bluuebunny/crossref_metadata_2025 huggingface dataset:
A time-series meta-transcriptomic analysis reveals the seasonal, host, and gender structure of mosquito viromes
Authors: Feng Yun , Gou Qin-yu , Yang Wei-hong , Wu Wei-chen , Wang Juan , Holmes Edward C , Liang Guodong , Shi Mang
Published: January 2022

Although metagenomic sequencing has revealed high numbers of viruses in mosquitoes sampled globally, our understanding of how their diversity and abundance varies in time and space as well as by host species and gender remains unclear. To address this, we collected 23,109 mosquitoes over the course of 12 months from a bat-dwelling cave and a nearby village in Yunnan province, China. These samples were organized by mosquito species, mosquito gender, and sampling time for meta-transcriptomic sequencing. A total of 162 eukaryotic virus species were identified, of which 101 were novel, including representatives of seventeen RNA virus multi-family supergroups and four species of DNA virus from the families Parvoviridae, Circoviridae, and Nudiviridae. In addition, two known vector-borne viruses—Japanese encephalitis virus and Banna virus—were found. Analyses of the entire virome revealed strikingly different viral compositions and abundance levels in warmer compared to colder months, a strong host structure at the level of mosquito species, and no substantial differences between those viruses harbored by male and female mosquitoes. At the scale of individual viruses, some were found to be ubiquitous throughout the year and across four mosquito species, while most of the other viruses were season and/or host specific. Collectively, this study reveals the diversity, dynamics, and evolution of the mosquito virome at a single location and sheds new lights on the ecology of these important vector animals.
Insights into the geographical origin and phylogeographical patterns ofParadisaeabirds-of-paradise
Authors: Stelbrink Björn , Von Rintelen Thomas , Richter Kirsten , Finstermeier Knut , Frahnert Sylke , Cracraft Joel , Hofreiter Michael
Published: January 2022

Birds-of-paradise represent a textbook example for geographical speciation and sexual selection. Perhaps the most iconic genus is Paradisaea, which is restricted to New Guinea and a few surrounding islands. Although several species concepts have been applied in the past to disentangle the different entities within this genus, no attempt has been made so far to uncover phylogeographical patterns based on a genetic dataset that includes multiple individuals per species. Here, we applied amplicon sequencing for the mitochondrial fragment Cytb for a total of 69 museum specimens representing all seven Paradisaea species described and inferred both phylogenetic relationships and colonization pathways across the island. Our analyses show that the most recent common ancestor of the diverging lineages within Paradisaea probably originated in the Late Miocene in the eastern part of the Central Range and suggest that tectonic processes played a key role in shaping the diversification and distribution of species. All species were recovered as monophyletic, except for those within the apoda–minor–raggiana clade, which comprises the allopatric and parapatric species P. apoda, P. minor and P. raggiana. The comparatively young divergence times, together with possible instances of mitochondrial introgression and incomplete lineage sorting, suggest recent speciation in this clade.
History Is What We Make It
Authors: Kennedy Maureen Shawn
Published: January 2022

And we need to make it one we're proud of.
Drug Wins Designation as a Biosimilar Product to Humira
Authors: Aschenbrenner Diane S.
Published: January 2022

Adalimumab-adbm (Cyltezo) has been approved as an interchangeable biosimilar product to adalimumab (Humira). This means it can be substituted at the pharmacy for Humira without being specified in the prescription.

Nurses should inform patients who have been receiving Humira that they may receive Cyltezo instead, and that this is not a pharmacy error.
A Case of an Asymptomatic Older Adult
Authors: Kupchik Nicole , Green Joel
Published: January 2022

Editor's note: This is the next installment in a series on electrocardiogram (ECG) interpretation. Nurses in all settings should know the basics, as medications and physiological changes can cause cardiac arrhythmias. Each article will start with a brief case scenario and an ECG strip and then take you step by step through analyzing the heart rhythm.
Not an Impostor After All
Authors: Aksamit Inga
Published: January 2022

A retired nurse gets up to speed, with a little help from a nursing student.
Perceived risk factors for weight gain, barriers, and facilitators related to weight loss experienced by perimenopausal women: focus group discussion and thematic analysis
Authors: Chopra Sakshi , Ranjan Piyush , Malhotra Anita , Verma Aditi , Kumari Archana , Sharma K. Aparna , Sarkar Siddharth , Vikram Naval K.
Published: January 2022

Objective:

This study aims to understand middle-aged perimenopausal women's perspectives and beliefs regarding their body weight status, and evaluate the barriers, and facilitators associated weight loss.

Methods:

Five focus group discussions were conducted with perimenopausal women (aged 40-55 y) who were recruited through convenience and snowball sampling. Discussions were conducted to understand their experiences related to weight management during the perimenopausal period. The discussions were audio-recorded and transcribed and data analysis was done using Atlas.ti software to generate codes, subthemes, and themes from the discussions.

Results:

A total of 23 women with a mean age of 46.6 ± 5.6 years were recruited. Several themes of risk factors of weight gain emerged like difficulty in physical activity, unhealthy eating, overeating, and religious and cultural practices. Appearance and prevention of health-related issues emerged as motivators of initiating weight loss. Barriers faced during weight loss included themes like difficulty in managing diet and activity, stress, socialization, and lack of time. Facilitators of weight loss included intrinsic motivation, experiencing early results and confidence in self-regulation.

Conclusion:

Women during their perimenopausal phase of life encounter a range of barriers and challenges related to weight loss. An understanding of these barriers might be useful to consider while planning strategies to regulate their weight.
Reconstruction of Digital Defects with the Free Proximal Ulnar Artery Perforator Flap
Authors: Troisi Luigi , Zanchetta Francesco , Berner Juan Enrique , Mosillo Giuseppe , Pajardi Giorgio Eugenio
Published: January 2022

Background:

The aim of post-traumatic digital reconstruction is to restore form and function, allowing early rehabilitation. In the absence of feasible local options, free tissue transfer can be a versatile and reliable alternative. The aim of this study was to describe our experience with the use of the free proximal ulnar artery perforator flap (PUPF).

Methods:

Our prospectively maintained free flap database was inquired for patients that had undergone digital reconstructions with free PUPFs.

Results:

Six patients that underwent digital reconstruction were eligible. The ipsilateral forearm was donor site of choice, with all flaps based on a perforator of the ulnar artery, without the need to compromise the main vessel. A superficial vein was routinely included with the flap. No flap failures were encountered. Mean hospital stay was 5.5 days, and all patients achieved a satisfactory functional result.

Conclusions:

The proximal ulnar perforator free flap offers an alternative for finger reconstruction, having the advantage of including thin and hairless skin from the proximal ulnar forearm. The vascular anatomy of the ulnar perforators seems to be constant. Furthermore, donor site morbidity is low, as the ulnar artery is not harvested with the flap, the donor site defect can generally be closed directly, and the scar is well concealed.
Blockade of 20-hydroxyeicosatetraenoic acid receptor lowers blood pressure and alters vascular function in mice with smooth muscle-specific overexpression of CYP4A12-20-HETE synthase
Authors: Agostinucci Kevin , Hutcheson Rebecca , Hossain Sakib , Pascale Jonathan V. , Villegas Elizabeth , Zhang Frank , Adebesin Adeniyi Michael , Falck John R. , Gupte Sachin , Garcia Victor , Schwartzman Michal Laniado
Published: January 2022

Objective:

20-Hydroxyeicosatetraenoic acid (20-HETE) is a vasoactive eicosanoid exhibiting effects on vascular smooth muscle cell (VSMC) via G-protein coupled receptor 75 (GPR75) and include stimulation of contractility, migration, and growth. We examined whether VSMC-targeted overexpression of CYP4A12, the primary 20-HETE-producing enzyme in mice, is sufficient to promote hypertension.

Methods:

Mice with VSM-specific Cyp4a12 overexpression (Myh11-4a12) and their littermate controls (WT) were generated by crossbreeding Cyp4a12-floxed with Myh11-Cre mice. The 20-HETE receptor blocker, N-disodium succinate-20-hydroxyeicosa-6(Z),15(Z)-diencarboxamide (AAA), was administered in the drinking water. Experiments were carried out for 12 days. SBP was measured by tail cuff. Renal interlobar and mesenteric arteries were harvested for assessment of gene expression, 20-HETE levels, vascular contractility, vasodilation, and remodeling.

Results:

Vascular and circulatory levels of 20-HETE were several folds higher in Myh11-4a12 mice compared with WT. The Myh11-4a12 mice compared with WT were hypertensive (145 ± 2 vs. 127 ± 2 mmHg; P < 0.05) and their vasculature displayed a contractile phenotype exemplified by increased contractility, reduced vasodilatory capacity, and increased media to lumen ratio. All these features were reversed by the administration of AAA. The mechanism of increased contractility includes, at least in part, Rho-kinase activation followed by increased myosin light chain phosphorylation and activation of the contractile apparatus.

Conclusion:

VSM-specific Cyp4a12 overexpression is sufficient to alter VSM cell phenotype through changes in contractile markers and enhancement in contractility that promote hypertension and vascular dysfunction in a 20-HETE-dependent manner. The 20-HETE receptor GPR75 may represent a novel target for the treatment of hypertension and associated vascular conditions.
Pomalidomide in Patients With Relapsed and/or Refractory Multiple Myeloma: A Prospective Study Within the Nationwide Netherlands Cancer Registry
Authors: Wester Ruth , Dinmohamed Avinash G. , van der Holt Bronno , Zweegman Sonja , Minnema Monique , Croockewit Sandra , Levin Mark-David , Libourel Eduard , de Waal Esther , Sonneveld Pieter , Cornelissen Jan , Blijlevens Nicole , Broijl Annemiek
Published: January 2022

Patients with relapsed and/or refractory multiple myeloma (RRMM) generally have limited treatment options and a poor prognosis. Previous trials demonstrated that pomalidomide combined with low-dose dexamethasone (Pd) is effective in these patients with significant responses and improved progression-free survival (PFS). Pd has been approved in RRMM patients who received ≥2 prior lines of therapy. Here, we present the results of a population-based study of patients with RRMM treated with Pd in The Netherlands from time of pomalidomide approval. Using the nationwide Netherlands Cancer Registry, data from all nontrial patients with RRMM treated with Pd were collected. Data were analyzed of response, PFS, and overall survival (OS). A total of 237 patients were included in this analysis. Previous treatment consisted of a proteasome inhibitor in 227 patients (96%) and/or an immune-modulating agent in 235 patients (99%). One hundred forty patients (59%) were refractory to an immune-modulating agent in their last line of therapy. Median time from diagnosis to treatment with Pd was 4.9 years (interquartile range, 2.7–7.9), and the median number of prior treatments was 4 (interquartile range, 3–5). Median PFS and OS for all patients were 3.6 months (95% confidence interval [CI], 3.1–3.8) and 7.7 months (95% CI, 5.7–9.7), respectively. For patients achieving ≥PR, median PFS and OS were 10.6 months (95% CI, 8.3–12.9) and 16.3 months (95% CI, 13.6–23.2), respectively. This nationwide, population-based registry study confirms data shown in pivotal clinical trials on Pd. PFS in this analysis is comparable to PFS observed in those clinical trials.
Deoxy-sphingolipids, oxidative stress, and vitamin C correlate with qualitative and quantitative patterns of small fiber dysfunction and degeneration
Authors: Dohrn Maike F. , Dumke Christina , Hornemann Thorsten , Nikolin Stefan , Lampert Angelika , Espenkott Volker , Vollert Jan , Ouwenbroek Annabelle , Zanella Martina , Schulz Jörg B. , Gess Burkhard , Rolke Roman
Published: January 2022

Defined by dysfunction or degeneration of Aδ and C fibers, small fiber neuropathies (SFNs) entail a relevant health burden. In 50% of cases, the underlying cause cannot be identified or treated. In 100 individuals (70% female individuals; mean age: 44.8 years) with an idiopathic, skin biopsy–confirmed SFN, we characterized the symptomatic spectrum and measured markers of oxidative stress (vitamin C, selenium, and glutathione) and inflammation (transforming growth factor beta, tumor necrosis factor alpha), as well as neurotoxic 1-deoxy-sphingolipids. Neuropathic pain was the most abundant symptom (95%) and cause of daily life impairment (72%). Despite the common use of pain killers (64%), the painDETECT questionnaire revealed scores above 13 points in 80% of patients. In the quantitative sensory testing (QST), a dysfunction of Aδ fibers was observed in 70% and of C fibers in 44%, affecting the face, hands, or feet. Despite normal nerve conduction studies, QST revealed Aβ fiber involvement in 46% of patients' test areas. Despite absence of diabetes mellitus or mutations in SPTLC1 or SPTLC2, plasma 1-deoxy-sphingolipids were significantly higher in the sensory loss patient cluster when compared with those in patients with thermal hyperalgesia (P < 0.01) or those in the healthy category (P < 0.1), correlating inversely with the intraepidermal nerve fiber density (1-deoxy-SA: P < 0.05, 1-deoxy-SO: P < 0.01). Patients with arterial hypertension, overweight (body mass index > 25 kg/m2), or hyperlipidemia showed significantly lower L-serine (arterial hypertension: P < 0.01) and higher 1-deoxy-sphingolipid levels (arterial hypertension: P < 0.001, overweight: P < 0.001, hyperlipidemia: P < 0.01). Lower vitamin C levels correlated with functional Aβ involvement (P < 0.05). Reduced glutathione was lower in patients with Aδ dysfunction (P < 0.05). Idiopathic SFNs are heterogeneous. As a new pathomechanism, plasma 1-deoxy-sphingolipids might link the metabolic syndrome with small fiber degeneration.
Cardiocirculatory Stress in Professional Football (Soccer) Coaches
Authors: Meyer Tim , Demond Vera , Scharhag Jürgen
Published: January 2022

Objective:

It was intended to quantify cardiocirculatory stress and risk of professional football (soccer) coaches during competition.

Design:

Descriptive cross-sectional study.

Setting:

Medical screening examination and measurements during match.

Participants:

Seventeen coaches and 11 assistant coaches of the 2 highest German football leagues (male coaches; 46 ± 7 years; 8 ± 7 years in job).

Independent variables:

Professional football matches with highly competitive character were chosen and monitored for elicited cardiocirculatory stress and possible damage.

Main Outcome Measures:

Indicators of general health status, occurrence of arrhythmias, and course of heart rate and cardiac biomarkers (brain natriuretic peptide [BNP], troponin I) during the match.

Results:

Besides a few preexisting cardiovascular diseases, medical screening revealed a risk factor profile similar to the general population and above-average maximal/submaximal cycle ergometry performance: P
max 2.9 ± 0.5 W*kg−1; PWC130 1.9 ± 0.5 W*kg−1. No match-induced changes were detected for BNP (20.5 ± 9.4 to 19.7 ± 10.7 pg/mL; P = 0.48) and troponin I (12.6 ± 16.5 to 10.5 ± 14.1 ng/L; P = 0.31). Maximal heart rate during the first and second half was 127 ± 15 and 132 ± 19 beats per minute, respectively. No match-induced arrhythmias of higher degree were detected.

Conclusions:

Head and assistant coaches of German professional football teams do not show any match-induced cardiac damage, despite considerable cardiocirculatory stress. Possibly, their above-average fitness level saves them from more detrimental outcomes.
Electrically Evoked Auditory Late Responses as a Novel Method for Cochlear Implant Programming
Authors: Deniz Rişvan , Kara Eyyup , Deniz Burcu , Kara Halide Çetin , Yener Haydar Murat , Ataş Ahmet
Published: January 2022

Hypothesis:

Electrically evoked auditory late responses (eALR) are useful as an objective cochlear implant (CI) fitting method.

Background:

Different objective and behavioral methods are used for CI fitting. However, there is no objective method that indicates that the electrical signal reaches the auditory cortex. eALR is an indicator that electrical signals reach the auditory cortex, so our aim was to investigate the use of eALR as an objective method for CI programming.

Methods:

Two different programs were created for 21 unilateral Med-El CI users. In the first program, the most comfortable level (MCL) was adjusted with the electrical stapes reflex threshold (eSRT), and the threshold levels (THR) were behaviorally adjusted according to the user's feedback. In the second program, the MCL level was adjusted to a level where all the components of the eALR were clearly seen, and the user did not feel uncomfortable; the THR levels were adjusted to the lowest level where the eALR P1 wave could be seen. The results of the MCL and THR levels of the two programs and the free field tests conducted with both programs were compared.

Results:

While MCL levels did not differ significantly between the two programs, a significant difference was observed between THR levels. In addition, no significant difference was found between hearing and speech tests with CI in the free field.

Conclusion:

The results revealed no significant performance difference between the two programs and that eALR could be preferred as an objective method for MCL determination.
Incidence, Clinical Features, and Outcomes of Langerhans Cell Histiocytosis in the United States
Authors: Buhtoiarov Ilia N. , Mukherjee Sudipto , Radivoyevitch Tomas
Published: January 2022

Langerhans cell histiocytosis (LCH) is a disorder with highly diverse clinical manifestations. We explored if age, sex, race, organ system involved, and therapy approaches determine patient survival in the era of modern treatments. LCH patient data reported to the Surveillance, Epidemiology, and End Results (SEER) program in 2010-2016 (n=1282; age: 0 to 100 y) was analyzed. Age-specific LCH incidence flattening to a low level suggests an age cutoff for pediatric patients of 20 years. The overall survival probability is lower for patients 21 to 100 years old (P<0.0001), irrespective of sex and race. The commonest sites involved in the 0- to 20-year age group were bone, skin, and bone marrow; this shifted to lung, bone, and skin as the commonest disease sites in patients 21 to 100 years of age. The treatments applied differed between age groups, as younger versus older patients were more likely to receive chemotherapy-based treatment (48.4% vs. 17%; P<0.0001). There also was a trend toward nonwhite versus white patients being less likely to receive chemotherapy-based treatment (31.7% vs. 38.2%; P=0.067). Whereas there are treatment disparities related to LCH patient age and perhaps race, patient age is the strongest predictor of survival, with patients 21 to 100 years of age with lung, lymph node, skin, and bone marrow disease having the worst outcomes (P<0.0001).
Low health-related quality of life in adult individuals with multiple limb deficiencies compared with population-based reference values
Authors: Alexanderson H. , Frimore L. , Espinosa F. , Wikström M. , Stockselius A.
Published: January 2022

Background:

Knowledge on health-related quality of life (HRQoL) in multiple limb deficiencies (LDs) is limited.

Objectives:

To investigate self-reported HRQoL in multiple LDs, assess differences between congenital LD and acquired LD and sex, and to evaluate associations between the types of LDs, demographic variables, and HRQoL.

Study design:

Cross-sectional cohort study.

Methods:

A total of 106 individuals with multiple limb deficiencies treated at the EX-Center were invited by mail to fill out the Short Form-36 survey.

Results:

Responses from 62 participants, mean age ± SD 49.5 ± 14.2, showed that 43 had congenital LD and 19 had acquired LD. Responders reported reduced HRQoL in all Short Form-36 domains except Role-Emotional, compared with reference values (P < 0.05–<0.001). Individuals with a congenital LD reported worse Bodily Pain than acquired LD (P < 0.05), and women reported lower Physical Function than men (P < 0.05). Sick leave was negatively associated with physical composite score. Living in a rural area was positively associated with Mental Health (P < 0.01), and congenital LD was negatively associated with Vitality (P < 0.05).

Conclusions:

Individuals with multiple LDs in Sweden have lower HRQoL compared with reference values. There are significant associations between sick leave and physical function, rural living and mental health, and the type of LD and vitality.
Knee Injuries in the Elite American Football Player: A Descriptive Pictorial Imaging and Mechanism of Injury Review
Authors: Hernandez Ricardo J. , Lamplot Joseph D. , Hammond Kyle E. , Joshi Nirav B. , Wong Phillip K. , Umpirrez Monica , Singer Adam , Gonzalez Felix M.
Published: January 2022

Musculoskeletal injuries are common in American football, with an incidence ranging from approximately 10 to 35 per 1000 playing hours. Injuries occur more commonly in games than in practice. Although several studies have analyzed specific injury types in football, this review aims to describe the most common knee injuries sustained by American football players and to review the existing literature pertaining to the radiologic findings used in the diagnosis of these injuries.
Computed Tomography–Guided Lumbar Puncture: Advantages and Disadvantages
Authors: Ökçesiz İzzet , Dönmez Halil , Herdem Nevzat , Sarilar Ayşe Çağlar
Published: January 2022

Objective

This study aimed to evaluate the utility of computed tomography (CT) guidance in difficult lumbar puncture (LP) cases, which had a history of at least one unsuccessful blind attempt at LP (no imaging guidance), and to note potential advantages and disadvantages of the use of CT guidance.

Methods

In total, 32 CT-guided LP procedures performed between June 2019 and March 2021 were included. All LP indications were recorded. The procedures where the cerebrospinal fluid flow was provided by a single puncture were evaluated as “primary technical success.” “Secondary technical success” corresponded with the procedures in which additional puncture was necessary for the cerebrospinal fluid flow.

Results

Intrathecal nusinersen injections due to spinal muscular atrophy constituted the largest procedure group of this study. Among 32 procedures, primary and secondary technical success rates were 78.12% and 28.57%, respectively. There were no major procedural complications.

Conclusions

Computed tomography–guided LP is an effective interventional technique offering an alternative approach in the setting of difficult LP procedures.
18F-Fluciclovine Uptake in Intramuscular Injecting Site of Antiandrogen
Authors: Hsieh Te-Chun , Wu Yu-Chin , Kao Chia-Hung , Yen Kuo-Yang , Sun Shung-Shung
Published: January 2022

18F-fluciclovine, a radiolabeled amino acid analog, has been approved by US Food and Drug Administration for detecting lesions of biochemical recurrence of prostate adenocarcinoma with PET/CT. However, it is not specific for prostate cancer and has been found to be present in variety of malignant and benign etiologies. We herein present an interesting case of the incidental finding of increasing uptake of 18F-fluciclovine related to intramuscular injection of antiandrogen.
In Situ Simulation as a Tool to Longitudinally Identify and Track Latent Safety Threats in a Structured Quality Improvement Initiative for SARS-CoV-2 Airway Management
Authors: Jafri Farrukh N. , Yang Christina J. , Kumar Anshul , Torres Rafael E. , Ahmed Sadia T. , Seneviratne Namal , Zarowin Diana , Bajaj Komal , Edwards Roger A.
Published: January 2022

Background

In situ simulation has emerged as a powerful tool for identifying latent safety threats (LSTs). After the first wave of the SARS-CoV-2 pandemic, an urban community emergency department (ED) identified opportunities for improvement surrounding acute airway management and particularly focused on infection control precautions, equipment availability, and interprofessional communication during acute resuscitation. Using the Model for Improvement, a hybrid in situ/quality improvement initiative was implemented using Plan-Do-Study-Act (PDSA) cycles to enhance systems for intubating patients with SARS-CoV-2.

Methods

Three PDSA cycles consisting of 10 simulations each were conducted from June 2020 through February 2021. Latent safety threats (LST) were identified through an in situ simulation scenario involving a patient with SARS-CoV-2 in acute respiratory failure. LSTs were collected through structured debriefs focused on (1) infection control, (2) equipment availability, and (3) communication. The SAFER-Matrix was used to score LSTs according to frequency and likelihood of harm by members of the ED QI team (SAFER score). The research team worked with the same QI leaders to implement action plans based on scored threats using cause-and-effect and driver diagrams. The Donabedian model was used to conceptually evaluate the quality of interventions upon conclusion of the third PDSA cycle.

Results

The median SAFER score decreased from 10.94 in PDSA cycle 1 to 6.77 in PDSA cycle 2 to 4.71 in PDSA cycle 3. Across all identified LSTs, the SAFER score decreased by 3.114 for every additional PDSA cycle (P = 0.0167). When evaluating for threats identified as being primarily structure based, there was a decrease in SAFER score of 1.28 per every additional PDSA cycle (P = 0.001). There was a decrease in total count of LST of 0.20 per additional simulation run (P = 0.02) after controlling for shift type, census, perceived workload, team size, and prior attendance in simulations across all PDSA cycles.

Conclusions

This study presents a blueprint for the utilization of in situ simulation through multiple waves of the SARS-CoV-2 pandemic to identify LSTs and use the SAFER score as a surrogate marker to monitor the impact of interventions for a safer environment for both medical staff and patients.
Structural Racism and Breast Cancer-specific Survival
Authors: Goel Neha , Westrick Ashly C. , Bailey Zinzi D. , Hernandez Alexandra , Balise Raymond R. , Goldfinger Erica , Antoni Michael H. , Stoler Justin , Kesmodel Susan B. , Kobetz Erin N.
Published: January 2022

Objective:

To analyze the effect of economic and racial/ethnic residential segregation on breast cancer-specific survival (BCSS) in South Florida, a diverse metropolitan area that mirrors the projected demographics of many United States regions.

Summary Background Data:

Despite advances in diagnosis and treatment, racial and economic disparities in BCSS. This study evaluates these disparities through the lens of racial and economic residential segregation, which approximate the impact of structural racism.

Methods:

Retrospective cohort study of stage I to IV breast cancer patients treated at our institution from 2005 to 2017. Our exposures include index of concentration at the extremes, a measurement of economic and racial neighborhood segregation, which was computed at the census-tract level using American Community Survey data. The primary outcome was BCSS.

Results:

Random effects frailty models predicted that patients living in low-income neighborhoods had higher mortality compared to those living in high-income neighborhoods [hazard ratios (HR): 1.56, 95% confidence interval (CI): 1.23–2.00]. Patients living in low-income non-Hispanic Black and Hispanic neighborhoods had higher mortality compared to those living in high-income non-Hispanic White (NHW) neighborhoods (HR: 2.43, 95%CI: 1.72, 3.43) and (HR: 1.99, 95%CI: 1.39, 2.84), after controlling for patient characteristics, respectively. In adjusted race-stratified analysis, NHWs living in low-income non-Hispanic Black neighborhoods had higher mortality compared to NHWs living in high-income NHW neighborhoods (HR: 4.09, 95%CI: 2.34–7.06).

Conclusions:

Extreme racial/ethnic and economic segregation were associated with lower BCSS. We add novel insight regarding NHW and Hispanics to a growing body of literature that demonstrate how the ecological effects of structural racism—expressed through poverty and residential segregation—shape cancer survival.
Balancing enrollment and mortality in hemorrhage control trials: A secondary analysis of the PROPPR trial
Authors: Abraham Peter J. , Gonzalez-Sigler Irina , Reynolds Lindy , Griffin Russell L. , Gelbard Rondi B. , Kerby Jeffrey D. , Holcomb John B. , Jansen Jan O.
Published: January 2022

BACKGROUND

Designing clinical trials on hemorrhage control requires carefully balancing the need for high enrollment numbers with the need of focusing on the sickest patients. The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial enrolled patients within 2 hours of arrival to the emergency department for a trial of injured patients at risk for massive transfusion. We conducted a secondary analysis to determine how time-to-randomization affected patient outcomes and the balance between enrollment and mortality.

METHODS

Patients from the Pragmatic Randomized Optimal Platelet and Plasma Ratios trial were compared based on 30-minute time to randomization intervals. Outcomes included 24-hour and 30-day mortality, time to hemostasis, adverse events, and operative procedures. Additional analyses were conducted based on treatment arm allocation, mechanism of injury, and variation in start time (arrival vs. randomization).

RESULTS

Randomization within 30 minutes of arrival was associated with higher injury severity (median Injury Severity Score, 29 vs. 26 overall; p < 0.01), lower systolic blood pressure (median, 91 vs. 102 mm Hg overall; p < 0.01), and increased penetrating mechanism (50% vs. 47% overall; p < 0.01). Faster time-to-randomization was associated with increased 24-hour (20% for 0- to 30 minute entry, 9% for 31-minute to 60-minute entry, 10% for 61-minute to 90-minute entry, 0% for 91-minute to 120-minute entry; p < 0.01) and 30-day mortality (p < 0.01). There were no significant associations between time-to-randomization and adverse event occurrence, operative interventions, or time to hemostasis.

CONCLUSION

Increasing time to randomization in this large multicenter randomized trial was associated with increased survival. Fastest randomization (within 0–30 minutes) was associated with highest 24-hour and 30-day mortality, but only 57% of patients were enrolled within this timeframe. Only 3% of patients were enrolled within the last 30-minute window (91–120 minutes), with none of them dying within the first 24 hours. For a more optimal balance between enrollment and mortality, investigators should consider shortening the time to randomization when planning future clinical trials of hemorrhage control interventions.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic; Level II.
Higher Proinflammatory Cytokines Are Associated With Increased Antibody Titer After a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients
Authors: Karaba Andrew H. , Zhu Xianming , Benner Sarah E. , Akinde Olivia , Eby Yolanda , Wang Kristy H. , Saraf Sharada , Garonzik-Wang Jacqueline M. , Klein Sabra L. , Bailey Justin R. , Cox Andrea L. , Blankson Joel N. , Durand Christine M. , Segev Dorry L. , Werbel William A. , Tobian Aaron A.R.
Published: January 2022

Background.

Solid organ transplant recipients (SOTRs) are at increased risk for severe COVID-19 and exhibit lower antibody responses to SARS-CoV-2 vaccines. This study aimed to determine if prevaccination cytokine levels are associated with antibody response to SARS-CoV-2 vaccination.

Methods.

A cross-sectional study was performed among 58 SOTRs before and after two-dose mRNA vaccine series, 35 additional SOTRs before and after a third vaccine dose, and comparison to 16 healthy controls (HCs). Antispike antibody was assessed using the IgG Euroimmun ELISA. Electrochemiluminescence detection-based multiplexed sandwich immunoassays (Meso Scale Diagnostics) were used to quantify plasma cytokine and chemokine concentrations (n = 20 analytes) and compare concentrations between SOTRs and HCs, stratified by ultimate antibody response to the vaccine using Wilcoxon-rank-sum test with false discovery rates computed to correct for multiple comparisons.

Results.

In the study population, 100% of HCs, 59% of SOTRs after 2 doses and 63% of SOTRs after 3 doses had a detectable antibody response. Multiple baseline cytokines were elevated in SOTRs versus HCs. There was no significant difference in baseline cytokine levels between SOTRs with high versus low-titer antibodies after 2 doses of vaccine. However, as compared with poor antibody responders, SOTRs who went on to develop a high-titer antibody response to a third dose of vaccine had significantly higher prethird dose levels of several innate immune cytokines including IL-17, IL-2Ra, IL-6, IP-10, MIP-1α, and TNF-α (false discovery rates < 0.05).

Conclusions.

A specific inflammatory profile may be associated with developing higher antibodies in response to a third dose of SARS-CoV-2 vaccine in SOTRs.
Hymenobacter terricola sp. nov., isolated from Antarctic soil
Authors: Chen Ya , Zhu Lin , Bai Pengze , Cui Siqi , Xin Yuhua , Zhang Ying , Zhang Jianli
Published: January 2022

Strain 3F2T was isolated from a soil sample obtained from the surface of Deception Island, Antarctica. The isolate was a Gram-stain-negative, aerobic, non-motile, rod-shaped bacterium, and its colonies were red to pink in colour. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain 3F2T belonged to the genus

Hymenobacter

, family

Hymenobacteraceae

and was most closely related to

Hymenobacter sedentarius

DG5BT (97.0% sequence similarity),

Hymenobacter soli

PB17T (96.9%),

Hymenobacter terrae

DG7AT (96.8%) and

Hymenobacter rufus

S1-2-2-6T (96.5%). Growth occurred at 4–20 °C (optimum, 10 °C), up to 1.0 % (w/v) NaCl (optimum, 0%) and pH 6.0–8.0 (optimum, pH 7.0). The chemotaxonomic characteristics of strain 3F2T, which had MK-7 as its predominant menaquinone and summed feature 3 (C16:1
ω7c and/or C16:1
ω6c), iso-C15:0, anteiso-C15:0 and C16:1
ω5c as its major fatty acids, were consistent with classification in the genus

Hymenobacter

. The polar lipid profile of strain 3F2T comprised phosphatidylethanolamine, two unidentified aminolipids, two unidentified aminophospholipids and three unidentified polar lipids. The genome of strain 3F2T was 6.56 Mbp with a G+C content of 61.5 mol%. Average nucleotide identity (ANI) values between 3F2T and the other species of the genus

Hymenobacter

were found to be low (ANIm <87.0%, ANIb <82.0% and OrthoANIu <83.0%). Furthermore, digital DNA–DNA hybridization and average amino acid identity values between strain 3F2T and the closely related species ranged from 20.0 to 26.3% and from 64.0 to 81.1 %, respectively. Based on the results of our phylogenetic, phenotypic, genotypic and chemotaxonomic analyses, it is concluded that strain 3F2T represents a novel species within the genus

Hymenobacter

, for which the name Hymenobacter terricola sp. nov. is proposed. The type strain is 3F2T (=KCTC 72468T=CGMCC 1.13716T).
Spiractinospora alimapuensis gen. nov., sp. nov., isolated from marine sediment of Valparaíso Bay (Chile) and proposal for reclassification of two species of the genus Nocardiopsis
Authors: Claverías Fernanda P. , Serna-Cardona Néstor , Cumsille Andrés , Zamora-Leiva Leonardo , Riesco Raúl , Couve Eduardo , Trujillo Martha E. , Cámara Beatriz
Published: January 2022

An alkaliphilic actinobacterium, designated VN6-2T, was isolated from marine sediment collected from Valparaíso Bay, Chile. Strain VN6-2T formed yellowish-white branched substrate mycelium without fragmentation. Aerial mycelium was well developed, forming wavy or spiral spore chains. Strain VN6-2T exhibited a 16S rRNA gene sequence similarity of 93.9 % to

Salinactinospora qingdaonensis

CXB832T, 93.7 % to

Murinocardiopsis flavida

14-Be-013T, and 93.7 % to

Lipingzhangella halophila

14-Be-013T. Genome sequencing revealed a genome size of 5.9 Mb and an in silico G+C content of 69.3 mol%. Both of the phylogenetic analyses based on 16S rRNA gene sequences and the up-to-date bacterial core gene sequences revealed that strain VN6-2T formed a distinct monophyletic clade within the family

Nocardiopsaceae

. Chemotaxonomic assessment of strain VN6-2T showed that the major fatty acids were iso-C16 : 0, anteiso-C17 : 0 and 10-methyl-C18 : 0, and the predominant respiratory quinones were MK-9, MK-9(H2) and MK-9(H4). Whole-cell hydrolysates contained meso-diaminopimelic acid as the cell-wall diamino acid, and ribose and xylose as the diagnostic sugars. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, aminophospholipids, glycolipid and phospholipid. Based on the results of this polyphasic study, a novel genus, Spiractinospora gen. nov., is proposed within the family

Nocardiopsaceae

and the type species Spiractinospora alimapuensis gen. nov., sp. nov. The type strain is VN6-2T (CECT 30026T, CCUG 66258T). On the basis of the phylogenetic results herein, we also propose that Nocardiopsis arvandica and Nocardiopsis litoralis are later heterotypic synonyms of

Nocardiopsis sinuspersici

and

Nocardiopsis kunsanensis

, respectively, for which emended descriptions are given.
Visualising Viruses
Authors: Slater Annabel , Nair Naina , Suétt Rachael , Mac Donnchadha Rian , Bamford Connor , Jasim Seema , Livingstone Daniel , Hutchinson Edward
Published: January 2022

Viruses pose a challenge to our imaginations. They exert a highly visible influence on the world in which we live, but operate at scales we cannot directly perceive and without a clear separation between their own biology and that of their hosts. Communication about viruses is therefore typically grounded in mental images of virus particles. Virus particles, as the infectious stage of the viral replication cycle, can be used to explain many directly observable properties of transmission, infection and immunity. In addition, their often striking beauty can stimulate further interest in virology. The structures of some virus particles have been determined experimentally in great detail, but for many important viruses a detailed description of the virus particle is lacking. This can be because they are challenging to describe with a single experimental method, or simply because of a lack of data. In these cases, methods from medical illustration can be applied to produce detailed visualisations of virus particles which integrate information from multiple sources. Here, we demonstrate how this approach was used to visualise the highly variable virus particles of influenza A viruses and, in the early months of the COVID-19 pandemic, the virus particles of the then newly characterised and poorly described SARS-CoV-2. We show how constructing integrative illustrations of virus particles can challenge our thinking about the biology of viruses, as well as providing tools for science communication, and we provide a set of science communication resources to help visualise two viruses whose effects are extremely apparent to all of us.
Comparative genomics of Bordetella pertussis isolates from New Zealand, a country with an uncommonly high incidence of whooping cough
Authors: Ring Natalie , Davies Heather , Morgan Julie , Sundaresan Maithreyi , Tiong Audrey , Preston Andrew , Bagby Stefan
Published: January 2022

Whooping cough, the respiratory disease caused by

Bordetella pertussis

, has undergone a wide-spread resurgence over the last several decades. Previously, we developed a pipeline to assemble the repetitive

B. pertussis

genome into closed sequences using hybrid nanopore and Illumina sequencing. Here, this sequencing pipeline was used to conduct a more high-throughput, longitudinal screen of 66 strains isolated between 1982 and 2018 in New Zealand. New Zealand has a higher incidence of whooping cough than many other countries; usually at least twice as many cases per 100000 people as the USA and UK and often even higher, despite similar rates of vaccine uptake. To the best of our knowledge, these strains are the first New Zealand

B. pertussis

isolates to be sequenced. The analyses here show that, on the whole, genomic trends in New Zealand

B. pertussis

isolates, such as changing allelic profile in vaccine-related genes and increasing pertactin deficiency, have paralleled those seen elsewhere in the world. At the same time, phylogenetic comparisons of the New Zealand isolates with global isolates suggest that a number of strains are circulating in New Zealand, which cluster separately from other global strains, but which are closely related to each other. The results of this study add to a growing body of knowledge regarding recent changes to the

B. pertussis

genome, and are the first genetic investigation into

B. pertussis

isolates from New Zealand.
The evolutionary history of mammoth wasps (Hymenoptera: Scoliidae)
Authors: Khouri Z. , Gillung J.P. , Kimsey L.S.
Published: January 2022

Scoliid wasps comprise a clade of aculeate insects whose larvae are parasitoids of scarabaeid beetle grubs. While scoliids have been studied and used as biological control agents, research into the group’s evolution, as well as the stability of scoliid taxonomy, has been limited by a lack of reliable phylogenies. We use ultraconserved element (UCE) data under concatenation and the multispecies coalescent to infer a phylogeny of the Scoliidae. In order to mitigate potential issues arising from model misspecification, we perform data filtering experiments using posterior predictive checks and matched-pairs tests of symmetry. Our analyses confirm the position ofProscoliaas sister to all other extant scoliids. We also find strong support for a sister group relationship between the campsomerine genusColpaand the Scoliini, rendering the Campsomerini non-monophyletic. Campsomerini excludingColpa(hereafter Campsomerinisensu stricto) is inferred to be monophyletic, with the Australasian genusTrisciloarecovered as sister to the remaining members of the group. Out of nine genera in which more than one species was sampled,Campsomeriella,Dielis,Megascolia, andScoliaare inferred to be non-monophyletic. Analyses incorporating fossil data indicate an Early Cretaceous origin of the crown Scoliidae, with the split between Scoliini +Colpaand Campsomerinis.s.most probably occurring in the Late Cretaceous. Posterior means of Scoliini +Colpaand Campsomerinis.s.crown ages are estimated to be in the Paleogene, though age 95% HPD intervals extend slightly back past the K-Pg boundary, and analyses including fossils of less certain placement result in more posterior mass on older ages. Our estimates of the stem ages of Nearctic scoliid clades are consistent with dispersal across Beringia during the Oligocene or later Eocene. Our study provides a foundation for future research into scoliid wasp evolution and biogeography by being the first to leverage genome-scale data and model-based methods. However, the precision of our dating analyses is constrained by the paucity of well-preserved fossils reliably attributable to the scoliid crown group. Despite concluding that the higher-level taxonomy of the Scoliidae is in dire need of revision, we recommend that taxonomic changes be predicated on datasets that extend the geographic and taxonomic sampling of the current study.
CD39 Identifies Tumor-Reactive CD8 T cells in Patients With Lung Cancer
Authors: Chow Andrew , Uddin Fathema Z. , Mangarin Levi , Rizvi Hira , Dobrin Anton , Tischfield Sam , Quintanal-Villalonga Alvaro , Chan Joseph M. , Shah Nisargbhai , Allaj Viola , Manoj Parvathy , Mattar Marissa , Meneses Maximiliano , Liu Michael , Landau Rebecca , Ward Mariana , Kulick Amanda , Kwong Charlene , Wierzbicki Matthew , Yavner Jessica , Chavan Shweta S. , Farillas Abigail , Holland Aliya , Sridhar Harsha , Ciampricotti Metamia , Hirschhorn Daniel , Richards Allison L , Donoghue Mark T.A. , Heller Glenn , Klebanoff Christopher A. , Hellmann Matthew D. , de Stanchina Elisa , Sen Triparna , Wolchok Jedd D. , Merghoub Taha , Rudin Charles M.
Published: January 2022

The repertoire of tumor-infiltrating lymphocytes (TILs) can be vast, and many of these TILs are not endowed with tumor reactivity. While a number of reports have shown that tumor-reactive TILs express CD39, few reports have demonstrated that conversely, CD39 can be leveraged to serve as a proxy of tumor-reactive CD8 T cells. Using single-cell CITE/RNA/TCRseq, we show that CD39+ CD8 T cells in human lung cancers demonstrate transcriptional and proteomic features of exhaustion, tumor reactivity, and clonal expansion. Moreover, TCR cloning revealed that CD39 enriched for tumor-reactive CD8 T cell clones. Flow cytometry of 440 lung cancer specimens revealed that CD39 level on CD8 T cells is only weakly correlated with tumoral features that currently guide lung cancer therapy, such as histology, driver mutation, PD-L1 and tumor mutation burden. PD-1 axis blockade, but not cytotoxic chemotherapy, increased intratumoral CD39+ CD8 T cells. CD39 correlated with PD-1 expression on CD8 T cells and high pre-treatment/early-on-treatment levels were associated with improved clinical outcomes, but not immune-related adverse events, from immune checkpoint blockade therapy. This comprehensive profiling of the clinical, pathological and molecular features highlights the utility of CD39 as a proxy for tumor-reactive CD8 T cells in human lung cancer.
Bioinspired Stretchable Transducer for Wearable Continuous Monitoring of Respiratory Patterns in Humans and Animals
Authors: Cotur Yasin , Olenik Selin , Asfour Tarek , Bruyns-Haylett Michael , Kasimatis Michael , Tanriverdi Ugur , Gonzalez-Macia Laura , Lee Hong Seok , Kozlov Andrei S. , Güder Firat
Published: January 2022

We report a bio-inspired continuous wearable respiration sensor modeled after the lateral line system of fish which is used by the fish for detecting mechanical disturbances in the water. Despite the clinical importance of monitoring respiratory activity in humans and animals, continuous measurements of breathing patterns and rates are rarely performed in or outside of clinics. This is largely due to conventional sensors being too inconvenient or expensive for wearable sensing for most individuals and animals. The bio-inspired air-silicone composite transducer is placed on the chest and measures respiratory activity by continuously measuring the force applied to an air channel embedded inside a silicone-based elastomeric material. The force applied on the surface of the transducer during breathing changes the air pressure inside the channel which is measured using a commercial pressure sensor and mixed-signal wireless electronics. We extensively characterized the transducer produced in this work and tested it with humans, dogs, and laboratory rats. The bio-inspired air-silicone composite transducer may enable the early detection of a range of disorders that result in altered patterns of respiration. The technology reported can also be combined with artificial intelligence and cloud computing to algorithmically detect illness in humans and animals remotely, reducing unnecessary visits to clinics.