bluuebunny/crossref_metadata_2025 huggingface dataset:
Fostering Change Through Occupation-Based Intervention: An International Joint Group Concept Mapping Study
Authors: Wæhrens Eva Ejlersen , Nielsen Kristina Tomra , Cutchin Malcolm , Fritz Heather , Jonsson Hans , la Cour Karen
Published: September 2021

Further consolidation and clarity regarding occupation as a means to foster change in interventions are needed. The study aimed to utilize the knowledge of occupational scholars to systematically determine what is required to use occupation as means to foster change within occupation-based interventions and to generate a conceptual model from those results. Group Concept Mapping involved the following: preparation, generation of ideas, structuring of statements, data analysis, interpretation of maps, and development of conceptual model. Fifty-two international occupational scholars brainstormed 125 ideas. A cluster rating map with nine clusters posed the foundation for a conceptual model with seven themes, namely, artful use of occupation, evidence-based use of occupation, collaboration to promote occupation, coordinating intervention fit, client factors, sociocultural context, and structural influences. The conceptual model, capturing dimensions and dynamics required for using occupation to foster change, may guide future research into occupation-based interventions.
Narrow Notch Width and Low Anterior Cruciate Ligament Volume Are Risk Factors for Anterior Cruciate Ligament Injury: A Magnetic Resonance Imaging-Based Study
Authors: Gupta Ravi , Jhatiwal Sanjay , Kapoor Anil , Kaur Ravinder , Soni Ashwani , Singhal Akash
Published: September 2021

Background:

The relationship between anterior cruciate ligament (ACL) injury and anatomical structures is still a topic of debate.

Purpose:

The aim of this study was to compare knee geometry in demographically matched ACL-injured and ACL-intact athletes.

Methods:

We conducted a case-control study comparing 2 groups, each consisting of 55 professional athletes (44 men and 11 women): 1 group with complete ACL tears (cases) and 1 group with intact ACLs (controls). The groups were compared using magnetic resonance imaging (MRI) in terms of intercondylar notch geometry, tibial plateau characteristics, and ACL volume.

Results:

Among cases and controls, we found the cases had lower notch width (20.24 ± 2.68 mm vs. 22.04 ± 2.56 mm, respectively) and notch width index (0.29 ± 0.03 vs. 0.31 ± 0.03, respectively). The mean ACL volume in the cases (1181.63 mm3 ± 326 mm3) was also lower than in controls (1352.61 mm3 ± 279.84 mm3). The parameters of tibial slope geometry were comparable between groups. In addition, women had lower ACL volume than men (1254 ± 310 mm3 vs. 890 ± 267 mm3, respectively) and higher medial posterior tibial slope (4.76 ± 2.6 vs. 6.63 ± 1.83, respectively). Among cases, women had narrower notch width than men (16.9 ± 2.42 mm vs. 21.08 ± 2.03 mm). However, notch width index was comparable between male (0.3 ± 0.02) and female (0.28 ± 0.03) cases.

Conclusion:

Our findings suggest that narrow notch width and low ACL volume may enhance the risk of ACL injury among athletes. There was no association found between posterior tibial slope and ACL injury between athletes with injured ACLs and controls. Further study is indicated.
Focused Assessment with Sonography for Trauma (FAST) training for first-year resident physicians at a university hospital in Japan: A longitudinal, observational study
Authors: Ota Koshi , Oba Koji , Ito Yuri , Cheng Jacky , Ota Kanna , Takasu Akira
Published: September 2021

Background:

Ultrasound training is an essential part of residency programs during emergency medicine rotations for first-year trainees (postgraduate year 1). The Focused Assessment with Sonography for Trauma examination used to assess for internal bleeding in trauma patients is one of the essential skills postgraduate year 1 residents must acquire during the emergency medicine rotation.

Method:

A prospective, longitudinal, observational study of postgraduate year 1 residents during a 2-month long emergency medicine rotation conducted from 1 April 2019 to 31 May 2021. The primary outcome was the mean difference between the hands-on Focused Assessment with Sonography for Trauma examination scores of the first week of the emergency medicine rotation and the same hands-on Focused Assessment with Sonography for Trauma examination scores of the last week of the emergency medicine rotation. All postgraduate year 1 residents had open access to the ultrasound machine to practice examining on other postgraduate year 1 residents or could use it on real patients under supervision of emergency medicine physicians.

Result:

A total of 91 postgraduate year 1 residents (65 male and 26 female) were recruited and submitted to the hands-on Focused Assessment with Sonography for Trauma test in both the first and last weeks of the rotation. The mean test score for the postgraduate year 1 residents in the first week was 7.81 (standard deviation = 2.11). The mean test score in the last week was 16.17 (standard deviation = 2.60). The primary outcome of this study was the score difference between the first and last weeks (mean = 8.35, 95% confidence interval = 7.73 to 8.94, p < 0.001, paired t-test).

Conclusion:

Hands-on practical Focused Assessment with Sonography for Trauma training for postgraduate year 1 residents during emergency medicine rotations significantly improved their Focused Assessment with Sonography for Trauma test scores.
Perspectives of LGBTQ Youth and Pediatricians in the Primary Care Setting: A Systematic Review
Authors: Stern Molly
Published: September 2021

Objectives:

Conduct a systematic review designed to determine needs and experiences of LGBTQ adolescents in the pediatric primary care setting and to the ability of primary care practitioners to provide the most inclusive care to LGBTQ adolescents.

Methods:

PubMed, CINAHL, and Embase searches using the following keywords: LGBTQ, Adolescents, Pediatrics, Sexual-Minority, Gender-Identity, and primary care, to identify peer-reviewed publications from 1998 to 2017 that focused on stigma in the healthcare setting related to LGBTQ youth and the knowledge of healthcare providers on enhancing care for their sexual and gender minority patients. Article inclusion criteria include: primary research studies conducted in a pediatric primary care describing LGBTQ patients, pediatric patients as described by the American Academy of Pediatrics (AAP), and written in the English language. Articles were excluded if they used inaccurate definitions for LGBTQ identity, inappropriate patient ages outside of those defined by the AAP, and studies not in a pediatric primary care setting.

Results:

Four articles were identified for the review. Of the included articles, the majority of LGBTQ adolescents experience stigma in the healthcare setting. A limited number of physicians providing care to LGBTQ adolescents felt equipped to care for their sexual-minority patients due to lack of education and resources.

Conclusions:

The education of physicians should include a more detailed approach to providing care to the LGBTQ population, particularly to those training to become pediatricians. A standard guide to treating LGBTQ adolescents could eliminate stigma in the healthcare setting.
Connecting Mobile Application Features with Perceived Benefits in Determining Post-adoption Behaviour
Authors: Aslam Wajeeha , Arif Imtiaz , Atiq Zeeshan , Hussain Faraz
Published: September 2021

This study aims to identify the perception of users, regarding characteristics of retail mobile applications (apps) on perceived benefits and their impact on post-adoption behaviour. On 264 useful responses, exploratory factor analysis, confirmatory factor analysis and structural equation model were applied via using SPSS 22 and Amos 22. The results showed that mobile app features, that is, perceived ubiquity, perceived informativeness, perceived personalization and perceived entertainment significantly impact mobile app usefulness and playful engagement. Only perceived informativeness has an insignificant impact on playful engagement. Both mobile app usefulness and playful engagement have a significant impact on mobile app stickiness, whereas they do not have any impact on mobile app word of mouth (WOM). Mobile stickiness also has a significant impact on mobile app WOM. This study highlights the post-adoption behaviour of the consumer towards retail mobile apps and expands practical knowledge of consumers’ behaviour towards using retail mobile apps.
When Internal Migration Fails: A Case Study of Central American Youth Who Relocate Internally Before Leaving Their Countries
Authors: Escamilla García Angel Alfonso
Published: September 2021

Executive Summary

This paper examines the experiences of Central American youth who have attempted internal relocation before migrating internationally. Based on interviews and participant observation with Guatemalan, Honduran, and Salvadoran youth migrating through Mexico, this paper shows how youth from the Northern Countries of Central America turn to their domestic networks to escape labor exploitation and gang violence before undertaking international journeys. The paper further demonstrates how those domestic networks lead youth into contexts of poverty and violence similar to those they seek to escape, making their internal relocation a disappointment. The failure of their internal relocation attempts makes them turn to international migrant networks as their next option. This paper sheds light on the underexplored issue of internal migration among Central American youth and that migration's synergy with Central American youths’ migration to the United States. The paper finds that internal relocation is unsuccessful when the internal destination fails to resolve the issues from which youth are attempting to escape. This failure ultimately triggers their departure from their home country.
Oysteropolis: Animals in coastal gentrification
Authors: Brooks Andrew , Hubbard Phil
Published: September 2021

Gentrification scholars have increasingly acknowledged the importance of socio-nature in encouraging the revaluation of place. Yet relatively little has been said about the role that non-human animals play in changing the material, sensory and affective qualities of place and the ways that they provoke capital investment. In this paper, we provide a corrective by exploring the role of the oyster in the ongoing gentrification of a coastal community (Whitstable in Kent, South East England). The complex natural and social history of oysters in Whitstable shows that how animal agency has contributed to processes of gentrification. Oysters are visceral objects whose affective qualities create hierarchies of taste and distaste through processes of desire and disgust. This animal is a marker of class change that positions the ‘local’ within wider circuits of consumption. Further, oysters are labouring bodies that reconstitute the coastal ecosystem on which the town depends. The arguments illustrate that non-human animals can be – economically, culturally and ecologically – vital and lively components within the dynamic material processes that support gentrification.
Comparison of 2-year outcomes with CAR T cells (ZUMA-1) vs salvage chemotherapy in refractory large B-cell lymphoma
Authors: Neelapu Sattva S. , Locke Frederick L. , Bartlett Nancy L. , Lekakis Lazaros J. , Reagan Patrick M. , Miklos David B. , Jacobson Caron A. , Braunschweig Ira , Oluwole Olalekan O. , Siddiqi Tanya , Lin Yi , Crump Michael , Kuruvilla John , Van Den Neste Eric , Farooq Umar , Navale Lynn , DePuy Venita , Kim Jenny J. , Gisselbrecht Christian
Published: September 2021

The SCHOLAR-1 international retrospective study highlighted poor clinical outcomes and survival among patients with refractory large B-cell lymphoma (LBCL) treated with conventional chemotherapy. Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated durable responses in patients with refractory LBCL in the pivotal phase 1/2 ZUMA-1 study (NCT02348216). Here, we compared SCHOLAR-1 with the 2-year outcomes of ZUMA-1. Prior to comparison of clinical outcomes, propensity scoring (based on a broad set of prognostic covariates) was used to create balance between ZUMA-1 and SCHOLAR-1 patients. In the pivotal phase 2 portion of ZUMA-1, 101 patients received axi-cel and were evaluable for response and survival. In SCHOLAR-1, 434 and 424 patients were evaluable for response and survival, respectively. ZUMA-1 patients were more heavily pretreated than were SCHOLAR-1 patients. The median follow-up was 27.1 months in ZUMA-1. The objective response rate (ORR) and complete response rate were 83% and 54% in ZUMA-1 vs 34% and 12% in SCHOLAR-1, respectively. The 2-year survival rate was 54% in ZUMA-1 and 20% in SCHOLAR-1, and a 73% reduction in the risk of death was observed in ZUMA-1 vs SCHOLAR-1. These results were consistent with those of an additional standardization analysis in which strata were limited to 2 prognostic factors (refractory categorization and presence/absence of stem cell transplant after refractoriness to chemotherapy) to conserve sample size. Despite the limitations of a nonrandomized analysis, these results indicate that axi-cel produces durable responses and a substantial survival benefit vs non–CAR T-cell salvage regimens for patients with refractory LBCL.
Enhanced self-renewal of human long-term hematopoietic stem cells by a sulfamoyl benzoate derivative targeting p18INK4C
Authors: Li Yinghui , Zhang Wenshan , Zhang Yu , Ding Yahui , Yang Ming , He Mei , Liu Xiaolei , Gu Jiali , Xu Shiqi , Feng Zhiwei , Li Yafang , Yin Jingjing , Gao Huier , Song Henan , Xu Hui , Wang Chaoqun , Ji Qing , Ma Shihui , Yang Wanzhu , Yuan Weiping , Xie Xiang-Qun , Cheng Tao , Gao Yingdai
Published: September 2021

The use of umbilical cord blood transplant has been substantially limited by the finite number of hematopoietic stem and progenitor cells in a single umbilical cord blood unit. Small molecules that not only quantitatively but also qualitatively stimulate enhancement of hematopoietic stem cell (HSC) self-renewal ex vivo should facilitate the clinical use of HSC transplantation and gene therapy. Recent evidence has suggested that the cyclin-dependent kinase inhibitor, p18INK4C (p18), is a critical regulator of mice HSC self-renewal. The role of p18 in human HSCs and the effect of p18 inhibitor on human HSC expansion ex vivo need further studies. Here we report that knockdown of p18 allowed for an increase in long-term colony-forming cells in vitro. We then identified an optimized small molecule inhibitor of p18, 005A, to induce ex vivo expansion of HSCs that was capable of reconstituting human hematopoiesis for at least 4 months in immunocompromised mice, and hence, similarly reconstituted secondary recipients for at least 4 more months, indicating that cells exposed to 005A were still competent in secondary recipients. Mechanistic studies showed that 005A might delay cell division and activate both the Notch signaling pathway and expression of transcription factor HoxB4, leading to enhancement of the self-renewal of long-term engrafting HSCs and the pool of progenitor cells. Taken together, these observations support a role for p18 in human HSC maintenance and that the p18 inhibitor 005A can enhance the self-renewal of long-term HSCs.
IKZF1 alterations are not associated with outcome in 498 adults with B-precursor ALL enrolled in the UKALL14 trial
Authors: Mitchell Rachel J. , Kirkwood Amy A. , Barretta Emilio , Clifton-Hadley Laura , Lawrie Emma , Lee SooWah , Leongamornlert Daniel , Marks David I. , McMillan Andrew K. , Menne Tobias F. , Papaemmanuil Elli , Patel Bela , Patrick Pip , Rowntree Clare J. , Zareian Nahid , Alapi Krisztina Zuborne , Moorman Anthony V. , Fielding Adele K.
Published: September 2021

IKZF1 deletions (ΔIKZF1) are commonly detected in B-precursor acute lymphoblastic leukemia (ALL; B-ALL) and are widely assumed to have a significant impact on outcome. We compared the ability of multiplex ligand-dependent probe amplification (MLPA) and polymerase chain reaction (PCR) to detect ΔIKZF1 and to determine the impact on event-free survival of patients with precursor B-ALL aged 23 to 65 years recruited to the completed trial UKALL14 (ISRCTN 66541317). From 655 recruits with BCR-ABL1+ and BCR-ABL1− B-ALL, all available diagnostic DNA samples (76% of the recruited population) were screened by multiplex end point PCR covering 4 deletions: dominant-negative (DN) Δ4-7 or the loss of function Δ2-7, Δ4-8, and Δ2-8 (n = 498), MLPA (n = 436), or by both (n = 420). Although patients with BCR-ABL1− ΔIKZF1 were more likely to have minimal residual disease at the end of induction, we did not find any impact of ΔIKZF1 (including subgroup analysis for DN or loss-of-function lesions) or the IKZF1plus genotype on event-free, overall survival, or relapse risk by univariable or multivariable analyses. Consistent with the technical approach, MLPA not only detected a wider range of deletions than PCR but also failed to detect some PCR-detected lesions. The main difference between our study and others reporting an association between ΔIKZF1 and outcome is the older age of participants in our population. The impact of ΔIKZF1 in ALL may be less marked in an older population of patients. Our study underscores the need for analyses in large, harmonized data sets. This trial was registered at www.clinicaltrials.gov as #NCT01085617.
Avelumab in relapsed/refractory classical Hodgkin lymphoma: phase 1b results from the JAVELIN Hodgkins trial
Authors: Herrera Alex F. , Burton Catherine , Radford John , Miall Fiona , Townsend William , Santoro Armando , Zinzani Pier Luigi , Lewis David , Fowst Camilla , Brar Satjit , Huang Bo , Thall Aron , Collins Graham P.
Published: September 2021

The 9p24.1 chromosomal alteration in classical Hodgkin lymphoma (cHL) is associated with increased expression of programmed death ligand 1 (PD-L1)/PD-L2 and an immunosuppressive tumor microenvironment. Blockade of PD-L1/PD-1 interactions with avelumab (anti–PD-L1) is hypothesized to restore antitumor immunity. JAVELIN Hodgkins was a phase 1b, multiple-dose, open-label, randomized, parallel-arm trial of avelumab in patients with relapsed/refractory (R/R) cHL. Primary end points included avelumab target occupancy by dose/schedule in peripheral blood immune cells and pharmacokinetic parameters. Secondary end points included safety and antitumor activity. Four dose levels and 2 dosing schedules were investigated: 70, 350, and 500 mg administered every 2 weeks; 500 mg every 3 weeks; and 10 mg/kg every 2 weeks. Thirty-one patients with R/R cHL were randomized; 9 (29.0%) and 20 (64.5%) had received 3 or ≥4 prior anticancer treatments, respectively. Target occupancy of >90% was observed across all treatment arms, throughout the dosing interval. Avelumab pharmacokinetic data were similar to those previously reported. The most common treatment-related adverse events of any grade were infusion-related reaction (30.0%), nausea (20.0%), increased alanine aminotransferase and rash (16.7% each), and fatigue (13.3%). The objective response rate (ORR) in all randomized patients was 41.9%, with a complete response rate of 19.4%; ORR in those with prior allogeneic hematopoietic stem cell transplant (allo-HSCT) was 55.6%. Due to decreased use of allo-HSCT in patients with R/R cHL, the expansion phase enrolling post–allo-HSCT patients was terminated. Avelumab was tolerable and demonstrated antitumor activity in heavily pretreated patients with cHL, suggesting that PD-L1 blockade may be sufficient for therapeutic benefit in cHL. This trial was registered at www.clinicaltrials.gov as #NCT02603419.
Outcomes of patients with CLL sequentially resistant to both BCL2 and BTK inhibition
Authors: Lew Thomas E. , Lin Victor S. , Cliff Edward R. , Blombery Piers , Thompson Ella R. , Handunnetti Sasanka M. , Westerman David A. , Kuss Bryone J. , Tam Constantine S. , Huang David C. S. , Seymour John F. , Roberts Andrew W. , Anderson Mary Ann
Published: September 2021

Covalent Bruton tyrosine kinase inhibitors (BTKi’s) and the B-cell lymphoma 2 (BCL2) inhibitor venetoclax have significantly improved outcomes for patients with chronic lymphocytic leukemia (CLL), especially those with biologically adverse disease. Patients with CLL resistant to their first targeted agent (TA) can be effectively treated with the alternative class. However, relapses are expected with second-line TA therapy, and the clinical challenge of double class-resistant disease is now emerging with increasing frequency. To define the characteristics and outcomes of patients with double class-resistant disease, we retrospectively analyzed 17 patients who developed progressive disease (PD) on both TA classes for CLL (venetoclax, then BTKi, n=12; BTKi, then venetoclax, n = 5). The cohort was heavily pretreated (median lines of prior therapy, 4) and enriched for adverse disease genetics (complex karyotype, 12 of 12 tested [100%]; del(17p)/TP53 mutations, 15 of 17 [88%]). The median time to progression on prior venetoclax was 24 months (range, 6-94 months) and was 25 months (range, 1-55 months) on prior BTKi. Progression on second-line TA was manifest as progressive CLL in 11 patients and as Richter transformation in 6. The median overall survival after progression on second-line TA was 3.6 months (95% confidence interval, 2-11 months). Patients with double class-resistant CLL have a dismal prognosis, representing a group of high unmet need.
Frequent mutated B2M, EZH2, IRF8, and TNFRSF14 in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype
Authors: de Groen Ruben AL , van Eijk Ronald , Boehringer Stefan , van Wezel Tom , Raghoo Richard , Ruano Dina , Jansen Patty M , Briaire-de Bruijn Inge , de Groot Fleur A , Kleiverda Karin , te Boome Liane , Terpstra Valeska , Levenga Henriette , Nicolae-Cristea Alina , Posthuma Eduardus Franciscus , Focke-Snieders Isabelle , Hardi Lizan , den Hartog Wietske C.E. , Bohmer Lara H. , Hogendoorn Pancras C.W. , van den Berg Anke , Diepstra Arjan , Nijland Marcel , Lugtenburg Pieternella J , Kersten Marie José , Pals Steven T. , Veelken Hendrik , Bovee Judith V.M.G. , Cleven Arjen , Vermaat Joost S.P.
Published: September 2021

Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is a rare extranodal lymphoma subtype. This retrospective study elucidates the currently unknown genetic background of a large clinically well-annotated cohort of DLBCL with osseous localizations (O-DLBCL), including PB-DLBCL. 103 O-DLBCL patients were included and compared with 63 (extra)nodal non-osseous (NO)-DLBCLs with germinal center B-cell phenotype (NO-DLBCL-GCB). Cell-of-origin (COO) was determined by immunohistochemistry and gene-expression-profiling (GEP) using (extended)-NanoString/Lymph2Cx. Mutational profiles were identified with targeted next-generation deep-sequencing, including 52 B-cell lymphoma-relevant genes. O-DLBCLs, including 34 PB-DLBCL, were predominantly classified as GCB-phenotype based on immunohistochemistry (74%) and NanoString analysis (88%). Unsupervised hierarchical clustering of an extended-NanoString/Lymph2Cx demonstrated significantly different GEP-clusters for PB-DLBCL as opposed to NO-DLBCL-GCB (P<0.001). Expression levels of 23 genes of two different targeted GEP-panels, indicated a centrocyte-like phenotype for PB-DLBCL, whereas NO-DLBCL-GCB showed a centroblast-like constitution. PB-DLBCL had significantly more frequent mutations in four GCB-associated genes, i.e. B2M, EZH2, IRF8, and TNFRSF14, compared to NO-DLBCL-GCB (P=0.031, P=0.010, P=0.047, and P=0.003). PB-DLBCL with its corresponding specific mutational profile were significantly associated with a superior overall survival compared to equivalent Ann Arbor limited-stage I/II NO-DLBCL-GCB (P=0.011). This study is the first to demonstrate that PB-DLBCL is characterized by a GCB-phenotype, with a centrocyte-like GEP-pattern and a GCB-associated mutational profile (both involved in immune surveillance) and a favorable prognosis. These novel biology-associated features provide evidence that PB-DLBCL represents a distinct extranodal DLBCL entity and its specific mutational landscape holds potential for targeted therapies (e.g. EZH2-inhibitors).
Mesh Force Modelling and Parametric Studies for Compound Oscillatory Roller Reducer
Authors: Wei Changxu , Song Chaosheng , Zhu Caichao , Liang Chengcheng , Hu Long
Published: September 2021

A compound oscillatory roller reducer (CORR) with a first-stage gear transmission and a second-stage oscillatory roller transmission is presented. The transmission principle of oscillatory roller transmission is introduced, and the tooth profile equation of the inner gear is derived. The analytical model of mesh force considering the installation errors and manufacturing errors is proposed. Then, parametric studies considering different errors on the mesh force are conducted. Results show that the design parameters are significant factors for mesh force. The mesh force is reduced by 17% as the eccentricity of disk cam increases from 2.5 mm to 4 mm. When the radius of the movable roller increases from 7 mm to 20 mm, the mesh force decreases by 8%. As the radius of disk cam increases from 125 mm to 170 mm, the mesh force is decreased by 26.5%. For the impacts of errors, the mesh force has a noticeable fluctuation when these errors exist including the manufacturing error of disk cam, the installation error of disk cam and the manufacturing error of movable roller change. The prototype of the reducer is manufactured and preliminary run-in test proved the feasibility of the transmission principle.
HIF-1α/JMJD1A signaling regulates inflammation and oxidative stress following hyperglycemia and hypoxia-induced vascular cell injury
Authors: Zhao Min , Wang Shaoting , Zuo Anna , Zhang Jiaxing , Wen Weiheng , Jiang Weiqiang , Chen Hong , Liang Donghui , Sun Jia , Wang Ming
Published: September 2021

Background

Endothelial cell (EC) injury accelerates the progression of diabetic macrovascular complications. Hypoxia is an important cause of EC injury. Hypoxia-inducible factor-1 alpha (HIF-1α) is an important hypoxia regulatory protein. Our previous studies showed that high-glucose and hypoxic conditions could upregulate HIF-1α expression and enhance EC inflammatory injury, independently of the nuclear factor kappa-B (NF-κB) pathway. However, it is not clear whether HIF-1α plays a role in vascular disease through epigenetic-related mechanisms.

Methods

We conducted gene expression analysis and molecular mechanistic studies in human umbilical vein endothelial cells (HUVECs) induced by hyperglycemia and hypoxia using RNA sequencing (RNA-seq) and small interfering HIF-1α (si-HIF-1α). We determined HIF-1α and Jumonji domain-containing protein 1 A (JMJD1A) expression by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot, analyzed inflammatory protein secretion in the cell supernatant by enzymelinked immunosorbent assay (ELISA), and assessed protein interaction between HIF-1α and JMJD1A by chromatin immunoprecipitation (Ch-IP). We used the Cell Counting Kit8 (CCK-8) assay to analyze cell viability, and assessed oxidative stress indicators by using a detection kit and flow cytometry.

Results

High glucose and hypoxia up-regulated HIF-1α expression, and down-regulated HIF-1α decreased the level of inflammation and oxidative stress in HUVECs. To determine the downstream pathways, we observed histone demethylases genes and related pathway by RNA-sEq. Among these, JMJD1A was the most upregulated gene in histone demethylases. Moreover, we observed that HIF-1α bound to the promoter of JMJD1A, and the ameliorative effects of si-HIF-1α on oxidative stress and inflammatory cytokines in high-glucose and hypoxia-induced HUVECs were reversed by JMJD1A overexpression. Furthermore, knockdown of JMJD1A decreased inflammatory and oxidative stress injury. To determine the JMJD1A-related factors, we conducted gene expression analysis on JMJD1A-knockdown HUVECs. We observed that downregulation of inflammation and the oxidative stress pathway were enriched and FOS and FOSB might be important protective transcription factors.

Conclusions

These findings provide novel evidence that the HIF-1α/JMJD1A signaling pathway is involved in inflammation and oxidative stress in HUVECs induced by high glucose and hypoxia. Also, this pathway might act as a novel regulator of oxidative stress and inflammatory-related events in response to diabetic vascular injury and thus contribute to the pathological progression of diabetes and vascular disease.
Integrative lncRNA landscape reveals lncRNA-coding gene networks in the secondary cell wall biosynthesis pathway of moso bamboo (Phyllostachys edulis)
Authors: Wang Jiongliang , Hou Yinguang , Wang Yu , Zhao Hansheng
Published: September 2021

Background

LncRNAs are extensively involved in plant biological processes. However, the lack of a comprehensive lncRNA landscape in moso bamboo has hindered the molecular study of lncRNAs. Moreover, the role of lncRNAs in secondary cell wall (SCW) biosynthesis of moso bamboo is elusive.

Results

For comprehensively identifying lncRNA throughout moso bamboo genome, we collected 231 RNA-Seq datasets, 1 Iso-Seq dataset, and 1 full-length cDNA dataset. We used a machine learning approach to improve the pipeline of lncRNA identification and functional annotation based on previous studies and identified 37,009 lncRNAs in moso bamboo. Then, we established a network of potential lncRNA-coding gene for SCW biosynthesis and identified SCW-related lncRNAs. We also proposed that a mechanism exists in bamboo to direct phenylpropanoid intermediates to lignin or flavonoids biosynthesis through the PAL/4CL/C4H genes. In addition, we identified 4 flavonoids and 1 lignin-preferred genes in the PAL/4CL/C4H gene families, which gained implications in molecular breeding.

Conclusions

We provided a comprehensive landscape of lncRNAs in moso bamboo. Through analyses, we identified SCW-related lncRNAs and improved our understanding of lignin and flavonoids biosynthesis.
The augment of regulatory T cells undermines the efficacy of anti-PD-L1 treatment in cervical cancer
Authors: Xu Fengying , Zhang Fengying , Wang Qian , Xu Ying , Xu Shuifang , Zhang Caihong , Wang Lihua
Published: September 2021

Background

Immune checkpoint inhibitors have aroused great expectation of tumor eradication. However, the effect of anti-PD-L1 treatment for cervical cancer is unsatisfactory and the underlying antagonist to anti-PD-L1 efficacy is remained to be studied. Here, we investigated the anti-tumor effect of anti-PD-L1 treatment in cervical tumor model and identified the antagonist to the therapeutic efficacy of anti-PD-L1 treatment.

Results

We found that PD-L1 exhibited a moderate expression in both cervical tumor cell lines and clinical samples compared to other tumor types and the para-tumor tissue respectively. Interestingly, our results showed that the anti-PD-L1 treated mice were dichotomously divided into responsive and unresponsive group after five cycles of anti-PD-L1 treatment although all the mice had the same genome background. In addition, the unresponsive tumors showed less tumor necrosis area and higher immunosuppression activity induced by regulatory T cells (Tregs) population than the responsive ones. Furthermore, we found that anti-PD-L1 treatment autonomously upregulated Tregs proliferation and frequency in multiple immune organs, and, most importantly, Tregs depletion significantly depressed the tumor growth rate and tumor weight compared with either anti-PD-L1 or anti-CD25 treatment alone. Finally, we observed that the upregulating effector CD8+ T cell is associated with the better therapeutic effect of anti-PD-L1 therapy post Tregs depletion.

Conclusions

Anti-PD-L1 treatment upregulates Tregs frequency and proliferation in tumor model, and the depletion of Tregs may be a useful adjuvant strategy for anti-PD-L1 therapy of cervical cancer.
Primary care professionals’ experiences during the first wave of the COVID-19 pandemic in Greece: a qualitative study
Authors: Smyrnakis Emmanouil , Symintiridou Despoina , Andreou Martha , Dandoulakis Michael , Theodoropoulos Elias , Kokkali Stamatia , Manolaki Chrysanthi , Papageorgiou Dimitra Iosifina , Birtsou Charis , Paganas Aristofanis , Stachteas Panagiotis , Vlachopoulos Nikolaos , Pagkozidis Ilias , Zeimbekis Akis , Roka Violeta , Giakoumis Anastasios , Kotsani Marina , Avakian Ioanna , Makridou Efthymia , Gavana Magda , Haidich Anna-Bettina , Avgerinou Christina
Published: September 2021

Background

The coronavirus outbreak (COVID-19) tested health care systems worldwide. This qualitative study aimed to explore and understand the experiences, beliefs and concerns of Primary Care Professionals (PCPs) regarding the preparedness and response of primary care to the first wave of the pandemic in Greece, a country where a public structured primary care system has been developing.

Methods

We conducted semi-structured telephone interviews with 33 PCPs (General Practitioners, community General Internal Medicine Specialists, community Paediatricians and nurses) recruited from all regions of Greece after the first wave of the pandemic (June 2020). Interviews were transcribed verbatim, data were anonymised and analysed. Thematic analysis was applied developing a conceptual framework.

Results

Four main themes were identified: a) Primary care unit adaptation and issues faced during the pandemic; b) Management of suspected COVID-19 cases; c) Management of non-suspected cases; d) Consequences of the pandemic. In the first phase of the pandemic, remote management of suspected cases and their referral to the hospital were preferred as a result of a shortage of personal protective equipment and inaccessibility to coronavirus testing in primary care. Due to the discontinuation of regular medical services and the limited in-person contact between doctors and patients, chronic disease management and prevention programmes were left behind. Social and emotional consequences of the pandemic, such as workplace stigma, isolation and social seclusion, deriving from fear of viral transmission, as well as burnout symptoms and exhaustion were commonly experienced among PCPs. Positive consequences of the pandemic were considered to be the recognition of the importance of an empowered public healthcare system by citizens and the valuable insight, knowledge and experience professionals gained in times of crisis.

Conclusions

Primary care has a key role to play during and after the pandemic by using its information infrastructure to identify at-risk groups, detect new cases of COVID-19, provide care according to needs, and carry out vaccination programmes. Central coordination and empowerment of primary care will increase its effectiveness, via public awareness, holistic patient management, and unburdening of hospitals.
A case report of rhino-facial mucormycosis in a non-diabetic patient with COVID-19: a systematic review of literature and current update
Authors: Mohammadi Faezeh , Badri Milad , Safari Shapoor , Hemmat Nima
Published: September 2021

Background

COVID-19 disease may be associated with a wide range of bacterial and fungal infections. We report a patient with COVID-19 infection who developed rhino-facial mucormycosis during treatment with corticosteroids.

Case presentation

A 59-year-old non-diabetic male patient was admitted with a diagnosis of COVID-19 based on positive RT-PCR and CT of the lungs. Due to sever lung involvement, he was treated with methylprednisolone. The patient was re-admitted to hospital, due to nasal obstruction and left side facial and orbital swelling, several days after discharge. In sinus endoscopic surgery, debridement was performed and the specimens were sent to pathology and mycology laboratories. A nasal biopsy showed wide hyphae without septa. The sequenced PCR product revealedRhizopus oryzae. Despite all medical and surgical treatment, the patient died. In addition, the characteristics of patients with COVID-19-associated mucormycosis were reviewed in 44 available literatures. In most studies, diabetes mellitus was the most common predisposing factor for mucormycosis.

Conclusion

Our report highlights the need for assessing the presence of mucormycosis in patients with COVID-19 and also it shows that physicians should consider the potential for secondary invasive fungal infections in COVID-19 cases.
Neuronal intranuclear inclusion disease presented with recurrent vestibular migraine-like attack: a case presentation
Authors: Zhao Danhua , Zhu Sha , Xu Qinlan , Deng Jianwen , Wang Zhaoxia , Liu Xianzeng
Published: September 2021

Background

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder characterized by dementia, tremor, episodic encephalopathy and autonomic nervous dysfunction. To date, vestibular migraine (VM)-like attack has never been reported in cases with NIID. Here, we describe an 86-year-old patient with NIID who presented with recurrent vertigo associated with headache for more than 30 years.

Case presentation

An 86-year-old Chinese woman with vertigo, headache, weakness of limbs, fever, and disturbance of consciousness was admitted to our hospital. She had suffered from recurrent vertigo associated with headache since her 50 s,followed by essential tremor and dementia. On this admission, brain magnetic resonance imaging revealed high intensity signals along the corticomedullary junction on diffusion weighted imaging (DWI). Peripheral neuropathy of the extremities was detected through electrophysiological studies. We diagnosed NIID after detecting eosinophilic intranuclear inclusions in the ductal epithelial cells of sweat glands and identifying an abnormal expansion of 81 GGC repeats in the 5’UTR of NOTCH2NLC gene.

Conclusions

VM-like attack may be associated with NIID.
Head and neck squamous cell carcinoma cell lines have an immunomodulatory effect on macrophages independent of hypoxia and toll-like receptor 9
Authors: Ishizu Tamiko , Eichin Dominik , Padzik Artur , Tuominen Sanni , Grénman Reidar , Salmi Marko , Grönroos Tove J. , Tuomela Johanna M.
Published: September 2021

Background

A low tissue oxygen level, < 1% O2, is a typical characteristic inside of solid tumors in head and neck cancer (HNSCC) affecting a wide array of cell populations, such as macrophages. However, the mechanisms of how hypoxia influences macrophages are not yet fully elucidated. Our research aimed to study the effect of soluble mediators produced by hypoxic cancer cells on macrophage polarization. Furthermore, we studied the effect of a hypoxic microenvironment on the expression of tumorigenic toll-like receptor 9 (TLR9) and the consecutive macrophage polarization.

Methods

Conditioned media (CMNOX or CMHOX) from cell lines UT-SCC-8, UT-SCC-74A, FaDu, MDA-MB-231 and HaCat cultured under normoxic (21% O2) and hypoxic (1% O2) conditions were used to polarize human monocyte-derived macrophages. Macrophage polarization was measured by flow cytometry and the production of cytokine mRNA using Taqman qPCR. To study the role of TLR9 in macrophage polarization, the lentiviral CRISPR/Cas9 method was used to establish a stable FaDuTLR9def clone.

Results

Our results demonstrate that the soluble mediators produced by the cancer cells under normoxia polarize macrophages towards a hybridized M1/M2a/M2c phenotype. Furthermore, the results suggest that hypoxia has a limited role in altering the array of cancer-produced soluble factors affecting macrophage polarization and cytokine production. Our data also indicates that increased expression of TLR9 due to hypoxia in malignant cells does not markedly influence the polarization of macrophages. TLR9 transcriptional response to hypoxia is dissimilar to a HIF1-α-regulated LDH-A. This may indicate a context-dependent expression of TLR9 under hypoxia.

Conclusions

HNSCC cell lines affect both macrophage activity (polarization) and functionality (cytokines), but with exception to iNOS expression, the effects appear independent of hypoxia and TLR9.
Cannabinoid exposure as a major driver of pediatric acute lymphoid Leukaemia rates across the USA: combined geospatial, multiple imputation and causal inference study
Authors: Reece Albert Stuart , Hulse Gary Kenneth
Published: September 2021

Background

Acute lymphoid leukaemia (ALL) is the commonest childhood cancer whose incidence is rising in many nations. In the USA, between 1975 and 2016, ALL rates (ALLRs) rose 93.51% from 1.91 to 3.70/100,000 <  20 years. ALL is more common in Caucasian-Americans than amongst minorities. The cause of both the rise and the ethnic differential is unclear, however, prenatal cannabis exposure was previously linked with elevated childhood leukaemia rates. We investigated epidemiologically if cannabis use impacted nationally on ALLRs, its ethnic effects, and if the relationship was causal.

Methods

State data on overall, and ethnic ALLR from the Surveillance Epidemiology and End Results databank of the Centre for Disease Control (CDC) and National Cancer Institute (NCI) were combined with drug (cigarettes, alcoholism, cannabis, analgesics, cocaine) use data from the National Survey of Drug Use and Health; 74.1% response rate. Income and ethnicity data was from the US Census bureau. Cannabinoid concentration was from the Drug Enforcement Agency Data. Data was analyzed in R by robust and spatiotemporal regression.

Results

In bivariate analyses a dose-response relationship was demonstrated between ALLR and Alcohol Use Disorder (AUD), cocaine and cannabis exposure, with the effect of cannabis being strongest (β-estimate = 3.33(95%C.I. 1.97, 4.68),P = 1.92 × 10− 6). A strong effect of cannabis use quintile on ALLR was noted (Chi.Sq. = 613.79,P = 3.04 × 10− 70). In inverse probability weighted robust regression adjusted for other substances, income and ethnicity, cannabis was independently significant (β-estimate = 4.75(0.48, 9.02),P = 0.0389). In a spatiotemporal model adjusted for all drugs, income, and ethnicity, cannabigerol exposure was significant (β-estimate = 0.26(0.01, 0.52),P = 0.0444), an effect increased by spatial lagging (THC: β-estimate = 0.47(0.12, 0.82),P = 0.0083). After missing data imputation ethnic cannabis exposure was significant (β-estimate = 0.64(0.55, 0.72),P = 3.1 × 10− 40). 33/35 minimum e-Values ranged from 1.25 to 3.94 × 1036indicative of a causal relationship. Relaxation of cannabis legal paradigms had higher ALLR (Chi.Squ.Trend = 775.12,P = 2.14 × 10− 112). Cannabis legal states had higher ALLR (2.395 ± 0.039 v. 2.127 ± 0.008 / 100,000,P = 5.05 × 10− 10).

Conclusions

Data show that ALLR is associated with cannabis consumption across space-time, is associated with the cannabinoids, THC, cannabigerol, cannabinol, cannabichromene, and cannabidiol, contributes to ethnic differentials, demonstrates prominent quintile effects, satisfies criteria for causality and is exacerbated by cannabis legalization.
A novel tool for predicting the survival of endoprosthesis used for reconstruction of the knee following tumor resection: a retrospective cohort study
Authors: Pang Cheng-gang , Yang Xiong-gang , Zhao Yun-long , Liu Yan-cheng , Hu Yong-cheng
Published: September 2021

Background

Prosthesis-related complications, after knee reconstruction with endoprosthesis during operation for tumors around the knee, remain an unresolved problem which necessitate a revision or even an amputational surgery. The purpose of the current study was to identify significant risk factors associated with implant failure, and establish a novel model to predict survival of the prosthesis in patients operated with endoprostheses for tumor around knee.

Methods

We retrospectively reviewed the clinical database of our institution for patients who underwent knee reconstruction due to tumors. A total of 203 patients were included, including 123 males (60.6%) and 80 (39.4%) females, ranging in age from 14 to 77 years (mean: 34.3 ± 17.3 years). The cohort was randomly divided into training (n = 156) and validation (n = 47) samples. Univariable COX analysis was used for initially identifying potential independent predictors of prosthesis survival with the training group (p < 0.150). Multivariate COX proportional hazard model was selected to identify final significant prognostic factors. Using these significant predictors, a graphic nomogram, and an online dynamic nomogram were generated for predicting the prosthetic survival. C-index and calibration curve were used for evaluate the discrimination ability and accuracy of the novel model, both in the training and validation groups.

Results

The 1-, 5-, and 10-year prosthetic survival rates were 94.0, 90.8, and 83.0% in training sample, and 96.7, 85.8, and 76.9% in validation sample, respectively. Anatomic sites, length of resection and length of prosthetic stem were independently associated with the prosthetic failure according to multivariate COX regression model (p<0.05). Using these three significant predictors, a graphical nomogram and an online dynamic nomogram model were generated. The C-indexes in training and validation groups were 0.717 and 0.726 respectively, demonstrating favourable discrimination ability of the novel model. And the calibration curve at each time point showed favorable consistency between the predicted and actual survival rates in training and validation samples.

Conclusions

The length of resection, anatomical location of tumor, and length of prosthetic stem were significantly associated with prosthetic survival in patients operated for tumor around knee. A user-friendly novel online model model, with favorable discrimination ability and accuracy, was generated to help surgeons predict the survival of the prosthesis.
Prognostic impact of tumor length in esophageal Cancer: a systematic review and Meta-analysis
Authors: Wang Zhao Yang , Jiang Yuan Zhu , Xiao Wen , Xue Xian Biao , Zhang Xiang Wei , Zhang Lin
Published: September 2021

Background

In clinical studies, it has been observed that esophageal cancer (EC) patient prognosis can be very different even for those patients with tumors of the same TNM stage. Tumor length has been analysed as a possible independent prognostic factor in many studies, but no unanimous conclusion has been reached. Therefore, this review used a meta-analysis to evaluate the association between tumor length and prognosis in EC patients.

Methods

A systematic search for relevant articles was performed in PubMed, Web of Science, and Embase. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used as effective measures to estimate the correlation between tumor length and prognosis, including overall survival, disease-free survival, progression-free survival, disease-specific survival, and cancer-specific survival. STATA 15.0 software was used to perform the meta-analysis and the data synthesis.

Results

Finally, 41 articles with 28,973 patients were included in our study. The comprehensive statistical results showed that long tumors are an independent prognostic parameter associated with poor overall survival (OS) (HR = 1.30; 95% CI: 1.21–1.40, p < .001) and disease-free survival (DFS) (HR = 1.38; 95% CI: 1.18–1.61, p < .001) in EC patients. Subgroup analyses also suggested a significant correlation between long tumors and poor OS. Sensitivity analysis and publication bias evaluation confirmed the reliability and stability of the results. Similar results were obtained in the analyses of progression-free survival (PFS), disease-specific survival (DSS), and cancer-specific survival (CSS).

Conclusion

The results of this meta-analysis showed that long tumors were related to poor OS, DFS, PFS, DSS and CSS in EC patients. Tumor length might be an important predictor of prognosis in EC patients, and it can be used as an independent staging index. Further well-designed and large-scale prospective clinical studies are needed to confirm these findings.