bluuebunny/crossref_metadata_2025_split huggingface dataset:
The accuracy of gypsum casts obtained from the disinfected extended-pour alginate impressions through prolonged storage times
Authors: Sharif Rania A. , Abdelaziz Khalid M. , Alshahrani Najla M. , Almutairi Fatimah S. , Alaseri Mohrah A. , Abouzeid Hoda L. , Elagib Mohamed F. A. 
Published: June 2021

Abstract
Background
Manufacturers of the extended-pour alginates claimed their dimensional stability through prolonged storage. No data confirmed the ability of these materials to maintain their dimensions and the reproduced oral details following their chemical disinfection. Therefore, this study evaluated the dimensional stability and surface detail reproduction of gypsum casts obtained from disinfected extended-pour alginate impressions through different storage time intervals.

Methods
Two hundred and forty three hydrocolloid impressions were made from one conventional (Tropicalgin) and two extended-pour (Hydrogum 5 and Chromaprint premium) alginates. These impressions were subjected to none, spray and immersion disinfection before their storage in 100% humidity for 0, 72 and 120 h. The dimensional stability and the surface detail reproduction were indirectly evaluated under low angle illumination on the resulted gypsum casts. At α = 0.05, the parametric dimensional stability data were analyzed using One-Way ANOVA and Tukey’s comparisons, while the nonparametric detail reproduction data were analyzed using KrusKal Wallis and Mann–Whitney's tests.

Results
All gypsum casts exhibited a degree of expansion; however, the recorded expansion values did not differ between test categories (P > 0.05). Generally, casts obtained from spray-disinfected impressions showed lower detail accuracy (P < 0.05). Immersion-disinfected extended-pour alginates produced casts with better detail accuracy following 120 h of storage (P < 0.05).

Conclusion
All alginates materials offer comparable cast dimensions under different testing circumstances. Extended-pour alginates offer casts with superior surface details following their immersion disinfection and 120 h of storage. Spray-disinfection using 5.25% sodium hypochlorite affects the surface details of casts obtained from conventional and extended-pour alginates adversely.
Building family caregiver skills using a simulation-based intervention for care of patients with cancer: protocol for a randomized controlled trial
Authors: Mazanec Susan R. , Blackstone Eric , Daly Barbara J. 
Published: June 2021

Abstract
Background
Family caregivers of patients with cancer undergoing radiation therapy experience significant distress and challenges related to high symptom burden and complex care demands. This is particularly true for caregivers of patients with head and neck, esophageal, anal, rectal, and lung cancers, who are often receiving combined-modality treatment and may have tracheostomy tubes, gastrostomy tubes, or colostomies/ileostomies. This study aims to evaluate a simulation-based nursing intervention to provide information, support, and training to caregivers during radiation therapy.

Methods
This randomized controlled trial will include a sample of 180 patients and their family caregivers. Caregivers assigned to the control group will receive usual care and an informational booklet from the National Cancer Institute (NCI). Those in the intervention group will receive usual care, the NCI booklet, and three meetings with a nurse interventionist during radiation treatment followed by a booster call two weeks posttreatment. Intervention sessions focus on themes consistent with the trajectory of radiation therapy: the patient experience/needs, the caregiver experience and dyad communication, and transition to survivorship. Outcomes are measured at baseline, end of treatment (T2), and 4 (T3) and 20 (T4) weeks posttreatment, with the primary outcome being caregiver anxiety at T4.

Discussion
This trial is innovative in its use of simulation in a psychoeducational intervention for family caregivers. The intervention is administered at point-of-care and aimed at feasibility for integration into clinical practice. Patient quality of life and healthcare utilization measures will assess how providing support and training to the caregiver may impact patient outcomes.

Trial registration
The trial was registered on 08/14/2019 at ClinicalTrials.gov (identifier NCT04055948).
The Wnt-specific astacin proteinase HAS-7 restricts head organizer formation in Hydra
Authors: Ziegler Berenice , Yiallouros Irene , Trageser Benjamin , Kumar Sumit , Mercker Moritz , Kling Svenja , Fath Maike , Warnken Uwe , Schnölzer Martina , Holstein Thomas W. , Hartl Markus , Marciniak-Czochra Anna , Stetefeld Jörg , Stöcker Walter , Özbek Suat 
Published: June 2021

Abstract
Background
The Hydra head organizer acts as a signaling center that initiates and maintains the primary body axis in steady state polyps and during budding or regeneration. Wnt/beta-Catenin signaling functions as a primary cue controlling this process, but how Wnt ligand activity is locally restricted at the protein level is poorly understood. Here we report a proteomic analysis of Hydra head tissue leading to the identification of an astacin family proteinase as a Wnt processing factor.

Results
Hydra astacin-7 (HAS-7) is expressed from gland cells as an apical-distal gradient in the body column, peaking close beneath the tentacle zone. HAS-7 siRNA knockdown abrogates HyWnt3 proteolysis in the head tissue and induces a robust double axis phenotype, which is rescued by simultaneous HyWnt3 knockdown. Accordingly, double axes are also observed in conditions of increased Wnt activity as in transgenic actin::HyWnt3 and HyDkk1/2/4 siRNA treated animals. HyWnt3-induced double axes in Xenopus embryos could be rescued by coinjection of HAS-7 mRNA. Mathematical modelling combined with experimental promotor analysis indicate an indirect regulation of HAS-7 by beta-Catenin, expanding the classical Turing-type activator-inhibitor model.

Conclusions
We show the astacin family protease HAS-7 maintains a single head organizer through proteolysis of HyWnt3. Our data suggest a negative regulatory function of Wnt processing astacin proteinases in the global patterning of the oral-aboral axis in Hydra.
Unraveling synonymous and deep intronic variants causing aberrant splicing in two genetically undiagnosed epilepsy families
Authors: Li Qiang , Wang Yiting , Pan Yijun , Wang Jia , Yu Weishi , Wang Xiaodong 
Published: June 2021

Abstract
Background
Variants identified through parent–child trio-WES yield up to 28–55% positive diagnostic rate across a variety of Mendelian disorders, there remain numerous patients who do not receive a genetic diagnosis. Studies showed that some aberrant splicing variants, which are either not readily detectable by WES or could be miss-interpreted by regular detecting pipelines, are highly relevant to human diseases.

Methods
We retrospectively investigated the negative molecular diagnostics through trio-WES for 15 genetically undiagnosed patients whose clinical manifestations were highly suspected to be genetic disorders with well-established genotype–phenotype relationships. We scrutinized the synonymous variants from WES data and Sanger sequenced the suspected intronic region for deep intronic variants. The functional consequences of variants were analyzed by in vitro minigene experiments.

Results
Here, we report two abnormal splicing events, one of which caused exon truncating due to the activation of cryptic splicing site by a synonymous variant; the other caused partial intron retention due to the generation of splicing sites by a deep intronic variant.

Conclusions
We suggest that, despite initial negative genetic test results in clinically highly suspected genetic diseases, the combination of predictive bioinformatics and functional analysis should be considered to unveil the genetic etiology of undiagnosed rare diseases.
Development of IL-15/IL-15Rα sushi domain-IgG4 Fc complexes in Pichia pastoris with potent activities and prolonged half-lives
Authors: Xu Huan , Shi Mingyang , Shao Changsheng , Li Hao , Wu Jing , Yu Yin , Fang Fang , Guo Yugang , Xiao Weihua 
Published: June 2021

Abstract
Background
Interleukin-15 (IL-15) is a critical cytokine for the development, proliferation, and function of natural killer (NK) cells, NKT cells, and CD8+ memory T cells and has become one of the most promising protein molecules for the treatment of cancer and viral diseases. However, there are several limitations in applying IL-15 in therapy, such as its low yield in vitro, limited potency, and short half-life in vivo. To date, there are several recombinant IL-15 agonists based on configurational modifications that are being pursued in the treatment of cancer, such as ALT-803, which are mainly produced from mammalian cells.

Results
In this study, we designed two different forms of the IL-15 complex, which were formed by the noncovalent assembly of IL-15 with dimeric or monomeric sushi domain of IL-15 receptor α (SuIL-15Rα)-IgG4 Fc fusion protein and designated IL-15/SuIL-15Rα-dFc and IL-15/SuIL-15Rα-mFc, respectively. The two IL-15 complexes were expressed in Pichia pastoris (P. pastoris), and their activities and half-lives were evaluated and compared. Pharmacokinetic analysis showed that IL-15/SuIL-15Rα-dFc had a half-life of 14.26 h while IL-15/SuIL-15Rα-mFc had a half-life of 9.16 h in mice, which were much longer than the 0.7-h half-life of commercial recombinant human IL-15 (rhIL-15). Treatment of mice with intravenous injection of the two IL-15 complexes resulted in significant increases in NK cells, NKT cells, and memory CD8+ T cells, which were not observed after rhIL-15 treatment. Treatment of human peripheral blood mononuclear cells (PBMCs) from healthy donors with the two IL-15 complexes yielded enhanced NK and CD8+ T cell activation and proliferation, which was comparable to the effect of rhIL-15.

Conclusions
These findings indicate that the IL-15/SuIL-15Rα-dFc and IL-15/SuIL-15Rα-mFc produced in P. pastoris exhibit potent activities and prolonged half-lives and may serve as superagonists for immunotherapy in further research and applications.
Progress and challenges of integrated drug efficacy surveillance for uncomplicated malaria in Thailand
Authors: Sudathip Prayuth , Saejeng Aungkana , Khantikul Nardlada , Thongrad Thannikar , Kitchakarn Suravadee , Sugaram Rungniran , Lertpiriyasuwat Cheewanan , Areechokchai Darin , Gopinath Deyer , Sintasath David , Ringwald Pascal , Naowarat Sathapana , Pinyajeerapat Niparueradee , Bustos Maria Dorina , Shah Jui A. 
Published: June 2021

Abstract
Background
Integrated drug efficacy surveillance (iDES) was formally introduced nationally across Thailand in fiscal year 2018 (FY2018), building on a history of drug efficacy monitoring and interventions. According to the National Malaria Elimination Strategy for Thailand 2017–2026, diagnosis is microscopically confirmed, treatment is prescribed, and patients are followed up four times to ensure cure.

Methods
Routine patient data were extracted from the malaria information system for FY2018–FY2020. Treatment failure of first-line therapy was defined as confirmed parasite reappearance within 42 days for Plasmodium falciparum and 28 days for Plasmodium vivax. The primary outcome was the crude drug efficacy rate, estimated using Kaplan–Meier methods, at day 42 for P. falciparum treated with dihydroartemisinin–piperaquine plus primaquine, and day 28 for P. vivax treated with chloroquine plus primaquine; day 60 and day 90 efficacy were secondary outcomes for P. vivax.

Results
The proportion of patients with outcomes recorded at day 42 for P. falciparum malaria and at day 28 for P. vivax malaria has been increasing, with FY2020 follow-up rates of 61.5% and 57.2%, respectively. For P. falciparum malaria, day 42 efficacy in FY2018 was 92.4% (n = 249), in FY2019 93.3% (n = 379), and in FY2020 98.0% (n = 167). Plasmodium falciparum recurrences occurred disproportionally in Sisaket Province, with day 42 efficacy rates of 75.9% in FY2018 (n = 59) and 49.4% in FY2019 (n = 49), leading to an update in first-line therapy to pyronaridine–artesunate at the provincial level, rolled out in FY2020. For P. vivax malaria, day 28 efficacy (chloroquine efficacy) was 98.5% in FY2018 (n = 2048), 99.1% in FY2019 (n = 2206), and 99.9% in FY2020 (n = 2448), and day 90 efficacy (primaquine efficacy) was 94.8%, 96.3%, and 97.1%, respectively.

Conclusions
In Thailand, iDES provided operationally relevant data on drug efficacy, enabling the rapid amendment of treatment guidelines to improve patient outcomes and reduce the potential for the spread of drug-resistant parasites. A strong case-based surveillance system, integration with other health system processes, supporting biomarker collection and molecular analyses, and cross-border collaboration may maximize the potential of iDES in countries moving towards elimination.
Application of MALDI-TOF MS to assess clinical characteristics, risk factors, and outcomes associated with anaerobic bloodstream infection: a retrospective observational study
Authors: Watanabe Tsuyoshi , Hara Yuki , Yoshimi Yusuke , Yokoyama-kokuryo Waka , Fujita Yoshiro , Yokoe Masamichi , Noguchi Yoshinori 
Published: June 2021

Abstract
Background
Correctly identifying anaerobic bloodstream infections (BSIs) is difficult. However, a new technique, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), enables more accurate identification and appropriate treatment. Anaerobic BSIs identified by MALDI-TOF MS were retrospectively analyzed to determine the clinical and microbiological features and patient outcomes based on the anaerobic genera or group.

Methods
Medical records of patients with anaerobic BSIs were used to conduct a single-center retrospective cohort study from January 2016 to December 2020 in Nagoya, Japan. Multivariate logistic regression analysis was performed to determine the independent risk factors for in-hospital mortality.

Results
Of the 215 patients with anaerobic BSIs, 31 had multiple anaerobic organisms in the blood culture, including 264 total episodes of anaerobic BSIs. Bacteroides spp. were isolated the most (n = 74), followed by gram-positive non-spore-forming bacilli (n = 57), Clostridium spp. (n = 52), gram-positive anaerobic cocci (GPAC) (n = 27), and gram-negative cocci (n = 7). The median patient age was 76 years; 56.7% were male. The most common focal infection site was intra-abdominal (36.7%). The in-hospital mortality caused by anaerobic BSIs was 21.3%, and was highest with Clostridium spp. (36.5%) and lowest with GPAC (3.7%). Age, solid tumors, and Clostridium spp. were independent risk factors for in-hospital mortality.

Conclusions
We identified current anaerobic BSI trends using MALDI-TOF MS and reported that mortality in patients with anaerobic BSIs patients was highest with Clostridium spp. infections.
Self-assembling ferritin-dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells
Authors: Palombarini Federica , Masciarelli Silvia , Incocciati Alessio , Liccardo Francesca , Di Fabio Elisa , Iazzetti Antonia , Fabrizi Giancarlo , Fazi Francesco , Macone Alberto , Bonamore Alessandra , Boffi Alberto 
Published: June 2021

Abstract
Background
In recent years, the use of ferritins as nano-vehicles for drug delivery is taking center stage. Compared to other similar nanocarriers, Archaeoglobus fulgidus ferritin is particularly interesting due to its unique ability to assemble-disassemble under very mild conditions. Recently this ferritin was engineered to get a chimeric protein targeted to human CD71 receptor, typically overexpressed in cancer cells.

Results
Archaeoglobus fulgidus chimeric ferritin was used to generate a self-assembling hybrid nanoparticle hosting an aminic dendrimer together with a small nucleic acid. The positively charged dendrimer can indeed establish electrostatic interactions with the chimeric ferritin internal surface, allowing the formation of a protein-dendrimer binary system. The 4 large triangular openings on the ferritin shell represent a gate for negatively charged small RNAs, which access the internal cavity attracted by the dense positive charge of the dendrimer. This ternary protein-dendrimer-RNA system is efficiently uptaken by acute myeloid leukemia cells, typically difficult to transfect. As a proof of concept, we used a microRNA whose cellular delivery and induced phenotypic effects can be easily detected. In this article we have demonstrated that this hybrid nanoparticle successfully delivers a pre-miRNA to leukemia cells. Once delivered, the nucleic acid is released into the cytosol and processed to mature miRNA, thus eliciting phenotypic effects and morphological changes similar to the initial stages of granulocyte differentiation.

Conclusion
The results here presented pave the way for the design of a new family of protein-based transfecting agents that can specifically target a wide range of diseased cells.

Graphic abstract
Liver injury in COVID-19: clinical features and treatment management
Authors: Yu Dongdong , Du Qingru , Yan Shengguang , Guo Xu-Guang , He Yehao , Zhu Guodong , Zhao Kewei , Ouyang Shi 
Published: June 2021

AbstractSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread to many countries around the world. In addition to lung disease, severe cases also displayed varying degrees of liver injury. This article will describe the latest developments regarding coronavirus and the pathogenesis of liver injury, the prone population and clinical characteristics of these patients, as well as providing some suggestions for clinical treatment.
On pickles: biological and sociocultural links between fermented foods and the human gut microbiome
Authors: Flachs Andrew , Orkin Joseph D. 
Published: June 2021

AbstractBackgroundThe composition of the human microbiome varies considerably in diversity and density across communities as a function of the foods we eat and the places we live. While all foods contain microbes, humans directly shape this microbial ecology through fermentation. Fermented foods are produced from microbial reactions that depend on local environmental conditions, fermentation practices, and the manner in which foods are prepared and consumed. These interactions are of special interest to ethnobiologists because they link investigations of how people shape and know the world around them to local knowledge, food traditions, local flora, and microbial taxa.MethodsIn this manuscript, we report on data collected at a fermentation revivalist workshop in Tennessee. To ask how fermentation traditions are learned and influence macro and micro ecologies, we conducted interviews with eleven people and participated in a four-day craft fermentation workshop. We also collected 46 fermented food products and 46 stool samples from workshop participants eating those fermented foods.ResultsWe identified ten major themes comprised of 29 sub-themes drawn from 326 marked codes in the transcripts. In combination, this analysis allowed us to summarize key experiences with fermentation, particularly those related to a sense of authenticity, place, health, and the discovery of tactile work. From the 605 amplicon sequence variants (ASVs) shared between food and fecal samples, we identified 25 candidate ASVs that are suspected to have been transmitted from fermented food samples to the gut microbiomes of the workshop participants. Our results indicate that many of the foods prepared and consumed during the workshop were rich sources of probiotic microbes.ConclusionsBy combining these qualitative social and quantitative microbiological data, we suggest that variation in culturally informed fermentation practices introduces variation in bacterial flora even among very similar foods, and that these food products can influence gut microbial ecology.
The use of extracorporeal shock wave therapy for the treatment of bone marrow oedema — a systematic review and meta-analysis
Authors: Häußer Jonathan , Wieber Juliane , Catalá-Lehnen Philip 
Published: June 2021

Abstract
Background
Extracorporeal shock wave therapy (ESWT) has been used for various pathologies associated with bone marrow oedema (BME). However, it is still not clear whether ESWT may be favourable in the treatment of BME. Therefore, the aim of this systematic review was to assess the efficacy of ESWT for the treatment of BME.

Methods
MEDLINE was searched for relevant literature with no time constraints. Both randomized and non-randomized trials were included. Case reports and conference abstracts were excluded. Titles and abstracts were screened and full-text articles of included studies were retrieved. Data on the effect of ESWT on pain, function, and the BME area on magnet resonance imaging were extracted.

Results
Pain, function, and magnet resonance imaging results all improved across the studies — regardless of whether it was a randomized or non-randomized study. This effect was consistent across multiple pathologies such as osteonecrosis of the femoral head, BME associated with knee osteoarthritis, Kienböck’s disease, and osteitis pubis. The meta-analysis showed that pain (after 1 month: weighted mean difference (WMD) = − 2.23, 95% CI − 2.58 to − 1.88, P < 0.0001; after 3–6 month: WMD = − 1.72, 95% CI − 2.52 to − 0.92, P < 0.00001) and function (after 1 month: WMD = − 1.59, 95% CI − 2.04 to − 1.14, P < 0.0001; after 3–6 month: WMD = − 2.06, 95% CI − 3.16 to − 0.96, P = 0.0002; after ≥ 12 month: WMD = − 1.20, 95% CI − 1.83 to − 0.56, P = 0.0002) was reduced in terms of ESWT treatment compared to a control group.

Conclusions
Based on the available evidence, ESWT may be an adequate option for conservative therapy in pathologies involving BME.

Trial registration
PROSPERO, CRD42021201719. Registered 23 December 2020
Raloxifene retards the progression of adjacent segmental intervertebral disc degeneration by inhibiting apoptosis of nucleus pulposus in ovariectomized rats
Authors: Sun Qi , Nan Xin-Yu , Tian Fa-Ming , Liu Fang , Ping Shao-Hua , Zhou Zhuang , Zhang Liu 
Published: June 2021

Abstract
Background
Adjacent segmental intervertebral disk degeneration (ASDD) is a major complication secondary to lumbar fusion. Although ASSD pathogenesis remains unclear, the primary cause of intervertebral disk degeneration (IVDD) development is apoptosis of nucleus pulposus (NP). Raloxifene (RAL) could delay ASDD by inhibiting NP apoptosis.

Methods
An ASDD rat model was established by ovariectomy (OVX) and posterolateral spinal fusion (PLF) on levels 4–5 of the lumbar vertebrae. Rats in the treatment groups were administered 1 mg/kg/d RAL by gavage for 12 weeks, following which, all animals were euthanized. Lumbar fusion, apoptosis, ASDD, and vertebrae micro-architecture were evaluated.

Results
RAL maintained intervertebral disk height (DHI), delayed vertebral osteoporosis, reduced histological score, and inhibited apoptosis. The OVX+PLF+RAL group revealed upregulated expression of aggrecan and B-cell lymphoma-2 (bcl2), as well as significantly downregulated expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), metalloproteinase-13 (MMP-13), caspase-3, BCL2-associated X (bax), and transferase dUTP nick end labeling (TUNEL) staining. Micro-computed tomography (Micro-CT) analysis revealed higher bone volume fraction (BV/TV), bone mineral density (BMD), and trabecular number (Tb.N), and lower trabecular separation (Tb.Sp) in OVX+PLF+RAL group than in the OVX+PLF group.

Conclusions
RAL can postpone ASDD development in OVX rats through inhibiting extracellular matrix metabolic imbalance, NP cell apoptosis, and vertebral osteoporosis. These findings showed RAL as a potential therapeutic target for ASDD.