bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetes Self-Management Education and Support Culturally Tailored for African Americans: COVID-19-Related Factors Influencing Restart of the TX STRIDE Study
Authors: Steinhardt Mary A. , Brown Sharon A. , Lehrer H. Matthew , Dubois Susan K. , Wright Jaylen I. , Whyne Erum Z. , Sumlin Lisa L. , Harrison Louis , Woo Jihun
Published: July 2021

Purpose

The purpose of this substudy was to determine the most acceptable way to restart the Texas Strength Through Resilience in Diabetes Education (TX STRIDE) study safely using remote technologies. Following the emergence of COVID-19, all in-person TX STRIDE intervention and data collection sessions were paused.

Methods

Qualitative descriptive methods using telephone interviews were conducted during the research pause. A structured interview guide was developed to facilitate data collection and coding. Forty-seven of 59 Cohort 1 participants were interviewed (mean age = 60.7 years; 79% female; mean time diagnosed with type 2 diabetes = 11 years).

Results

Data categories and subcategories were generated from the interview responses and included: personal experiences with COVID-19, effects of COVID-19 on diabetes self-management, psychosocial and financial effects of COVID-19, and recommendations for program restart. Although some participants lacked technological knowledge, they expressed eagerness to learn how to use remote meeting platforms to resume intervention and at-home data-collection sessions. Six months after the in-person intervention was paused, TX STRIDE restarted remotely with data collection and class sessions held via Zoom. A majority of participants (72.9%) transitioned to the virtual platform restart.

Conclusions

Qualitative findings guided the appropriate implementation of technology for the study, which facilitated a successful restart. High retention of participants through the study transition provides evidence that participants are invested in learning how to manage their diabetes despite the challenges and distractions imposed by COVID-19.
Targeting B-cell receptor and PI3K signaling in diffuse large B-cell lymphoma
Authors: Xu Wendan , Berning Philipp , Lenz Georg
Published: July 2021

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous diagnostic category comprising distinct molecular subtypes characterized by diverse genetic aberrations that dictate patient outcome. As roughly one-third of patients with DLBCL are not cured by current standard chemoimmunotherapy, a better understanding of the molecular pathogenesis is warranted to improve outcome. B-cell receptor (BCR) signaling is crucial for the development, growth, and survival of normal B cells and a substantial fraction of malignant B cells. Various analyses revealed genetic alterations of central components of the BCR or its downstream signaling effectors in some subtypes of DLBCL. Thus, BCR signaling and the downstream NF-κB and phosphatidylinositol 3-kinase (PI3K) cascades have been proposed as potential targets for the treatment of patients with DLBCL. As one of the main effectors of BCR activation, PI3K-mediated signals play a crucial role in the pathogenesis and survival of DLBCL. In this review, we summarize our current understanding of BCR signaling with a special focus on the PI3K pathway in DLBCL and how to use this knowledge therapeutically.
BCL2 and MCL1 inhibitors for hematologic malignancies
Authors: Roberts Andrew W. , Wei Andrew H. , Huang David C. S.
Published: July 2021

BCL2 and MCL1 are commonly expressed prosurvival (antiapoptotic) proteins in hematologic cancers and play important roles in their biology either through dysregulation or by virtue of intrinsic importance to the cell-of-origin of the malignancy. A new class of small-molecule anticancer drugs, BH3 mimetics, now enable specific targeting of these proteins in patients. BH3 mimetics act by inhibiting the prosurvival BCL2 proteins to enable the activation of BAX and BAK, apoptosis effectors that permeabilize the outer mitochondrial membrane, triggering apoptosis directly in many cells and sensitizing others to cell death when combined with other antineoplastic drugs. Venetoclax, a specific inhibitor of BCL2, is the first approved in class, demonstrating striking single agent activity in chronic lymphocytic leukemia and in other lymphoid neoplasms, as well as activity against acute myeloid leukemia (AML), especially when used in combination. Key insights from the venetoclax experience include that responses occur rapidly, with major activity as monotherapy proving to be the best indicator for success in combination regimens. This emphasizes the importance of adequate single-agent studies for drugs in this class. Furthermore, secondary resistance is common with long-term exposure and often mediated by genetic or adaptive changes in the apoptotic pathway, suggesting that BH3 mimetics are better suited to limited duration, rather than continuous, therapy. The success of venetoclax has inspired development of BH3 mimetics targeting MCL1. Despite promising preclinical activity against MYC-driven lymphomas, myeloma, and AML, their success may particularly depend on their tolerability profile given physiological roles for MCL1 in several nonhematologic tissues.
A STAT5B–CD9 axis determines self-renewal in hematopoietic and leukemic stem cells
Authors: Kollmann Sebastian , Grausenburger Reinhard , Klampfl Thorsten , Prchal-Murphy Michaela , Bastl Klavdija , Pisa Hanja , Knab Vanessa M. , Brandstoetter Tania , Doma Eszter , Sperr Wolfgang R. , Lagger Sabine , Farlik Matthias , Moriggl Richard , Valent Peter , Halbritter Florian , Kollmann Karoline , Heller Gerwin , Maurer Barbara , Sexl Veronika
Published: July 2021

The transcription factors signal transducer and activator of transcription 5A (STAT5A) and STAT5B are critical in hematopoiesis and leukemia. They are widely believed to have redundant functions, but we describe a unique role for STAT5B in driving the self-renewal of hematopoietic and leukemic stem cells (HSCs/LSCs). We find STAT5B to be specifically activated in HSCs and LSCs, where it induces many genes associated with quiescence and self-renewal, including the surface marker CD9. Levels of CD9 represent a prognostic marker for patients with STAT5-driven leukemia, and our findings suggest that anti-CD9 antibodies may be useful in their treatment to target and eliminate LSCs. We show that it is vital to consider STAT5A and STAT5B as distinct entities in normal and malignant hematopoiesis.
High-dose AraC is essential for the treatment of ML-DS independent of postinduction MRD: results of the COG AAML1531 trial
Authors: Hitzler Johann , Alonzo Todd , Gerbing Robert , Beckman Amy , Hirsch Betsy , Raimondi Susana , Chisholm Karen , Viola Shelton , Brodersen Lisa , Loken Michael , Tong Spencer , Druley Todd , O’Brien Maureen , Hijiya Nobuko , Heerema-McKenney Amy , Wang Yi-Chang , Shore Reuven , Taub Jeffrey , Gamis Alan , Kolb E. Anders , Berman Jason N.
Published: July 2021

Myeloid leukemia in children with Down syndrome (ML-DS) is associated with young age and somatic GATA1 mutations. Because of high event-free survival (EFS) and hypersensitivity of the leukemic blasts to chemotherapy, the prior Children’s Oncology Group protocol ML-DS protocol (AAML0431) reduced overall treatment intensity but lacking risk stratification, retained the high-dose cytarabine course (HD-AraC), which was highly associated with infectious morbidity. Despite high EFS of ML-DS, survival for those who relapse is rare. AAML1531 introduced therapeutic risk stratification based on the previously identified prognostic factor, measurable residual disease (MRD) at the end of the first induction course. Standard risk (SR) patients were identified by negative MRD using flow cytometry (<0.05%) and did not receive the historically administered HD-AraC course. Interim analysis of 114 SR patients revealed a 2-year EFS of 85.6% (95% confidence interval [CI], 75.7-95.5), which was significantly lower than for MRD− patients treated with HD-AraC on AAML0431 (P = .0002). Overall survival at 2 years was 91.0% (95% CI, 83.8-95.0). Twelve SR patients relapsed, mostly within 1 year from study entry and had a 1-year OS of 16.7% (95% CI, 2.7-41.3). Complex karyotypes were more frequent in SR patients who relapsed compared with those who did not (36% vs 9%; P = .0248). MRD by error-corrected sequencing of GATA1 mutations was piloted in 18 SR patients and detectable in 60% who relapsed vs 23% who did not (P = .2682). Patients with SR ML-DS had worse outcomes without HD-AraC after risk classification based on flow cytometric MRD.
Introduction to a review series on small-molecule targeted therapies for lymphoid malignancies
Authors: Roberts Andrew W. , Stevenson Freda K.
Published: July 2021

Targeted therapies have been central to improvements in the treatment of hematologic malignancies. We present a review series edited by Andrew Roberts and Freda Stevenson focusing on Bruton tyrosine kinase inhibitors, phosphoinositide 3-kinase inhibitors, and BH3 mimetics and their role in the treatment of chronic lymphocytic leukemia, non-Hodgkin lymphomas and acute myeloid leukemia.
CoFe2O4-Quantum Dots for Synergistic Photothermal/Photodynamic Therapy of Non-small-Cell Lung Cancer Via Triggering Apoptosis by Regulating PI3K/AKT Pathway
Authors: Liu Jingfeng , Shi Xiaoying , Zhang Rongjun , Zhang Miaomiao , He Juan , Chen Jian , Wang Zheng , Wang Qingwen
Published: July 2021

Non-small-cell lung cancer (NSCLC) has become the second most diagnosed malignant tumors worldwide. As our long-term interests in seeking nanomaterials to develop strategies of cancer therapies, we herein constructed novel CoFe2O4-quantum dots (QDs) with outstanding synergistic photothermal/photodynamic property which suppressed NSCLC efficiently without apparent toxicity. We showed that the combination of CoFe2O4-QDs + NIR treatment induces apoptosis of NSCLC cells. In addition, the CoFe2O4-QDs + NIR treatment also promotes reactive oxygen species generation to trigger cell death through regulating PI3K/AKT pathway. Moreover, the CoFe2O4-QDs + NIR treatment successfully eliminates tumor xenografts in vivo without apparent toxic effects. Taken together, we reported that the novel nanomaterials CoFe2O4-QDs could exhibit enhanced synergistic photothermal therapy and photodynamic therapy effect on killing NSCLC without toxicity, which could be a promising photosensitizer for NSCLC therapy.
Targeted immune epitope prediction to HHLA2 and MAGEB5 protein variants as therapeutic approach to related viral diseases
Authors: Achinko Daniel A. , Dormer Anton , Narayanan Mahesh , Norman Elton F.
Published: July 2021

Background

Targeted immunotherapy is mostly associated with cancer treatment wherein designed molecules engage signaling pathways and mutant proteins critical to the survival of the cell. One of several genetic approaches is the use of in silico methods to develop immune epitopes targeting specific antigenic regions on related mutant proteins. In a recent study we showed a functional association between the gamma retrovirus HERV-H Long Terminal Associating (HHLA1, HHLA2 and HHLA3) proteins and melanoma associated antigen of the B class proteins (MAGEB5), with a resultant decrease in expression of HLA class I and II immune variants. HLA-C and HLA-DRB5 were the main HLA class I and II Immune variants, respectively, that showed expression changes across viral samples of interest. Specific immune variants for HLA-C and HLA-DRB5 were filtered for the top ten based on their relative frequency of counts across the samples.

Results

Protein variants for HHLA1, HHLA2, HHLA3 and MAGEB5 were used to predict antigenic epitope peptides to immune peptide-MHC class I and II binding using artificial neural networks. For IC50 peptide scores (PS) ≥ 0.5 with a transformed binding ability between 0 and 1, the top 5 epitopes identified for all targeted genes HHLA1,2 & 3 and MAGEB5 were qualified as strong or weak binders according to the threshold. Domain analysis using NCBI Conserved Domain Database (CDD) identified HHLA2 with immunoglobulin-like domains (Ig_C1-set) and MAGEB5 with the MAGE Homology Domain (MHD). Linear regression showed a statistical correlation (P < 0.001) for HHLA2 and MAGEB5 predicted epitope peptides to HLA-C but not HLA-DRB5. The prediction model identified HLA-C variant 9 (HLA-C9, BAA08825.1 HLA-B*1511) at 1.1% as the most valuable immune target for clinical considerations. Identification of the 9-mer epitope peptide within the domain showed for HHLA2: YANRTSLFY (PS = 0.5837) and VLAYYLSSSQNTIIN (PS = 0.77) for HLA-C and HLA-DRB5, respectively and for MAGEB5, peptides: FVRLTYLEY (PS = 0.5293) and YPAHYQFLWGPRAYT (PS = 0.62) for HLA-C and HLA-DRB5, respectively.

Conclusion

Specific immune responses to targeted epitope peptides and their prediction models, suggested co-expression and co-evolution for HHLA2 and MAGEB5 in viral related diseases. HHLA2 and MAGEB5 could be considered markers for virus related tumors and targeted therapy for oncogenic diseases.
Mid-term (up to 12 years) clinical and echocardiographic outcomes of percutaneous transvenous mitral commissurotomy in patients with rheumatic mitral stenosis
Authors: Dadjo Yahya , Moshkani Farahani Maryam , Nowshad Reza , Sadeghi Ghahrodi Mohsen , Moaref Alireza , Kojuri Javad
Published: July 2021

Background

Rheumatic heart disease (RHD) is still a concerning issue in developing countries. Among delayed RHD presentations, rheumatic mitral valve stenosis (MS) remains a prevalent finding. Percutaneous transvenous mitral commissurotomy (PTMC) is the intervention of choice for severe mitral stenosis (MS). We aimed to assess the mid-term outcome of PTMC in patients with immediate success.

Methods

In this retrospective cohort study, out of 220 patients who had undergone successful PTMC between 2006 and 2018, the clinical course of 186 patients could be successfully followed. Cardiac-related death, undergoing a second PTMC or mitral valve replacement (MVR) were considered adverse cardiac events for the purpose of this study. In order to find significant factors related to adverse cardiac outcomes, peri-procedural data for the studied patients were collected.The patients were also contacted to find out their current clinical status and whether they had continued secondary antibiotic prophylaxis regimen or not. Those who had not suffered from the adverse cardiac events were additionally asked to undergo echocardiographic imaging, in order to assess the prevalence of mitral valve restenosis, defined as mitral valve area (MVA) < 1.5 cm2 and loss of ≥ 50% of initial area gain.

Results

During the mean follow-up time of 5.69 ± 3.24 years, 31 patients (16.6% of patients) had suffered from adverse cardiac events. Atrial fibrillation rhythm (p = 0.003, HR = 3.659), Wilkins echocardiographic score > 8 (p = 0.028, HR = 2.320) and higher pre-procedural systolic pulmonary arterial pressure (p = 0.021, HR = 1.031) were three independent predictors of adverse events and immediate post-PTMC mitral valve area (IMVA) ≥ 2 cm2 (p < 0.001, HR = 0.06) was the significant predictor of event-free outcome. Additionally, follow-up echocardiographic imaging detected mitral restenosis in 44 patients (23.6% of all patients). The only statistically significant protective factor against restenosis was again IMVA ≥ 2 cm2 (p = 0.001, OR = 0.240).

Conclusion

The mid-term results of PTMC are multifactorial and may be influenced by heterogeneous peri-procedural determinants. IMVA had a great impact on the long-term success of this procedure. Continuing secondary antibiotic prophylaxis was not a protective factor against adverse cardiac events in this study. (clinicaltrial.gov registration: NCT04112108).
Preoperative stereotactic radiosurgery for brain metastases: the STEP study protocol for a multicentre, prospective, phase-II trial
Authors: Ginzac Angeline , Dupic Guillaume , Brun Lucie , Molnar Ioana , Casile Mélanie , Durando Xavier , Verrelle Pierre , Lemaire Jean-Jacques , Khalil Toufic , Biau Julian
Published: July 2021

Background

Surgery is an important therapeutic option for brain metastases. Currently, postoperative stereotactic radiosurgery (SRT) leads to 6-month and 1-year local control estimated at 70 and 62% respectively. However, there is an increased risk of radio-necrosis and leptomeningeal relapse. Preoperative SRT might be an alternative, providing local control remains at least equivalent. It is an innovative concept that could enable the stereotactic benefits to be retained with advantages over post-operative SRT.

Methods

STEP has been designed as a national, multicentre, open-label, prospective, non-randomized, phase-II trial. Seventeen patients are expected to be recruited in the study from 7 sites and they will be followed for 12 months. Patients with more than 4 distinct brain metastases, including one with a surgical indication, and an indication for SRT and surgery, are eligible for enrolment. The primary objective of the trial is to assess 6-month local control after preoperative SRT. The secondary objectives include the assessment of local control, radio-necrosis, overall survival, toxicities, leptomeningeal relapse, distant control, cognitive function, and quality of life. The experimental design is based on a Flemming plan.

Discussion

There is very little data available in the literature on preoperative SRT: there have only been 3 American single or two-centre retrospective studies. STEP is the first prospective trial on preoperative SRT in Europe. Compared to postoperative stereotactic radiotherapy, preoperative stereotactic radiotherapy will enable reduction in the irradiated volume, leptomeningeal relapse and the total duration of the combined treatment (from 4 to 6 weeks to a few days).

Trial registration number

Clinicaltrials.gov: NCT04503772, registered on August 07, 2020. Identifier with the French National Agency for the Safety of Medicines and Health Products (ANSM): N°ID RCB 2020-A00403–36, registered in February 2020. Protocol: version 4, 07 December 2020.
Myopic foveal detachment associated with pachychoroid characteristics
Authors: Shin Yong Kyun , Han Sun Hyup , Kang Se Woong , Kim Sang Jin , Kim A Young
Published: July 2021

Purpose

To describe myopic nontractional foveal detachment associated with pachychoroid diseases.

Methods

This retrospective study included 15 myopic eyes which had nontractional serous foveal detachment. The eyes were divided into myopic central serous chorioretinopathy (CSC) group (n = 8) and a myopic pachychoroid neovascularization (PNV) group (n = 7) according to the presence of type 1 choroidal neovascularization on multimodal imaging. The findings of multimodal imaging and treatment response were described.

Results

In myopic CSC group, pachychoroid features such as pachyvessels, choroidal vascular hyperpermeability and punctate hyperfluorescent spots were noted in 8 eyes (100%), 8 eyes (100%), 5 eyes (62.5%) respectively. The above features were noted in 7 eyes (100%), 5 eyes (83.3%), 5 eyes (83.3%), respectively, in the myopic PNV group. Five of 8 eyes in myopic CSC and all 7 eyes received treatment including anti-vascular endothelial growth factor injection and/or photodynamic therapy. However, only five eyes had a complete response.

Conclusions

The pachychoroid phenotype may coexist with high myopia and lead to myopic nontractional serous foveal detachment. Our series suggest that the response to treatment for these conditions would be limited.
The health implications of distrust in the food system: findings from the dimensions of trust in food systems scale (DOTIFS scale)
Authors: Tonkin Emma , Webb Trevor , Henderson Julie , Ward Paul R. , Coveney John , Meyer Samantha B. , McCullum Dean , Wilson Annabelle M.
Published: July 2021

Background

Consumer trust in food systems is essential for consumers, food industry, policy makers and regulators. Yet no comprehensive tool for measuring consumer trust in food systems exists. Similarly, the impact that trust in the food system has on health-related food behaviours is yet to be empirically examined. The aim of this research was to develop a comprehensive instrument to measure trust in the food system (the Dimensions of Trust in Food Systems Scale (DOTIFS scale) and use it to explore whether trust in the food system impacts consumers’ health-related behaviours.

Methods

The DOTIFS scale was developed using sociological theories of trust and pre-existing instruments measuring aspects of trust. It was pilot tested and content validity was assessed with 85 participants. A mixed-methods exploration of the health-related behaviours of 18 conveniently sampled Australian consumers with differing trust scores determined by the DOTIFS scale was then conducted. During March–July 2019 shopping- and home-observations were used to assess participants’ food safety practices and exposure to public health fortification programs, while the CSIRO Healthy Diet Score determined their adherence to national dietary guidelines.

Results

The DOTIFS scale was found to have high comprehension, ease of use and content validity. Statistical analysis showed scale scores significantly trended as predicted by participants’ stated level of trust. Differences were found in the way individuals with more or less trust in the food system comply with national dietary guidelines, are exposed to public health fortification programs, and adhere to recommended food safety practices.

Conclusions

The DOTIFS scale is a comprehensive, sociologically- and empirically- informed assessment of consumer trust in food systems that can be self-administered online to large populations and used to measure changes in consumer trust over time. The differences in health-related behaviours between individuals with varying levels of trust warrant further investigation.
Determinants of multiple partner fertility among males in Uganda: a cross-sectional study
Authors: Candia Douglas Andabati , Kisangala Ephraim
Published: July 2021

Background

Multiple-partner fertility is a relatively new area of study, especially in Sub-Saharan Africa. This study focused on identifying determinants of multiple partner fertility among males in Uganda.

Method

The assessment was carried out using a logistic regression model and secondary data from the 2016 Uganda Demographic and Health Survey.

Results

Among the males, 42% had children with multiple partners. Older age, being Muslim, and being divorced or separated increased the likelihood of multiple partner fertility whereas residing in the Western region, reporting an age at first sex above 19 years and being married or cohabiting reduced the likelihood. Increase in number of wives or partners and lifetime sex partners resulted into a higher likelihood of multiple partner fertility.

Conclusion

There is need to come up with policies and programs aimed at increasing the age at first sex so as to reduce the likelihood of multiple partner fertility among males in Uganda. Government and other stakeholders such as cultural and religious institutions should sensitize and educate the masses on the negative outcomes of having children with multiple partners and promote fidelity for those in marriage. There is also need to increase modern contraceptive use and coverage.
Rationale and design of REGULATE: an observational study protocol for relationship between plasma metabolome and the efficacy of systemic glucocorticoid in acute exacerbation of chronic obstructive pulmonary disease
Authors: Li Qiu-Yu , An Zhuo-Yu , Pan Zi-Han , Qi Rui-Ying
Published: July 2021

Background

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) significantly increases the mortality of patients with COPD. Guidelines have recommended systemic glucocorticoid as a regular treatment. Recently, evidence has shown that systemic glucocorticoid cannot be a benefit to all of the patients with AECOPD. Thus, the problem that how the clinicians can screen the patients who can benefit from systemic glucocorticoid needs to be solved urgently. This study is aimed to detect the metabolic biomarkers and metabolic pathways that are related to the efficacy of systemic glucocorticoid and contribute to the precise treatment of COPD.

Methods and design

In this study, we will utilize ultraperformance liquid chromatography/mass spectrometry (LC–MS) and gas chromatography/mass spectrometry (GC–MS) methods for the analysis of the metabolites in AECOPD patients and compare the metabolites profiles between patients with systemic glucocorticoid treatment success group and treatment failure group. We aim to detect the metabolic biomarkers and metabolic pathways that are related to the efficacy of systemic glucocorticoid and contribute to the precise treatment of COPD.

Discussion

Previous studies have found that plasma metabolome changed significantly after dexamethasone treatment in healthy participants. Furthermore, inter-person variability was high and remained uninfluenced by treatment, suggesting the potential of metabolomics for predicting the efficacy and side effects of systemic glucocorticoid. Therefore, we hypothesized that metabolome changes in patients with AECOPD may be associated with the efficacy of systemic glucocorticoid.

Trial registration Clinicaltrials.gov registration number NCT04710849. Registered 15 January 2021, https://clinicaltrials.gov/ct2/show/NCT04710849.
Cyclophosphamide for interstitial lung disease-associated acute respiratory failure: mortality, clinical response and radiological characteristics
Authors: van Gemert Johanna P. , van den Berk Inge A. H. , Nossent Esther J. , Heunks Leo M. A. , Jonkers Rene E. , Vlaar Alexander P. , Bonta Peter I.
Published: July 2021

Background

Treatment for interstitial lung disease (ILD) patients with acute respiratory failure (ARF) is challenging, and literature to guide such treatment is scarce. The reported in-hospital mortality rates of ILD patients with ARF are high (62–66%). Cyclophosphamide is considered a second-line treatment in steroid-refractory ILD-associated ARF. The first aim of this study was to evaluate the in-hospital mortality in patients with ILD-associated ARF treated with cyclophosphamide. The second aim was to compare computed tomographic (CT) patterns and physiological and ventilator parameters between survivors and non-survivors.

Methods

Retrospective analysis of patients with ILD-associated ARF treated with cyclophosphamide between February 2016 and October 2017. Patients were categorized into three subgroups: connective tissue disease (CTD)-associated ILD, other ILD or vasculitis. In-hospital mortality was evaluated in the whole cohort and in these subgroups. Clinical response was determined using physiological and ventilator parameters: Sequential Organ Failure Assessment Score (SOFA), PaO2/FiO2 (P/F) ratio and dynamic compliance (Cdyn) before and after cyclophosphamide treatment. The following CT features were quantified: ground-glass opacification (GGO) proportion, reticulation proportion, overall extent of parenchymal disease and fibrosis coarseness score.

Results

Fifteen patients were included. The overall in-hospital mortality rate was 40%. In-hospital mortality rates for CTD-associated ILD, other ILD and vasculitis were 20, 57, and 33%, respectively. The GGO proportion (71% vs 45%) was higher in non-survivors. There were no significant differences in the SOFA score, P/F ratio or Cdyn between survivors and non-survivors. However, in survivors the P/F ratio increased from 129 to 220 mmHg and Cdyn from 75 to 92 mL/cmH2O 3 days after cyclophosphamide treatment. In non-survivors the P/F ratio hardly changed (113–114 mmHg) and Cdyn even decreased (27–20 mL/cmH2O).

Conclusion

In this study, we found a mortality rate of 40% in patients treated with cyclophosphamide for ILD-associated ARF. Connective tissue disease-associated ILD and vasculitis were associated with a lower risk of death. In non-survivors, the CT GGO proportion was significantly higher. The P/F ratio and Cdyn in survivors increased after 3 days of cyclophosphamide treatment.
The relation between incisal guidance angle and the growth and development of temporomandibular joint: a multi-cross-sectional retrospective study
Authors: Li Ying , Zhou Wenwen , Wu Yan , Dai Hongwei , Zhou Jianping
Published: July 2021

Background

The incisal guidance angle (IGA) is related to temporomandibular joint (TMJ), and changes to the IGA are often involved in the prosthetic and orthodontic treatment of anterior teeth. However, the influence of incisal guidance on the growth, development and remodelling of the TMJ is not yet clear. The aim of this study was to investigate age-related morphological differences in the TMJ in subjects with different IGAs.

Methods

Cone-beam computed tomography (CBCT) images of 274 patients were included (group 1, IGA < 45°; group 2, 45° ≤ IGA ≤ 60°; group 3, IGA > 60°). Each group was then divided into 4 age groups (group a, 6–12 years; group b, 13–16 years; group c, 17–25 years; group d, 26–33 years). TMJ morphology was assessed by linear measurements, angular measurements, and subjective evaluations. The IGA and occlusal plane angle were also measured.

Results

Anterior inclination of condyle (AIC) increased with age in the three IGA groups but decreased from 17 years onward in group 2 (P < 0.05). In the age groups analysis, the AIC in group 1 was smaller than that in group 3 but larger than that in group 2 (P > 0.05). Articular eminence inclination (AEI) decreased with age in group 1 (P = 0.027) but increased with age in group 3 (P = 0.053). The AEI in group 2 was larger than that in group 1 at 17–25 years (P = 0.046), and it was larger in group 3 than in group 1 at 26–33 years (P = 0.047). The IGA had a weak correlation with AEI (P < 0.05).

Conclusion

The articular fossa of patients with shallower incisal guidance changed to a flatter shape with age, whereas the condylar anterior slope and articular eminence of patients with steeper incisal guidance changed towards a steeper alignment. There was a correlation between IGA and TMJ shape.
Chiropractic students’ experiences on the use of virtual radiography simulation: a pilot observational study
Authors: Shanahan Madeleine , Molyneux Tom , Vindigni Dein
Published: July 2021

Background

Virtual radiography provides students with an opportunity to practise their clinical skills in patient positioning and evaluating radiographic images. The purpose of this pilot study was to introduce Projection VR™, a software radiography simulation program, into a student chiropractic program and evaluate its potential application as a teaching and learning tool.

Methods

Undergraduate chiropractic students, enrolled in a radiographic course (unit within the chiropractic program), were invited to attend a scheduled laboratory where they were introduced to, and undertook purposefully designed activities using the radiography simulation. At the end of this activity, students were asked to complete an online survey (see Virtual Radiography Survey) to describe their experiences of the educational value of the software program. Descriptive statistics were used to evaluate outcomes. Content analysis was performed for free-text comments provided by respondents with key themes provided by the predetermined quantitative categories of the questionnaire.

Results

Responses were received from 44 out of the 47 students who attended the scheduled laboratory (response rate 92%). Overall students were positive about this simulation identifying that it was easy to use (95%) and that they could control the equipment as needed (95%). The main reported benefits included students being enabled to repeat tasks until they were satisfied with the results (98%) and being able to quickly assess images and determine if changes needed to be made (98%). Participants reported improvement in their understanding of the effect of exposure factors on patient radiation dose (93%) as well as their technical image evaluation (84%) and problem-solving skills (80%).

Conclusions

The results of this study suggest that virtual radiography is a valuable complementary resource in providing chiropractic students with radiographic knowledge and skills.
Intra- and inter-rater reliability of an electronic health record audit used in a chiropractic teaching clinic system: an observational study
Authors: Injeyan H. Stephen , Hogg-Johnson Sheilah , Abdulla Sean , Chow Ngai , Cox Jocelyn , Ridding Anthony , Jacobs Craig
Published: July 2021

Background

There is a dearth of information about health education clinical file audits in the context of completeness of records and demonstrating program-wide competency achievement. We report on the reliability of an audit instrument used for electronic health record (EHR) audits in the clinics of a chiropractic college in Canada.

Methods

The instrument is a checklist built within an electronic software application designed to pull data automatically from the EHR. It consists of a combination of 61 objective (n = 20) and subjective (n = 41) elements, representing domains of standards of practice, accreditation and in-house educational standards. Trained auditors provide responses to the elements and the software yields scores indicating the quality of clinical record per file.

A convenience sample of 24 files, drawn randomly from the roster of 22 clinicians, were divided into three groups of eight to be completed by one of three auditors in the span of 1 week, at the end of which they were transferred to another auditor. There were four audit cycles; audits from cycles 1 and 4 were used to assess intra-rater (test-retest) reliability and audits from cycles 1, 2 and 3 were used to assess inter-rater reliability. Percent agreement (PA) and Kappa statistics (K) were used as outcomes. Scatter plots and intraclass correlation (ICC) coefficients were used to assess standards of practice, accreditation, and overall audit scores.

Results

Across all 3 auditors test-retest reliability for objective items was PA 89% and K 0.75, and for subjective items PA 82% and K 0.63. In contrast, inter-rater reliability was moderate at PA 82% and K 0.59, and PA 70% and K 0.44 for objective and subjective items, respectively. Element analysis indicated a wide range of PA and K values inter-rater reliability of many elements being rated as poor. ICC coefficient calculations indicated moderate reliability for the domains of standards of practice, accreditation, and overall file scores.

Conclusion

The file audit process has substantial test-retest reliability and moderate inter-rater reliability. Recommendations are made to improve reliability outcomes. These include modifying the audit checklist with a view of improving clarity of elements, and enhancing uniformity of auditor responses by increased training aided by preparation of an audit guidebook.
Both Conifer II and Gnetales are characterized by a high frequency of ancient mitochondrial gene transfer to the nuclear genome
Authors: Kan Sheng-Long , Shen Ting-Ting , Ran Jin-Hua , Wang Xiao-Quan
Published: July 2021

Background

Mitochondrial gene transfer/loss is common in land plants, and therefore the fate of missing mitochondrial genes has attracted more and more attention. The gene content of gymnosperm mitochondria varies greatly, supplying a system for studying the evolutionary fate of missing mitochondrial genes.

Results

Here, we studied the tempo and pattern of mitochondrial gene transfer/loss in gymnosperms represented by all 13 families, using high-throughput sequencing of both DNA and cDNA. All 41 mitochondrial protein-coding genes were found in cycads, Ginkgo and Pinaceae, whereas multiple mitochondrial genes were absent in Conifer II and Gnetales. In Conifer II, gene transfer from mitochondria to the nucleus followed by loss of the mitochondrial copy was common, but complete loss of a gene in both mitochondrial and nuclear genomes was rare. In contrast, both gene transfer and loss were commonly found in Gnetales. Notably, in Conifer II and Gnetales, the same five mitochondrial genes were transferred to the nuclear genome, and these gene transfer events occurred, respectively, in ancestors of the two lineages. A two-step transfer mechanism (retroprocessing and subsequent DNA-mediated gene transfer) may be responsible for mitochondrial gene transfer in Conifer II and Gnetales. Moreover, the mitochondrial gene content variation is correlated with gene length, GC content, hydrophobicity, and nucleotide substitution rates in land plants.

Conclusions

This study reveals a complete evolutionary scenario for variations of mitochondrial gene transferring in gymnosperms, and the factors responsible for mitochondrial gene content variation in land plants.
Fine-tuning the expression of pathway gene in yeast using a regulatory library formed by fusing a synthetic minimal promoter with different Kozak variants
Authors: Xu Liping , Liu Pingping , Dai Zhubo , Fan Feiyu , Zhang Xueli
Published: July 2021

Background

Tailoring gene expression to balance metabolic fluxes is critical for the overproduction of metabolites in yeast hosts, and its implementation requires coordinated regulation at both transcriptional and translational levels. Although synthetic minimal yeast promoters have shown many advantages compared to natural promoters, their transcriptional strength is still limited, which restricts their applications in pathway engineering.

Results

In this work, we sought to expand the application scope of synthetic minimal yeast promoters by enhancing the corresponding translation levels using specific Kozak sequence variants. Firstly, we chose the reported UASF-E-C-Core1 minimal promoter as a library template and determined its Kozak motif (K0). Next, we randomly mutated the K0to generate a chimeric promoter library, which was able to drive green fluorescent protein (GFP) expression with translational strengths spanning a 500-fold range. A total of 14 chimeric promoters showed at least two-fold differences in GFP expression strength compared to the K0control. The best one named K528even showed 8.5- and 3.3-fold increases in fluorescence intensity compared with UASF-E-C-Core1 and the strong native constitutive promoter PTDH3, respectively. Subsequently, we chose three representative strong chimeric promoters (K540, K536, and K528) from this library to regulate pathway gene expression. In conjunction with thetHMG1gene for squalene production, the K528variant produced the best squalene titer of 32.1 mg/L in shake flasks, which represents a more than 10-fold increase compared to the parental K0control (3.1 mg/L).

Conclusions

All these results demonstrate that this chimeric promoter library developed in this study is an effective tool for pathway engineering in yeast.
LncRNA HOTAIR promotes proliferation and inhibits apoptosis by sponging miR-214-3p in HPV16 positive cervical cancer cells
Authors: Zhou Yu , Wang Yuqing , Lin Mingying , Wu Daiqian , Zhao Min
Published: July 2021

Background

Cervical cancer (CC) is one of the most common gynaecological malignancies all around the world. The mechanisms of cervical carcinoma formation remain under close scrutiny. The long non-coding RNAs (lncRNA) and microRNAs (miRNAs) play important roles in controlling gene expression and promoting the development and progression of cervical cancer by acting as competitive endogenous RNA (ceRNA). However, the roles of lncRNA associated with ceRNAs in cervical carcinogenesis remains unknown. In this study, the expression of long non-coding RNA HOTAIR was investigated in HPV16 positive cervical cancer cells, the candidate miRNAs and target genes were identified to clarify putative ceRNAs of HOTAIR/miRNA in cervical cancer cells.

Methods

The proliferation ability of cells was measured by CCK8 and EdU incorporation assays and cell apoptosis was analyzed by flow cytometry. The expression of HOTAIR, miR-214-3p, HPV16 E7 mRNA were detected by qRT-PCR. As for searching for the interaction between miR-214-3p and HOTAIR, the binding sites for miR-214-3p on HOTAIR was predicted by starbase v2.0 database, then dual-luciferase assay was used to verify the binding sites. In addition, Gene Ontology (GO) and protein–protein interaction (PPI) network analysis of target genes of miR-214-3p were performed with bioinformatics analysis. The potential signal pathway regulated by HOTAIR/miR-214-3p was predicted by KEGG enrichment analysis and confirmed by qPCR and WB analysis in cervical cancer cells.

Results

Our results showed that expression of HOTAIR was up-regulated, while that of miR-214-3p was down-regulated in HPV16-positive cervical cancer cells. The expression status of HPV16 E7 played an important role in regulating expression of HOTAIR or miR-214-3p in cervical cancer cells. HOTAIR knockdown could significantly inhibited cell proliferate ability and promote cellular apoptosis, whereas the inhibition of miR-214-3p expression partially reversed such results. Bioinformatics analysis identified 1451 genes as target genes of miR-214-3p. The Gene ontology (GO) and KEGG Pathway enrichment analysis showed that these target genes were mainly related to regulation of cell communication, protein binding, enzyme binding and transferase activity, and Wnt ligand biogenesis. Pathway enrichment analysis results showed that the predicted target genes were significantly enriched in Wnt/β-catenin signaling pathway. Finally, our results confirmed that miR-214-3p could significantly inhibit β-catenin expression in HPV16 positive cancer cells by qPCR and WB analysis.

Conclusion

HOTAIR could act as a ceRNA through binding to miR-214-3p, promote cell proliferation and inhibit the apoptosis of HPV16 positive cervical cancer. HOTAIR/miR-214-3p/Wnt/β-catenin signal pathway might played important regulated roles in HPV16 positive cervical cancer. Our results provided new insight into defining novel biomarkers for cervical cancer.
Decreased prevalence of the Plasmodium falciparum Pfcrt K76T and Pfmdr1 and N86Y mutations post-chloroquine treatment withdrawal in Katete District, Eastern Zambia
Authors: Mulenga Mwenda C. , Sitali Lungowe , Ciubotariu Ilinca I. , Hawela Moonga B. , Hamainza Busiku , Chipeta James , Mharakurwa Sungano
Published: July 2021

Background

In 2002, Zambia withdrew chloroquine as first-line treatment for Plasmodium falciparum malaria due to increased treatment failure and worldwide spread of chloroquine resistance. The artemisinin combination regimen, artemether–lumefantrine, replaced chloroquine (CQ) as first choice malaria treatment. The present study determined the prevalence of CQ resistance molecular markers in the Pfcrt and Pfmdr1 genes in Eastern Zambia at 9 and 13 years after the removal of drug pressure.

Methods

Samples collected from Katete District during the drug therapeutic efficacy assessments conducted in 2012 and 2016 were assayed by polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP) to determine the prevalence of genetic mutations, K76T on the Pfcrt gene and N86Y on the Pfmdr1 gene. A total of 204 P. falciparum-positive DBS samples collected at these two time points were further analysed.

Results

Among the samples analysed for Pfcrt K76T and Pfmdr1 N86Y in the present study, 112 (82.4%) P. falciparum-infected samples collected in 2012 were successfully amplified for Pfcrt and 94 (69.1%) for Pfmdr1, while 69 (65.7%) and 72 (68.6%) samples from 2016 were successfully amplified for Pfcrt and Pfmdr1, respectively. In 2012, the prevalence of Pfcrt 76K (sensitive) was 97.3%, 76T (resistant) was 1.8%, and 0.8% had both 76K and 76T codons (mixed). Similarly in 2012, the prevalence of Pfmdr1 86N (sensitive) was 97.9% and 86Y (resistant) was 2.1%. In the 2016 samples, the prevalence of the respective samples was 100% Pfcrt 76K and Pfmdr1 86N.

Conclusion

This study shows that there was a complete recovery of chloroquine-sensitive parasites by 2016 in Katete District, Eastern Zambia, 13 years following the withdrawal of CQ in the country. These findings add to the body of evidence for a fitness cost in CQ-resistant P. falciparum in Zambia and elsewhere. Further studies are recommended to monitor resistance countrywide and explore the feasibility of integration of the former best anti-malarial in combination therapy in the future.
Endocrine disrupting chemical-associated hair product use during pregnancy and gestational age at delivery: a pilot study
Authors: Preston Emma V. , Fruh Victoria , Quinn Marlee R. , Hacker Michele R. , Wylie Blair J. , O’Brien Karen , Mahalingaiah Shruthi , James-Todd Tamarra
Published: July 2021

Background

Prenatal endocrine disrupting chemical (EDC) exposure has been associated with increased risk of preterm birth. Non-Hispanic Black women have higher incidence of preterm birth compared to other racial/ethnic groups and may be disproportionately exposed to EDCs through EDC-containing hair products. However, research on the use of EDC-associated hair products during pregnancy and risk of preterm birth is lacking. Therefore, the objective of this pilot study was to estimate associations of prenatal hair product use with gestational age at delivery in a Boston, Massachusetts area pregnancy cohort.

Methods

The study population consisted of a subset of participants enrolled in the Environmental Reproductive and Glucose Outcomes (ERGO) Study between 2018 and 2020. We collected self-reported data on demographics and hair product use using a previously validated questionnaire at four prenatal visits (median: 12, 19, 26, 36 weeks’ gestation) and abstracted gestational age at delivery from medical records. We compared gestational age and hair product use by race/ethnicity and used linear regression to estimate covariate-adjusted associations of product use and frequency of use at each study visit with gestational age at delivery. Primary models were adjusted for maternal age at enrollment and delivery method.

Results

Of the 154 study participants, 7% delivered preterm. Non-Hispanic Black participants had lower mean gestational age at delivery compared to non-Hispanic White participants (38.2 vs. 39.2 weeks) and were more likely to report ever and more frequent use of hair products. In regression models, participants reporting daily use of hair oils at visit 4 had lower mean gestational age at delivery compared to non-users (β: -8.3 days; 95% confidence interval: -14.9, -1.6). We did not find evidence of associations at earlier visits or with other products.

Conclusions

Frequent use of hair oils during late pregnancy may be associated with shorter gestational duration. As hair oils are more commonly used by non-Hispanic Black women and represent potentially modifiable EDC exposure sources, this may have important implications for the known racial disparity in preterm birth.
Role of CRISPR-Cas system on antibiotic resistance patterns of Enterococcus faecalis
Authors: Gholizadeh Pourya , Aghazadeh Mohammad , Ghotaslou Reza , Rezaee Mohammad Ahangarzadeh , Pirzadeh Tahereh , Cui Longzhu , Watanabe Shinya , Feizi Hadi , Kadkhoda Hiva , Kafil Hossein Samadi
Published: July 2021

Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems are one of the factors which can contribute to limiting the development and evolution of antibiotic resistance in bacteria. There are three genomic loci of CRISPR-Cas in Enterococcus faecalis. In this study, we aimed to assess correlation of the CRISPR-Cas system distribution with the acquisition of antibiotic resistance among E. faecalis isolates. A total of 151 isolates of E. faecalis were collected from urinary tract infections (UTI) and dental-root canal (DRC). All isolates were screened for phenotypic antibiotic resistance. In addition, antibiotic resistance genes and CRISPR loci were screened by using polymerase chain reaction. Genomic background of the isolates was identified by random amplified polymorphic DNA (RAPD)-PCR. The number of multidrug-resistant E. faecalis strains were higher in UTI isolates than in DRC isolates. RAPD-PCR confirmed that genomic background was diverse in UTI and DRC isolates used in this study. CRISPR loci were highly accumulated in gentamycin-, teicoplanin-, erythromycin-, and tetracycline-susceptible strains. In concordance with drug susceptibility, smaller number of CRISPR loci were identified in vanA, tetM, ermB, aac6’-aph(2”), aadE, and ant(6) positive strains. These data indicate a negative correlation between CRISPR-cas loci and antibiotic resistance, as well as, carriage of antibiotic resistant genes in both of UTI and DRC isolates.