bluuebunny/crossref_metadata_2025 huggingface dataset:
Prescribers’ satisfaction with delivering medications for opioid use disorder
Authors: Knudsen Hannah K. , Brown Randy , Jacobson Nora , Horst Julie , Kim Jee-Seon , Kim Hanna , Madden Lynn M. , Haram Eric , Molfenter Todd
Published: October 2021

Background

Expanding access to medications for opioid use disorder (MOUD), such as buprenorphine and extended release (XR) naltrexone, is critical to addressing the US opioid epidemic, but little is known about prescriber satisfaction with delivering these two types of MOUD. The current study describes the satisfaction of prescribers delivering buprenorphine and XR-naltrexone while examining whether satisfaction is associated with current patient census and organizational environment.

Methods

As part of a cluster randomized clinical trial (RCT) focused on expanding access to medication for opioid use disorder, 41 MOUD prescribers in Florida, Ohio, and Wisconsin completed a web-based survey. The survey included measures of prescriber satisfaction with delivering buprenorphine treatment and XR-naltrexone. In addition, the survey measured several prescriber characteristics and their perceptions of the organizational environment.

Results

Prescribers were generally satisfied with their work in delivering these two types of MOUD. Prescribers reporting a greater number of patients (r = .46, p = .006), those who would recommend the center to others (r = .56, p < .001), and those reporting positive relationships with staff (r = .56, p < .001) reported significantly greater overall satisfaction with delivering buprenorphine treatment. Prescribers who more strongly endorsed feeling overburdened reported lower overall buprenorphine satisfaction (r = -.37, p = .02). None of the prescriber characteristics or perceptions of the organizational environment were significantly associated with overall satisfaction with delivering XR-naltrexone treatment.

Conclusions

The generally high levels of satisfaction with both types of MOUD is notable given that prescriber dissatisfaction can lead to turnover and impact intentions to leave the profession. Future research should continue to explore the prescriber characteristics and organizational factors associated with satisfaction in providing different types of MOUD.

Registration

ClinicalTrials.gov. NCT02926482. Date of registration: September 9, 2016. https://clinicaltrials.gov/ct2/show/NCT02926482.
Poor outcomes of revision total knee arthroplasty in patients with septic loosening compared to patients with aseptic loosening
Authors: Baek Ji-Hoon , Lee Su Chan , Jin Hosun , Kim Jin-Woo , Ahn Hye Sun , Nam Chang Hyun
Published: October 2021

Background

The purpose of this study was to compare the functional outcomes, activity levels, mortalities, implant survival rates, and complications in revision total knee arthroplasty (TKA) of patients with septic loosening with those in patients with aseptic loosening over a minimum 10-year follow-up period.

Methods

A cohort of 78 patients (36 septic loosening and 42 aseptic loosening) was selected between January 2008 and December 2009. The functional outcomes, activity levels, mortalities, implant survival rates, and complications of revision TKA in patients with septic and aseptic loosening were compared.

Results

The mean Knee Society knee scores in the septic and aseptic groups improved from 36.7 and 37.4 preoperatively to 65.3 and 76.8 points at the final follow-up, respectively (p < 0.05). Outdoor ambulatory patients at the final follow-up included 20 of 29 (69.0%) patients in the septic group and 35 of 39 (89.7%) patients in the aseptic group (p < 0.05). The cumulative mortality rates in the septic and aseptic groups were 19.4% (7/36) and 7.1% (3/42) (p = 0.102) at final follow-up, respectively. Kaplan–Meier survivorship analysis with re-revision of either component as an endpoint in the septic and aseptic groups estimated 86.5% and 95.5% chance of survival for 10 years, respectively.

Conclusions

Revision TKA in patients with septic loosening had worse functional outcomes and higher mortality over a minimum 10-year follow-up period compared with that in patients with aseptic loosening.

Level of evidence

IV.
Elevated tumor markers in a benign lung disease
Authors: Chen Quan , Lu Qijue , Fei Xiang , Li Chunguang , Li Bai
Published: October 2021

Background

This study aimed to determine the underlying pathophysiologic mechanism of elevated carbohydrate antigen 19-9 (CA19-9) in pulmonary sequestration (PS) patients.

Materials and methods

Four pulmonary sequestration patients, 12 pneumonia patients and 12 healthy adult volunteers were prospectively studied. Specimens from another 34 pulmonary sequestration patients were retrospectively analyzed. Serum CA19-9 levels of 4 patients were tested before and 1 week, 1 month and 3 months after surgery. The CA19-9 levels of 12 pneumonia patients and 12 healthy adult volunteers were tested as controls. The expression and localization of CA19-9 in diseased lesions and corresponding normal lung tissues were analyzed by Immunohistochemical (IHC). Hematoxylin–eosin (HE) staining was performed to observe the pathological changes in pulmonary sequestration tissues.

Results

Serum CA19-9 levels were significantly higher in the 4 patients (797.3 ± 316 IU/ml) than in the pneumonia patients (10.07 ± 5.01 IU/ml) and healthy volunteers (9.85 ± 4.12 IU/ml). In addition, serum CA19-9 levels decreased dramatically after the focus was removed. Positive staining of CA19-9 was found in 70% (24/34) of pulmonary sequestration tissues, and CA19-9 was mainly expressed in the bronchial mucus. In the 4 diseased lesions, deformed alveolar structure and inflammatory cell infiltration were observed, and the degree of damage was positively correlated with serum CA19-9 levels.

Conclusions

CA19-9 could be generated by abnormal columnar epithelia in pulmonary sequestration tissues and was transported into circulation after alveoli damage. CA19-9 could serve as an adjuvant diagnostic marker in pulmonary sequestration.
A deep learning method for predicting knee osteoarthritis radiographic progression from MRI
Authors: Schiratti Jean-Baptiste , Dubois Rémy , Herent Paul , Cahané David , Dachary Jocelyn , Clozel Thomas , Wainrib Gilles , Keime-Guibert Florence , Lalande Agnes , Pueyo Maria , Guillier Romain , Gabarroca Christine , Moingeon Philippe
Published: October 2021

Background

The identification of patients with knee osteoarthritis (OA) likely to progress rapidly in terms of structure is critical to facilitate the development of disease-modifying drugs.

Methods

Using 9280 knee magnetic resonance (MR) images (3268 patients) from the Osteoarthritis Initiative (OAI) database , we implemented a deep learning method to predict, from MR images and clinical variables including body mass index (BMI), further cartilage degradation measured by joint space narrowing at 12 months.

Results

Using COR IW TSE images, our classification model achieved a ROC AUC score of 65%. On a similar task, trained radiologists obtained a ROC AUC score of 58.7% highlighting the difficulty of the classification task. Additional analyses conducted in parallel to predict pain grade evaluated by the WOMAC pain index achieved a ROC AUC score of 72%. Attention maps provided evidence for distinct specific areas as being relevant in those two predictive models, including the medial joint space for JSN progression and the intra-articular space for pain prediction.

Conclusions

This feasibility study demonstrates the interest of deep learning applied to OA, with a potential to support even trained radiologists in the challenging task of identifying patients with a high-risk of disease progression.
Improving hospital-based point-of-care ultrasound cleaning practices using targeted interventions: a pre–post study
Authors: Van Kalsbeek Daniel , Enroth Karl , Lyden Elizabeth , Rupp Mark E. , Smith Christopher J.
Published: October 2021

Background

Point-of-care ultrasound (POCUS) devices are becoming more widely used in healthcare and have the potential to act as fomites. The objective of this project was to study the thoroughness of cleaning of POCUS machines before and after a quality improvement initiative. We designed a mixed-methods, pre/post study which took place over the course of one year at a university-affiliated health center. Cleaning rates of four ultrasound machines used by hospital medicine and critical care medicine services were evaluated using fluorescent marking. Interventions targeted physicians’ knowledge of best practices and improved access to cleaning supplies. Pre- and post-intervention cleaning rates were compared using a generalized linear model. The impact of the corona virus disease of 2019 (COVID-19) pandemic on baseline cleaning rates was also evaluated. Physicians’ attitudes and knowledge of cleaning practices were evaluated via unpaired pre/post surveys.

Results

There was significant improvement in thoroughness of cleaning following intervention (pre 0.62, SE 0.05; post 0.89, SE 0.07), p < 0.0001). There was no difference in baseline cleaning rates before (0.63, SE 0.09) and after (0.61, SE 0.1) the onset of the COVID-19 pandemic (p = 0.78). Post-intervention surveying found improved understanding of guideline-based cleaning practice, better performance on knowledge-based questions, and fewer reported barriers to machine cleaning.

Conclusion

Thoroughness of cleaning of POCUS machines can be improved with practical interventions that target knowledge and access to cleaning supplies.
Guidelines for pre-analytical conditions for assessing the methylation of circulating cell-free DNA
Authors: Kerachian Mohammad Amin , Azghandi Marjan , Mozaffari-Jovin Sina , Thierry Alain R.
Published: October 2021

Methylation analysis of circulating cell-free DNA (cirDNA), as a liquid biopsy, has a significant potential to advance the detection, prognosis, and treatment of cancer, as well as many genetic disorders. The role of epigenetics in disease development has been reported in several hereditary disorders, and epigenetic modifications are regarded as one of the earliest and most significant genomic aberrations that arise during carcinogenesis. Liquid biopsy can be employed for the detection of these epigenetic biomarkers. It consists of isolation (pre-analytical) and detection (analytical) phases. The choice of pre-analytical variables comprising cirDNA extraction and bisulfite conversion methods can affect the identification of cirDNA methylation. Indeed, different techniques give a different return of cirDNA, which confirms the importance of pre-analytical procedures in clinical diagnostics. Although novel techniques have been developed for the simplification of methylation analysis, the process remains complex, as the steps of DNA extraction, bisulfite treatment, and methylation detection are each carried out separately. Recent studies have noted the absence of any standard method for the pre-analytical processing of methylated cirDNA. We have therefore conducted a comprehensive and systematic review of the important pre-analytical and analytical variables and the patient-related factors which form the basis of our guidelines for analyzing methylated cirDNA in liquid biopsy.
Atypical presentation of autoimmune hepatitis–primary sclerosing cholangitis overlap syndrome associated with hypereosinophilia: a case report and review of the literature
Authors: Hatami Behzad , Rahmani Seraji Hamide , fallahi Mohaddese
Published: October 2021

Background

Autoimmune hepatitis–primary sclerosing cholangitis overlap syndrome is a form of autoimmune hepatitis with cholestatic features and is characterized by negative anti-mitochondrial antibody and cholangiographic changes on magnetic resonance cholangiopancreatography or endoscopic retrograde cholangiopancreatography. Peripheral blood hypereosinophilia in conjunction with autoimmune hepatitis–primary sclerosing cholangitis overlap syndrome has not been reported yet. Here we present a case of autoimmune hepatitis–primary sclerosing cholangitis overlap syndrome with hypereosinophilia.

Case presentation

A 33-year-old Iranian man with the fatigue, jaundice, elevated liver enzymes and alkaline phosphatase, and hypereosinophilia was referred to our hospital. Viral and autoimmune hepatitis were excluded, and secondary workups for hypereosinophilia were all negative. Magnetic resonance cholangiopancreatography showed beaded appearance of intra- and extrahepatic biliary tree, and liver biopsy revealed interface hepatitis. Therefore, the diagnosis of autoimmune hepatitis–primary sclerosing cholangitis overlap syndrome was made, and prednisolone, azathioprine, and ursodeoxycholic acid was initiated. His jaundice and peripheral blood eosinophilia resolved after 2 weeks, and he became completely asymptomatic.

Conclusion

Eosinophils might contribute to the clinical presentation and disease complications.
Expression of cytokines in dairy cattle mammary gland parenchyma during chronic staphylococcal infection
Authors: Kawecka-Grochocka Ewelina , Zalewska Magdalena , Rzewuska Magdalena , Kościuczuk Ewa , Ząbek Tomasz , Sakowski Tomasz , Marczak Sylwester , Bagnicka Emilia
Published: October 2021

The study aim was to determine the expression of genes potentially related to chronic mastitis at the mRNA and protein levels, viz. chemokine C–C motif receptor 1 (CCR1), C–C motif chemokine ligand 2 (CCL2), C–C motif chemokine ligand 5 (CXCL5), tumor necrosis factor α (TNFα), interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 18 (IL-18), in bovine mammary gland parenchyma. The study examines the differences in expression of selected genes between cows with chronic mastitis caused by coagulase-positive (CoPS) or coagulase-negative staphylococci (CoNS) and those with healthy udders (H). Samples were collected from the udder quarters from 40 Polish Holstein–Friesian cows; 54 of these samples were chosen for analysis based on microbiological analysis of milk taken two days before slaughter. They were categorized into three groups: CoPS (N = 27), CoNS (N = 14) and H (N = 13). The RNA expression was analyzed by RT-qPCR and protein concentration by ELISA. No differences in the mRNA levels of seven genes (TNFα, IL-18, CCR1, IL-1β, CCL2, IL-8, IL-6) and four proteins (TNFα, IL-18, CCR1, IL-1β) were identified between the CoPS and H groups. Higher transcript levels of CXCL5 (p ≤ 0.05) gene were noted in CoPS than in H. Compared to H, higher concentrations of IL-8 and CXCL5 (p ≤ 0.05) were observed in CoPS (0.05 < p < 0.1) and CCL2 (0.05 < p < 0.1) in CoNS, while lower levels of Il-6 were found in CoPS. This may suggest that during chronic mastitis the organism stops producing pro-inflammatory cytokines, probably to protect the host tissues against their damage during prolonged infection.
Neuromedin B promotes chondrocyte differentiation of mesenchymal stromal cells via calcineurin and calcium signaling
Authors: Maumus Marie , Fonteneau Guillaume , Ruiz Maxime , Assou Said , Boukhaddaoui Hassan , Pastoureau Philippe , De Ceuninck Frédéric , Jorgensen Christian , Noel Danièle
Published: October 2021

Background

Articular cartilage is a complex tissue with poor healing capacities. Current approaches for cartilage repair based on mesenchymal stromal cells (MSCs) are often disappointing because of the lack of relevant differentiation factors that could drive MSC differentiation towards a stable mature chondrocyte phenotype.

Results

We used a large-scale transcriptomic approach to identify genes that are modulated at early stages of chondrogenic differentiation using the reference cartilage micropellet model. We identified several modulated genes and selected neuromedin B (NMB) as one of the early and transiently modulated genes. We found that the timely regulated increase of NMB was specific for chondrogenesis and not observed during osteogenesis or adipogenesis. Furthermore, NMB expression levels correlated with the differentiation capacity of MSCs and its inhibition resulted in impaired chondrogenic differentiation indicating that NMB is required for chondrogenesis. We further showed that NMB activated the calcineurin activity through a Ca2+-dependent signaling pathway.

Conclusion

NMB is a newly described chondroinductive bioactive factor that upregulates the key chondrogenic transcription factor Sox9 through the modulation of Ca2+ signaling pathway and calcineurin activity.

Graphical abstract
On discrete weighted Hardy type inequalities and properties of weighted discrete Muckenhoupt classes
Authors: Saker S. H. , Rabie S. S. , Agarwal R. P.
Published: October 2021

In this paper, first we prove some new refinements of discrete weighted inequalities with negative powers on finite intervals. Next, by employing these inequalities, we prove that the self-improving property (backward propagation property) of the weighted discrete Muckenhoupt classes holds. The main results give exact values of the limit exponents as well as the new constants of the new classes. As an application, we establish the self-improving property (forward propagation property) of the discrete Gehring class.
New version of fractional Simpson type inequalities for twice differentiable functions
Authors: Hezenci Fatih , Budak Hüseyin , Kara Hasan
Published: October 2021

Simpson inequalities for differentiable convex functions and their fractional versions have been studied extensively. Simpson type inequalities for twice differentiable functions are also investigated. More precisely, Budak et al. established the first result on fractional Simpson inequality for twice differentiable functions. In the present article, we prove a new identity for twice differentiable functions. In addition to this, we establish several fractional Simpson type inequalities for functions whose second derivatives in absolute value are convex. This paper is a new version of fractional Simpson type inequalities for twice differentiable functions.
TREM2 modulates differential deposition of modified and non-modified Aβ species in extracellular plaques and intraneuronal deposits
Authors: Joshi Pranav , Riffel Florian , Kumar Sathish , Villacampa Nàdia , Theil Sandra , Parhizkar Samira , Haass Christian , Colonna Marco , Heneka Michael T. , Arzberger Thomas , Herms Jochen , Walter Jochen
Published: October 2021

Progressive accumulation of Amyloid-β (Aβ) deposits in the brain is a characteristic neuropathological hallmark of Alzheimer’s disease (AD). During disease progression, extracellular Aβ plaques undergo specific changes in their composition by the sequential deposition of different modified Aβ species. Microglia are implicated in the restriction of amyloid deposits and play a major role in internalization and degradation of Aβ. Recent studies showed that rare variants of the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) are associated with an increased risk for AD. Post-translational modifications of Aβ could modulate the interaction with TREM2, and the uptake by microglia. Here, we demonstrate that genetic deletion of TREM2 or expression of a disease associated TREM2 variant in mice lead to differential accumulation of modified and non-modified Aβ species in extracellular plaques and intraneuronal deposits. Human brains with rare TREM2 AD risk variants also showed altered deposition of modified Aβ species in the different brain lesions as compared to cases with the common variant of TREM2. These findings indicate that TREM2 plays a critical role in the development and the composition of Aβ deposits, not only in extracellular plaques, but also intraneuronally, that both could contribute to the pathogenesis of AD.
Clinical significance of lactate clearance in patients with cardiogenic shock: results from the RESCUE registry
Authors: Park Ik Hyun , Yang Jeong Hoon , Jang Woo Jin , Chun Woo Jung , Oh Ju Hyeon , Park Yong Hwan , Ko Young-Guk , Yu Cheol Woong , Kim Bum Sung , Kim Hyun-Joong , Lee Hyun Jong , Jeong Jin-Ok , Gwon Hyeon-Cheol
Published: October 2021

Background

Limited data are available on the clinical significance of lactate clearance (LC) in patients with cardiogenic shock (CS). This study investigated the prognostic role of LC in CS patients.

Methods

We analyzed data from 628 patients in the RESCUE registry, a multicenter, observational cohort enrolled between January 2014 and December 2018. Univariable logistic regression analysis was performed to determine the prognostic implications of 24 h LC, and then patients were divided into two groups according to the cut-off value of 24 h LC (high lactate clearance [HLC] group vs. low lactate clearance [LLC] group). The primary outcome was in-hospital mortality. We also assessed all-cause mortality at 12 month follow-up and compared the prognostic performance of 24 h LC according to initial serum lactate level.

Results

In the univariable logistic regression analysis, 24 h LC was associated with in-hospital mortality (odds ratio 0.989, 95% confidence interval [CI] 0.985–0.993,p < 0.001), and the cut-off value for the LC of the study population was 64%. The HLC group (initial 24 h LC ≥ 64%, n = 333) had a significantly lower incidence of in-hospital death than the LLC group (n = 295) (25.5% in the HLC group vs. 42.7% in the LLC group,p < 0.001). During 12 months of follow-up, the cumulative incidence of all-cause death was significantly lower in the HLC group than in the LLC group (33.0% vs. 48.8%; hazard ratio 0.55; 95% CI 0.42–0.70;p < 0.001). In subgroup analysis, 24 h LC predicted in-hospital mortality better in patients with initial serum lactate > 5 mmol/L than in those with serum lactate ≤ 5 mmol/L (c-statistics of initial serum lactate > 5 mmol/L = 0.782 vs. c-statistics of initial serum lactate ≤ 5 mmol/L = 0.660,p = 0.011).

Conclusions

Higher LC during the early phase of CS was associated with reduced risk of in-hospital and 12 month all-cause mortalities. Patients with LC ≥ 64% during the 24 h after CS onset could expect a favorable prognosis, especially those with an initial serum lactate > 5 mmol/L.

Trial registration:RESCUE (REtrospective and prospective observational Study to investigate Clinical oUtcomes and Efficacy of left ventricular assist device for Korean patients with cardiogenic shock), NCT02985008, Registered December 5, 2016—retrospectively and prospectively registered,https://clinicaltrials.gov/ct2/show/record/NCT02985008
Effects of dexamethasone on immune dysfunction and ventilator-associated pneumonia in COVID-19 acute respiratory distress syndrome: an observational study
Authors: Cour Martin , Simon Marie , Argaud Laurent , Monneret Guillaume , Venet Fabienne
Published: October 2021

Dexamethasone improves survival of patients with COVID-19 acute respiratory distress syndrome, but might shorten the delay between the start of invasive mechanical ventilation and the occurrence of ventilator-associated pneumonia, suggesting possible worsening of COVID-19-induced immune dysfunction with this treatment. In a prospective observational study, we found that mechanically ventilated patients with COVID-19 treated with dexamethasone presented earlier ventilator-associated pneumonia, had significantly lower monocyte Human Leukocyte Antigen-DR expression and number of circulating CD4 + cells after ICU admission, than those not treated with corticoids.
The gut microbiome and metabolome of Himalayan Griffons (Gyps himalayensis): insights into the adaptation to carrion-feeding habits in avian scavengers
Authors: Wang Wen , Gao Xiaolong , Zheng Sisi , Lancuo Zhuoma , Li Ying , Zhu Lilin , Hou Jianping , Hai Jiayi , Long Xin , Chen Hanxi , Druzyaka Alexey , Sharshov Kirill
Published: October 2021

Background

Himalayan Griffons (Gyps himalayensis), large scavenging raptors widely distributed in Qinghai-Tibetan Plateau, have evolved a remarkable ability to feed on carcasses without suffering any adverse effects. The gut microbiome plays an important role in animal physiological and pathological processes, and has also been found to play a health protective role in the vulture adaptation to scavenging. However, the microbial taxonomic diversity (including nonculturable and culturable microbes), functions, and metabolites related to Himalayan Griffons have not been fully explored.

Methods

In the present study, the 28 fecal samples of the Himalayan Griffons and 8 carrion samples were collected and sequenced using high-throughput 16S rRNA gene sequencing methods to analyze the composition and functional structures of the microbiomes. Twelve fecal samples of the Himalayan Griffons were analyzed using untargeted Liquid Chromatography Mass Spectroscopy (LC–MS) to identify metabolites. We used different culture conditions to grow Himalayan Griffons gut microbes. Inhibitory effects of gut beneficial bacteria on 5 common pathogenic bacteria were also tested using the Oxford cup method.

Results

According to the results of the culture-independent method, a high abundance of four major phyla in Himalayan Griffons were identified, including Fusobacteria, Firmicutes, Bacteroidetes, and Proteobacteria. The most abundant genera were Fusobacterium, followed by Clostridium_sensu_stricto_1, Cetobacterium, Epulopiscium, and Bacteroides. The predicted primary functional categories of the Himalayan Griffons’ gut microbiome were associated with carbohydrate and amino acid metabolism, replication and repair, and membrane transport. LC–MS metabolomic analysis showed a total of 154 metabolites in all the fecal samples. Cultivation yielded 184 bacterial isolates with Escherichia coli, Enterococcus faecium, Enterococcus hirae, and Paeniclostridium sordellii as most common isolates. Moreover, 7 potential beneficial gut bacteria isolated showed certain inhibition to 5 common pathogenic bacteria.

Conclusions

Our findings broaden and deepen the understanding of Himalayan Griffons’ gut microbiome, and highlighted the importance of gut microbiome-mediated adaptation to scavenging habits. In particular, our results highlighted the protective role of gut beneficial bacteria in the Himalayan Griffons against pathogenic bacteria that appear in rotten food resources.
Evaluation of bioactivity and phytochemical screening of endophytic fungi isolated from Ceriops decandra (Griff.) W. Theob, a mangrove plant in Bangladesh
Authors: Munshi Mita , Sohrab Md. Hossain , Begum Mst. Nadira , Rony Sattyajit Roy , Karim Md. Adnan , Afroz Farhana , Hasan Md. Nazmul
Published: October 2021

Background

Due to increasing number of individuals within the world having health issues caused by varied cancers, drug-resistant microorganism, parasitic protozoans, and fungi could be a cause for alarm. Endophyte’s are a unique source of medicinal compounds which requires an intensive seek for newer and simpler agents to handle these sickness issues is currently advancing. This study explores the description of endophytic fungi of Ceriops decandra (Griff.) W. Theob., a mangrove plant growing in mangrove forest, Sundarban, Bangladesh.

Methods

The endophytic fungi of experimental plants were identified by DNA amplification and sequencing of the internal transcribed spacer (ITS) region Moreover, cytotoxicity, antioxidant and antimicrobial tests were assessed. In addition, the screening of extracts was performed by visual detection using UV light.

Results

Three fungi namely CEDBE-1, CEDLE-6 and CEDLE-10 (internal strain no) were isolated as endophytic fungi and identified as Fusarium oxysporum, Clonostachys spp. and Fusarium solani respectively on the basis of morphological characteristics and DNA sequencing. The isolates were cultured at 280 C±2 for 21 days in Potato Dextrose Agar (PDA) media. The extracts of fungal isolates were examined at 100 µg/disc concentration for the screening of antibacterial activity and exhibited no activity against tested human pathogenic bacteria. The strain CEDBE-1 showed highest antioxidant activity of IC50 value of 31.07 µg/mL comparing with the positive control ascorbic acid (0.74) and BHA (7.79) µg/mL. All isolates exhibited strong cytotoxic activity using brine shrimp lethality bioassay compared with the positive control tamoxifen. Preliminary chemical screening of the fungal extracts by thin layer chromatography technique revealed the presence of various compounds.

Conclusions

The findings indicate that endophytic fungal isolates explored from C. decandra has diversified biological activities which may be potential source of leads for new drug development.
Depression among health workers caring for patients with COVID-19 in Egypt
Authors: Elgohary Hayam Mohamed , Sehlo Mohammad Gamal , Bassiony Medhat Mohamed , Youssef Usama Mahmoud , Elrafey Dina Sameh , Amin Shimaa Ibrahim
Published: October 2021

Background

Health care workers caring for patients with COVID-19 pandemic are prone to extraordinary stressors and psychological problems. The aim of this study was to estimate the prevalence and risk factors of major depressive disorder among health care providers who are caring for patients with COVID-19.

Methods

Two hundred-seventy of health care workers were screened for depressive symptoms by DASS-21 Questionnaire. Only 152 of the participants accepted to be interviewed using SCID-I for diagnosis of major depressive disorder.

Results

According to DASS-21, 28.1% of HCWs had mild-to-moderate depressive symptoms, and 64.8% with severe symptoms. Of 152 who were interviewed using SCID-I, 74.3% were diagnosed with major depression disorder.

Young age, decreased sleep hours, female sex, past history of a psychiatric disease, fear of COVID-19 infection for themselves or their relatives, and fear of death with COVID-19 for themselves or their relatives were significant predictors for major depressive disorder and its severity.

Conclusion

Major depressive disorder is common among HCWs during COVID-19 pandemic. Screening for depression, particularly for young females, and early treatment are recommended.
A pilot study comparing dural puncture epidural with 27G Whitacre needle and conventional lumbar epidural labor analgesia
Authors: Jadon Ashok , Srivastawa Surabhi , Sinha Neelam , Chakraborty Swastika , Bakshi Apoorva , Singh Bhupendra
Published: October 2021

Background

The dural puncture epidural (DPE) technique is relatively a new technique of labor analgesia and has been advocated with the advantage of faster onset of pain relief. However, there are differences of opinion regarding the efficacy of the DPE technique and the size of the spinal needle to be used for the DPE. Various studies have suggested that DPE can only be done with a larger gauge of a spinal needle; however, recent studies have variable observations. We have compared the conventional lumbar epidural analgesia and DPE using a 27G pencil-point needle to assess the efficacy of DPE and its possible side effects.

Results

The time to achieve a 50% reduction in VAS was 7.06 ± 0.79 min in group CLE (n = 15) and 5.0 ± 1.06 min in group DPE (n = 15) (difference of two means was 2.06, 95% CI [1.36, 2.75], t = 5.99, p < 0.0001). The time to achieve VAS < 3 in group CLE was 14.93 ± 1.98 min, and in the group DPE, it was 10.13 ± 1.45 min (difference of two means was 4.8, 95% CI [3.52, 6.09], t = 7.55, p < 0.0001). The mode of delivery, APGAR scores, and side effects were comparable (p > 0.05).

Conclusions

DPE provided faster relief of labor pain than the conventional labor epidural analgesia. There were no added side effects by DPE in conventional lumbar epidural analgesia for labor. A 27G Whitacre pencil-point needle can be used for DPE.

Trial registration

CTRI, CTRI/2020/08/027060. Registered on 10/08/2020. Trial registered prospectively. CTRI website URL: http://ctri.nic.in
East African quintessential plants claimed to be used as blood purifiers, cleansers, detoxifiers and tonics: an appraisal of ethnobotanical reports and correlation with reported bioactivities
Authors: Omara Timothy
Published: October 2021

Background

Blood cleansing, purification, detoxification or strengthening is an ancient folkloric East African practice without any validated scientific underpinnings. This study was undertaken to retrieve ethnobotanical information and reported bioactivities of plants claimed to be blood purifiers, cleansers, detoxifiers and tonics in Eastern Africa and correlate their claimed use with scientific studies to find out whether there is any justification for their use in this ancient practice.

Method

An elaborate review was performed in electronic databases (PubMed, Science Direct, Scopus, Springer Link, Wiley Online Library, Taylor & Francis Online, SciFinder, Google Scholar, Web of Science) and the Google search engine to retrieve information on ethnomedicinal plants used in East Africa in blood purification, detoxification, cleansing or strengthening and their investigated bioactivities related to their use in this traditional practice.

Results

The search retrieved 74 plant species from 45 families distributed among 66 genera with some documented bioactivities, though, with little correlation with their traditional utilization in blood purification, cleansing, detoxification and strengthening. Some justification of the link between blood purification, cleansing, detoxification and strengthening and the use of the plants as antiplatelet aggregation, vasorelaxant, bronchodilatory, antihyperlipidaemic, cardioprotective, antiatherosclerotic and immunomodulatory agents were evident, but majorly antimicrobial activity has been investigated in most species. Thus, only 15 (20.2%) of the plant species (Allium sativum,Moringa oleifera,Olea capensis,Clausena anisata,Centella asiatica,Nasturtium officinale,Solanum nigrum,Withania somnifera,Rubus apetalus,Delonix elata,Persia americana,Aloe vera,Azadirachta indica,Echinacea angustifoliaandDioscorea bulbifera) could be directly correlated with studies pertaining to blood health.

Conclusion

Medicinal plants used in blood purification, cleansing, detoxification and strengthening in East Africa play a holistic role in rejuvenation of overall human health. Few studies have examined their bioactivities pertaining to blood health. Thus, bioactivities and pharmacological activities (such as blood thinning, hypolipemic, cardioprotective, immunomodulatory, tonic and renoprotective properties) and phytochemicals of the claimed plants warrant further research as these could lead to discovery of chemical scaffolds of lead compounds that can be used in modern blood purification.
Blood pressure, body mass index lowering and ketogenesis in Qigong Bigu
Authors: Hong Bin , Luo Runqi , Cao Dezhi , Zhang Man , Fang Kewei , Guo Jianhong , Liao Jianxiang
Published: October 2021

Background

Hypertension is one of the most common comorbid conditions of epilepsy. Hypertension and epilepsy may be related to each other. Qigong Bigu practice induces a similar effect as fasting in the first week. As ketogenesis is induced during ketogenic diet therapy, we hypothesize that ketogenesis is detectable and related body weight loss would occur during the first week of Qigong Bigu practice.

Methods

During the prospective observational study, 34 healthy adult participants attended the Qigong Bigu practice for one week. The blood pressure, body weight, calorie consumption, blood glucose and beta-hydroxybutyrate level were measured.

Results

The body weight and body mass index decreased by 2.39 ± 1.34 kg (95%CI 1.92–2.85) and 0.94 ± 0.57 (95%CI 0.73–1.15), respectively, after five days of practice (P < 0.001). The systolic and diastolic blood pressure decreased by 17.86 ± 14.17 mmHg (95%CI 12.36–23.35) and 9.75 ± 7.45 mmHg (95%CI 6.86–12.64), respectively (P < 0.001). The average five-day calorie consumption was 1197.47 ± 569.97 kcal (95%CI 998.60–1396.35). Meanwhile, no symptomatic hypoglycemia or other significant side effects were observed. The blood beta-hydroxybutyrate level increased to a nutritional level of 1.15 ± 1.12 mmol/L (95%CI 0.76–1.62). The calorie consumption negatively correlated to the beta-hydroxybutyrate level in the blood. The loss of body weight and the decrease of body mass index were positively correlated to the blood beta-hydroxybutyrate level.

Conclusions

Qigong Bigu can decrease the blood pressure, the body weight and the body mass index in healthy adult participants. The fasting stage of Qigong Bigu is accompanied by ketogenesis. Clinical trial of Qigong Bigu in hypertension and epilepsy patients might be worthwhile. The blood beta-hydroxybutyrate might be used as a biomarker to evaluate the effect of Qigong Bigu practice during fasting.

Trial registration

ChiCTR1800016923.
Pediatric Cancer Data Commons: Federating and Democratizing Data for Childhood Cancer Research
Authors: Plana Alejandro , Furner Brian , Palese Monica , Dussault Nicole , Birz Suzi , Graglia Luca , Kush Maura , Nicholson James , Hecker-Nolting Stefanie , Gaspar Nathalie , Rasche Mareike , Bisogno Gianni , Reinhardt Dirk , Zwaan C. Michel , Koscielniak Ewa , Frazier A. Lindsay , Janeway Katherine , S. Hawkins Douglas , Kolb E. Anders , Cohn Susan L. , Pearson Andrew D. J. , Volchenboum Samuel L.
Published: October 2021

The international pediatric oncology community has a long history of research collaboration. In the United States, the 2019 launch of the Children's Cancer Data Initiative puts the focus on developing a rich and robust data ecosystem for pediatric oncology. In this spirit, we present here our experience in constructing the Pediatric Cancer Data Commons (PCDC) to highlight the significance of this effort in fighting pediatric cancer and improving outcomes and to provide essential information to those creating resources in other disease areas. The University of Chicago's PCDC team has worked with the international research community since 2015 to build data commons for children's cancers. We identified six critical features of successful data commons design and implementation: (1) establish the need for a data commons, (2) develop and deploy the technical infrastructure, (3) establish and implement governance, (4) make the data commons platform easy and intuitive for researchers, (5) socialize the data commons and create working knowledge and expertise in the research community, and (6) plan for longevity and sustainability. Data commons are critical to conducting research on large patient cohorts that will ultimately lead to improved outcomes for children with cancer. There is value in connecting high-quality clinical and phenotype data to external sources of data such as genomic, proteomics, and imaging data. Next steps for the PCDC include creating an informed and invested data-sharing culture, developing sustainable methods of data collection and sharing, standardizing genetic biomarker reporting, incorporating radiologic and molecular analysis data, and building models for electronic patient consent. The methods and processes described here can be extended to any clinical area and provide a blueprint for others wishing to develop similar resources.
Modified FOLFIRINOX Versus CISGEM Chemotherapy for Patients With Advanced Biliary Tract Cancer (PRODIGE 38 AMEBICA): A Randomized Phase II Study
Authors: Phelip Jean marc , Desrame Jérôme , Edeline Julien , Barbier Emilie , Terrebonne Eric , Michel Pierre , Perrier Hervé , Dahan Laetitia , Bourgeois Vincent , Akouz Faiza Khemissa , Soularue Emilie , Ly Valérie Lebrun , Molin Yann , Lecomte Thierry , Ghiringhelli François , Coriat Romain , Louafi Samy , Neuzillet Cindy , Manfredi Sylvain , Malka David ,   for the PRODIGE 38 AMEBICA Investigators/Collaborators
Published: October 2021

PURPOSE

Whether triplet chemotherapy is superior to doublet chemotherapy in advanced biliary tract cancer (BTC) is unknown.

METHODS

In this open-label, randomized phase II-III study, patients with locally advanced or metastatic BTC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) to receive oxaliplatin, irinotecan, and infusional fluorouracil (mFOLFIRINOX), or cisplatin and gemcitabine (CISGEM) for a maximum of 6 months. We report the results of the phase II part, where the primary end point was the 6-month progression-free survival (PFS) rate among the patients who received at least one dose of treatment (modified intention-to-treat population) according to Response Evaluation Criteria in Solid Tumors version 1.1 (statistical assumptions: 6-month PFS rate ≥ 59%, 73% expected).

RESULTS

A total of 191 patients (modified intention-to-treat population, 185: mFOLFIRINOX, 92; CISGEM, 93) were randomly assigned in 43 French centers. After a median follow-up of 21 months, the 6-month PFS rate was 44.6% (90% CI, 35.7 to 53.7) in the mFOLFIRINOX arm and 47.3% (90% CI, 38.4 to 56.3) in the CISGEM arm. Median PFS was 6.2 months (95% CI, 5.5 to 7.8) in the mFOLFIRINOX arm and 7.4 months (95% CI, 5.6 to 8.7) in the CISGEM arm. Median overall survival was 11.7 months (95% CI, 9.5 to 14.2) in the mFOLFIRINOX arm and 13.8 months (95% CI, 10.9 to 16.1) in the CISGEM arm. Adverse events ≥ grade 3 occurred in 72.8% of patients in the mFOLFIRINOX arm and 72.0% of patients in the CISGEM arm (toxic deaths: mFOLFIRINOX arm, two; CISGEM arm, one).

CONCLUSION

mFOLFIRINOX triplet chemotherapy did not meet the primary study end point. CISGEM doublet chemotherapy remains the first-line standard in advanced BTC.
KLF17 promotes human naïve pluripotency but is not required for its establishment
Authors: Lea Rebecca A. , McCarthy Afshan , Boeing Stefan , Fallesen Todd , Elder Kay , Snell Phil , Christie Leila , Adkins Sarah , Shaikly Valerie , Taranissi Mohamed , Niakan Kathy K.
Published: October 2021

Current knowledge of the transcriptional regulation of human pluripotency is incomplete, with lack of interspecies conservation observed. Single-cell transcriptomics analysis of human embryos previously enabled us to identify transcription factors, including the zinc-finger protein KLF17, that are enriched in the human epiblast and naïve human embryonic stem cells (hESCs). Here, we show that KLF17 is expressed coincident with the known pluripotency-associated factors NANOG and SOX2 across human blastocyst development. We investigate the function of KLF17 using primed and naïve hESCs for gain- and loss-of-function analyses. We find that ectopic expression of KLF17 in primed hESCs is sufficient to induce a naïve-like transcriptome and that KLF17 can drive transgene-mediated resetting to naïve pluripotency. This implies a role for KLF17 in establishing naïve pluripotency. However, CRISPR-Cas9-mediated knockout studies reveal that KLF17 is not required for naïve pluripotency acquisition in vitro. Transcriptome analysis of naïve hESCs identifies subtle effects on metabolism and signalling pathways following KLF17 loss of function, and possible redundancy with other KLF paralogues. Overall, we show that KLF17 is sufficient, but not necessary, for naïve pluripotency under the given in vitro conditions.
His domain protein tyrosine phosphatase and Rabaptin-5 couple endo-lysosomal sorting of EGFR with endosomal maturation
Authors: Parkinson Gabrielle , Roboti Peristera , Zhang Ling , Taylor Sandra , Woodman Philip
Published: October 2021

His domain protein tyrosine phosphatase (HD-PTP; also known as PTPN23) collaborates with endosomal sorting complexes required for transport (ESCRTs) to sort endosomal cargo into intralumenal vesicles, forming the multivesicular body (MVB). Completion of MVB sorting is accompanied by maturation of the endosome into a late endosome, an event that requires inactivation of the early endosomal GTPase Rab5 (herein referring to generically to all isoforms). Here, we show that HD-PTP links ESCRT function with endosomal maturation. HD-PTP depletion prevents MVB sorting, while also blocking cargo from exiting Rab5-rich endosomes. HD-PTP-depleted cells contain hyperphosphorylated Rabaptin-5 (also known as RABEP1), a cofactor for the Rab5 guanine nucleotide exchange factor Rabex-5 (also known as RABGEF1), although HD-PTP is unlikely to directly dephosphorylate Rabaptin-5. In addition, HD-PTP-depleted cells exhibit Rabaptin-5-dependent hyperactivation of Rab5. HD-PTP binds directly to Rabaptin-5, between its Rabex-5- and Rab5-binding domains. This binding reaction involves the ESCRT-0/ESCRT-III binding site in HD-PTP, which is competed for by an ESCRT-III peptide. Jointly, these findings indicate that HD-PTP may alternatively scaffold ESCRTs and modulate Rabex-5–Rabaptin-5 activity, thereby helping to coordinate the completion of MVB sorting with endosomal maturation.
Increased cellular detoxification, cytoskeletal activities and protein transport explain physiological stress in a lagoon sponge
Authors: Beepat Sandeep S. , Davy Simon K. , Oakley Clinton A. , Mashini Amirhossein , Peng Lifeng , Bell James J.
Published: October 2021

Tropical lagoon-inhabiting organisms live in highly irradiated ecosystems and are particularly susceptible to thermal stress resulting from climate change. However, despite living close to their thermal maxima, stress response mechanisms found in these organisms are poorly understood. We used a novel physiological–proteomic approach for sponges to describe the stress response mechanisms of the lagoon-inhabiting sponge Amphimedon navalis, when exposed to elevated seawater temperatures of +2°C and +4°C relative to a 26°C ambient temperature for 4 weeks. After 4 weeks of thermal exposure, the buoyant weight of the sponge experienced a significant decline, while its pumping rates and oxygen consumption rates significantly increased. Proteome dynamics revealed 50 differentially abundant proteins in sponges exposed to elevated temperature, suggesting that shifts in the sponge proteome were potential drivers of physiological dysfunction. Thermal stress promoted an increase in detoxification proteins, such as catalase, suggesting that an excess of reactive oxygen species in sponge cells was responsible for the significant increase in oxygen consumption. Elevated temperature also disrupted cellular growth and cell proliferation, promoting the loss of sponge biomass, and the high abundance of multiple α-tubulin chain proteins also indicated an increase in cytoskeletal activities within sponge cells, which may have induced the increase in sponge pumping rate. Our results show that sustained thermal exposure in susceptible lagoonal sponges may induce significant disruption of cellular homeostasis, leading to physiological dysfunction, and that a combined physiological–proteomic approach may provide new insights into physiological functions and cellular processes occurring in sponges.
“Black ring-shaped burn” in button battery ingestion is not a burn — Comparison with charring using spectral CT
Authors: Shinkawa Norihiro , Meiri Takayuki , Kakizaki Eiji , Sonoda Ai , Yukawa Nobuhiro
Published: October 2021

Objectives:

To compare “black ring-shaped burn” (BRSB) and charring using spectral computed tomography (CT).

Methods:

Spectral CT was performed using chicken pectoralis minor muscle, processed in three ways and unprocessed as a control: a) BRSB generated by bringing the negative pole surface of a 3 V button battery (BB) into contact with the muscle; b) BRSB caused by a 1.5 V BB; c) charring caused by broiling; and d) control. Attenuation values were compared between BRSB and charring. Muscles were formalin-fixed and stained with Perls’ Prussian blue.

Results:

Attenuation values from polychromatic 120-kVp images were significantly higher for BRSBs than for charring. In the spectral Hounsfield unit curve, attenuation values for BRSBs were higher for lower energy. Histopathologically, BRSBs stained positively with Perls’ Prussian blue.

Conclusions:

This study using spectral CT revealed that BRSB contains metal and confirmed the presence of Fe3+ histopathologically. BRSB differs from charring due to burns.

Advances in knowledge:

The exact composition of BRSB remains unclear, but this report is the first to show that BRSB differs from charring using spectral CT. Clarification of the composition of BRSB is expected to facilitate the development of more effective BRSB removal therapy.