bluuebunny/crossref_metadata_2025 huggingface dataset:
Histone tail analysis reveals H3K36me2 and H4K16ac as epigenetic signatures of diffuse intrinsic pontine glioma
Authors: An Shejuan , Camarillo Jeannie M. , Huang Tina Yi-Ting , Li Daphne , Morris Juliette A. , Zoltek Madeline A. , Qi Jin , Behbahani Mandana , Kambhampati Madhuri , Kelleher Neil L. , Nazarian Javad , Thomas Paul M. , Saratsis Amanda M.
Published: November 2020

Background

Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric brainstem tumor. Most DIPGs harbor a histone H3 mutation, which alters histone post-translational modification (PTM) states and transcription. Here, we employed quantitative proteomic analysis to elucidate the impact of the H3.3K27M mutation, as well as radiation and bromodomain inhibition (BRDi) with JQ1, on DIPG PTM profiles.

Methods

We performed targeted mass spectrometry on H3.3K27M mutant and wild-type tissues (n = 12) and cell lines (n = 7).

Results

We found 29.2 and 26.4% of total H3.3K27 peptides were H3.3K27M in mutant DIPG tumor cell lines and tissue specimens, respectively. Significant differences in modification states were observed in H3.3K27M specimens, including at H3K27, H3K36, and H4K16. In addition, H3.3K27me1 and H4K16ac were the most significantly distinct modifications in H3.3K27M mutant tumors, relative to wild-type. Further, H3.3K36me2 was the most abundant co-occurring modification on the H3.3K27M mutant peptide in DIPG tissue, while H4K16ac was the most acetylated residue. Radiation treatment caused changes in PTM abundance in vitro, including increased H3K9me3. JQ1 treatment resulted in increased mono- and di-methylation of H3.1K27, H3.3K27, H3.3K36 and H4K20 in vitro.

Conclusion

Taken together, our findings provide insight into the effects of the H3K27M mutation on histone modification states and response to treatment, and suggest that H3K36me2 and H4K16ac may represent unique tumor epigenetic signatures for targeted DIPG therapy.
CompLement C5 Antibodies for decreasing brain injury after aneurysmal Subarachnoid Haemorrhage (CLASH): study protocol for a randomised controlled phase II clinical trial
Authors:   on behalf of the CLASH study group, Koopman Inez , Rinkel Gabriel J. E. , Vergouwen Mervyn D. I.
Published: November 2020

Background

The inflammatory response after aneurysmal subarachnoid haemorrhage (aSAH) has been associated with early brain injury, delayed cerebral ischaemia, poor functional outcome, and case fatality. In experimental SAH studies, complement C5 antibodies administered shortly after SAH reduced brain injury with approximately 40%. Complement component C5 may be a new therapeutic target to reduce brain injury and hereby improve the outcome after aSAH. We aim to investigate the pharmacodynamic efficacy and safety of eculizumab (complement C5 antibody) in patients with aSAH.

Methods

A randomised, controlled, open-label, phase II clinical trial with blinded outcome assessment. Eculizumab (1200 mg) is administered intravenously < 12 h, on day 3 and on day 7 after ictus. Patients in the intervention group receive prophylactic antibiotics for 4 weeks, and those with a central line or an external ventricular shunt and a positive fungal or yeast culture also receive prophylactic antifungal therapy for 4 weeks. The primary outcome is C5a concentration in the cerebrospinal fluid (CSF) on day 3 after ictus. Secondary outcomes include the occurrence of adverse events, inflammatory parameters in the blood and CSF, cerebral infarction on magnetic resonance imaging, and clinical and cognitive outcomes. We aim to evaluate 26 patients with CSF assessments, 13 in the intervention group and 13 in the comparator group. To compensate for early case fatality and inability to obtain CSF, we will include 20 patients per group.

Discussion

The CLASH trial is the first trial to investigate the pharmacodynamic efficacy and safety of eculizumab in the early phase after aSAH.

Trial registration

Netherlands Trial RegisterNTR6752. Registered on 27 October 2017

European Clinical Trials Database (EudraCT)2017-004307-51
Effect of “motivational interviewing” and “information, motivation, and behavioral skills” counseling interventions on choosing the mode of delivery in pregnant women: a study protocol for a randomized controlled trial
Authors: Shirzad Mahboubeh , Shakibazadeh Elham , Rahimi Foroushani Abbas , Abedini Mehrandokht , Poursharifi Hamid , Babaei Sohrab
Published: November 2020

Background

Cesarean section is an important surgical procedure, when normal vaginal delivery imposes a risk to mother and/or baby. The World Health Organization states the ideal rate for Cesarean section to be between 10 and 15% of all births. In recent decades, the rate has been increased dramatically worldwide. This paper explains the protocol of a randomized controlled trial that aims to compare the effect of “motivational interviewing” and “information, motivation, and behavioral skills” counseling interventions on choosing mode of delivery in pregnant women.

Methods

A four-armed, parallel-design randomized controlled trial will be conducted on pregnant women. One hundred and twenty women will be randomly assigned to four groups including three intervention groups and one control group. The intervention groups included the following: (1) motivational interviewing; (2) face-to-face information, motivation, and behavioral skills model; and (3) information, motivation, and behavioral skills model provided using a mobile application. The inclusion criteria include being literate, being in gestational age from 24 to 32 weeks, being able to speak Persian, having no complications in the current pregnancy, having no indications for Cesarean section, and having enough time to participate in the intervention. The primary outcome of the study is the mode of delivery. The secondary outcomes are women’s intention to undergo Cesarean section and women’s self-efficacy.

Discussion

The interventions of this protocol have been programmed to reduce unnecessary Cesarean sections. Findings may contribute to a rise in normal vaginal delivery, and the effective intervention may be extended for use in national Cesarean section plans.

Trial registration

Iran Randomized Clinical Trial Center IRCT20151208025431N7. Registered on December 07, 2018.
Update to the FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke: statistical analysis plan for the trials and for the individual patient data meta-analysis
Authors:   On behalf of the FOCUS, AFFINITY and EFFECTS trialists, Mead Gillian Elizabeth , Graham Catriona , Billot Laurent , Näsman Per , Lundström Erik , Lewis Steff , Hankey Graeme J. , Hackett Maree L. , Forbes John , Dennis Martin
Published: November 2020

Background

Three large trials of fluoxetine for stroke recovery (FOCUS (fluoxetine or control under supervision), AFFINITY (the Assessment oF FluoxetINe In sTroke recovery) and EFFECTS (Efficacy oF Fluoxetine—a randomisEd Controlled Trial in Stroke)) have been collaboratively designed with the same basic protocol to facilitate an individual patient data analysis (IPDM). The statistical analysis plan for the three individual trials has already been reported in Trials, including a brief description of the IPDM. In this protocol, we describe in detail how we will perform the IPDM.

Methods/design

Data from EFFECTS and AFFINITY will be transferred securely to the FOCUS statistician, who will perform a one-stage IPDM and a two-stage IPDM. For the one-stage IPDM, data will be combined into a single data set and the same analyses performed as described for the individual trials. For the two-stage IPDM, the results for the three individual trials will be combined using fixed effects meta-analyses.

The primary and secondary outcome domains for the IPDM are the same as for individual trials. We will also perform analyses according to several subgroups including country of recruitment, ethnicity and trial. We will also explore the effects of fluoxetine on our primary and secondary outcomes in subgroups defined by combinations of characteristics.

We also describe additional research questions that will be addressed using the combined data set, and published subsequently, including predictors of important post-stroke problems such as seizures, low mood and bone fractures.

Discussion

An IPDM of our three large trials of fluoxetine for stroke recovery will allow us to provide the most precise estimates of any risks and benefits of fluoxetine vs placebo, to detect reliably a smaller overall effect size than those detectable by the individual trials, to better determine the effects of fluoxetine vs placebo in subgroups of patients and outcomes and to broaden the generalisability of the results. Also, we may identify differences in treatment effects between studies.

Trial registration

FOCUS: ISRCTN ISRCTN83290762. Registered on 23 May 2012. EudraCT 2011-005616-29. Registered on 3 February 2012.

AFFINITY: Australian New Zealand Clinical Trials Registry ACTRN12611000774921. Registered on 22 July 2011.

EFFECTS: ISRCTN ISRCTN13020412. Registered on 19 December 2014. ClinicalTrials.gov NCT02683213. Registered on 2 February 2016. EudraCT 2011-006130-16. Registered on 8 August 2014.
Metabolism, morphology and transcriptome analysis of oscillatory behavior of Clostridium butyricum during long-term continuous fermentation for 1,3-propanediol production
Authors: Zhou Jin-Jie , Shen Jun-Tao , Wang Xiao-Li , Sun Ya-Qin , Xiu Zhi-Long
Published: November 2020

Background

Oscillation is a special cell behavior in microorganisms during continuous fermentation, which poses threats to the output stability for industrial productions of biofuels and biochemicals. In previous study, a spontaneous oscillatory behavior was observed inClostridium butyricum-intensive microbial consortium in continuous fermentation for 1,3-propanediol (1,3-PDO) production from glycerol, which led to the discovery of oscillation in speciesC. butyricum.

Results

Spontaneous oscillations byC. butyricumtended to occur under glycerol-limited conditions at low dilution rates. At a glycerol feed concentration of 88 g/L and a dilution rate of 0.048 h−1, the oscillatory behavior ofC. butyricumwas observed after continuous operation for 146 h and was sustained for over 450 h with an average oscillation period of 51 h. During oscillations, microbial glycerol metabolism exhibited dramatic periodic changes, in which productions of lactate, formate and hydrogen significantly lagged behind that of other products including biomass, 1,3-PDO and butyrate. Analysis of extracellular oxidation–reduction potential and intracellular ratio of NAD+/NADH indicated that microbial cells experienced distinct redox changes during oscillations, from oxidized to reduced state with decreasing of growth rate. Meanwhile,C. butyricumS3 exhibited periodic morphological changes during oscillations, with aggregates, elongated shape, spores or cell debris at the trough of biomass production. Transcriptome analysis indicated that expression levels of multiple genes were up-regulated when microbial cells were undergoing stress, including that for pyruvate metabolism, conversion of acetyl-CoA to acetaldehyde as well as stress response.

Conclusion

This study for the first time systematically investigated the oscillatory behavior ofC. butyricumin aspect of occurrence condition, metabolism, morphology and transcriptome. Based on the experimental results, two hypotheses were put forward to explain the oscillatory behavior: disorder of pyruvate metabolism, and excessive accumulation of acetaldehyde.
Partial laryngectomy and reconstruction with rotation of the epiglottis in the treatment of a rare laryngeal schwannoma: a case report
Authors: Costa Claudiney Candido , Ramos Hugo Valter Lisboa , Alves Wilder , Lamounier Pauliana , Velasco Leandro de Castro , El Cheikh Mikhael Romanholo
Published: November 2020

Background

Neurogenic tumors of the larynx are rare, with few cases having been reported in the literature. Schwannomas are responsible for 0.1% of all benign tumors of the larynx. They arise in the sheaths of the peripheral, autonomic, and cranial nerves. The objective of this report is to describe a case of a bulky laryngeal schwannoma, the surgical procedure for its removal, and the long-term patient follow-up.

Case presentation

A 19-year-old Brazilian woman presented to our institution with a complaint of progressive dyspnea over the preceding year, as well as dysphonia, dysphagia for solids, and globus pharyngeus. Direct rigid laryngoscopy showed a supraglottic tumor obstructing approximately 90% of the larynx. With the symptoms progressing to severe dyspnea, an emergency tracheostomy was performed. After infusion of intravenous contrast, magnetic resonance imaging revealed a mass lesion with intense, heterogeneous contrast enhancement along the posterior wall of the hypopharynx, blocking all of the lumen and measuring 2.8 cm and 2.2 cm at its largest diameters. The image suggested a neoplastic lesion. The patient underwent open surgery for tumor resection. Her postsurgical recovery was uncomplicated. Histopathology and immunohistochemistry revealed the tumor to be a laryngeal schwannoma.

Conclusion

The definitive diagnosis of laryngeal lesions can be difficult, and histopathology plays a pivotal role. Laryngeal schwannomas are rare; however, tumors can become large and may ultimately lead to airway obstruction.
Factors affecting the delivery of complex rehabilitation interventions in research with neurologically impaired adults: a systematic review
Authors: Holmes Jain Anne , Logan Philippa , Morris Richard , Radford Kathryn
Published: November 2020

Background

Rehabilitation research does not always improve patient outcomes because of difficulties implementing complex health interventions. Identifying barriers and facilitators to implementation fidelity is critical. Not reporting implementation issues wastes research resources and risks erroneously attributing effectiveness when interventions are not implemented as planned, particularly progressing from single to multicentre trials. The Consolidated Framework for Implementation Research (CFIR) and Conceptual Framework for Implementation Fidelity (CFIF) facilitate identification of barriers and facilitators. This review sought to identify barriers and facilitators (determinants) affecting implementation in trials of complex rehabilitation interventions for adults with long-term neurological conditions (LTNC) and describe implementation issues.

Methods

Implementation, complex health interventions and LTNC search terms were developed. Studies of all designs were eligible. Searches involved 11 databases, trial registries and citations. After screening titles and abstracts, two reviewers independently shortlisted studies. A third resolved discrepancies. One reviewer extracted data in two stages; 1) descriptive study data, 2) units of text describing determinants. Data were synthesised by (1) mapping determinants to CFIF and CFIR and (2) thematic analysis.

Results

Forty-three studies, from 7434 records, reported implementation determinants; 41 reported both barriers and facilitators. Most implied determinants but five used implementation theory to inform recording. More barriers than facilitators were mapped onto CFIF and CFIR constructs. “Patient needs and resources”, “readiness for implementation”, “knowledge and beliefs about the intervention”, “facilitation strategies”, “participant responsiveness” were the most frequently mapped constructs. Constructs relating to the quality of intervention delivery, organisational/contextual aspects and trial-related issues were rarely tapped. Thematic analysis revealed the most frequently reported determinants related to adherence, intervention perceptions and attrition.

Conclusions

This review has described the barriers and facilitators identified in studies implementing complex interventions for people with LTNCs. Early adoption of implementation frameworks by trialists can simplify identification and reporting of factors affecting delivery of new complex rehabilitation interventions. It is vital to learn from previous experiences to prevent unnecessary repetitions of implementation failure at both trial and service provision levels. Reported facilitators can provide strategies for overcoming implementation issues. Reporting gaps may be due to the lack of standardised reporting methods, researcher ignorance and historical reporting requirements.

Systemic review registration

PROSPERO CRD42015020423
Respiratory syncytial virus prophylaxis for prevention of recurrent childhood wheeze and asthma: a systematic review
Authors: Quinn Lauren Alexandra , Shields Michael D. , Sinha Ian , Groves Helen E.
Published: November 2020

Background

Acute bronchiolitis caused by respiratory syncytial virus (RSV) has been associated with greater risk of recurrent wheezing and asthma. However, it is unclear whether this association is causal. RSV-specific monoclonal antibodies have been shown to reduce RSV-related hospitalisations in high-risk infants, but the longer-term follow-up has given conflicting evidence for prevention of recurrent wheeze or asthma.

Objective

We performed a systematic review and meta-analysis to determine whether monoclonal antibody prophylaxis against RSV bronchiolitis reduces the risk of subsequent recurrent wheeze or asthma. If so, this may support the hypothesis of causality.

Methods

Studies were identified via an online database search using Embase, MEDLINE, PubMed, Web of Science and the Cochrane Library. Manufacturers of monoclonal antibodies were contacted directly for unpublished data. The intervention of interest was RSV monoclonal antibody prophylaxis, and the primary outcome measure was recurrent wheeze and/or asthma. Studies were screened according to inclusion/exclusion criteria. Included studies were evaluated for quality and assessed for bias independently by 3 reviewers using the ‘Grading of Recommendations Assessment, Development and Evaluation’ (GRADE) approach. Results were extracted into 2 × 2 outcome tables and a meta-analysis carried out producing forest plots based on relative risk. Heterogeneity was assessed using theI2statistic.

Results

The search identified 141 articles, which, after screening, resulted in eight studies (2 randomised controlled trials), thus including 11,195 infants in the meta-analysis. The overall result demonstrated a non-statistically significant reduction in relative risk of developing recurrent wheeze or asthma (RR 0.60; 95% CI 0.31 to 1.16). Study quality was generally low with evidence of publication bias and statistical heterogeneity. However, sub-group analysis excluding studies deemed to be ‘very low’ quality showed a relative risk of 0.42 (95% CI 0.22 to 0.80,p= 0.008). A further sub-group analysis for infants aged 32 to < 36 weeks showed a statistically significant relative risk of 0.35 (95% CI 0.14 to 0.86,p= 0.02).

Discussion

We did not identify an overall statistically significant benefit. However, our two sub-group analyses did find statistically significant benefits of monoclonal antibody therapy on the risk of recurrent wheeze and asthma. The main limitation of this study is the lack of high-quality randomised controlled trials, highlighting the need for more research in this field.
Hyers–Ulam stability of functional inequalities: a fixed point approach
Authors: Batool Afshan , Nawaz Sundas , Ege Ozgur , de la Sen Manuel
Published: November 2020

Using the fixed point method, we prove the Hyers–Ulam stability of a cubic and quartic functional equation and of an additive and quartic functional equation in matrix Banach algebras.
A linearized conservative Galerkin–Legendre spectral method for the strongly coupled nonlinear fractional Schrödinger equations
Authors: Fei Mingfa , Zhang Guoyu , Wang Nan , Huang Chengming
Published: November 2020

In this paper, based on Galerkin–Legendre spectral method for space discretization and a linearized Crank–Nicolson difference scheme in time, a fully discrete spectral scheme is developed for solving the strongly coupled nonlinear fractional Schrödinger equations. We first prove that the proposed scheme satisfies the conservation laws of mass and energy in the discrete sense. Then a prior bound of the numerical solutions in$L^{\infty }$L∞-norm is obtained, and the spectral scheme is shown to be unconditionally convergent in$L^{2}$L2-norm, with second-order accuracy in time and spectral accuracy in space. Finally, some numerical results are provided to validate our theoretical analysis.
Microarray analysis identification of key pathways and interaction network of differential gene expressions during osteogenic differentiation
Authors: Khodabandehloo Fatemeh , Taleahmad Sara , Aflatoonian Reza , Rajaei Farzad , Zandieh Zahra , Nassiri-Asl Marjan , Eslaminejad Mohamadreza Baghaban
Published: November 2020

Background

Adult bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stem cells that can differentiate into three lineages. They are suitable sources for cell-based therapy and regenerative medicine applications. This study aims to evaluate the hub genes and key pathways of differentially expressed genes (DEGs) related to osteogenesis by bioinformatics analysis in three different days. The DEGs were derived from the three different days compared with day 0.

Results

Gene expression profiles of GSE37558 were obtained from the Gene Expression Omnibus (GEO) database. A total of 4076 DEGs were acquired on days 8, 12, and 25. Gene ontology (GO) enrichment analysis showed that the non-canonical Wnt signaling pathway and lipopolysaccharide (LPS)-mediated signaling pathway were commonly upregulated DEGs for all 3 days. KEGG pathway analysis indicated that the PI3K-Akt and focal adhesion were also commonly upregulated DEGs for all 3 days. Ten hub genes were identified by CytoHubba on days 8, 12, and 25. Then, we focused on the association of these hub genes with the Wnt pathways that had been enriched from the protein-protein interaction (PPI) by the Cytoscape plugin MCODE.

Conclusions

These findings suggested further insights into the roles of the PI3K/AKT and Wnt pathways and their association with osteogenesis. In addition, the stem cell microenvironment via growth factors, extracellular matrix (ECM), IGF1, IGF2, LPS, and Wnt most likely affect osteogenesis by PI3K/AKT.
Marital separation and contact with primary healthcare services for mental health problems: a register-based study
Authors: Reneflot Anne , Øien-Ødegaard Carine , Hauge Lars Johan
Published: November 2020

Background

Marital separation is associated with mental health problems, but little is known about how this translates into healthcare use. In this study, we examine the relationship between marital separation and primary healthcare use for mental health problems.

Methods

We used data covering the period from 2005 to 2015 from the Norwegian Population Register, Statistics Norway’s Educational Registration System and the Norwegian Health Economics Database. Data were analyzed using logistic regression analysis. To control for time invariant characteristics, we estimated fixed-effect models.

Results

Marital separation was associated with increased contact with primary healthcare services for mental health problems (MH-consultations). The prevalence of MH-consultations peaked during the year of marital separation. MH-consultations were more common following marital separation than prior to the separation. This pattern remained significant in the fixed-effect models.

Conclusions

Men and women who experienced marital separation were more likely to consult primary healthcare services for mental health problems than those who remained married. Our study suggests that several mechanisms are in play. The prevalence of MH-consultations of those who eventually separated were higher several years prior to the separation. This lends support to selection mechanisms, whereas the sharp rise in the prevalence of MH-consultations around the time of marital separation coupled to higher levels several years after separation, indicate that marital separation induces both transient stress and leads to more lasting strain.
Attenuation of LPS-induced acute lung injury by continentalic acid in rodents through inhibition of inflammatory mediators correlates with increased Nrf2 protein expression
Authors: Ali Hassan , Khan Ashrafullah , Ali Jawad , Ullah Hadayat , Khan Adnan , Ali Hussain , Irshad Nadeem , Khan Salman
Published: November 2020

Background

Acute lung injury (ALI) together with acute respiratory distress syndrome (ARDS) are associated with high rate of mortality and morbidity in patients. In the current study, the anti-inflammatory effects of continentalic acid (CNT) in LPS-induced acute lung injury model was explored.

Methods

The acute lung injury model was established by administering LPS (5 mg/kg) intraperitonealy. Following LPS administration, the survival rate, temperature changes and lung Wet/Dry ratio were assessed. The antioxidants (GSH, GST, Catalase and SOD) and oxidative stress markers (MDA, NO, MPO) were evaluated in all the treated groups. Similarly, the cytokines such as IL-1β, IL-6 and TNF-α were analyzed using ELISA assay. The histological changes were determined using H and E staining, while Nrf2 and iNOS level were determined using immunohistochemistry analysis. The molecular docking analysis was performed to assess the pharmacokinetics parameters and interaction of the CNT with various protein targets.

Results

The results showed that CNT dose dependently (10, 50 and 100 mg/kg) reduced mortality rate, body temperature and lungs Wet/Dry ratio. CNT post-treatment significantly inhibited LPS-induced production of pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α. The CNT post-treatment markedly improved the hematological parameters, while significantly reduced the MPO (indicator of the neutrophilic infiltration) activity compared to the LPS treated group. Furthermore, the CNT (100 mg/kg) post-administration remarkably inhibited the lung Wet/Dry ratio. The CNT (100 mg/kg) treated group showed marked reduction in the oxidative stress markers such as malonaldehyde (MDA) and Nitric oxide (NO) concentration, while induced the level of the anti-oxidant enzymes such as GST, GSH, Catalase and SOD. Similarly, the CNT markedly reduced the iNOS expression level, while induced the Nrf2 protein expression. Additionally, the molecular docking study showed significant binding interaction with the Nrf2, p65, Keap1, HO-1, IL-1β, IL-6, TNF-α and COX-2, while exhibited excellent physicochemical properties.

Conclusion

The CNT showed marked protection against the LPS-induced lung injury and improved the behavioral, biochemical and histological parameters. Furthermore, the CNT showed significant interaction with several protein targets and exhibited better physicochemical properties.
Consolidative allogeneic hematopoietic stem cell transplantation after chimeric antigen receptor T-cell therapy for relapsed/refractory B-cell acute lymphoblastic leukemia: who? When? Why?
Authors: Jiang Huiwen , Hu Yu , Mei Heng
Published: November 2020

Although anti-CD19 chimeric antigen receptor (CAR) T-cell therapy shows good efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), it fails to improve long-term leukemia-free survival (LFS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CAR T-cell therapy has emerged as a promising strategy to prolong LFS. Nevertheless, which patients are likely to benefit from consolidative allo-HSCT, as well as the optimal therapeutic window, remain to be explored. Recent clinical data indicate that patients with complex karyotypes, adverse genes, and high pre-infusion minimal residual disease (MRD) by flow cytometry in the bone marrow, were at high risk of relapse after CAR T-cell therapy. High pre-lymphodepletion lactate dehydrogenase, low pre-lymphodepletion platelet count, absence of fludarabine in lymphodepletion, persistent leukemic sequence by high throughput sequencing in bone marrow after CAR T-cell infusion, and early loss of CAR T cells have also been linked to relapse after CAR T-cell therapy. In patients having these risk factors, consolidative allo-HSCT after CAR T-cell therapy may prolong LFS. Allo-HSCT provides optimal clinical benefit in patients with MRD-negative complete remission, typically within three months after CAR T-cell therapy. Herein, we summarize the clinical data on consolidative allo-HSCT after anti-CD19 CAR T-cell therapy, as well as the potential factors associated with allo-HSCT benefit. We also discuss the optimal therapeutic window and regimen of consolidative allo-HSCT. Finally, and most importantly, we provide recommendations for the assessment and management of r/r B-ALL patients undergoing anti-CD19 CAR T-cell therapy.
A case of recurrent malignant phyllodes tumor undergoing nipple-sparing mastectomy with immediate breast reconstruction
Authors: Morioka Emi , Noguchi Masakuni , Noguchi Miki , Inokuchi Masafumi , Shimada Ken-ichi , Shioya Akihiro , Aikawa Akane , Minato Hiroshi , Earashi Mitsuharu
Published: November 2020

Background

Although the primary treatment for malignant phyllodes tumor (PT) is complete surgical excision with either breast-conserving surgery or total mastectomy, recent technical advances have led to the adoption of nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR).

Case presentation

A 28-year-old woman noticed a mass in her left breast that was rapidly increasing in size. She underwent tumor excision and a histological diagnosis of marked degenerative and necrotic induration suggested benign PT. One year later, however, she was found to have recurrent masses in the left breast on follow-up mammography and sonography. Needle biopsy was performed and the tumor was diagnosed as borderline or malignant PT. She underwent NSM and sentinel lymph-node biopsy with IBR using a tissue expander. Histological examination of the mastectomy specimen showed multiple fibroepithelial tumors with marked stromal overgrowth, focal necrosis, and hemorrhage. Stromal cells showed pleomorphism and a maximal mitotic rate of approximately 25 per 10 high-power fields. The tumor was diagnosed as malignant PT. She did not receive adjuvant chemotherapy or radiation treatment. At 3-year follow-up, the patient remains free of disease and highly satisfied with the cosmetic results.

Conclusions

NSM with IBR is not a contraindication for malignant PT. It is both curative and can offer an appealing cosmetic option for localized malignant PT.
A predictable smoothing evolution model for computer-controlled polishing
Authors: Hou Jing , Lei Pengli , Liu Shiwei , Chen Xianhua , Wang Jian , Deng Wenhui , Zhong Bo
Published: November 2020

Quantitative prediction of the smoothing of mid-spatial frequency errors (MSFE) is urgently needed to realize process guidance for computer controlled optical surfacing (CCOS) rather than a qualitative analysis of the processing results. Consequently, a predictable time-dependent model combining process parameters and an error decreasing factor (EDF) were presented in this paper. The basic smoothing theory, solution method and modification of this model were expounded separately and verified by experiments. The experimental results show that the theoretical predicted curve agrees well with the actual smoothing effect. The smoothing evolution model provides certain theoretical support and guidance for the quantitative prediction and parameter selection of the smoothing of MSFE.
Palaeogeographic reconstruction of a fluvio-marine transitional system in Narmada rift basin, India — Implications on Late Cretaceous global sea-level rise
Authors: Bhattacharya Biplab , Jha Suparna , Mondal Prantik
Published: November 2020

Rising sea-levels in tectonically active epicontinental basins often lead to varied depositional settings and palaeogeography, mostly influenced by the net accommodation resulting from mutual interference of the extent and nature of landward encroachment by the sea and the net sedimentation. The Cenomanian Nimar Sandstone Formation, Bagh Group, Narmada rift basin, uniquely portrays the effect of sea-level rise within an intra-cratonic setting and attributes to the corresponding palaeogeographic changes in west-central India. An integrated sedimentological–sequence-stratigraphic study of the broadly fining-upward Nimar Sandstone Formation (thickness ~ 20–30 m) depicts the actual nature of changeover from a fluvial to a marine-dominated transitional depositional setting. Detailed sedimentological study reveals total seventeen facies, grouped in five facies associations, viz., the channel-fill facies association (FA-1), the overbank facies association (FA-2), the fluvial-dominated fluvio-tidal facies association (FA-3), the tide-dominated fluvio-tidal facies association (FA-4), and the shoreface facies association (FA-5). Overall facies architecture indicates a west-to-eastward marine encroachment, resulting in stacking of three distinct palaeo-depositional conditions: (i) an initial fluvial system with channel and overbank, changing into a tide-influenced fluvial bay-head delta in the inner estuary, followed by (ii) marine encroachment leading to a tide-dominated central estuary with inter- to sub-tidal settings, and finally, (iii) with further intense marine encroachments, a wave-reworked open shore condition in the outer estuary zone. The overall fining-up succession with a systematic change from fluvial to marine-dominated depositional systems points to a landward shift of the shoreline, signifying a major transgressive event correlated to the Cenomanian global sea-level rise. Characteristic stratal stacking patterns point to four coarsening- and fining-up hemicycles, embedded within the major transgressive succession. These high-frequency cycles attest to the varied interplay of sedimentation, tectonics and sea-level changes, and the resultant net accommodations. A palaeogeographic model is proposed based on the high-frequency transgressive–regressive hemicycles, which envisages the evolution of the depositional environments in relation to the Cenomanian eustatic rise in the intra-cratonic riftogenic fluvio-marine transitional basinal setup.
Culture, eating behavior, and infectious disease control and prevention
Authors: Zhou Mingzhu , Zhang Na , Zhang Man , Ma Guansheng
Published: November 2020

Humans need to obtain nutrients from foods for survival and health. Culture and belief play important roles in food selection and intake. Throughout human history, dietary factor has been one of the important factors inducing and causing outbreaks of infectious diseases. If unhealthy eating behavior, like eating raw/undercooked food or meat and products from wild animals, are not abandoned, foodborne infectious diseases will remain an important risk factor of outbreaks and epidemics. The misconception of dietary culture is one of the important factors that triggers unhealthy eating behavior. Therefore, it is vital to change people’s conceptions and knowledge about what is healthy to eat, in order to completely eliminate unhealthy eating behavior and prevent the recurrence of foodborne infectious diseases. Meanwhile, many factors such as family, society, region, and religion should be involved in.
Factors explaining variation in recommended care pathways following hospital-presenting self-harm: a multilevel national registry study
Authors: Griffin Eve , Gunnell David , Corcoran Paul
Published: November 2020

Background

People who present to hospital following self-harm are at high risk of suicide. Despite this, there are considerable variations in the management of this group across hospitals and the factors influencing such variations are not well understood.

Aims

The aim of this study was to identify the specific hospital and individual factors associated with care pathways following hospital-presenting self-harm.

Method

Data on presentations to hospitals by those aged 18 years and over were obtained from the National Self-Harm Registry Ireland for 2017 and 2018. Factors associated with four common outcomes following self-harm (self-discharge, medical and psychiatric admission and psychosocial assessment before discharge) were examined using multilevel Poisson regression models.

Results

Care pathways following self-harm varied across hospitals and were influenced by both hospital and individual factors. Individual factors were primarily associated with self-discharge (including male gender, younger age and alcohol involvement), medical admission (older age, drug overdose as a sole method and ambulance presentations) and psychiatric admission (male gender, methods associated with greater lethality and older age). The hospital admission rate for self-harm was the only factor associated with all outcomes examined. The availability of psychiatric in-patient facilities and specialist mental health staff contributed to variation in psychiatric admissions and psychosocial assessments prior to discharge. Hospital factors explained the majority of observed variation in the provision of psychosocial assessments.

Conclusions

Characteristics of the presenting hospital and hospital admission rates influence the recommended care pathways following self-harm. Provision of onsite mental health facilities and specialist mental health staff has a strong impact on psychiatric care of these patients.
Osteoporosis and the Risk of Parkinson’s Disease: A Nationwide, Propensity Score–Matched, Longitudinal Follow-up Study
Authors: Feng Shih-Hao , Huang Ya-Ping , Yeh Kuo-Cheng , Pan Shin-Liang
Published: November 2020

Context

Osteoporosis and Parkinson’s disease (PD) often co-occur, and even patients with early-stage PD may have reduced bone-mineral density levels. This may imply that osteoporosis is associated with a higher risk of PD.

Objectives

This work aimed to determine whether patients with osteoporosis are at a higher risk of subsequently developing PD.

Design and Setting

A retrospective cohort study was conducted using Taiwan’s National Health Insurance Research Database.

Participants

A total of 23 495 individuals age 50 to 80 years who had osteoporosis between 2002 and 2006 were enrolled in the osteoporosis group. The comparison group comprised 23 495 propensity score–matched patients without osteoporosis. Their propensity scores were computed using a logistic regression model that included age, sex, comorbid conditions, and socioeconomic status.

Results

The hazard ratio (HR) of PD for the osteoporosis group was 1.31 times larger than that of the comparison group (95% CI, 1.13-1.50, P < .001). The PD-free survival rate of the osteoporosis group was also significantly lower than that of the comparison group (P < .001). The analyses stratified by sex showed that women with osteoporosis appeared to have a higher magnitude of PD HR (HR 1.50; 95% CI, 1.27-1.77, P < .001) than their male counterparts (HR 1.23; 95% CI, 0.93-1.64, P = .15).

Conclusions

The present study’s results suggest that osteoporosis is related to an increased risk of PD, especially among women.
Multimodality cardiac imaging in the 21st century: evolution, advances and future opportunities for innovation
Authors: Daubert Melissa A , Tailor Tina , James Olga , Shaw Leslee J , Douglas Pamela S , Koweek Lynne
Published: November 2020

Cardiovascular imaging has significantly evolved since the turn of the century. Progress in the last two decades has been marked by advances in every modality used to image the heart, including echocardiography, cardiac magnetic resonance, cardiac CT and nuclear cardiology. There has also been a dramatic increase in hybrid and fusion modalities that leverage the unique capabilities of two imaging techniques simultaneously, as well as the incorporation of artificial intelligence and machine learning into the clinical workflow. These advances in non-invasive cardiac imaging have guided patient management and improved clinical outcomes. The technological developments of the past 20 years have also given rise to new imaging subspecialities and increased the demand for dedicated cardiac imagers who are cross-trained in multiple modalities. This state-of-the-art review summarizes the evolution of multimodality cardiac imaging in the 21st century and highlights opportunities for future innovation.
Increased chemokines levels in patients with chronic obstructive pulmonary disease: correlation with quantitative computed tomography metrics
Authors: Hao Wendong , Li Manxiang , Pang Yamei , Du Weiping , Huang Xiaoqi
Published: November 2020

Objective:

We sought to explore the relationships between multiple chemokines with spirometry, inflammatory mediators and CT findings of emphysema, small airways disease and bronchial wall thickness.

Methods:

All patients with COPD (n = 65) and healthy control subjects (n = 23) underwent high-resolution CT, with image analysis determining the low attenuation area (LAA), ratio of mean lung attenuation on expiratory and inspiratory scans (E/I MLD) and bronchial wall thickness of inner perimeter of a 10-mm diameter airway (Pi10). At enrollment, subjects underwent pulmonary function studies, chemokines and inflammatory mediators measurements.

Results:

Multiple chemokines (CCL2, CCL3, CCL5, CX3CL1, CXCL8, CXCL9, CXCL10, CXCL11 and CXCL12) and inflammatory mediators (MMP-9, MMP-12, IL-18 and neutrophil count) were markedly increased in the serum of COPD patients compared with healthy controls. There were associations between small airway disease (E/I MLD) and CCL11, CXCL8, CXCL10, CXCL11, CXCL12 and CX3CL1. Especially CXCL8 and CX3CL1 are strongly associated with E/I MLD (r = 0.74, p < 0.001; r = 0.76, p < 0.001, respectively). CXCL8, CXCL12 and CX3CL1 were moderately positively correlated with emphysema (%LAA) (r = 0.49, p < 0.05; r = 0.51, p < 0.05; r = 0.54, p < 0.01, respectively). Bronchial wall thickness (Pi10）showed no significant differences between the COPD and healthy controls,，but there was an association between Pi10 and FEV1% in COPD patients (r=−0.420, p = 0.048). Our statistical results showed that there were not any associations between airway wall thickness (Pi10) and chemokines.

Conclusion:

Pulmonary chemokines levels are closely associated with the extent of gas trapping, small airways disease and emphysema identified on high-resolution chest CT scan.

Advances in knowledge:

This study combines quantitative CT analysis with multiplex chemokines and inflammatory mediators to identify a new role of pathological changes in COPD.
A review of staging chest CT in trunk and extremity soft tissue sarcoma
Authors: Saifuddin Asif , Shafiq Hassan , Rajakulasingam Ramanan , Tan Alan , O’Donnell Paul , Khoo Michael
Published: November 2020

Objectives:

To determine the incidence of pulmonary metastases on chest CT in trunk and extremity soft tissue sarcoma based on two size criteria, and to identify factors associated with metastases.

Methods:

Retrospective review of chest CT studies in patients with trunk and extremity soft tissue sarcoma over an 18-month period. Data collected included patient age/sex, tumour location, size and relationship to fascia. All chest CTs were reviewed for the presence of metastases which were diagnosed according to two size criteria: multiple nodules > 5 mm in size or multiple nodules > 10 mm in size. Follow-up CT studies were reviewed in cases initially considered indeterminate.

Results:

127 males and 73 females were included (mean age 57.1 years; range 10–90 years). 147 (73.5%) tumours were deep to the fascia and 53 (26.5%) superficial. Tumour size classified according to the 12 AJCC 2019 criteria was: T1 = 52, T2 = 76, T3 = 39, T4 = 33. Based on nodule size >5 mm, 73 (36.5%) patients had no metastases, 42 (21%) had metastases, while 85 (42.5%) studies were indeterminate. Based on nodule size >10 mm, 73 (36.5%) patients had no metastases, 28 (14%) had metastases, while 99 (49.5%) studies were indeterminate. Larger maximum dimension of the primary tumour was a risk factor for pulmonary metastases using both size criteria.

Conclusion:

The incidence of pulmonary metastases at presentation in trunk and extremity soft tissue sarcoma is 14–21%. 42.5–49.5% of chest CTs were indeterminate.

Advances in knowledge:

The incidence of pulmonary metastases at presentation in trunk and extremity soft tissue sarcoma is 14–21%. Indeterminate pulmonary nodules are also very common.
Diagnosis of cracked teeth using cone-beam computed tomography: literature review and clinical experience
Authors: Gao Antian , Cao Dantong , Lin Zitong
Published: November 2020

Cone-beam computed tomography (CBCT) has been widely used in diagnosis of vertical root fractures (VRFs) in recent years. According to the American Association of Endodontists (AAE) classification, there are five types of cracked teeth and VRF is one of them. Due to the variability and overlapping of the cracks and fractures, some narrow fractures on the roots of VRFs could not be detected by CBCT, and some wide cracks on the crown of cracked teeth could be detected by CBCT. In this review, we firstly discussed the value of CBCT in the diagnosis of the AAE five types of cracked teeth and presented CBCT manifestations of some typical cases. Secondly, we summarized the factors influencing the diagnosis of cracks/fractures using CBCT, namely, CBCT device-related factors, patient-related factors, and evaluator-related factors. The possible strategies to improve the diagnostic accuracy in the clinic practice are also discussed in this part. Finally, we compared the differences of root fractures with lateral canals and external root resorption on CBCT images.
Nowe stanowisko Plantago maritima (Plantaginaceae) w Wielkopolsce
Authors: Czarna Aneta
Published: November 2020

Plantago maritima is obligatory halophyte vulnerable (VU) in Poland. The new local population was found on 20 August 2013. It was located on a roadside about 4 km from Nowogród Bobrzański, beside the road to Zielona Góra. It was composed of two flowering clumps, which fruited later (22 October 2013).
Mchy i wątrobowce rezerwatu Molenda (Polska środkowa)
Authors: Dobrowolska Paulina , Staniaszek-Kik Monika
Published: November 2020

The paper presents the results of studies on bryophyte flora of the Molenda forest reserve located in the Central Poland. Fifteen species of liverworts and 73 species of mosses were found. Twenty one of these species are considered to be partially protected by law, three endangered and ten rare in the region. Epigean bryophyte constitute the largest ecological group in the bryophyte flora, consisting of 55 species (62% of total flora), followed by epixylic species which are represented by 48 species (54%). The most interesting were taxa threatened and regionally rare, such as Nowellia curvifolia (Dicks.) Mitt., Callicla­dium haldanianum (Grev.) H.A. Crum, Dicranoweisia cirrata (Hedw.) Lindb., Orthodicranum tauricum (Sapjegin) Smirnova, Orthodontium lineare Schwägr., Orthotrichum pulchellum Brunt., O. stramineum Hornsch. ex Brid., Sciu­ro-hypnum refle­xum (Starke) Ignatov & Huttunen, Ulota bruchii Hornsch. ex Brid. and U. crispa (Hedw.) Brid.