bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Nutritional Support Based on the Dietary Anti-Inflammatory Index on Cancer-Related Fatigue in Lung Cancer Patients Undergoing Chemotherapy
Authors: Zhang Yanmei , Cui Guanjun , Xiu Yang , Zhao Mei
Published: May 2022

Background

Cancer-related fatigue is one of the most common symptoms reported by cancer patients and is considered to be related to inflammation.

Objective

This study aimed to explore the effects of nutritional support based on the dietary anti-inflammatory index on cancer-related fatigue in lung cancer patients undergoing chemotherapy.

Methods

This was a randomized controlled trial with 106 lung cancer patients who were divided into either the anti-inflammatory diet group (n = 53) or the usual diet group (n = 53) for 3 months. The primary outcome was cancer-related fatigue. Secondary outcomes included high sensitivity C-reactive protein (hs-CRP) concentrations, nutritional status, and quality of life. Repeated-measures analysis of variance was used to examine the effectiveness of this intervention.

Results

The anti-inflammatory diet improved fatigue (−1.99 ± 1.78, P < .001), hs-CRP levels (−4.15 [−11.87, −0.58], P < .001), Patient-Generated Subjective Global Assessment (−2.53 ± 3.11, P = .030), and albumin concentrations (2.83 ± 0.59, P < .001) compared with the usual diet after 3 months. Simultaneously, in the repeated-measures analysis of variance, the differences in fatigue (F = 5.536, P < .001), hs-CRP levels (F = 6.918, P < .001), and albumin concentrations (F = 2.727, P = .048) were statistically significant for the group-by-time interaction.

Conclusion

The study provided evidence for the positive effect of nutritional support based on the dietary anti-inflammatory index on cancer-related fatigue, hs-CRP levels, nutritional status, and quality of life in lung cancer patients undergoing chemotherapy.

Implication for Practice

With an anti-inflammatory diet, nurses can help these patients improve their overall quality of life.
Symptom Profiles and Related Factors Among Breast Cancer Patients Undergoing Endocrine Therapy
Authors: Jing Feng , Zhu Zheng , Qiu Jiajia , Tang Lichen , Xu Lei , Xing Weijie
Published: May 2022

Background

To provide person-centered symptom management, the interindividual variability in breast cancer patients merits further exploration. However, how sociodemographic and clinical characteristics influence symptom profile membership in endocrine therapy for breast cancer is still unknown.

Objectives

This study aimed to explore symptom profiles of breast cancer patients undergoing endocrine therapy and to identify sociodemographic and clinical characteristics among symptom subgroup members.

Methods

A cross-sectional study was conducted, and participants were invited to complete a general information questionnaire and Functional Assessment of Cancer Therapy-Endocrine Subscale. Latent profile analysis, univariate analysis, and multinomial logistic regression were performed to explore symptom profiles and identify interindividual variability.

Results

Three distinct subgroups were identified: “all high” (9.8%), “all moderate but high sexual symptoms” (25.4%), and “all low” (64.8%). Age, body mass index, main payment source for medical expenses, type of endocrine therapy, and history of breast cancer treatment were factors that determined membership in these 3 symptom subgroups.

Conclusion

Patients’ demographic and clinical characteristics were associated with their endocrine therapy–related symptom profiles. In general, those younger in age who pay out of pocket for medical expenses, use aromatase inhibitors, present a history of chemotherapy, and have a higher body mass index have a greater risk of symptom burden.

Implication for Practice

The findings of this study will contribute to implementing individual cancer care based on the characteristics and needs of patient subgroups, which may improve the allocation of medical resources and provide interventions tailored to patients’ unique needs.
Adverse Childhood Experiences and Their Impact on Sleep in Adults
Authors: Vadukapuram Ramu , Shah Kaushal , Ashraf Sahar , Srinivas Sushma , Elshokiry Amir Bishay , Trivedi Chintan , Mansuri Zeeshan , Jain Shailesh
Published: May 2022

Adverse childhood experiences (ACEs) before the age of 18 years are pervasive and noteworthy public health concerns. The ACEs are associated with sleep disorders in later life. In this study, we conduct a systematic review to explore the effects of ACEs on sleep in adulthood. Using Medical Subject Headings keywords, we searched Medline, PubMed, PubMed Central, the American Psychological Association PsycArticles, and PsychInfo databases to evaluate the association between ACEs and sleep disturbances. ACEs increase the odds of developing chronic short sleep duration, that is, <6 hours of sleep per night compared with optimal sleep duration of 7–9 hours per night during adulthood. The ACEs are positively associated with poor sleep characteristics such as short sleep duration and long-term sleep problems. Clinicians should pay close attention to developmental trauma care, access community health programs, and help develop better coping skills, resiliency, and good sleep habits in their patients.
The How and the Why of Including Children: Experiential Learning in Teaching Physical Therapist Students
Authors: Wynarczuk Kimberly D. , Gagnon Kendra , Fiss Alyssa LaForme , Kendall Eydie , Schreiber Joseph , Rapport Mary Jane
Published: May 2022

Purpose:

This study describes experiential learning (EL) activities with children and the rationale for using EL. Experiential learning with children in entry-level doctor of physical therapy (DPT) education has not been described.

Methods:

Eighteen pediatric educators from accredited DPT programs participated in semistructured, in-depth interviews. Researchers analyzed written interview transcriptions using an iterative, consensus-building, thematic analysis approach.

Results:

Educators described their EL activities. Educators' rationale for using EL grouped around 4 themes: (1) EL is valued by multiple stakeholders, (2) EL provides an additional learning modality, (3) EL introduces students to pediatric physical therapy, and (4) EL addresses standards and competencies for DPT education.

Conclusions:

This research provides a rich description of EL with children and rationale for integrating EL in DPT education. These findings may inform educators and program directors regarding the value of EL and the investment of resources to support EL in DPT education.

Supplemental Video Abstract available

at: http://links.lww.com/PPT/A386
Programmed Death Ligand 1 (PD-L1) Expression and CD8+ Tumor-infiltrating Lymphocyte-based Tumor Immune Microenvironment Classification in Gynecologic Carcinosarcoma: Prognostic Impact and Implications for Therapy
Authors: Ordner Jeffrey , Gutierrez Amezcua Jose M. , Marcus Alan , Shukla Pratibha S.
Published: May 2022

To investigate the prevalence and prognostic significance of programmed death ligand-1 (PD-L1) expression and CD8+ tumor-infiltrating lymphocytes (TILs) in gynecologic carcinosarcoma, 81 cases (68 uterine, 12 ovarian, and 1 fallopian tube) were immunostained with PD-L1 and CD8 using tissue microarrays (3 mm core diameter) from intratumoral areas with the highest TILs. Tumor proportion score (TPS) ≥1% and combined positive score (CPS) ≥1 were considered positive for PD-L1. CD8+ TILs were counted in each core, and CD8+ TIL density (CD8TILD) was calculated. Cases were classified as CD8Neg (<1.4/mm2 CD8TILD), CD8Pos (≥1.4/mm2 CD8TILD) and CD8HIGH (≥14/mm2 CD8TILD) and grouped into 4 tumor immune microenvironment (TIME) groups: (1) PD-L-1Pos/CD8Pos, (2) PD-L1Neg/CD8Neg, (3) PD-L1Pos/CD8Neg, and (4) PD-L1Neg/CD8Pos. PD-L1 expression by TPS and CPS was detected in 19.8% and 39.6% cases, respectively. Kaplan-Meier curves with log-rank analysis showed that higher density of CD8+ TILs were associated with longer overall survival (OS) (P=0.05 for CD8Pos and P=0.014 for CD8HIGH), and CD8HIGH status was associated with longer OS irrespective of tumor stage (P=0.045, hazard ratio: 0.11, 95% confidence interval: 0.014–0.951). Thirty-three percent of patients belonged to TIME group 1. PD-L1 expression and TIME groups were not associated with OS or progression-free survival. We found that high density of CD8+ TILs is an independent indicator of better OS. In 33% cases PD-L1 expression is associated with increased CD8+ TILs (“acquired immune evasion” pattern of PD-L1 expression), hence they may benefit from anti PD-1/PD-L1 therapy. PD-L1 expression alone and TIME groups do not affect survival in gynecologic carcinosarcoma.
Volumetric Assessment of Hippocampus and Subcortical Gray Matter Regions in Alzheimer Disease and Amnestic Mild Cognitive Impairment
Authors: Topkan Tuğberk Andaç , Erdogan Nesrin , Barutcu Berrak , Cindil Emetullah , Tali E. Turgut , Karaman Yahya
Published: May 2022

Background:

Quantitative MRI assessment methods have limited utility due to a lack of standardized methods and measures for Alzheimer disease (AD) and amnestic mild cognitive impairment (aMCI).

Objective:

To employ a relatively new and easy-to-use quantitative assessment method to reveal volumetric changes in subcortical gray matter (GM) regions, hippocampus, and global intracranial structures as well as the diagnostic performance and best thresholds of total hippocampal volumetry in individuals with AD and those with aMCI.

Method:

A total of 74 individuals—37 with mild to moderate AD, 19 with aMCI, and 18 with normal cognition (NC)—underwent a 3T MRI. Fully automated segmentation and volumetric measurements were performed.

Results:

The AD and aMCI groups had smaller volumes of amygdala, nucleus accumbens, and hippocampus compared with the NC group. These same two groups had significantly smaller total white matter volume than the NC group. The AD group had smaller total GM volume compared with the aMCI and NC groups. The thalamus in the AD group showed a subtle atrophy. There were no significant volumetric differences in the caudate nucleus, putamen, or globus pallidus between the groups.

Conclusion:

The amygdala and nucleus accumbens showed atrophy comparable to the hippocampal atrophy in both the AD and aMCI groups, which may contribute to cognitive impairment. Hippocampal volumetry is a reliable tool for differentiating between AD and NC groups but has substantially less power in differentiating between AD and aMCI groups. The loss of total GM volume differentiates AD from aMCI and NC.
Pseudophaeobacter flagellatus sp. nov., isolated from coastal water
Authors: Guan Yong , Jiang Yue , Kim Young-Min , Yu Seung Yeob , Choi Seung-Hyeon , Choe Hanna , Li Zhun , Lee Mi-Kyung
Published: May 2022

A Gram-stain-negative, aerobic, motile, rod-shaped novel bacterial strain, designated as MA21411-1T, was isolated from the Korean coast. The colonies were white-yellow-coloured, smooth, convex and entire, spherical and 1.0–1.8 mm in diameter. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain MA21411-1T is closely related to species of the genus

Pseudophaeobacter

. The 16S rRNA gene sequence similarities between strain MA21411-1T and

Pseudophaeobacter arcticus

DSM 23566T,

Phaeobacter porticola

DSM 103148T and

Pseudophaeobacter leonis

DSM 25627T were 98.31, 97.80 and 97.28 %, respectively. Strain MA21411-1T has a draft genome size of 4 294 042 bp, annotated with 4125 protein-coding genes, and 53 tRNA, three rRNA and one tmRNA genes. The genomic DNA G+C content was 59.2 mol%. Comparative genome analysis revealed that the average nucleotide identity, digital DNA–DNA hybridization and average amino acid identity values among strain MA21411-1T and other related species were below the cut-off levels of 95, 70 and 95.5 %, respectively. The growth temperature range for growth was 15–28 °C (optimum, 25 °C), pH range was 6.0–9.0 (optimum, pH 6.0), and salt tolerance range was 0.5–4 % (optimum 0.5 %). Ubiquinone-10 was the sole quinone present in MA21411-1T and all three closely related strains. The major cellular fatty acid (>10 %) of the strain was summed feature 8 (C18 : 1
 ω7c and/or C18 : 1
 ω6c). The polar lipid profile contained phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and four unidentified polar lipids. Based on the phylogenetic tree, as well as phenotypic, chemotaxonomic and genomic features, strain MA21411-1T represents a novel species of the genus

Pseudophaeobacter

, for which the name Pseudophaeobacter flagellatus sp. nov. is proposed. The type strain is MA21411-1T (=KCTC 92095T=GDMCC 1.2988T).
Apilactobacillus zhangqiuensis sp. nov. and Apilactobacillus xinyiensis sp. nov., isolated from the gut of honeybee (Apis mellifera)
Authors: Li Ting Ting , Gu Chun Tao
Published: May 2022

Three Gram-stain-positive bacterial strains (designated F502-1T, F575-4T and F582-1) were isolated from the gut of honeybee (Apis mellifera). These strains were characterized using a polyphasic taxonomic approach. Results of 16S rRNA gene sequence analysis indicated that strain F502-1T was phylogenetically related to the type strains of

Apilactobacillus kunkeei

,

Apilactobacillus nanyangensis

and

Apilactobacillus apinorum

, having 98.7–99.9 % 16S rRNA gene sequence similarities, 84.6–92.5 % pheS sequence similarities and 95.2–99.0 % rpoA sequence similarities, and that strains F575-4T and F582-1 were closely related to the type strain of

Apilactobacillus ozensis

, having 99.7 and 99.4 % 16S rRNA gene sequence similarities, respectively. Strains F575-4T and F582-1 had less than 88.7 % pheS and 96.4 % rpoA sequence similarities to strain F502-1T and type strains of all

Apilactobacillus

species. The average nucleotide identity and digital DNA–DNA hybridization values between strains F502-1T, F575-4T, F582-1 and type strains of all

Apilactobacillus

species were less than 91.3 and 43.5 %, respectively, confirming that they represent two novel species within the genus

Apilactobacillus

. Based upon the data obtained in the present study, two novel species, Apilactobacillus zhangqiuensis sp. nov. and Apilactobacillus xinyiensis sp. nov., are proposed and the type strains are F502-1T (=JCM 34500T=CCTCC AB 2021026T) and F575-4T (=JCM 34501T=CCTCC AB 2021028T), respectively.
Accelerating single-cell genomic analysis with GPUs
Authors: Nolet Corey , Lal Avantika , Ilango Rajesh , Dyer Taurean , Movva Rajiv , Zedlewski John , Israeli Johnny
Published: May 2022

Single-cell genomic technologies are rapidly improving our understanding of cellular heterogeneity in biological systems. In recent years, technological and computational improvements have continuously increased the scale of single-cell experiments, and now allow for millions of cells to be analyzed in a single experiment. However, existing software tools for single-cell analysis do not scale well to such large datasets. RAPIDS is an open-source suite of Python libraries that use GPU computing to accelerate data science workflows. Here, we report the use of RAPIDS and GPU computing to accelerate single-cell genomic analysis workflows and present open-source examples that can be reused by the community.
Coupled Mutual Inhibition and Mutual activation motifs as tools for cell-fate control
Authors: Sabuwala Burhanuddin , Hari Kishore , Abhishek S V , Jolly Mohit Kumar
Published: May 2022

Multistability is central to biological systems as it plays a key role in adaptation, evolvability, and differentiation. Multistability can be achieved by integrating positive feedback loops into the regulation. The simplest of such feedback loops are a) a mutual inhibition (MI) loop, b) a mutual activation (MA) loop, and, c) self-activation. While it is established that all three motifs can give rise to bistability, the characteristic differences in the bistability exhibited by each of these motifs is relatively less understood. Here, we use ODE-based simulations across a large ensemble of parameter sets and initial conditions to study the characteristics of the bistability of these motifs and their limits in the parameter space. We also examine the behavior of these motifs under mutual degradation and self-activation. Finally, we investigate the utility of these motifs for achieving coordinated expression through cyclic and parallel coupling. Through our analysis, we found that MI-based architectures offer robustness in maintaining distinct multistability and allow for coordination among multiple genes. This coordination paves way for understanding the naturally occurring gene regulatory network and may also help in the better design of robust and controllable synthetic networks.
Types of occupational accidents and their predictors at construction sites in Lusaka city
Authors: Simutenda P. , Zambwe M. , Mutemwa R.
Published: May 2022

Objective

To determine the types of occupational accidents and their predictors at construction sites in Lusaka city.

Methods

A qualitative research design which explored the views, experiences, and beliefs of construction workers. A sample size of seven participants who were previously involved in at least one construction accident was drawn purposively. Data was collected by interviewing participants using a semi-structured interview schedule and a voice recorder. The data from the voice recorder was then transcribed in verbatim format. Thematic evaluation was used for data analysis.

Findings

Two themes were identified:- types of occupational accidents and predictors of accidents. The types of construction accidents included crane or hoist accidents, slips, and falls from heights, gas leaks, fires and explosions, forklift, trench, electrocutions, machinery, moving or failing object, caught-between and exposure to dangerous chemicals. Predictors of construction site accidents were mainly human factors and site conditions.

Conclusion

The study established the types of accidents and their predictors The types of accidents established can cause immerse human suffering and even death. Therefore, effective accident prevention policies need to be devised, adhered to and continuously reviewed.
Investigation of a SARS-CoV-2 outbreak in a Texas summer camp resulting from a single introduction
Authors: Swetnam Daniele M. , Alvarado R. Elias. , Sotcheff Stephanea , Mitchell Brooke M. , McConnell Allan , Machado Rafael R.G. , Saada Nehad , Haseltine Florence P. , Maknojia Sara , Smith Anajane , Ren Ping , Keiser Philip , Weaver Scott C. , Routh Andrew
Published: May 2022

SARS-CoV-2 is the etiological agent responsible for the COVID-19 pandemic. It is estimated that only 10 aerosol-borne virus particles are sufficient to establish a secondary infection with SARS-CoV-2. However, the dispersal pattern of SARS-CoV-2 is highly variable and only 10– 20% of cases are responsible for up 80% of secondary infections. The heterogeneous nature of SARS-CoV-2 transmission suggests that super-spreader events play an important role in viral transmission. Super-spreader events occur when a single person is responsible for an unusually high number of secondary infections due to a combination of biological, environmental, and/or behavioral factors. While super-spreader events have been identified as a significant factor driving SARS-CoV-2 transmission, epidemiologic studies have consistently shown that education settings do not play a major role in community transmission. However, an outbreak of SARS-CoV-2 was recently reported among 186 children (aged 10-17) and adults (aged 18 +) after attending an overnight summer camp in Texas in June 2021. To understand the transmission dynamics of the outbreak, RNA was isolated from 36 nasopharyngeal swabs collected from patients that attended the camp and 19 control patients with no known connection to the outbreak. Genome sequencing on the Oxford Nanopore platform was performed using the ARTIC approaches for library preparation and bioinformatic analysis. SARS-CoV-2 amplicons were produced from all RNA samples and >70% of the viral genome was successfully reconstructed with >10X coverage for 46 samples. Phylogenetic methods were used to estimate the transmission history and suggested that the outbreak was the result of a single introduction. We also found evidence for secondary transmission from campers to the community. Together, these findings demonstrate that super-spreader events may occur during large gatherings of children.
Subthreshold Nanosecond Laser Treatment of Intermediate AMD without Reticular Pseudodrusen: Real-world Three-year Follow-up Study
Authors: Worsley David R. , Louise Jennie , Bull Susan P.
Published: May 2022

Purpose

Subthreshold nanosecond laser (SNL) has been proposed to reduce the risk of intermediate age-related macular degeneration (iAMD) progressing to late AMD. The phase 3 LEAD Study post-hoc analysis indicates a potentially large benefit from SNL treatment of eyes without reticular pseudodrusen. This real-world study reports the three-year outcomes of SNL treatment of iAMD without RPD.

Methods

An observational retrospective single-centre cohort study of all patients with iAMD, centre-involving very large soft drusen (≥250 μm diameter) without RPD, treated with SNL and with three-year follow up. The primary outcome measured was progression to late AMD; neovascular AMD (nAMD) or geographic atrophy (GA).

Results

There were 120 eyes of 64 patients. At baseline, the cohort had a high risk profile; drusen median area, volume and largest diameter were 0.70mm2(IQR: 0.20 to 1.50), 0.03mm3(IQR: 0.01 to 0.08) and 835μm (IQR: 446.50 to 1398.50) respectively; hyperreflective foci were present in 56.67%; and hyporeflective drusen cores in 25.83%. Eyes had a mean of 3.03 treatments. By three years, progression to late AMD occurred in 5.83% of eyes, all to GA. Visual acuity was stable or improved in 80% of eyes.

Conclusion

The three-year progression rate was low compared with published 36-month natural histories of iAMD without RPD. The progression rate was similar to the LEAD study SNL-treated group of iAMD without RPD. This study supports the hypothesis that SNL for iAMD without RPD may reduce progression to late AMD. Further investigation is warranted.
A completeness indicator of gestational and congenital syphilis information in Brazil
Authors: de Oliveira Guilherme Lopes , Ferreira Andrêa JF , Guilherme Santana José , Lana Raquel Martins , Cardoso Andrey Moreira , Teles Carlos , Fiaccone Rosemeire L. , Aquino Rosana , Santos Soares Maria Auxiliadora , Paixão Enny S. , dos Santos Idália Oliveira , Salvi Leonardo , Barreto Mauricio L. , Ichihara Maria Yury
Published: May 2022

Objective

To evaluate the quality of information on gestational syphilis (GS) and congenital syphilis (CS) on the Notifiable Diseases Information System (SINAN-Syphilis Brazil) by compiling and validating completeness indicators between 2007 and 2018.

Materials and methods

Overall, care and socioeconomic completeness scores were compiled based on selected variables, using weights assigned by specialists. The completeness scores were analysed, considering the region and area of residence, pregnant race/colour, and year of case notification. Pearson’s correlation coefficients were used to validate the scores obtained by the weighted average method, compared with the values obtained through principal component analysis (PCA).

Result

Most of the variables selected presented a good or excellent degree of completeness for GS and CS, except for clinical classification, pregnant woman’s level of education, partner’s treatment, and child’s race/colour, which were classified as poor or very poor. The overall (89.93% versus 89.69%) and socioeconomic (88.71% versus 88.24%) completeness scores for GS and CS, respectively, were classified as regular, while the care score (GS-90, 88%, and CS-90, 72%) was good, although there were improvements over time. Differences in the overall, care and socioeconomic completeness scores according to region, area of residence, and ethnic-racial groups were reported for syphilis notifications. A strong linear correlation (>0.90) was observed between the completeness scores estimated through the weighted average method and PCA.

Conclusion

Improvements in the completeness of GS and CS notifications have been observed in recent years, highlighting the variables which form the care score, compared to the socioeconomic scores, despite differences between regions, area of residence, and ethnic-racial groups. The weighted average was a viable methodological alternative easily operationalised to estimate data completeness scores, allowing routine monitoring of the completeness of gestational and congenital syphilis records.
Specifying uniform eligibility criteria to strengthen causal inference studies of long-term outcomes of COVID-19
Authors: Erqou Sebhat , Zullo Andrew R , Jiang Lan , Khetpal Vishal , Berkowitz Julia , Shah Nishant R. , Echouffo-Tcheugui Justin B. , Rudolph James L. , Choudhary Gaurav , Wu Wen-Chih
Published: May 2022

Background

Causal interpretation of findings from existing epidemiological studies on long-term clinical outcomes of coronavirus disease 2019 (COVID-19) may be limited by the choice of comparator (control) group.

Objective

We compare two approaches to control group selection (based on requirement for negative SARS-CoV-2 test for eligibility) in long-term clinical outcomes after COVID-19 in patients with history of heart failure (HF).

Design

Retrospective cohort study using data from February 1, 2020 to July 31, 2021. Setting: Veteran Health Administration (VHA).

Participants

We studied two cohorts of Veterans with COVID-19 and history of HF which selected comparison group using two different approaches. In Cohort I, Veterans with HF who tested for positive for SARS-CoV-2 were age, sex, and race matched to Veterans with no evidence of COVID-19 in 1:5 ratio. In Cohort II Veterans with HF who tested positive for SARS-CoV-2 were age, sex, and race matched with Veterans with HF who tested negative for SARS-CoV-2 within +/-15 days of the positive test date within the same VHA facility.

Exposure

COVID-19 as determined by a positive SARS-CoV-2 test.

Main Outcomes and Measures

1-year all-cause mortality and hospital admissions beyond the first 30 days after COVID-19 diagnosis. Adjusted hazard ratios (HRs) accounting for comorbidity and 95% confidence intervals were calculated.

Results

Cohort I comprised 13,722 Veterans with HF with COVID-19 (mean [SD] age 72.0 [10.2] years, 2.4% female, 71.1% White) and 60,956 matched controls not known to have COVID-19. Cohort II comprised 6,725 Veterans with HF with COVID-19 (mean [SD] age 72.5 [7.5] years, 0.1% female, 80.8% White) and 6,726 matched controls with negative SARS-CoV-2 test. The adjusted HRs for 1-year mortality and hospital admission beyond the first 30 days after diagnosis of COVID-19 were 1.40 (1.32-1.49) and 1.34 (1.28-1.41), respectively, in analysis of Cohort-I (where the comparator group was not required to test negative for SARS-CoV-2). However, in Cohort-II (using the second comparator group specifying negative SARS-CoV-2 test for eligibility), the associations were markedly attenuated; adjusted HRs 1.05 (0.95-1.17) and 1.07 (0.96-1.19), respectively.

Conclusions

We found significant attenuation of associations between COVID-19 and long-term risk of mortality and hospital admissions beyond the first 30 days among patient with existing HF, when comparing with a control group selected based on a negative SARS-CoV-2 test versus control group not known to have COVID-19. The findings have implications for the design of studies of long-term CVD (and non-CVD) outcome of COVID-19.
Adverse PFAS effects on mouse oocyte in vitro maturation are associated with carbon-chain length and inclusion of a sulfonate group
Authors: Feng Jianan , Soto-Moreno Edgar J. , Prakash Aashna , Balboula Ahmed Z. , Qiao Huanyu
Published: May 2022

Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals that are used in products such as non-stick cookware, stain-resistant coating, and food packaging. PFAS are characterized by their fluorinated carbon chains that make them hard to degrade and bioaccumulate in human and animals. Toxicological studies have shown PFAS toxic effects: cytotoxicity, immunotoxicity, neurotoxicity, and reproductive toxicity. Two major categories of PFAS are perfluoroalkyl carboxylic acid (PFCA) and perfluoroalkyl sulfonic acid (PFSA). In this study, we used a mouse-oocyte-in-vitro-maturation (IVM) system to study how the structures of PFAS, such as carbon-chain length and functional groups, determine their reproductive toxicity. We found the toxicity of PFAS is elevated with increasing carbon-chain length and the inclusion of the sulfonate group. Specifically, at 600 µM, perfluorohexanesulfonic acid (PFHxS) and perfluorooctanesulfonic acid (PFOS) reduced the rates of both germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) as well as induced the formation of relatively large polar bodies. However, the shorter PFSA, perfluorobutanesulfonic acid (PFBS), and all PFCA did not show similar adverse cytotoxicity. We further examined mitochondria and cytoskeleton, two essential factors for cell division, in PFOS- and PFHxS-treated oocytes. We found that 600 µM PFHxS and PFOS exposure induced excess reactive oxygen species (ROS) and decreased mitochondrial membrane potential (MMP). Cytoskeleton analysis revealed that PFHxS and PFOS exposure induced chromosome misalignment, abnormal F-actin organization, elongated the spindle formation, and symmetric division in the treated oocytes. Together, our study provides new information on the structure-toxicity relationship of PFAS.

Synopsis

Reproductive toxicity of PFAS, a group of persistent organic pollutants, is determined by their chemical structures.
The Arabidopsis ATP-Binding Cassette E protein ABCE2 is a conserved component of the translation machinery
Authors: Navarro-Quiles Carla , Mateo-Bonmatí Eduardo , Candela Héctor , Robles Pedro , Martínez-Laborda Antonio , Fernández Yolanda , Šimura Jan , Ljung Karin , Rubio Vicente , Ponce María Rosa , Micol José Luis
Published: May 2022

ATP-Binding Cassette E (ABCE) proteins dissociate cytoplasmic ribosomes after translation terminates, and contribute to ribosome recycling, thus linking translation termination to initiation. This function has been demonstrated to be essential in animals, fungi, and archaea, but remains unexplored in plants.

In most species, ABCE is encoded by a single-copy gene; by contrast,Arabidopsis thalianahas twoABCEparalogs, of whichABCE2seems to conserve the ancestral function. We isolatedapiculata7-1 (api7-1), a viable, hypomorphic allele ofABCE2,which has a pleiotropic morphological phenotype reminiscent of mutations affecting ribosome biogenesis factors and ribosomal proteins. We also studiedapi7-2, a null, recessive lethal allele ofABCE2.

Co-immunoprecipitation experiments showed that ABCE2 physically interacts with components of the translation machinery. An RNA-seq study of theapi7-1mutant showed increased responses to iron and sulfur starvation. We also found increased transcript levels of genes related to auxin signaling and metabolism.

Our results support a conserved role for ABCE proteins in ribosome recycling in plants, as previously shown for the animal, fungal, and archaeal lineages. In plants, the ABCE2 protein seems important for general growth and vascular development, likely due to an indirect effect through auxin metabolism.
The energy landscape reshaped by strain-specific mutations underlies the long-range epistasis in NS1 evolution of influenza A virus
Authors: Kim Iktae , Dubrow Alyssa , Zuniga Bryan , Zhao Baoyu , Sherer Noah , Bastiray Abhishek , Li Pingwei , Cho Jae-Hyun
Published: May 2022

The mechanisms underlying how individual mutations affect the protein energy landscape are crucial for understanding how proteins evolve. However, predicting mutational effects remains challenging because of epistasis—the nonadditive interactions between mutations. Here, we investigate the biophysical mechanism of strain-specific epistasis in the nonstructural protein 1 (NS1) of the influenza A virus (IAV). To understand the molecular basis of epistasis, we conducted comprehensive analyses of four NS1s of IAV strains that emerged between 1918 and 2004. We find that strain-specific mutations of NS1s are near-neutral with respect to the association with the p85β subunit of PI3K. However, the individual residues on the p85β-binding interface show long-range epistatic interactions with strain-specific mutations. We reveal that strain-specific mutations reshaped the energy landscape of NS1, leading to long-range epistasis. Our findings offer a high-resolution mechanism of how near-neutral mutations silently alter the biophysical energy landscapes, resulting in diverse background effects during molecular evolution.
Free meals during breeding: increased resource access does not benefit Arcic-nesting shorebirds
Authors: Montagano Laurent , Lecomte Nicolas
Published: May 2022

Abstract

Arctic ecosystems are facing intensifying impacts of climate change, notably an increase in air temperature that can boost local productivity. Yet whether such resource surge can benefit declining migratory birds is unclear. Here we experimentally increased prey abundance and measure its effect on the body condition, nesting patterns, and nesting success of the white-rumped sandpiper (Calidris fuscicollis). We captured females at the beginning and at the end of their incubation to assess body condition and we installed small temperature probes inside their nests to measure their incubation recess. To estimate nest survival, we regularly monitored experimental and control nests during two consecutive summers (2016–2017). For both experimental years with contrasting nest success (73% vs. 21%), we found no evidence of an effect of our supplementation experiment mimicking an increased abundance of arthropods in the Canadian Arctic. This suggests that in situ resources are not limiting during incubation. Breeding strategies and success in shorebirds seem to be driven by inter-individual traits related to body condition upon the initiation of incubation.
CAR-T Engager Proteins Optimize Anti-CD19 CAR-T Cell Therapies for Lymphoma
Authors: Su Lihe , Wu Lan , Lobb Roy R. , Rennert Paul D. , Ambrose Christine
Published: May 2022

B cell lymphoma therapy has been transformed by CD19-targeting cellular therapeutics that induce high clinical response rates and impressive remissions in relapsed and refractory patients. However, approximately half of all patients who respond to CD19-directed cell therapy relapse, the majority within six months. One characteristic of relapse is loss or reduction of CD19 expression on malignant B cells. We designed a unique therapeutic to prevent and reverse relapses due to lost or reduced CD19 expression. This novel biologic, a CAR T Engager, binds CD20 and displays the CD19 extracellular domain. This approach increases the apparent CD19 antigen density on CD19-positive/CD20-positive lymphoma cells, and prevents CD19 antigen-oss induced relapse, as CD19 bound to CD20 remains present on the cell surface. We demonstrate that this novel therapeutic prevents and reverses lymphoma relapse in vitro and prevents CD19-negative lymphoma growth and relapse in vivo.
Reticular Adhesion Formation is Mediated by Flat Clathrin Lattices and Opposed by Fibrillar Adhesions
Authors: Hakanpää Laura , Abouelezz Amr , Lenaerts An-Sofie , Culfa Seyda , Algie Michael , Bärlund Jenny , Katajisto Pekka , McMahon Harvey T. , Almeida-Souza Leonardo
Published: May 2022

Reticular adhesions (RAs) consist of integrin αvβ5 and harbor flat clathrin lattices (FCLs), long-lasting structures with similar molecular composition to clathrin mediated endocytosis (CME) carriers. Why FCLs and RAs colocalize is not known. Here, we show that FCLs assemble RAs in a process controlled by fibronectin (FN) and its receptor, integrin αvβ5. We observed that cells on FN-rich matrices displayed fewer FCLs and RAs. CME machinery inhibition abolished RAs and live-cell imaging showed that RA establishment requires FCL co-assembly. The inhibitory activity of FN was mediated by the activation of integrin α5β1 at Tensin1-positive fibrillar adhesions. Conventionally, endocytosis disassembles cellular adhesions by internalization of their components. Our results present a novel paradigm in the relationship between these two processes by showing that endocytic proteins can actively function in the assembly of cell adhesions. Furthermore, we show this novel adhesion assembly mechanism is coupled to cell migration via a unique crosstalk between cell matrix adhesions.
Spatially Resolved Metabolites in Stable and Vulnerable Human Atherosclerotic Plaques Identified by Mass Spectrometry Imaging
Authors: Seeley Erin H. , Liu Zhipeng , Yuan Shuai , Stroope Chad , Cockerham Elizabeth , Rashdan Nabil , Finney Alexandra C , Kumar Dhananjay , Das Sandeep , Razani Babak , Liu Wanqing , Traylor James , Rom Oren , Pattillo Christopher , Yurdagul Arif
Published: May 2022

Impairments in carbohydrate, lipid, and amino acid metabolism drive features of plaque instability. However, where these impairments occur within the atheroma remains largely unknown. Therefore, we sought to characterize the spatial distribution of metabolites within stable and unstable atherosclerosis in both the fibrous cap and necrotic core. Atherosclerotic tissue specimens were scored based on the Stary classification scale and subdivided into stable and unstable atheromas. After performing mass spectrometry imaging (MSI) on these samples, we identified over 850 metabolite-related peaks. Using MetaboScape, METASPACE, and HMDB, we confidently annotated 170 of these metabolites and found over 60 of these were different between stable and unstable atheroma. We then integrated these results with an RNA-sequencing dataset comparing stable and unstable human atherosclerosis. Upon integrating our MSI results with the RNA-seq dataset, we discovered that pathways related to lipid metabolism and long-chain fatty acids were enriched in stable plaques, whereas reactive oxygen species, aromatic amino acid, and tryptophan metabolism were increased in unstable plaques. Acylcarnitines and acylglycines were increased in stable plaques whereas tryptophan metabolites were enriched in unstable plaques. Evaluating spatial differences in stable plaques revealed lactic acid in the necrotic core, whereas pyruvic acid was elevated in the fibrous cap. In unstable plaques, 5-hydroxyindole-acetic acid was enriched in the fibrous cap. Our work herein represents the first step to defining an atlas of metabolic pathways involved in plaque destabilization in human atherosclerosis. We anticipate this will be a valuable resource and open new avenues of research in cardiovascular disease.

GRAPHICAL ABSTRACT
Thymus Antibody-Secreting Cells Represent a Tissue Specific Population That Possess an Activated Cellular Phenotype
Authors: Pioli KimAnh T. , Lau Kin H. , Pioli Peter D.
Published: May 2022

Antibody-secreting cells (ASCs) are key contributors to humoral immunity through immunoglobulin production and the potential to be long-lived. ASCs have been recently identified in the thymus (THY) which is of interest as autoreactive THY B cells regulate T cell tolerance. Here, we showed that the young female THY was skewed towards higher production of ASCs relative to males. However, these differences disappeared with age. Intravenous labeling combined with blockade of CD154(CD40L) suggested that THY ASCs were generatedin situin a T cell dependent fashion. Single cell RNA-sequencing revealed that THY ASCs possessed a transcriptional signature indicative of interferon signaling and activation. Flow cytometry confirmed that THY ASCs had increased levels of Toll-like receptor 7 as well as the activation markers CD69 and major histocompatibility class II. Overall, THY ASCs are a unique population that require further investigation to fully appreciate their biological significance.
Diminished motor neuron activity driven by abnormal astrocytic GLAST glutamate transporter activity in spinal muscular atrophy is not fully restored after lentiviral SMN delivery
Authors: Welby Emily , Ebert Allison D.
Published: May 2022

Spinal muscular atrophy (SMA) is a pediatric neuromuscular disease characterized by the loss of the lower spinal motor neurons due to survival motor neuron (SMN) deficiency. Motor neuron dysfunction at the glutamatergic afferent synapse is observed during early stages of SMA disease progression, which could be targeted therapeutically prior to cell death. However, the motor neuron cell autonomous and non-cell autonomous disease mechanisms driving this phenotype remain unclear. Our study reveals a non-cell autonomous SMN-associated disease mechanism affecting glutamate transporter (GLAST) activity in astrocytes that contributes to human motor neuron dysfunction in SMA. Transcriptomic analysis of SMA patient human induced pluripotent stem cell (iPSC)-derived astrocytes identified a significant downregulation of genes associated with astrocytic regulation of the synapse, including glutamate neurotransmission. This finding was substantiated by our microelectrode array analysis of motor neuron activity, which was severely diminished specifically in the presence of patient-derived astrocytes. Co-culturing patient-derived motor neurons with healthy-derived astrocytes showed comparable firing rates and bursting activity to healthy-derived motor neurons, suggesting diminished neural activity is an astrocyte-mediated phenotype in this system. Towards defining astrocyte-intrinsic defects that could induce motor neuron dysfunction, we identified abnormally low levels of excitatory amino acid transporter (EAAT1/GLAST) in patient-derived astrocytes, which when selectively inhibited in healthy co-cultures could phenocopy the diminished neural activity previously observed in patient-derived co-cultures. Caveolin-1, an SMN-interacting lipid raft protein associated with glutamate transporter regulation, showed increased protein levels and accumulation in patient astrocytes. Both GLAST and caveolin-1 phenotypes could be partially rescued via lentiviral-mediated SMN re-expression in patient astrocytes. Together, our work defines a novel SMN-associated disease mechanism involving abnormal glutamate transporter activity and regulation in astrocytes that can directly diminish motor neuron function in SMA.
Ultra high-throughput whole-genome methylation sequencing reveals trajectories in precancerous polyps to early colorectal adenocarcinoma
Authors: Lee Hayan , Krieger Gat , Clark Tyson , Khan Aziz , Hanson Casey Ryan , Zhu Yizhou , Bararpour Nasim , Horning Aaron M. , Esplin Edward D. , Nevins Stephanie , Weimer Annika K. , Meiri Eti , Gilad Shlomit , Benjamin Sima , Lebanony Danit , Iremadze Nika , Oberstrass Florian , Jaimovich Ariel , Greenleaf William , Ford James M. , Lipson Doron , Shipony Zohar , Snyder Michael P.
Published: May 2022

Aberrant shifts in DNA methylation have long been regarded as an early marker for cancer onset and progression. To chart DNA methylation changes that occur during the transformation from normal healthy colon tissue to malignant colorectal cancer (CRC), we collected over 50 samples from 15 familial adenomatous polyposis (FAP) and non-FAP colorectal cancer patients, and generated 30-70x whole-genome methylation sequencing (WGMS) runs via the novel Ultima Genomics ultra high-throughput sequencing platform. We observed changes in DNA methylation that occur early in the malignant transformation process, in gene promoters and in distal regulatory elements. Among these changes are events of hyper-methylation which are associated with a bivalent “poised” chromatin state at promoters and are CRC-specific. Distal enhancers show nonlinear dynamics, lose methylation in the progression from normal mucosa to dysplastic polyps but regain methylation in the adenocarcinoma state. Enhancers that gain chromatin accessibility in the adenocarcinoma state and are enriched with HOX transcription factor binding sites, a marker of developmental genes. This work demonstrates the feasibility of generating large high quality WGMS data using the Ultima Genomics platform and provides the first detailed view of methylation dynamics during CRC formation and progression in a model case.
The Network Zoo: a multilingual package for the inference and analysis of biological networks
Authors: Guebila Marouen Ben , Wang Tian , Lopes-Ramos Camila M. , Fanfani Viola , Weighill Deborah , Burkholz Rebekka , Schlauch Daniel , Paulson Joseph N. , Altenbuchinger Michael , Sonanwane Abhijeet , Lim James , Calderer Genis , van Ijzendoorn David , Morgan Daniel , Marin Alessandro , Chen Cho-Yi , Song Alex , Shutta Kate , DeMeo Dawn , Padi Megha , Platig John , Kuijjer Marieke L. , Glass Kimberly , Quackenbush John
Published: May 2022

Inference and analysis of cellular biological networks requires software tools that integrate multi-omic data from various sources. The Network Zoo (netZoo; netzoo.github.io) is an open-source software suite to model biological networks, including context-specific gene regulatory networks and multi-omics partial correlation networks, to conduct differential analyses, estimate community structure, and model the transitions between biological states. The netZoo builds on our ongoing development of network methods, harmonizing the implementations in various computing languages (R, Python, MATLAB, and C) and between methods to allow a better integration of these tools into analytical pipelines. To demonstrate the value of this integrated toolkit, we analyzed the multi-omic data from the Cancer Cell Line Encyclopedia (CCLE) by inferring gene regulatory networks for each cancer cell line and associating network features with other phenotypic attributes such as drug sensitivity. This allowed us to identify transcription factors that play a critical role in both drug resistance and cancer development in melanoma. We also used netZoo to build a pan-cancer, multi-tiered CCLE map and used it to identify known metabolic hallmarks of cancer and to estimate novel context-specific elements that mediate post-transcriptional regulation. Because the netZoo tools are open-source and there is a growing community of both users and developers, we built an ecosystem to support community contributions, share use cases, and visualize networks online. As additional data types become available and our suite of methods grows, we will expand “the zoo” to incorporate an increasingly sophisticated collection of tools for network inference and analysis.