bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystal Mush Growth and Collapse on a Steep Wall: The Marginal Border Series of the Skaergaard Intrusion, East Greenland
Authors: Holness Marian B , Humphreys Madeleine C S , Namur Olivier , Andersen Jens C Ø , Tegner Christian , Nielsen Troels F D
Published: December 2021

The Skaergaard Intrusion of East Greenland solidified as a closed system, with the development of progressively more fractionated material at the roof, floor and vertical walls of the magma chamber. We argue, using field observations of the exposed western margin together with detailed microstructural and geochemical analysis, that the mush on the vertical walls of the Skaergaard Intrusion reached a maximum thickness of ~180 m, and was highly unstable. Material was lost both continuously, due to non-retention of poorly consolidated material, and during episodic collapse events. The almost complete absence in the wall rocks of material formed in LZc times (following the saturation of the bulk magma in Fe-Ti oxides) was likely to have been caused by a collapse event, perhaps related to faulting of the actively extending Greenlandic margin. A second major collapse of the MBS occurred during the later stages of solidification, with the greatest loss of material occurring in a region of the wall with an unusually thick mush, creating a transient and localised increase in the thickness of the floor mush. This work demonstrates the importance of vertical walls in supplying loose, disaggregated material to form mobile magmatic slurries that may contribute to floor cumulates or be entrained and erupted in long-lived systems.
Key characteristics including sex, sexual orientation and internet use associated with worse mental health among university students in Brazil and implications
Authors: de Paula Waléria , Pereira João Marcos , Guimarães Nathalia Sernizon , Godman Brian , Nascimento Renata Cristina Rezende Macedo do , Meireles Adriana Lúcia
Published: December 2021

Background

The symptoms of anxiety and depression disorders are multifactorial and can trigger a series of problems especially among university students. The aim of this study was to assess the prevalence and associated factors with anxiety and depression symptoms among first-semester university students at a Federal University in Brazil given the paucity of such data and the first semester is the most stressfultime.

Methods

Cross-sectional study with first-semester university students. The questionnaire included socio-demographic variables, lifestyles, health conditions and the Depression Anxiety Stress Scales. Descriptive analysis was performed, followed by bivariate analysis and Poisson regression analysis.

Results

Three hundred and fifty-six students (65.2%) across a range of courses in their first semester participated. The prevalence of anxiety was 42.5% and depression 33.2%. Regarding symptoms of anxiety and depression disorders, a positive association was observed among females, non-heterosexual, non-white skin color, excessive internet use, lack of physical activity, not attending university parties, having psychological counseling, history of anxiety in first- or second-degree relatives, poor self-rated health and use of psychotropic medicines.

Conclusions

Due to the high prevalence of anxiety and depression symptoms, the importance of developing programs to promote mental and physical health of university students is highlighted.
Dicalcium silicate-induced mitochondrial dysfunction and autophagy-mediated macrophagic inflammation promotes osteogenic differentiation of BMSCs
Authors: Luo Qianting , Li Xingyang , Zhong Wenchao , Cao Wei , Zhu Mingjing , Wu Antong , Chen Wanyi , Ye Zhitong , Han Qiao , Natarajan Duraipandy , Pathak Janak L , Zhang Qingbin
Published: December 2021

Dicalcium silicate (Ca2SiO4, C2S) has osteogenic potential but induces macrophagic inflammation. Mitochondrial function plays a vital role in macrophage polarization and macrophagic inflammation. The mitochondrial function of C2S-treated macrophages is still unclear. This study hypothesized: (i) the C2S modulates mitochondrial function and autophagy in macrophages to regulate macrophagic inflammation, and (ii) C2S-induced macrophagic inflammation regulates osteogenesis. We used RAW264.7 cells as a model of macrophage. The C2S (75–150 μg/ml) extract was used to analyze the macrophagic mitochondrial function and macrophage-mediated effect on osteogenic differentiation of mouse bone marrow-derived mesenchymal stem cells (BMSCs). The results showed that C2S extract (150 μg/ml) induced TNF-α, IL-1β and IL-6 production in macrophages. C2S extract (150 μg/ml) enhanced reactive oxygen species level and intracellular calcium level but reduced mitochondrial membrane potential and ATP production. TEM images showed reduced mitochondrial abundance and altered the mitochondrial morphology in C2S (150 μg/ml)-treated macrophages. Protein level expression of PINK1, Parkin, Beclin1 and LC3 was upregulated but TOMM20 was downregulated. mRNA sequencing and KEGG analysis showed that C2S-induced differentially expressed mRNAs in macrophages were mainly distributed in the essential signaling pathways involved in mitochondrial function and autophagy. The conditioned medium from C2S-treated macrophage robustly promoted osteogenic differentiation in BMSCs. In conclusion, our results indicate mitochondrial dysfunction and autophagy as the possible mechanism of C2S-induced macrophagic inflammation. The promotion of osteogenic differentiation of BMSCs by the C2S-induced macrophagic inflammation suggests the potential application of C2S in developing immunomodulatory bone grafts.
Altered functional connectivity density and couplings in postpartum depression with and without anxiety
Authors: Cheng Bochao , Zhou Yushan , Kwok Veronica P Y , Li Yuanyuan , Wang Song , Zhao Yajun , Meng Yajing , Deng Wei , Wang Jiaojian
Published: December 2021

Postpartum depression (PPD) is the most common psychological health issue among women, which often comorbids with anxiety (PPD-A). PPD and PPD-A showed highly overlapping clinical symptoms. Identifying disorder-specific neurophysiological markers of PDD and PPD-A is important for better clinical diagnosis and treatments. Here, we performed functional connectivity density (FCD) and resting-state functional connectivity (rsFC) analyses in 138 participants (45 unmedicated patients with first-episode PPD, 31 PDD-A patients and 62 healthy postnatal women, respectively). FCD mapping revealed specifically weaker long-range FCD in right lingual gyrus (LG.R) for PPD patients and significantly stronger long-range FCD in left ventral striatum (VS.L) for PPD-A patients. The follow-up rsFC analyses further revealed reduced functional connectivity between dorsomedial prefrontal cortex (dmPFC) and VS.L in both PPD and PPD-A. PPD showed specific changes of rsFC between LG.R and dmPFC, right angular gyrus and left precentral gyrus, while PPD-A represented specifically abnormal rsFC between VS.L and left ventrolateral prefrontal cortex. Moreover, the altered FCD and rsFC were closely associated with depression and anxiety symptoms load. Taken together, our study is the first to identify common and disorder-specific neural circuit disruptions in PPD and PPD-A, which may facilitate more effective diagnosis and treatments.
Clinical predictors of working memory performance in obstructive sleep apnea patients before and during extended wakefulness
Authors: Stevens David , D’Rozario Angela , Openshaw Hannah , Bartlett Delwyn , Rae Caroline D , Catcheside Peter , Wong Keith , Doug McEvoy R , Grunstein Ronald R , Vakulin Andrew
Published: December 2021

Study Objectives

Extended wakefulness (EW) and obstructive sleep apnea (OSA) impair working memory (WM), but their combined effects are unclear. This study examined the impact of EW on WM function in OSA patients and identified clinical predictors of WM impairment.

Methods

Following polysomnography (PSG), 56 OSA patients (mean ± SD, age 49.5 ± 8.9, apnea hypopnea index 38.1 ± 25.0) completed WM 2-back performance tasks 10 times over 24 h of wakefulness to assess average accuracy and completion times measured after 6–12 h awake (baseline) compared to 18–24 h awake (EW). Hierarchical cluster analysis classified participants with poorer versus better WM performance at baseline and during EW. Clinical predictors of performance were examined via regression and receiver operator characteristic (ROC) analyses.

Results

WM performance decreased following EW and showed consistent correlations with age, Epworth Sleepiness Score (ESS), total sleep time, and hypoxemia (O2 nadir and mean O2 desaturation) at baseline and with EW (all p < .01). O2 nadir and age were significant independent predictors of performance at baseline (adjusted R2 = 0.30, p < .01), while O2 nadir and ESS were predictors of WM following EW (adjusted R2 = 0.38, p < .001). ROC analysis demonstrated high sensitivity and specificity of models to predict poorer versus better performing participants at baseline (83% and 69%) and during EW (84% and 74%).

Conclusions

O2 nadir, age, and sleepiness show prognostic value for predicting WM impairment in both rested and sleep-deprived OSA patients and may guide clinicians in identifying patients most at risk of impaired WM under both rested and heightened sleep pressure conditions.

Clinical Trial Registration: This manuscript presents data collected as part of a larger trial—ANZCTR: Novel brain biomarkers of performance impairment in sleep apnea—https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363830, No. ACTRN12613001171707.
Polygamous settlors: When is a wife not a wife?
Authors: Cope Rowan
Published: December 2021

Wealthy nationals of countries outside of Europe, including in the Middle East, are beginning to discover the wealth preservation and succession planning advantages that discretionary trusts can afford them. Whilst this is positive for practitioners, the clash of cultures can cause difficulties for trustees (and their advisers) who are used to administering trusts for western traditional families. Not infrequently, settlors in this new cohort are nationals of countries which either expressly permit or tacitly tolerate polygamy. This article draws attention to the ambiguity around the recognition of such marriages in England and related jurisdictions, and the potential problems this may pose for trustees.
A “Hired Girl” Testifies Against the “Son of a Prominent Family”: Bastardy and Rape on the Nineteenth-Century Nebraska Plains
Authors: Devlin Donna Rae
Published: December 2021

In Red Cloud, Nebraska, in 1887, Anna “Annie” Sadilek (later Pavelka) pressed bastardy charges against the “son of a prominent family,” even though she could have, according to her pre-trial testimony, pressed charges for rape. To the literary world, Sadilek is better known as Ántonia Shimerda, the powerful protagonist in Willa Cather’s 1918 novel, My Ántonia. However, it is Sadilek’s real-life experience that allows us to better understand life on the Nebraska Plains, specifically through an examination of the state’s rape laws and the ways these laws were subsequently interpreted by the courts. The Nebraska Supreme Court, between 1877 and 1886, established the need for the state to prove force as a primary component of the definition for rape, drew boundaries around acceptable reporting times, and solidified their stance on the requirement of corroborating testimony. These factors led Sadilek to charge Charley Kaley not with rape but with bastardy, a civil suit, which almost guaranteed a successful outcome for Sadilek and her child because it would not burden the county or state with their financial welfare. In analyzing Sadilek’s choices before the law, this article demonstrates the complexities of the gendered legal systems facing women like Sadilek who sought justice for crimes of a sexual nature. Additionally significant, this article draws attention to a space and place that lacks significant study in regard to the sexual power dynamics of the nineteenth-century Great Plains West, a multicultural contact zone highly susceptible to the influences of hypermasculine control.
An Overview of Pathogens Associated with Biotic Stresses in Hemp Crops in Oregon, 2019 to 2020
Authors: Rivedal H. M. , Funke C. N. , Frost K. E.
Published: December 2021

Hemp (Cannabis sativa) acreage in Oregon has increased by approximately 240 times in the last 5 years, and a greater number of hemp diseases have been observed. This special report documents pathogens, particularly those causing virus and virus-like diseases, that have been detected from field and greenhouse-grown hemp crops in Oregon, based on plant samples submitted to the Hermiston Agricultural Research and Extension Center Plant Clinic of Oregon State University in 2019 and 2020. Symptoms and signs were used to evaluate disease types and determine diagnostic assays used on each submission. Plants with signs or symptoms of fungal or oomycete infection were cultured to isolate pathogenic organisms and plants with symptoms suspected to be caused by virus infection were assayed for the presence of Beet curly top virus (BCTV), viroids, and phytoplasmas using PCR, or reverse transcription (RT)-PCR. Diseases with fungal or oomycete, and virus causes accounted for 26.5 and 42.9% of submissions, respectively; coinfection of viral and fungal or oomycete pathogens were detected from 6.1% of submissions between 2019 and 2020. BCTV, a curtovirus, and hop latent viroid (HLVd) were the predominant pathogens detected from field and indoor grown hemp. Worland-like strains of BCTV represented 93% of all curtovirus detections. Eighty percent of HLVd detections occurred from plants that originated from indoor growing facilities. Based on BCTV vector, beet leafhopper, prevalence, field-grown hemp in western production regions may be affected by curly top and increasing hemp acreage in the landscape may have potential implications on other crops affected by curtoviruses. Virus and virus-like diseases could be a limiting factor for hemp production in some regions of the United States.
Evaluation of Damping-Off Tolerance in Spinach Cultivars in Field Soils and in a Standardized Lab Assay with Pythium ultimum
Authors: Magnée Kim J. H. , Postma Joeke , Groot Steven P. C. , Gort Gerrit , Lammerts van Bueren Edith T. , Scholten Olga E.
Published: December 2021

Spinach growers face increasing problems of damping-off in the production of fresh-market (baby-leaf) spinach due to increasing restrictions on chemical treatments. Damping-off-tolerant cultivars are increasingly important, requiring proper evaluation methods. From three locations in The Netherlands with a history of spinach cultivation and from one location in France, potential damping-off pathogens were isolated from the soil, identified to species or genus, and tested for their pathogenicity. Pythium ultimum was the most prevalent pathogen in those fields, causing spinach pre- and postemergence damping-off. Eight spinach cultivars with two or three seed lots each were evaluated at the same field locations and in a greenhouse with soil sampled from one of the Dutch field sites. Preemergence damping-off was more discriminating for differences among the cultivars than postemergence damping-off. Variation in levels of infection among trials, replicates, and seed lots of the same cultivars emphasized the need for a more standardized phenotyping assay. For such an assay, a cornmeal-sand-based inoculum with a pathogenic P. ultimum isolate was added to a substrate mixture of sand, perlite, and vermiculite and moistened until 50% water-holding capacity, in which spinach seeds were incubated for 10 days in a dark climate cabinet at 15°C, including a control treatment without P. ultimum inoculum. The assay showed reproducible results for discriminating differences in preemergence damping-off tolerance levels among seed lots. However, cultivar differences in preemergence damping-off tolerance levels could not be confirmed due to a large variation among seed lots that needs further investigation.
A Methodology for Calculation of Internal Dose Following Exposure to Radioactive Fallout from the Detonation of a Nuclear Fission Device
Authors: Anspaugh Lynn R. , Bouville André , Thiessen Kathleen M. , Hoffman F. Owen , Beck Harold L. , Gordeev Konstantin I. , Simon Steven L.
Published: December 2021

The purpose of this paper is to provide a methodology for the calculation of internal doses of radiation following exposure to radioactive fallout from the detonation of a nuclear fission device. Reliance is on methodology previously published in the open literature or in reports not readily available, though some new analysis is also included. Herein, we present two methodologic variations: one simpler to implement, the other more difficult but more flexible. The intention is to provide in one place a comprehensive methodology. Pathways considered are (1) the ingestion of vegetables and fruits contaminated by fallout directly, (2) the ingestion of vegetables and fruits contaminated by continuing deposition by rain- or irrigation-splash and resuspension, (3) the ingestion of vegetables and fruits contaminated by absorption of radionuclides by roots after tillage of soil, (4) the non-equilibrium transfer of short-lived radionuclides through the cow-milk and goat-milk food chains, (5) the equilibrium transfer of long lived radionuclides through milk and meat food chains, and (6) inhalation of descending fallout. Uncertainty in calculated results is considered. This is one of six companion papers that describe a comprehensive methodology for assessing both external and internal dose following exposures to fallout from a nuclear detonation. Input required to implement the dose-estimation model for any particular location consists of an estimate of the post-detonation external gamma-exposure rate and an estimate of the time of arrival of the fallout cloud. The additional data required to make such calculations are included in the six companion papers.
Poly(ADP-Ribose) Polymerase Inhibition in Small Cell Lung Cancer
Authors: Guo Matthew Z. , Marrone Kristen A. , Spira Alexander , Scott Susan C.
Published: December 2021

Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine malignancy with high and rapid relapse rates and poor outcomes. Treatment for SCLC has historically been limited by the lack of targetable driver genomic lesions, however recent developments in the underpinnings of genomic instability in SCLC and understanding of its transcriptional subtypes have led to increased interest in the use of poly(ADP-ribose) polymerase (PARP) inhibitors as a rationale therapy. Poly(ADP-ribose) polymerase inhibitors, historically designed to target BRCA1/2-mutated malignancies, capitalize on synthetic lethality in homologous recombination–deficient tumors. In this review, we outline the mechanistic rationale for the use of PARP inhibitors in treating SCLC and detail key clinical trials investigating their use in combination with chemotherapy and immunotherapy. We describe developments in the understanding of biomarkers for sensitivity to therapy and highlight further investigational directions for the use of PARP inhibitors in treating SCLC.
New Roles of Poly(ADP-Ribose) Polymerase Inhibitors in the Treatment of Breast Cancer
Authors: Harvey-Jones Elizabeth , Vinas Villaro Gemma , Tutt Andrew
Published: December 2021

Since the proof of concept of synthetic lethality between poly(ADP-ribose) polymerase inhibition and loss of BRCA1/2 homologous recombination (HR) function in preclinical models and early phase clinical trials, poly(ADP-ribose) polymerase inhibitors (PARPi) are increasing part of standard-of-care treatment for advanced breast cancers with BRCA gene mutations. The field has also recently seen benefits for PARPi in early breast cancer in those with germline BRCA1 and BRCA2 pathogenic mutations, and signals that synthetic lethal affects may occur in tumors with deficiencies in HR caused by germline, somatic, or epigenetic dysregulation of a number of HR genes. Despite the evidence of the synthetic lethal effects of PARPi, they are not always effective in HR defective cancers, and as they become part of standard of care in breast cancer, the study of prevalence of distinct mechanisms of resistance to PARPi and cross-resistance with other DNA-damaging agents such as platinum in breast cancer will be important and may inform therapy choices.
PARP Inhibition in Advanced Prostate Cancer
Authors: Fenton Sarah E. , Chalmers Zachary R. , Hussain Maha
Published: December 2021

In May 2020, the poly(ADP-ribose) polymerase (PARP) inhibitors rucaparib and olaparib were Food and Drug Administration approved for the management of metastatic castration-resistant prostate cancers. Rucaparib was approved for tumors that harbor alterations in BRCA1 and BRCA2 following progression on chemotherapy and androgen receptor–directed therapy, whereas olaparib was approved for tumors that harbor alterations in a broader range of DNA damage repair genes following progression on androgen receptor–directed therapy. Loss-of-function mutations in genes such as BRCA1 and BRCA2 increase reliance on PARP-mediated mechanisms of DNA repair, and inhibition of this pathway results in the accumulation of lethal levels of DNA damage. This dependence is advantageous in the management of prostate cancer, as mutations in DNA damage repair genes are frequent. This review summarizes the role of PARP in cell homeostasis, methods of targeting PARP in cancer cells, and current clinical trials in the management of advanced prostate cancer with PARP inhibitors.
The Clinical Challenges, Trials, and Errors of Combatting Poly(ADP-Ribose) Polymerase Inhibitors Resistance
Authors: Pham Melissa M. , Hinchcliff Emily , Avila Monica , Westin Shannon N.
Published: December 2021

The use of poly(ADP-ribose) polymerase inhibitor (PARPi) exploits synthetic lethality in solid tumors with homologous recombination repair (HRR) defects. Significant clinical benefit has been established in breast and ovarian cancers harboring BRCA1/2 mutations, as well as tumors harboring characteristics of “BRCAness.” However, the durability of treatment responses is limited, and emerging data have demonstrated the clinical challenge of PARPi resistance. With the expanding use of PARPi, the significance of PARP therapy in patients pretreated with PARPi remains in need of significant further investigation. Molecular mechanisms contributing to this phenomenon include restoration of HRR function, replication fork stabilization, BRCA1/2 reversion mutations, and epigenetic changes. Current studies are evaluating the utility of combination therapies of PARPi with cell cycle checkpoint inhibitors, antiangiogenic agents, phosphatidylinositol 3-kinase/AKT pathway inhibitors, MEK inhibitors, and epigenetic modifiers to overcome this resistance. In this review, we address the mechanisms of PARPi resistance supported by preclinical models, examine current clinical trials applying combination therapy to overcome PARPi resistance, and discuss future directions to enhance the clinical efficacy of PARPi.
Composite Tissue Columella Wedge Excision for Nasal Tip Overprojection
Authors: Röjdmark Jonas , Fischer Sebastian
Published: December 2021

Background:

The overprojected nasal tip is a challenge in facial surgery. Although several techniques are available, none has been proven to be superior. The aim of this study was to introduce a novel approach to overcome nasal tip overprojection and to evaluate its safety and efficacy.

Methods:

All patients with protruding nasal tip who underwent correction by means of a novel columella wedge technique were included in this study. In addition to detailed description of the novel surgical approach, its efficacy was analyzed by comparison of preoperative and postoperative nose dimensions. In addition, patients were examined during follow-up, and complication and revision rates were determined.

Results:

Forty-two patients were included in this study. Columella wedge technique involved resection of a 2- to 5-mm section of the middle part of the columella. Postoperatively, nose projection and length decreased by 9 and 12 percent, respectively. The relation between projection and length of the nose changed from 0.68 preoperatively to 0.61 postoperatively. This difference was statistically significant (p = 0.002). After a mean follow-up of 28 months (range, 6 to 144 months), revision operations were necessary in seven patients (16.7 percent). No instabilities, impairment of breathing, or other complications occurred.

Conclusion:

The introduced columella wedge technique is efficient and safe for correction of the overprojected nasal tip.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Treating autism spectrum disorder by intervening with gut microbiota
Authors: Tu Tingting , Zhao Changlin
Published: December 2021

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders with a high prevalence in childhood. The gut microbiota can affect human cognition and moods and has a strong correlation with ASD. Microbiota transplantation, including faecal microbiota transplantation (FMT), probiotics, breastfeeding, formula feeding, gluten-free and casein-free (GFCF) diet and ketogenic diet therapy, may provide satisfying effects for ASD and its related various symptoms. For instance, FMT can improve the core symptoms of ASD and gastrointestinal symptoms. Probiotics, breastfeeding and formula feeding, and GFCF diet can improve gastrointestinal symptoms. The core symptom score still needs to be confirmed by large-scale clinical randomized controlled studies. It is recommended to use a ketogenic diet to treat patients with epilepsy in ASD. At present, the unresolved problems include which of gut the microbiota are beneficial, which of the microorganisms are harmful, how to safely and effectively implant beneficial bacteria into the human body, and how to extract and eliminate harmful microorganisms before transplantation. In future studies, large sample and randomized controlled clinical studies are needed to confirm the mechanism of intestinal microorganisms in the treatment of ASD and the method of microbial transplantation.
Present and future distribution of bat hosts of sarbecoviruses: implications for conservation and public health
Authors: Muylaert Renata L. , Kingston Tigga , Luo Jinhong , Vancine Maurício Humberto , Galli Nikolas , Carlson Colin J. , John Reju Sam , Rulli Maria Cristina , Hayman David T. S.
Published: December 2021

Global changes in response to human encroachment into natural habitats and carbon emissions are driving the biodiversity extinction crisis and increasing disease emergence risk. Host distributions are one critical component to identify areas at risk of spillover, and bats act as reservoirs of diverse viruses. We developed a reproducible ecological niche modelling pipeline for bat hosts of SARS-like viruses (subgenus Sarbecovirus), given that since SARS-CoV-2 emergence several closely-related viruses have been discovered and sarbecovirus-host interactions have gained attention. We assess sampling biases and model bats’ current distributions based on climate and landscape relationships and project future scenarios. The most important predictors of species distribution were temperature seasonality and cave availability. We identified concentrated host hotspots in Myanmar and projected range contractions for most species by 2100. Our projections indicate hotspots will shift east in Southeast Asia in >2 °C hotter locations in a fossil-fueled development future. Hotspot shifts have implications for conservation and public health, as loss of population connectivity can lead to local extinctions, and remaining hotspots may concentrate near human populations.
TIMSCONVERT: A workflow to convert trapped ion mobility data to open data formats
Authors: Luu Gordon T. , Lizama-Chamu Itzel , McCaughey Catherine S. , Sanchez Laura M. , Wang Mingxun
Published: December 2021

Advances in mass spectrometry instrumentation have led to the development of mass spectrometers with ion mobility separation (IMS) capabilities and dual source instrumentation, but the current software ecosystem lacks interoperability with downstream data analysis using open-source software/pipelines. Here, we present TIMSCONVERT, a data conversion workflow from timsTOF fleX MS raw data files to size conscious mzML and imzML formats with minimal preprocessing to allow for compatibility with downstream data analysis tools, which we showcase with several examples using data acquired across different experiments and acquisition modalities on the timsTOF fleX.

Availability and Implementation

TIMSCONVERT and its documentation can be found at https://github.com/gtluu/timsconvert and is available as a standalone command line interface, Nextflow workflow, and online in the Global Natural Products Social (GNPS) platform (https://proteomics2.ucsd.edu/ProteoSAFe/index.jsp?params={%22workflow%22%3A%20%22TIMSCONVERT%22}).

Contact

Mingxun Wang, miw023@ucsd.edu

Supplementary Information

Supplementary data are available at Bioinformatics online.
Outcomes Associated with Expanded Take-Home Eligibility for Outpatient Treatment with Medications for Opioid Use Disorder: A Mixed-Methods Analysis
Authors: Nguyen Oanh Kieu , Steiger Scott , Snyder Hannah , Perrotta Matthew , Suen Leslie W. , Joshi Neena , Castellanos Stacy , Shapiro Brad , Makam Anil N. , Knight Kelly R.
Published: December 2021

Background

Access to medications for opioid use disorder (MOUD) in the U.S. is highly restricted. In March 2020, to reduce transmission of COVID-19, SAMHSA issued emergency regulations allowing up to two weeks of take-home doses for most patients.

Objectives

We evaluated the benefits and unintended consequences of these new regulations expanding take-home eligibility to inform MOUD policy post-pandemic

Methods

We conducted a mixed-methods evaluation of an opioid treatment program in San Francisco caring for a diverse, low-income urban population. We assessed clinic-level intake, retention, and take-home prescribing; individual-level acute care utilization and mortality; and patient/provider perceptions of benefits, harms and challenges of the new regulations.

Results

Clinic volume, intake and retention were largely unchanged after implementation of the new regulations, though the average monthly proportion of individuals receiving take-homes significantly increased from 31% to 47% (p<0.001). Among 506 established patients (≥90 days of care), the 10-month mortality was 2.7% among those who never received take-homes versus 3.2% among those newly started (p=0.79) and 0.8% among those with increases in take-homes (p=0.24). Individuals who never received take-homes had higher rates of emergency department visits (47.0%) and hospitalizations (19.7%) versus those with new starts (ED visits 29.2%, p<0.001; hospitalizations 14.3%, p=0.19) or increases in take-homes (ED visits 17.5%, p<0.001; hospitalizations 10.0%, p=0.02). Both patients and providers reported increased treatment flexibility, leading to increased engagement and stabilization.

Conclusions

Given the benefit and lack of appreciable harms, policymakers should consider extending expanded MOUD take-home eligibility after COVID-19, with careful monitoring for unintended outcomes.
High correlation between binding IgG (anti-RBD/S) and neutralizing antibodies against SARS-CoV-2 six months after vaccination
Authors: Guiomar Raquel , Santos Ana João , Melo Aryse Martins , Costa Inês , Matos Rita , Rodrigues Ana Paula , Kislaya Irina , Silva Anabela Santos , Roque Carla , Silva Carla , Aguiar Joaquim , Graça Fátima , Graça Antônio Silva , Machado Ausenda
Published: December 2021

Vaccination is considered the most important measure to control the COVID-19 pandemic. Extensive follow-up studies with distinct vaccines and populations are able to promote robust and reliable data to better understand the effectiveness of this pharmacologic strategy. In this sense, we present data regarding binding and neutralizing antibodies throughout time, from vaccinated and previously infected (PI) health care workers (HCW) in Portugal. We analyzed serum samples of 132 HCW, vaccinated and with previous SARS-CoV-2 infection. Samples were collected before vaccination (baseline, M1), at second dose vaccine uptake (M2), and 25-70 days (M3) and 150-210 days (M4) after the second dose for vaccinated individuals. The IgG (anti-RBD/S) antibody geometric mean titer found on vaccinated HCW at M2 (814.7 AU/ml; 95% CI 649.8-1021.5) were significantly higher than those found on PI HCW at recruitment (M1) (252.6 AU/ml; 95% CI 108.7 - 587.1), and the neutralizing antibodies (nAb) were similar between these groups, 93.2 UI/ml (95% CI 73.2-118.5) vs. 84.1 UI/ml (95% CI 40.4-155.9), respectively. We detected about 10-fold higher IgG (anti-RBD/S) antibodies titers in M3 when compared with M2, with a slightly but significant decrease in titers from 36 days after the second dose vaccine uptake. The increase of nAb titers were correlated with IgG (anti-RBD/S) antibodies titers, however, contrasting to IgG (anti-RBD/S) antibodies titers, we did not detect a decrease in nAb titer from 36 days after a second vaccine dose uptake. At M4, was observed a decrease of 8-fold in binding IgG (anti-RBD/S) and nAb. No significant differences in antibody titers were observed by sex, age or chronic diseases. Our results suggest that IgG (anti-RBD/S) antibodies titers and nAb titers could be correlated, but ongoing follow up of the cohort, is required to better understand this correlation, and the duration of the immune response.
Measuring the impact of COVID-19 vaccination and immunity waning: a modelling study for Portugal
Authors: Caetano Constantino , Morgado Maria Luísa , Patrício Paula , Leite Andreia , Machado Ausenda , Torres André , Pereira João Freitas , Namorado Sónia , Sottomayor Ana , Peralta André , Nunes Baltazar
Published: December 2021

Vaccination strategies to control COVID-19 have been ongoing worldwide since the end of 2020. Understanding their possible effect is key to prevent future disease spread. Using a modelling approach, this study intends to measure the impact of the COVID-19 Portuguese vaccination strategy on the effective reproduction number and explore three scenarios for vaccine effectiveness waning. Namely, the no-immunity-loss, 1-year and 3-years of immunity duration scenarios. We adapted an age-structured SEIR deterministic model and used Portuguese hospitalisation data for the model calibration. Results show that, although the Portuguese vaccination plan had a substantial impact in reducing overall transmission, it might not be sufficient to control disease spread. A significant vaccination coverage of those above 5 years old, a vaccine effectiveness against disease of at least 80% and softer non-pharmaceutical interventions (NPIs), such as mask usage and social distancing, would be necessary to control disease spread in the worst scenario considered. The immunity duration scenario of 1-year displays a resurgence of COVID-19 hospitalisations by the end of 2021, the same is observed in 3-year scenario although with a lower magnitude. The no-immunity-loss scenario presents a low increase in hospitalisations. In both the 1-year and 3-year scenarios, a vaccination boost of those above 65 years old would result in a 53% and 38% peak reduction of non-ICU hospitalisations, respectively. These results suggest that NPIs should not be fully phased-out but instead be combined with a fast booster vaccination strategy to reduce healthcare burden.
The economic burden of protecting islands from invasive alien species
Authors: Bodey Thomas W , Angulo Elena , Bang Alok , Bellard Céline , Fantle-Lepczyk Jean , Lenzner Bernd , Turbelin Anna , Watari Yuya , Courchamp Franck
Published: December 2021

Biological invasions represent a key threat to island ecosystems, with pronounced impacts across environments and economies. The ecological impacts have received substantial focus, but the economic costs have lacked synthesis at spatial and temporal scales. Here we utilise the InvaCost database, the most comprehensive global assessment of published economic costs of invasive species, to assess reported spend by cost types and socioeconomic sectors, and to examine temporal trends in spending, across islands that differ in their political geography - nation states, overseas territories or offshore islands of continental countries. We based this assessment on 1473 unique cost entries comprising 2914 annual costs totalling almost US$100 million in area-corrected costs between 1965-2020. We find that offshore islands of continental countries incur the greatest total and management costs. However, nation states incurred the greatest damage costs whilst substantially financing management actions, and spent an overall greater proportion of their GDP. In contrast, spending within overseas territories was significantly lower in all respects. The most impacted sector was authorities and stakeholders, demonstrating the key role of government in addressing island invasions. Temporal trends revealed continual increases in spending across all island types. This likely reflects ongoing introduction rates globally alongside an increased recognition of the importance of islands as biodiversity hotspots, and an appetite to tackle invasive species at larger and more socially complex scales. However, the high economic costs of invasions on islands substantiates the need to prevent them in order to avoid this dire threat to biodiversity and its burden on limited conservation resources.
Comparative analysis of gene prediction tools for viral genome annotation
Authors: González-Tortuero Enrique , Krishnamurthi Revathy , Allison Heather E. , Goodhead Ian B. , James Chloë E.
Published: December 2021

The number of newly available viral genomes and metagenomes has increased exponentially since the development of high throughput sequencing platforms and genome analysis tools. Bioinformatic annotation pipelines are largely based on open reading frame (ORF) calling software, which identifies genes independently of the sequence taxonomical background. Although ORF-calling programs provide a rapid genome annotation, they can misidentify ORFs and start codons; errors that might be perpetuated and propagated over time. This study evaluated the performance of multiple ORF-calling programs for viral genome annotation against the complete RefSeq viral database. Programs outputs varied when considering the viral nucleic acid type versus the viral host. According to the number of ORFs, Prodigal and Metaprodigal were the most accurate programs for DNA viruses, while FragGeneScan and Prodigal generated the most accurate outputs for RNA viruses. Similarly, Prodigal outperformed the benchmark for viruses infecting prokaryotes, and GLIMMER and GeneMarkS produced the most accurate annotations for viruses infecting eukaryotes. When the coordinates of the ORFs were considered, Prodigal scored high for all scenarios except for RNA viruses, where GeneMarkS generated the most reliable results. Overall, the quality of the coordinates predicted for RNA viruses was poorer than for DNA viruses, suggesting the need for improved ORF-calling programs to deal with RNA viruses. Moreover, none of the ORF-calling programs reached 90% accuracy for annotation of DNA viruses. Any automatic annotation can still be improved by manual curation, especially when the presence of ORFs is validated with wet-lab experiments. However, our evaluation of the current ORF-calling programs is expected to be useful for the improvement of viral genome annotation pipelines and highlights the need for more expression data to improve the rigor of reference genomes.
Computer Modeling of Radiofrequency Cardiac Ablation including Heartbeat-Induced Electrode Displacement
Authors: Pérez Juan J. , González-Suárez Ana , Nadal Enrique , Berjano Enrique
Published: December 2021

Background

The state of the art in computer modeling of radiofrequency catheter ablation (RFCA) only considers a static model, i.e. it does not allow modeling ablation electrode displacements induced by tissue movement due to heartbeats. This feature is theoretically required, since heartbeat-induced changes in contact force can be detected during this clinical procedure.

Methods

We built a 2D RFCA model coupling electrical, thermal and mechanical problems and simulated a standard energy setting (25 W – 30 s). The mechanical interaction between the ablation electrode and tissue was dynamically modeled to reproduce heartbeat-induced changes in the electrode insertion depth from 0.86 to 2.05 mm, which corresponded with contact forces between 10 and 30 g when cardiac tissue was modeled by a hyperelastic Neo-Hookean model with a Young’s modulus of 75 kPa and Poisson’s ratio of 0.49.

Results

The dynamic model computed a lesion depth of 5.86 mm, which is within the range of previous experimental results based on a beating heart for a similar energy setting and contact force (5.6−6.7 mm). Lesion size was practically identical (differences less than 0.02 mm) to that using a static model with the electrode inserted to an average depth (1.46 mm, equivalent to 20 g contact force).

Conclusions

The RFCA dynamic model including heartbeat-induced electrode displacement predicts lesion depth reasonably well compared to previous experimental results based on a beating heart model, however this is true only at a standard energy setting and moderate contact force.
Microtubule-associated IQD9 guides cellulose synthase velocity to shape seed mucilage
Authors: Yang Bo , Stamm Gina , Bürstenbinder Katharina , Voiniciuc Cătălin
Published: December 2021

Arabidopsis seeds release large capsules of mucilaginous polysaccharides, which are shaped by an intricate network of cellulosic microfibrils. Cellulose synthase complexes is guided by the microtubule cytoskeleton, but it is unclear which proteins mediate this process in the seed coat epidermis (SCE).

Using reverse genetics, we identified IQ67 DOMAIN 9 (IQD9) and KINESIN LIGHT CHAIN-RELATED 1 (KLCR1) as two highly expressed genes during seed development and comprehensively characterized their roles for cell wall polysaccharide biosynthesis and cortical microtubule (MT) organization.

Mutations in IQD9 as well as in KLCR1 lead to compact mucilage capsules with aberrant cellulose distribution, which can be rescued by transgene complementation. Double mutant analyses revealed that their closest paralogs (IQD10 and KLCR2, respectively) are not required for mucilage biosynthesis. IQD9 physically interacts with KLCR1 and localizes to cortical MTs to maintain their organization in SCE cells. Similar to the previously identified TONNEAU1 (TON1) RECRUITING MOTIF 4 (TRM4) protein, IQD9 is required to maintain the velocity of cellulose synthases.

Our results demonstrate that IQD9, KLCR1 and TRM4 are MT-associated proteins that are required for seed mucilage architecture. This study provides the first direct evidence that members of the IQD, KLCR and TRM families have overlapping roles in guiding the distribution of cell wall polysaccharides. Therefore, SCE cells provide an attractive system to further decipher the complex genetic regulation of polarized cellulose deposition.
Regulation of mitochondrial proteostasis by the proton gradient
Authors: Patron Maria , Tarasenko Daryna , Nolte Hendrik , Ghosh Mausumi , Ohba Yohsuke , Lasarzewski Yvonne , Ahmadi Zeinab Alsadat , Cabrera-Orefice Alfredo , Eyiama Akinori , Kellermann Tim , Rugarli Elena I. , Brandt Ulrich , Meinecke Michael , Langer Thomas
Published: December 2021

Mitochondria adapt to different energetic demands reshaping their proteome. Mitochondrial proteases are emerging as key regulators of these adaptive processes. Here, we use a multi-proteomic approach to demonstrate regulation of the m-AAA protease AFG3L2 by the mitochondrial proton gradient, coupling mitochondrial protein turnover to the energetic status of mitochondria. We identify TMBIM5 (previously also known as GHITM or MICS1) as a Ca2+/H+ exchanger in the mitochondrial inner membrane, which binds to and inhibits the m-AAA protease. TMBIM5 ensures cell survival and respiration, allowing Ca2+ efflux from mitochondria and limiting mitochondrial hyperpolarization. Persistent hyperpolarization, however, triggers degradation of TMBIM5 and activation of the m-AAA protease. The m-AAA protease broadly remodels the mitochondrial proteome and mediates the proteolytic breakdown of respiratory complex I to confine ROS production and oxidative damage in hyperpolarized mitochondria. TMBIM5 thus integrates mitochondrial Ca2+ signaling and the energetic status of mitochondria with protein turnover rates to reshape the mitochondrial proteome and adjust the cellular metabolism.
Glycine targets NINJ1-mediated plasma membrane rupture to provide cytoprotection
Authors: Borges Jazlyn P. , Sætra Ragnhild S. R. , Volchuk Allen , Bugge Marit , Kilburn Bridget , Goldenberg Neil M. , Flo Trude H. , Steinberg Benjamin E.
Published: December 2021

First recognized 35 years ago, glycine is known to protect cells against plasma membrane rupture from diverse types of tissue injury. This robust and widely observed effect has been speculated to target a late downstream process common to multiple modes of tissue injury. The molecular target of glycine cytoprotection, however, remains entirely elusive. We hypothesized that glycine targets ninjurin-1 (NINJ1), a newly identified executioner of plasma membrane rupture in pyroptosis, necrosis, and post-apoptotic cell death. NINJ1 is thought to cluster within the plasma membrane to cause cell rupture. Here, we first demonstrate that NINJ1 knockout functionally and morphologically phenocopies glycine cytoprotection in mouse and human macrophages stimulated to undergo lytic cell death. Next, we show that glycine treatment prevents NINJ1 clustering thereby preserving cellular integrity. By identifying NINJ1 as a glycine target, our data help resolve a long-standing mechanism of glycine cytoprotection. This new understanding will inform the development of cell preservation strategies to counter pathologic lytic cell death pathways.

Graphical abstract

Glycine is known to protect cells against plasma membrane rupture from diverse types of tissue injury by an unknown mechanism. The authors demonstrate that NINJ1, a newly identified executioner of plasma membrane rupture across lytic cell death pathways, is a glycine target and resolve a longstanding mechanism of glycine cytoprotection.
A two-component protein condensate of EGFR and Grb2 regulates Ras activation at the membrane
Authors: Lin Chun-Wei , Nocka Laura M. , Stinger Brittany , DeGrandchamp Joey , Lew Nugent , Alvarez Steven , Phan Henry , Kondo Yasushi , Kuriyan John , Groves Jay T.
Published: December 2021

We reconstitute a phosphotyrosine-mediated protein condensation phase transition of the ∼200 residue cytoplasmic tail of the epidermal growth factor receptor (EGFR) and the adaptor protein, Grb2, on a membrane surface. The phase transition depends on phosphorylation of the EGFR tail, which recruits Grb2, and the dimerization of Grb2, which provides the crosslinking element for condensation with EGFR. The Grb2 Y160 residue plays a structurally critical role in dimer formation, and phosphorylation or mutation of Y160 prevents EGFR:Grb2 condensation. By extending the reconstitution experiment to include the guanine nucleotide exchange factor, SOS, and its substrate Ras, we further find that EGFR condensation controls the ability of SOS to activate Ras. These results identify an EGFR:Grb2 protein condensation phase transition as a regulator of signal propagation from EGFR to the MAPK pathway.