bluuebunny/crossref_metadata_2025_split huggingface dataset:
Local and Systemic Overexpression of COMP-Ang1 Induces Ang1/Tie2-Related Thrombocytopenia and SDF-1/CXCR4-Dependent Anemia
Authors: Sim Hyun-Jaung , Bhattarai Govinda , Kim Min-Hye , So Han-Sol , Poudel Sher Bahadur , Cho Eui-Sic , Kook Sung-Ho , Lee Jeong-Chae 
Published: November 2022

Abstract
While supplemental angiopoietin-1 (Ang1) improves hematopoiesis, excessive Ang1 induces bone marrow (BM) impairment, hematopoietic stem cell (HSC) senescence, and erythropoietic defect. Here, we examined how excessive Ang1 disturbs hematopoiesis and explored whether hematopoietic defects were related to its level using K14-Cre;c-Ang1 and Col2.3-Cre;c-Ang1 transgenic mice that systemically and locally overexpress cartilage oligomeric matrix protein-Ang1, respectively. We also investigated the impacts of Tie2 inhibitor and AMD3100 on hematopoietic development. Transgenic mice exhibited excessive angiogenic phenotypes, but K14-Cre;c-Ang1 mice showed more severe defects in growth and life span with higher presence of Ang1 compared with Col2.3-Cre;c-Ang1 mice. Dissimilar to K14-Cre;c-Ang1 mice, Col2.3-Cre;c-Ang1 mice did not show impaired BM retention or senescence of HSCs, erythropoietic defect, or disruption of the stromal cell-derived factor 1 (SDF-1)/CXCR4 axis. However, these mice exhibited a defect in platelet production depending on the expression of Tie2 and globin transcription factor 1 (GATA-1), but not GATA-2, in megakaryocyte progenitor (MP) cells. Treatment with Tie2 inhibitor recovered GATA-1 expression in MP cells and platelet production without changes in circulating RBC in transgenic mice. Consecutive AMD3100 administration not only induced irrecoverable senescence of HSCs but also suppressed formation of RBC, but not platelets, via correlated decreases in number of erythroblasts and their GATA-1 expression in B6 mice. Our results indicate that genetic overexpression of Ang1 impairs hematopoietic development depending on its level, in which megakaryopoiesis is preferentially impaired via activation of Ang1/Tie2 signaling, whereas erythropoietic defect is orchestrated by HSC senescence, inflammation, and disruption of the SDF-1/CXCR4 axis.
A Coculture of Enterobacter and Comamonas Species Reduces Cadmium Accumulation in Rice
Authors: Wang Xing , Xu Qing , Hu Kang , Wang Gejiao , Shi Kaixiang 
Published: November 2022

The accumulation of cadmium (Cd) in plants is strongly impacted by soil microbes, but its mechanism remains poorly understood. Here, we report the mechanism of reduced Cd accumulation in rice by coculture of Enterobacter and Comamonas species. In pot experiments, inoculation with the coculture decreased Cd content in rice grain and increased the amount of nonbioavailable Cd in Cd-spiked soils. Fluorescence in situ hybridization and scanning electron microscopy detection showed that the coculture colonized in the rhizosphere and rice root vascular tissue and intercellular space. Soil metagenomics data showed that the coculture increased the abundance of sulfate reduction and biofilm formation genes and related bacterial species. Moreover, the coculture increased the content of organic matter, available nitrogen, and potassium and increased the activities of arylsulfatase, β-galactosidase, phenoloxidase, arylamidase, urease, dehydrogenase, and peroxidase in soils. In subsequent rice transcriptomics assays, we found that the inoculation with coculture activated a hypersensitive response, defense-related induction, and mitogen-activated protein kinase signaling pathway in rice. Heterologous protein expression in yeast confirmed the function of four Cd-binding proteins (HIP28-1, HIP28-4, BCP2, and CID8), a Cd efflux protein (BCP1), and three Cd uptake proteins (COPT4, NRAM5, and HKT6) in rice. Succinic acid and phenylalanine were subsequently proved to inhibit rice divalent Cd [Cd(II)] uptake and activate Cd(II) efflux in rice roots. Thus, we propose a model that the coculture protects rice against Cd stress via Cd immobilization in soils and reducing Cd uptake in rice. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Alternative Management Strategies and Impact of the Northern Root-Knot Nematode in Daylily Production
Authors: Howland Amanda D. , Cole Emilie , Poley Kristin , Quintanilla Marisol 
Published: November 2022

Bare-root production of Hemerocallis spp., daylily, is of major economic importance to Michigan's ornamental industry, but production of clean nursery material is challenging due to plant-parasitic nematodes. The northern root-knot nematode, Meloidogyne hapla, is the most important perennial ornamental pathogen in northern North America; it causes over 20% yield loss in Hemerocallis spp. production and reduces marketability and distribution. A field trial was established in 2018 to 2020 at a Michigan commercial nursery to determine effective and long-term management strategies to reduce nematode population levels. Eleven treatments were tested: a control, four bio-nematicides, two nematicides, a nematicide root dip, and three compost blends. Soil samples were taken three times per year, along with annual root samples and plant height measurements. Results indicated that TerraClean 5.0 (hydrogen peroxide) and Majestene 304 ( Chromobacterium subtsugae) nematicides best controlled M. hapla populations by 49 and 37%, respectively, compared with the control, whereas Indemnify (fluopyram) significantly increased plant biomass and yields by 31%. A greenhouse study was conducted to determine the impact of M. hapla on Hemerocallis spp. production by inoculating daylily with varying nematode inoculation densities. Even at low population levels, plant biomass reductions were observed, and M. hapla was readily able to reproduce on Hemerocallis spp. These experiments highlight the importance of managing M. hapla and provide effective, alternative management methods that can reduce the application of fumigants and prevent yield losses to increase profitability for ornamentals.
Development and Statistical Validation of E-Probe Diagnostic Nucleic Acid Analysis (EDNA) Assays for the Detection of Citrus Pathogens from Raw High-Throughput Sequencing Data
Authors: Dang Tyler , Wang Huizi , Espindola Andres S. , Habiger Josh , Vidalakis Georgios , Cardwell Kitty 
Published: November 2022

The cost for high-throughput sequencing (HTS) has decreased significantly and has made it possible for the application of this technology for routine plant diagnostics. There are constraints to the use of HTS as a diagnostic tool, including the need for dedicated personnel with a bioinformatic background for data analysis and the lack of a standardized analysis pipeline that makes evaluating and validating results generated at different HTS laboratories difficult. E-probe diagnostic nucleic acid analysis (EDNA) is an in-silico bioinformatic tool that utilizes short curated electronic probes (e-probes) designed from pathogen-specific sequences that allow users to detect and identify single or multiple pathogens of interest in raw HTS data sets. This platform streamlines the bioinformatic data analysis into a graphical user interface as a plant diagnostic tool used by diagnosticians. In this study, we describe the process for the development, validation, and use of e-probes for detection and identification of a wide range of taxonomically unique citrus pathogens that include citrus exocortis viroid, citrus tristeza virus, ‘ Candidatus Liberibacter asiaticus’, and Spiroplasma citri. We demonstrate the process for evaluating the analytical and diagnostic sensitivity and specificity metrics of the in-silico EDNA assays. In addition, we show the importance of including background noise (internal controls) to generate variance in noninfected samples for a valid statistical test using the quadratic discriminant analysis. The fully validated EDNA assays from this study can be readily integrated into existing citrus testing programs that utilize HTS. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Rh Immune Globulin After the Transfusion of RhD-Positive Blood in a Patient with a Partial D Antigen
Authors: Lesser Tal Henry , O'Malley Michael , Ehsanipoor Robert M. 
Published: November 2022

BACKGROUND:
Patients with a serologic weak D phenotype may demonstrate variable RhD expression. We present a case in which clinical management would have been simplified if RHD genotyping had been performed previously.

CASE:
A 33-year-old patient, G11P4155, presented with an incomplete miscarriage and was transfused RhD-positive packed red blood cells after typing RhD-positive. The patient had been historically typed RhD-negative by a different testing methodology. Indirect antiglobulin testing was performed, which revealed a serologic weak D phenotype. The patient was given 9,600 micrograms of Rh immune globulin. Molecular testing revealed a partial D antigen, which was originally thought to be at risk for alloimmunization; however, this has since been disproven.

CONCLUSION:
Although not yet universal practice, prenatal RHD genotyping for partial D antigen could have prevented the characterization of this patient as RhD-positive at the time of transfusion.
Association Between Giving Birth During the Early Coronavirus Disease 2019 (COVID-19) Pandemic and Serious Maternal Morbidity
Authors: Metz Torri D. , Clifton Rebecca G. , Hughes Brenna L. , Sandoval Grecio J. , Grobman William A. , Saade George R. , Manuck Tracy A. , Longo Monica , Sowles Amber , Clark Kelly , Simhan Hyagriv N. , Rouse Dwight J. , Mendez-Figueroa Hector , Gyamfi-Bannerman Cynthia , Bailit Jennifer L. , Costantine Maged M. , Sehdev Harish M. , Tita Alan T.N. , Macones George A. ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network
Published: November 2022

OBJECTIVE:
We aimed to evaluate whether delivering during the early the coronavirus disease 2019 (COVID-19) pandemic was associated with increased risk of maternal death or serious morbidity from common obstetric complications compared with a historical control period.

METHODS:
This was a multicenter retrospective cohort study with manual medical-record abstraction performed by centrally trained and certified research personnel at 17 U.S. hospitals. Individuals who gave birth on randomly selected dates in 2019 (before the pandemic) and 2020 (during the pandemic) were compared. Hospital, health care system, and community risk-mitigation strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in response to the early COVID-19 pandemic are described. The primary outcome was a composite of maternal death or serious morbidity from common obstetric complications, including hypertensive disorders of pregnancy (eclampsia, end organ dysfunction, or need for acute antihypertensive therapy), postpartum hemorrhage (operative intervention or receipt of 4 or more units blood products), and infections other than SARS-CoV-2 (sepsis, pelvic abscess, prolonged intravenous antibiotics, bacteremia, deep surgical site infection). The major secondary outcome was cesarean birth.

RESULTS:
Overall, 12,133 patients giving birth during and 9,709 before the pandemic were included. Hospital, health care system, and community SARS-CoV-2 mitigation strategies were employed at all sites for a portion of 2020, with a peak in modifications from March to June 2020. Of patients delivering during the pandemic, 3% had a positive SARS-CoV-2 test result during pregnancy through 42 days postpartum. Giving birth during the pandemic was not associated with a change in the frequency of the primary composite outcome (9.3% vs 8.9%, adjusted relative risk [aRR] 1.02, 95% CI 0.93–1.11) or cesarean birth (32.4% vs 31.3%, aRR 1.02, 95% CI 0.97–1.07). No maternal deaths were observed.

CONCLUSION:
Despite substantial hospital, health care, and community modifications, giving birth during the early COVID-19 pandemic was not associated with higher rates of serious maternal morbidity from common obstetric complications.

CLINICAL TRIALS REGISTRATION:
ClinicalTrials.gov, NCT04519502.
Long-term Relugolix Combination Therapy for Symptomatic Uterine Leiomyomas
Authors: Al-Hendy Ayman , Lukes Andrea S. , Poindexter Alfred N. , Venturella Roberta , Villarroel Claudio , McKain Laura , Li Yulan , Wagman Rachel B. , Stewart Elizabeth A. 
Published: November 2022

OBJECTIVE:
In the LIBERTY 1 and LIBERTY 2 placebo-controlled trials, once-daily relugolix combination therapy reduced menstrual blood loss volume and pain in women with heavy menstrual bleeding associated with uterine leiomyomas and was well tolerated, with preservation of bone mineral density (BMD) through 24 weeks. Here we report the long-term efficacy and safety of relugolix combination therapy treatment for up to 52 weeks.

METHODS:
Women with uterine leiomyoma–associated heavy menstrual bleeding who completed any treatment arm in either the LIBERTY 1 or LIBERTY 2 trial were eligible to enroll in a 28-week long-term extension study. All participants received once-daily relugolix combination therapy (40 mg relugolix, estradiol 1 mg, norethindrone acetate 0.5 mg) in the extension study. The primary efficacy endpoint was the proportion of women who achieved or maintained a menstrual blood loss volume of less than 80 mL and a 50% or greater reduction in menstrual blood loss volume from LIBERTY study baseline to the last 35 days of treatment (defined as responders). Analyses were conducted for all three randomized treatment groups from pivotal studies.

RESULTS:
Overall, 477 women enrolled, 476 were treated, and 363 (76.1%) completed 52 weeks. Among patients treated with relugolix combination therapy through 52 weeks (n=163), sustained improvement in heavy menstrual bleeding was observed in 87.7% (responders). The least squares mean menstrual blood loss volume reduction was 89.9%, with 70.6% of patients achieving amenorrhea. At week 52, 59.0% of patients with anemia at baseline had improvements in hemoglobin concentration of greater than 2 g/dL. Distress due to uterine leiomyoma–associated symptoms measured by the BPD (Bleeding and Pelvic Discomfort) scale score was reduced by 51.3 points. Sustained reductions in uterine and uterine leiomyoma volume were observed. Bone mineral density was preserved through week 52.

CONCLUSION:
Improvements in heavy menstrual bleeding and anemia and reduction of uterine leiomyoma–associated symptom burden were sustained through up to 52 weeks of treatment with relugolix combination therapy in women with uterine leiomyomas. No new safety concerns were identified, and BMD was maintained.

CLINICAL TRIALS REGISTRATION:

ClinicalTrials.gov, NCT03049735; NCT03103087; NCT03412890.

FUNDING SOURCE:
Myovant Sciences GmbH.
Guideline-Discordant Care in Early-Stage Vulvar Cancer
Authors: Bercow Alexandra S. , Rauh-Hain J. Alejandro , Melamed Alexander , Mazina Varvara , Growdon Whitfield B. , del Carmen Marcela G. , Goodman Annekathryn , Bouberhan Sara , Bregar Amy , Eisenhauer Eric L. , Molina George , Minami Christina 
Published: November 2022

OBJECTIVE:
To describe the use of National Comprehensive Cancer Network guideline-concordant inguinofemoral lymph node (LN) evaluation in individuals with early-stage vulvar cancer.

METHODS:
This retrospective cohort study identified patients with T1b and T2 vulvar squamous cell carcinoma diagnosed between 2012 and 2018 using the National Cancer Database. Factors associated with LN evaluation were examined using logistic regression analyses, adjusting for patient, disease, and facility-level characteristics. Kaplan-Meier survival analysis using log rank test and Cox regression was performed for the entire cohort and a subgroup of older patients, defined as individuals aged 80 years or older.

RESULTS:
Of the 5,685 patients with vulvar cancer, 3,756 (66.1%) underwent guideline-concordant LN evaluation. In our adjusted model, age 80 years or older (odds ratio [OR], 0.30; 95% CI 0.22–0.42) and Black race (OR 0.72; 95% CI 0.54–0.95) were associated with lower odds of LN evaluation. High-volume hospitals were associated with increased odds of LN evaluation compared with low-volume hospitals (OR 1.62; 95% CI 1.28–2.05). Older individuals who did not undergo LN evaluation had significantly worse overall survival than those with pathologically negative LNs (hazard ratio [HR] 0.45; 95% CI 0.37–0.55) and similar overall survival as those with pathologically positive LNs (HR 1.05; 95% CI 0.77–1.43).

CONCLUSION:
Guideline-concordant LN evaluation for early-stage vulvar squamous cell carcinoma is low. Lower utilization is associated with older age, Black race, and care at a low-volume hospital.
Demographic, Reproductive, and Medical Risk Factors for Intrauterine Device Expulsion
Authors: Anthony Mary S. , Zhou Xiaolei , Schoendorf Juliane , Reed Susan D. , Getahun Darios , Armstrong Mary Anne , Gatz Jennifer , Peipert Jeffrey F. , Raine-Bennett Tina , Fassett Michael J. , Saltus Catherine W. , Ritchey Mary E. , Ichikawa Laura , Shi Jiaxiao M. , Alabaster Amy , Wahdan Yesmean , Wang Jinyi , Xie Fagen , Merchant Maqdooda , Hunter Shannon , Chiu Vicki Y. , Postlethwaite Debbie , Rothman Kenneth J. , Im Theresa M. , Chillemi Giulia , Takhar Harpreet S. , Asiimwe Alex , Pisa Federica 
Published: November 2022

OBJECTIVE:
To explore to what extent intrauterine device (IUD) expulsion is associated with demographic and clinical risk factors.

METHODS:
The APEX-IUD (Association of Perforation and Expulsion of IntraUterine Devices) study was a U.S. cohort study using electronic health records from three integrated health care systems (Kaiser Permanente Northern California, Southern California, and Washington) and a health care information exchange (Regenstrief Institute). These analyses included individuals aged 50 years or younger with IUD insertions from 2001 to 2018. Intrauterine device expulsion cumulative incidence and incidence rates were estimated. Using Cox regression models, hazard ratios with 95% CIs were estimated before and after adjustment for risk factors of interest (age, race and ethnicity, parity, body mass index [BMI], heavy menstrual bleeding, and dysmenorrhea) and potential confounders.

RESULTS:
In total, 228,834 individuals with IUD insertion and no delivery in the previous 52 weeks were identified (184,733 [80.7%] with levonorgestrel-releasing intrauterine system). Diagnosis of heavy menstrual bleeding—particularly a diagnosis in both recent and past periods—was the strongest risk factor for IUD expulsion. Categories with the highest risk of IUD expulsion within each risk factor included individuals diagnosed with overweight, obesity, and morbid obesity; those in younger age groups, especially among those aged 24 years or younger; and in those with parity of four or more. Non-Hispanic White individuals had the lowest incidence and risk, and after adjustment, Asian or Pacific Islander individuals had the highest risk. Dysmenorrhea was not independently associated with expulsion risk when adjusting for heavy menstrual bleeding.

CONCLUSION:
Most risk factors for expulsion identified in this study appear consistent with known physiologic factors that affect uterine anatomy and physiology (age, BMI, heavy menstrual bleeding, parity). The increased risk of IUD expulsion among individuals of color warrants further investigation. Intrauterine devices are an effective long-term contraceptive; expulsion is uncommon, but patients should be counseled accordingly.

FUNDING SOURCE:
Bayer AG.

CLINICAL TRIALS REGISTRATION:
EU PAS register, EUPAS33461.
Tip of the J-pouch Leaks: Diagnosis, Management, and Long-term Pouch Survival
Authors: Holubar Stefan D. , Rajamanickam Raja Kumaran , Gorgun Emre , Lightner Amy L. , Valente Michael A. , Church James , Hull Tracy , Steele Scott R. 
Published: November 2022

BACKGROUND:
The standard of care for surgical treatment of ulcerative colitis is restorative proctocolectomy with ileal J-pouch. Leaks from tip of the J-pouch are a known complication but there is a paucity of literature regarding this type of leak.

OBJECTIVE:
To describe the diagnosis, management and long-term clinical outcomes of tip of the J-pouch leaks at our institution.

DESIGN:
Retrospective study of prospectively maintained Pouch Registry.

SETTING:
Quaternary inflammatory bowel disease referral center.

PATIENTS:
Patients with an ileal J-pouches diagnosed with tip of the J leaks.

MAIN OUTCOME MEASURES:
Pouch salvage rate, type of salvage procedures, and long-term Kaplan-Meier pouch survival.

RESULTS:
We identified 74 patients with leaks from the tip of the J-pouch. Pain (68.9%) and pelvic abscess (40.9%) were the most common presentations, while 10.8% of patients presented with an acute abdomen. The leak was diagnosed by imaging and/or endoscopy in 74.3%, but only discovered during surgical exploration in 25.6%. Some 63.5% were diagnosed only after loop ileostomy closure, while 32.4% were before ileostomy closure. The most common methods used for diagnosis were pouchoscopy (31.1%) and gastrograffin enema (28.4%). A definitive non-operative approach was attempted in 48.6%, but was successful in only 10.8% patients overall. Surgical repair was attempted in 89.2% of patients, while 4.5% had pouch excision. Salvage operations (n=63) included sutured or stapled repair of the tip of the J (65%), pouch excision with neo-pouch (25.4%), and pouch disconnection, repair and re-anastomosis (9.5%). Ultimately 10 (13.5%) patients required pouch excision, yielding an overall 5-year pouch survival rate of 86.3%.

LIMITATIONS:
Retrospective review; referral bias may limit the generalizability.

CONCLUSIONS:
Tip of the J-pouch leaks have variable clinical presentations and require a high index of suspicion. Pouch salvage surgery is required in the majority and is associated with a high pouch salvage rate. See Video Abstract at http://links.lww.com/DCR/C50.
Shave biopsy technique and hemostasis pearl
Authors: Twede Katherine Ada , Bui Aimee Kim , Burke Jennifer 
Published: November 2022

ABSTRACT
Nurse practitioners (NPs) are frequently called on to assess and diagnose patients presenting with suspicious or aggravated skin lesions. Performing shave biopsies and removing small neoplasms can be within the scope of a general NP. We offer a thorough review of shave biopsy methods, including required materials, photographic documentation, blade preparation and orientation, and hemostasis techniques. Diagnostic considerations when choosing a shave versus other biopsy techniques are reviewed as is the removal of lesions in cosmetically sensitive areas. Finally, a unique tip to diminish intraprocedure bleeding using aluminum chloride before procedure initiation is presented.