid (95% vs 68%, P < .005). Increased age of the healthcare worker was independently associated with lower rates of treatment acceptance (odds ratio [95% confidence interval]: 0.97 [0.94-0.99] per year), as was having an occupation of clinician (0.47 [0.26-0.85]) or researcher (0.34 [0.19-0.64]). Male gender was associated with higher treatment acceptance (1.90 [1.21-2.99]). Treatment completion was associated with being from a low- (9.49 [2.06-43.73]) or medium- (8.51 [3.93-18.44]) TB-burden country. CONCLUSIONS: Geographic and occupational factors affect acceptance and completion of LTBI therapy. Short-course regimens may improve adherence. Physicians, researchers, and HCP from high-TB-burden countries have lower treatment rates than other HCP. Improving LTBI treatment in HCP will require attending to cultural and occupational differences.

Symptom burden in patients with cancer who are experiencing unplanned hospitalization.

BACKGROUND: Inpatient supportive care programs often target patients with advanced solid tumors. To the authors' knowledge, few studies to date have characterized symptom burden in hospitalized patients with potentially curable cancers. The objective of the current study was to compare symptom burden, palliative care consultation, and readmission rates in hospitalized patients by cancer type and treatment intent. METHODS: The authors conducted a single-center study of hospitalized patients with cancer between 2014 and 2017. They assessed physical symptoms using the Edmonton Symptom Assessment System and psychological distress using the Patient Health Questionnaire-4 and the Primary Care PTSD (Posttraumatic Stress Disorder) Screen. Multivariate linear regression models were used to assess symptom burden, logistic regression was used to assess palliative care use, and competing risk regression was used to compare 90-day readmission risk. RESULTS: A total of 1549 patients were enrolled and surveyed. The majority of patients reported moderate to severe fatigue, poor well-being, and drowsiness with no significant differences noted by cancer type and treatment intent. Compared with other groups, patients with incurable solid cancer reported higher physical symptoms (beta coefficient [B], 4.73; P < .01) and symptoms of depression (B, 0.44; P < .01) and anxiety (B, 0.39; P < .01), but no difference in posttraumatic stress disorder. Among patients in the top quartile symptom burden according to the Edmonton Symptom Assessment System, the palliative care service was consulted in 14.7%, 7.9%, 25.0%, and 49.6%, respectively, of patients with potentially curable hematologic, potentially curable solid, incurable hematologic, and incurable solid cancers (P < .001). Compared with patients with potentially curable solid cancer, patients in each group experienced a higher risk of readmission within 90 days. CONCLUSIONS: Hospitalized patients with cancer experience substantial physical and psychological symptoms. Palliative care rarely is consulted for highly symptomatic patients with potentially curable cancers. Supportive care interventions should target the needs of symptomatic patients regardless of treatment intent.

Functional Impairment, Symptom Burden, and Clinical Outcomes Among Hospitalized Patients With Advanced Cancer.

BACKGROUND: National guidelines recommend regular measurement of functional status among patients with cancer, particularly those who are elderly or high-risk, but little is known about how functional status relates to clinical outcomes among hospitalized patients with advanced cancer. The goal of this study was to investigate how functional impairment is associated with symptom burden and healthcare utilization and clinical outcomes. PATIENTS AND METHODS: We conducted a prospective observational study of patients with advanced cancer with unplanned hospitalizations at Massachusetts General Hospital from September 2014 through March 2016. Upon admission, nurses assessed patients' activities of daily living (ADLs; mobility, feeding, bathing, dressing, and grooming). Patients with any ADL impairment on admission were classified as having functional impairment. We used the revised Edmonton Symptom Assessment System (ESAS-r) and Patient Health Questionnaire-4 to assess physical and psychological symptoms, respectively. Multivariable regression models were used to assess the relationships between functional impairment, hospital length of stay, and survival. RESULTS: Among 971 patients, 390 (40.2%) had functional impairment. Those with functional impairment were older (mean age, 67.18 vs 60.81 years; P<.001) and had a higher physical symptom burden (mean ESAS physical score, 35.29 vs 30.85; P<.001) compared with those with no functional impairment. They were also more likely to report moderate-to-severe pain (74.9% vs 63.1%; P<.001) and symptoms of depression (38.3% vs 23.6%; P<.001) and anxiety (35.9% vs 22.4%; P<.001). Functional impairment was associated with longer hospital length of stay (ß = 1.29; P<.001) and worse survival (hazard ratio, 1.73; P<.001). CONCLUSIONS: Hospitalized patients with advanced cancer who had functional impairment experienced a significantly higher symptom burden and worse clinical outcomes compared with those without functional impairment. These findings provide evidence supporting the routine assessment of functional status on hospital admission and using this to inform discharge planning, discussions about prognosis, and the development of interventions addressing patients' symptoms and physical function.

Estimating the biodiversity of terrestrial invertebrates on a forested island using DNA barcodes and metabarcoding data.

Invertebrates are a major component of terrestrial ecosystems, however, estimating their biodiversity is challenging. We compiled an inventory of invertebrate biodiversity along an elevation gradient on the temperate forested island of Hauturu, New Zealand, by DNA barcoding of specimens obtained from leaf litter samples and pitfall traps. We compared the barcodes and biodiversity estimates from this data set with those from a parallel DNA metabarcoding analysis of soil from the same locations, and with pre-existing sequences in reference databases, before exploring the use of combined data sets as a basis for estimating total invertebrate biodiversity. We obtained 1,282 28S and 1,610 COI barcodes from a total of 1,947 invertebrate specimens, which were clustered into 247 (28S) and 366 (COI) OTUs, of which ≤ 10% were represented in GenBank. Coleoptera were most abundant (730 sequenced specimens), followed by Hymenoptera, Diptera, Lepidoptera, and Amphipoda. The most abundant OTU from both the 28S (153 sequences) and COI (140 sequences) data sets was an undescribed beetle from the family Salpingidae. Based on the occurrences of COI OTUs along the elevation gradient, we estimated there are ~1,000 arthropod species (excluding mites) on Hauturu, including 770 insects, of which 344 are beetles. A DNA metabarcoding analysis of soil DNA from the same sites resulted in the identification of similar numbers of OTUs in most invertebrate groups compared with the DNA barcoding, but less than 10% of the DNA barcoding COI OTUs were also detected by the metabarcoding analysis of soil DNA. A mark-recapture analysis based on the overlap between these data sets estimated the presence of approximately 6,800 arthropod species (excluding mites) on the island, including ~3,900 insects. Estimates of New Zealand-wide biodiversity for selected arthropod groups based on matching of the COI DNA barcodes with pre-existing reference sequences suggested over 13,200 insect species are present, including 4,000 Coleoptera, 2,200 Diptera, and 2,700 Hymenoptera species, and 1,000 arachnid species (excluding mites). These results confirm that metabarcoding analyses of soil DNA tends to recover different components of terrestrial invertebrate biodiversity compared to traditional invertebrate sampling, but the combined methods provide a novel basis for estimating invertebrate biodiversity.

Differential gene expression in the evolution of sex pheromone communication in New Zealand's endemic leafroller moths of the genera Ctenopseustis and Planotortrix.

BACKGROUND: Sex pheromone communication in moths has attracted the attention of evolutionary biologists due to the vast array of pheromone compounds used, addressing questions of how this diversity arose and how male reception has evolved in step with the female signal. Here we examine the role of changing gene expression in the evolution of mate recognition systems in leafroller moths, particularly focusing on genes involved in the biosynthetic pathways of sex pheromones in female pheromone glands and the peripheral reception repertoire in the antennae of males. From tissue-specific transcriptomes we mined and compared a database of genes expressed in the pheromone glands and antennae of males and females of four closely related species of leafroller moths endemic to New Zealand, Ctenopseutis herana and C. obliquana, and Planotortrix excessana and P. octo. The peculiarity of this group, compared to other Lepidoptera, is the use of (Z)-5-tetradecenyl acetate, (Z)-7-tetradecenyl acetate, and (Z)-8-tetradecenyl acetate as sex pheromone components. RESULTS: We identify orthologues of candidate genes from the pheromone biosynthesis pathway, degradation and transport, as well as genes of the periphery olfactory repertoire, including large families of binding proteins, receptors and odorant degrading enzymes. The production of distinct pheromone blends in the sibling species is associated with the differential expression of two desaturase genes, deast5 and desat7, in the pheromone glands. In male antennae, three odorant receptors, OR74, OR76a and OR30 are over-expressed, but their expression could not be clearly associated with the detection of species-specific pheromones components. In addition these species contain duplications of all three pheromone binding proteins (PBPs) that are also differentially expressed among species. CONCLUSIONS: While in females differences in the expression of desaturases may be sufficient to explain pheromone blend differences among these New Zealand leafroller species, in males differential expression of several genes, including pheromone binding proteins, may underpin differences in the response by males to changing pheromone components among the species.

Characterization of Odorant Receptors from a Non-ditrysian Moth, Eriocrania semipurpurella Sheds Light on the Origin of Sex Pheromone Receptors in Lepidoptera.

Pheromone receptors (PRs) are essential in moths to detect sex pheromones for mate finding. However, it remains unknown from which ancestral proteins these specialized receptors arose. The oldest lineages of moths, so-called non-ditrysian moths, use short-chain pheromone components, secondary alcohols, or ketones, so called Type 0 pheromones that are similar to many common plant volatiles. It is, therefore, possible that receptors for these ancestral pheromones evolved from receptors detecting plant volatiles. Hence, we identified the odorant receptors (ORs) from a non-ditrysian moth, Eriocrania semipurpurella (Eriocraniidae, Lepidoptera), and performed functional characterization of ORs using HEK293 cells. We report the first receptors that respond to Type 0 pheromone compounds; EsemOR3 displayed highest sensitivity toward (2S, 6Z)-6-nonen-2-ol, whereas EsemOR5 was most sensitive to the behavioral antagonist (Z)-6-nonen-2-one. These receptors also respond to plant volatiles of similar chemical structures, but with lower sensitivity. Phylogenetically, EsemOR3 and EsemOR5 group with a plant volatile-responding receptor from the tortricid moth Epiphyas postvittana (EposOR3), which together reside outside the previously defined lepidopteran PR clade that contains the PRs from more derived lepidopteran families. In addition, one receptor (EsemOR1) that falls at the base of the lepidopteran PR clade, responded specifically to ß-caryophyllene and not to any other additional plant or pheromone compounds. Our results suggest that PRs for Type 0 pheromones have evolved from ORs that detect structurally-related plant volatiles. They are unrelated to PRs detecting pheromones in more derived Lepidoptera, which, in turn, also independently may have evolved a novel function from ORs detecting plant volatiles.

The effect of red-blood-cell transfusion on fatigue in hospitalized patients with anaemia.

BACKGROUND AND OBJECTIVE: Guidelines suggest that red-blood-cell transfusion decisions for most hospitalized patients be based on haemoglobin (Hb) concentration and the presence of symptoms of anaemia, including fatigue. However, studies differ in whether transfusion is associated with improvements in fatigue. One explanation is that the benefit of transfusion varies by baseline fatigue levels, which existing studies have not examined. The objective of this study was to determine whether the association between transfusion during hospitalization and improvements in fatigue 30 days postdischarge varies by baseline fatigue level. METHODS: A prospective observational study of hospitalized general medicine patients with any Hb <9 g/dl. Patients with sickle cell anaemia and gastrointestinal bleeding were excluded since these diagnoses have alternative transfusion practices. Patients with depression were excluded because their fatigue is not primarily due to anaemia. Fatigue was measured during an in-person interview and a 30-day postdischarge phone interview. Hb values and receipt of a transfusion were collected from hospital administrative data. Linear regression was used to test associations between 'change in fatigue', Hb concentration and receipt of a transfusion. RESULTS: Transfusion interacted with nadir Hb was associated with reduced fatigue postdischarge for patients with higher baseline fatigue (20% most fatigued: ß = 12, P = 0·02; 10% most fatigued: ß = 17, P = 0·02). Patients <50 years old with high baseline fatigue had large reductions in fatigue from transfusion (20%: ß = 23, P = 0·02; 10%: ß = 29, P = 0·03). CONCLUSIONS: Transfusion during hospitalization is associated with reduced fatigue 30 days postdischarge in patients with higher levels of baseline fatigue.