bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Change in Oral Microbiota of Children With Cleft Lip and Palate After Alveolar Bone Grafting
Authors: Zhang Kejia , Zhou Xuan , Qin Jinwei , Zhang Weibing , Pan Yongchu , Wang Hua , Lin Jiuxiang , Liu Luwei , Jia Yilin
Published: September 2021

To investigate the longitudinal influence of alveolar bone grafting on the oral microbiota of children with cleft lip and palate (CLP).

Twenty-eight children with nonsyndromic CLP were recruited and underwent secondary alveolar bone grafting at the first time. Unstimulated saliva and plaque samples were collected from the subjects preoperatively and at 2 days, 1 month, and 3 months postoperatively. The v3–v4 hypervariable regions of the 16S rRNA gene from bacterial DNA were sequenced using the Illumina MiSeq sequencing platform.

The alpha diversity of the saliva and plaque microbiota was significantly decreased at 2 days postoperatively and then increased at 1 and 3 months postoperatively. The saliva and plaque microbiota compositions at 2 days postoperatively differed from those at the other time points, and the microbiota compositions at 1 and 3 months postoperatively showed a gradual shift toward the preoperative composition. The saliva, but not plaque, microbiota composition 3 months postoperatively was similar to that preoperatively.

The effect of secondary alveolar bone grafting on the plaque microbiota in children with CLP lasted longer than the saliva microbiota. Alveolar bone grafting altered the saliva microbiota in children with CLP within 3 months postoperatively.
Considerations When Performing Arthrodesis in the Scleroderma Hand
Authors: Long Chao , Gong Jung Ho , Lifchez Scott D.
Published: September 2021

Background

Hand deformities secondary to scleroderma can limit activities of daily living and be associated with substantial disability. This study aimed to evaluate the outcomes following arthrodesis performed to treat digital contractures secondary to scleroderma.

Methods

We performed a retrospective review of all patients with scleroderma who underwent arthrodesis by a single surgeon from 2015 to 2020. We collected demographic information, operative variables, and outcomes variables. Our primary outcome was occurrence of any postoperative complication, which we defined to include wound dehiscence, digital ischemia, malunion, nonunion, cellulitis, and osteomyelitis. We calculated descriptive statistics and performed all analyses at the joint level.

Results

We identified 9 patients who underwent arthrodesis of 19 joints. All patients were women with a mean age of 55.3 years. At the time of surgery, most patients were taking disease-modifying antirheumatic drugs (DMARDs). Kirschner wires (K-wires) were used in most cases (n = 18), 15 of which were removed uneventfully at an average of 4.8 months after surgery. With a mean follow-up time of 15.4 months, the overall complication rate was 5.3% (n = 1). This patient developed digital ischemia in 1 of 4 operative digits, which became gangrenous and required amputation.

Conclusions

Our study suggests that arthrodesis can be performed safely in the scleroderma hand, even when patients are taking DMARDs. Given the uneventful K-wire removal in all joints and the high risk of exposure of buried hardware in this population, we recommend nonpermanent placement of K-wires. Hand surgeons may consider arthrodesis in the scleroderma hand before proceeding to revision amputation.
Two new α-Methoxy-γ-Pyrones From the Mangrove Sediment-Derived Streptomyces psammoticus SCSIO NS126
Authors: Li Kunlong , Zhou Mengdie , Su Ziqi , Yang Xiliang , Zhou Xuefeng , Huang Jingxia , Tao Huaming
Published: September 2021

Two new α-methoxy- γ-pyrone analogs, 2-methoxy-3-methyl-5,6-diethyl- γ-pyrone (2) and 2-methoxy-3,5-dimethyl-6-propyl- γ-pyrone (3), together with 2-methoxy-3,5-dimethyl-6-ethyl- γ-pyrone (1), firstly isolated from natural sources, were obtained from the EtOAc-solube extract of the mangrove sediment-derived actinomycete strain Streptomyces psammoticus SCSIO NS126, under the optimized fermentation conditions. Their structures were elucidated by detailed spectroscopic analysis and by comparison of their spectroscopic data with those reported in the literature. Those α-methoxy-γ-pyrones were evaluated for their acetylcholinesterase inhibitory activity; however, none of them exhibited obvious activity. Moreover, their biosynthetic relationship with piericidins was also discussed.
Carfilzomib‐associated pulmonary arterial hypertension in multiple myeloma
Authors: Yang Jenny Z. , Buckstaff Taylor , Narezkina Anna , Fernandes Timothy M.
Published: September 2021

Drug‐induced pulmonary arterial hypertension (PAH) is constantly evolving as new drugs are developed. Carfilzomib is a recently approved therapy for relapsed and refractory multiple myeloma. While it has been associated with cardiovascular adverse events, such as ischemic heart disease and heart failure, PAH has not been a well‐described side effect. We present two patients who developed PAH associated with initiation of carfilzomib. They both initially presented with severe dyspnea, had elevated right ventricular systolic pressure on transthoracic echocardiography and ultimately underwent right heart catheterization. With discontinuation of carfilzomib, both patients had improvement in hemodynamics. However, one patient required initiation of PAH‐targeted therapies and has had worsening right ventricular function again despite permanent discontinuation of carfilzomib. It is important to recognize the association between carfilzomib and PAH. Echocardiography can be an important initial screening tool. PAH from carfilzomib therapy may be reversible, especially if diagnosed early; however, extended follow‐up is essential.
Defining and treating high-grade B-cell lymphoma, NOS
Authors: Olszewski Adam J. , Kurt Habibe , Evens Andrew M.
Published: September 2021

High-grade B-cell lymphoma (HGBL), not otherwise specified (NOS), is a recently introduced diagnostic category for aggressive B-cell lymphomas. It includes tumors with Burkitt-like or blastoid morphology that do not have double-hit cytogenetics and that cannot be classified as other well-defined lymphoma subtypes. HBCLs, NOS, are rare and heterogeneous; most have germinal center B-cell phenotype, and up to 45% carry a single-hit MYC rearrangement, but otherwise, they have no unifying immunophenotypic or cytogenetic characteristics. Recent analyses using gene expression profiling (GEP) revealed that up to 15% of tumors currently classified as diffuse large B-cell lymphoma display an HGBL-like GEP signature, indicating a potential to significantly expand the HGBL category using more objective molecular criteria. Optimal treatment of HGBL, NOS, is poorly defined because of its rarity and inconsistent diagnostic patterns. A minority of patients have early-stage disease, which can be managed with standard R-CHOP–based approaches with or without radiation therapy. For advanced-stage HGBL, NOS, which often presents with aggressive disseminated disease, high lactate dehydrogenase, and involvement of extranodal organs (including the central nervous system [CNS]), intensified Burkitt lymphoma–like regimens with CNS prophylaxis may be appropriate. However, many patients diagnosed at age >60 years are not eligible for intensive immunochemotherapy. An improved GEP- and/or genomic-based pathologic classification that could facilitate HGBL-specific trials is needed to improve outcomes for all patients. In this review, we discuss the current clinicopathologic concept of HGBL, NOS, and existing data on its prognosis and treatment and delineate potential future taxonomy enrichments based on emerging molecular diagnostics.
IL-1 mediates microbiome-induced inflammaging of hematopoietic stem cells in mice
Authors: Kovtonyuk Larisa V. , Caiado Francisco , Garcia-Martin Santiago , Manz Eva-Maria , Helbling Patrick , Takizawa Hitoshi , Boettcher Steffen , Al-Shahrour Fatima , Nombela-Arrieta Cesar , Slack Emma , Manz Markus G.
Published: September 2021

Aging is associated with impaired hematopoietic and immune function caused in part by decreased fitness in the hematopoietic stem cell (HSC) population and an increased myeloid differentiation bias. The reasons for this aging-associated HSC impairment are incompletely understood. Here we demonstrate that older specific pathogen free (SPF) wild-type (WT) mice in contrast to young SPF mice produce more interleukin-1a and interleukin-1b (IL-1a/b) in steady-state bone marrow (BM), with most of the IL-1a/b being derived from myeloid BM cells. Furthermore, blood from steady-state older SPF WT mice contains higher levels of microbe-associated molecular patterns, specifically TLR4 and TLR8 ligands. In addition, BM myeloid cells from older mice produce more IL-1b in vitro, and older mice show higher and more durable IL-1a/b responses upon stimulation with lipopolysaccharide in vivo. To test whether HSC aging is driven by IL-1a/b, we evaluated HSCs from IL-1 receptor 1 (IL-1R1) knockout (KO) mice. Indeed, older HSCs from IL-1R1KO mice show significantly mitigated aging-associated inflammatory signatures. Moreover, HSCs from older IL-1R1KO and from germ-free mice maintain unbiased lymphomyeloid hematopoietic differentiation upon transplantation, thus resembling this functionality of young HSCs. Importantly, in vivo antibiotic suppression of microbiota or pharmacologic blockade of IL-1 signaling in older WT mice was similarly sufficient to reverse myeloid-biased output of their HSC populations. Collectively, our data define the microbiome/IL-1/IL-1R1 axis as a key, self-sustaining and also therapeutically partially reversible driver of HSC inflammaging.
Characterization of HLH-like manifestations as a CRS variant in patients receiving CD22 CAR T cells
Authors: Lichtenstein Daniel A. , Schischlik Fiorella , Shao Lipei , Steinberg Seth M. , Yates Bonnie , Wang Hao-Wei , Wang Yanyu , Inglefield Jon , Dulau-Florea Alina , Ceppi Francesco , Hermida Leandro C. , Stringaris Kate , Dunham Kim , Homan Philip , Jailwala Parthav , Mirazee Justin , Robinson Welles , Chisholm Karen M. , Yuan Constance , Stetler-Stevenson Maryalice , Ombrello Amanda K. , Jin Jianjian , Fry Terry J. , Taylor Naomi , Highfill Steven L. , Jin Ping , Gardner Rebecca A. , Shalabi Haneen , Ruppin Eytan , Stroncek David F. , Shah Nirali N.
Published: September 2021

Chimeric antigen receptor (CAR) T-cell toxicities resembling hemophagocytic lymphohistiocytosis (HLH) occur in a subset of patients with cytokine release syndrome (CRS). As a variant of conventional CRS, a comprehensive characterization of CAR T-cell–associated HLH (carHLH) and investigations into associated risk factors are lacking. In the context of 59 patients infused with CD22 CAR T cells where a substantial proportion developed carHLH, we comprehensively describe the manifestations and timing of carHLH as a CRS variant and explore factors associated with this clinical profile. Among 52 subjects with CRS, 21 (40.4%) developed carHLH. Clinical features of carHLH included hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, coagulopathy, hepatic transaminitis, hyperbilirubinemia, severe neutropenia, elevated lactate dehydrogenase, and occasionally hemophagocytosis. Development of carHLH was associated with preinfusion natural killer(NK) cell lymphopenia and higher bone marrow T-cell:NK cell ratio, which was further amplified with CAR T-cell expansion. Following CRS, more robust CAR T-cell and CD8 T-cell expansion in concert with pronounced NK cell lymphopenia amplified preinfusion differences in those with carHLH without evidence for defects in NK cell mediated cytotoxicity. CarHLH was further characterized by persistent elevation of HLH-associated inflammatory cytokines, which contrasted with declining levels in those without carHLH. In the setting of CAR T-cell mediated expansion, clinical manifestations and immunophenotypic profiling in those with carHLH overlap with features of secondary HLH, prompting consideration of an alternative framework for identification and management of this toxicity profile to optimize outcomes following CAR T-cell infusion.
The STAT3-MYC axis promotes survival of leukemia stem cells by regulating SLC1A5 and oxidative phosphorylation
Authors: Amaya Maria L. , Inguva Anagha , Pei Shanshan , Jones Courtney , Krug Anna , Ye Haobin , Minhajuddin Mohammad , Winters Amanda , Furtek Steffanie L. , Gamboni Fabia , Stevens Brett , D’Alessandro Angelo , Pollyea Daniel A. , Reigan Philip , Jordan Craig T.
Published: September 2021

Acute myeloid leukemia (AML) is characterized by the presence of leukemia stem cells (LSCs), and failure to fully eradicate this population contributes to disease persistence/relapse. Prior studies have characterized metabolic vulnerabilities of LSCs, which demonstrate preferential reliance on oxidative phosphorylation (OXPHOS) for energy metabolism and survival. In the present study, using both genetic and pharmacologic strategies in primary human AML specimens, we show that signal transducer and activator of transcription 3 (STAT3) mediates OXPHOS in LSCs. STAT3 regulates AML-specific expression of MYC, which in turn controls transcription of the neutral amino acid transporter gene SLC1A5. We show that genetic inhibition of MYC or SLC1A5 acts to phenocopy the impairment of OXPHOS observed with STAT3 inhibition, thereby establishing this axis as a regulatory mechanism linking STAT3 to energy metabolism. Inhibition of SLC1A5 reduces intracellular levels of glutamine, glutathione, and multiple tricarboxylic acid (TCA) cycle metabolites, leading to reduced TCA cycle activity and inhibition of OXPHOS. Based on these findings, we used a novel small molecule STAT3 inhibitor, which binds STAT3 and disrupts STAT3-DNA, to evaluate the biological role of STAT3. We show that STAT3 inhibition selectively leads to cell death in AML stem and progenitor cells derived from newly diagnosed patients and patients who have experienced relapse while sparing normal hematopoietic cells. Together, these findings establish a STAT3-mediated mechanism that controls energy metabolism and survival in primitive AML cells.
CXCR4 PET/MRI for follow-up of gastric mucosa–associated lymphoid tissue lymphoma after first-line Helicobacter pylori eradication
Authors: Mayerhoefer Marius E. , Raderer Markus , Lamm Wolfgang , Weber Michael , Kiesewetter Barbara , Rohrbeck Johannes , Simonitsch-Klupp Ingrid , Hacker Marcus , Leisser Asha , Nics Lukas , Schmitl Stefan , Wester Hans-Juergen , Haug Alexander
Published: September 2021

Posttreatment evaluation of gastric mucosa-associated lymphoid tissue (MALT) lymphoma currently relies on esophagogastroduodenoscopy with histological assessment of biopsies. Overexpression of the G protein–coupled C-X-C chemokine receptor type 4 (CXCR4) has been previously observed in MALT lymphoma. The aim of this prospective study was to evaluate positron emission tomography (PET) with the novel CXCR4 tracer [68Ga]Pentixafor as a potential alternative to follow up biopsies for assessment of residual disease (noncomplete remission [CR]) after first-line Helicobacter pylori eradication. Forty-six post–H pylori eradication [68Ga]Pentixafor–PET/magnetic resonance imaging (MRI) examinations of 26 gastric MALT lymphoma patients, and 20 [68Ga]Pentixafor–PET/MRI examinations of 20 control group patients without lymphoma, were analyzed. In the MALT lymphoma group, time-matched gastric biopsies were used as reference standard and showed CR in 6 cases. Pooled examination-based accuracy, sensitivity, specificity, and positive and negative predictive values of [68Ga]Pentixafor–PET for detection of residual gastric MALT lymphoma at follow-up were 97.0%, 95.0%, 100.0%, 100.0%, and 92.9%, respectively. Maximum and mean PET standardized uptake values showed moderate correlation with immunohistochemistry-based CXCR4+ cell counts, with correlation coefficients of r = 0.51 and r = 0.52 (P = .008 and P = .006). In summary, CXCR4 imaging with [68Ga]Pentixafor–PET may represent a promising test for assessment of residual gastric MALT lymphomas after H pylori eradication.
Medial closure supracondylar femoral osteotomy: an effective solution for long-term treatment of arthritic valgus knee?
Authors: Uboldi Francesco Mattia , Travi Martino , Tradati Daniele , Maione Alessio , Manunta Andrea Fabio , Berruto Massimo
Published: September 2021

Purpose

The aim of this work was to retrospectively analyze the clinical, subjective, and radiological results of medial closing-wedge distal femur osteotomy (MCW-DFO) for the treatment of osteoarthritis (OA) in valgus knee at medium- to long-term follow-up.

Materials and methods

A total of 57 patients (62 knees) treated with MCW-DFO between 1984 and 2018 were included in the study. Patient age at the time of the surgery ranged between 28 and 61 years (average: 48 years). All patients with a minimum follow-up of 4 years were contacted to request for them to undergo clinical, subjective, and radiological evaluation. Preoperative hip–knee–ankle (HKA) angle (i.e., preoperative valgus malalignment) was 8.6° ± 2°. Patients were evaluated using the following scales: the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Knee Society Score (KSS), the International Knee Documentation Committee (IKDC), the Visual Analog Scale (VAS), and the Numeric Rating Scale 11 (NRS-11).

Results

Mean follow-up was 11.6 ± 4.9 years, and a total of 17 patients (20 knees) were available for the last examination. At maximum follow-up, 4 patients underwent conversion to a total knee replacement (20%); their survival rate was 100% at 10 years and 66.7% at 15 years, as estimated using the Kaplan–Meier curve. The subjective Knee Society Score improved on average from 37.7 ± 10 to 63.9 ± 15.4. The objective Knee Society Score improved on average from 42.2 ± 11.7 to 75 ± 22.5. The pain detected through the VAS and NRS-11 scales improved from 56.7 ± 12.9 to 42 ± 17.1 and from 5.8 ± 1.1 to 4.4 ± 1.7, respectively. Thirteen patients (70%) required hardware removal at an average time of 19 ± 4 months due to a local nuisance.

Conclusions

MCW-DFO can improve symptoms in patients with osteoarthritis in a valgus knee at medium- to long-term follow-up, reducing the progression of osteoarthritis in properly selected patients.
Analysis of Actin and Focal Adhesion Organisation in U2OS Cells on Polymer Nanostructures
Authors: Vinje Jakob B. , Guadagno Noemi Antonella , Progida Cinzia , Sikorski Pawel
Published: September 2021

Background

In this work, we explore how U2OS cells are affected by arrays of polymer nanopillars fabricated on flat glass surfaces. We focus on describing changes to the organisation of the actin cytoskeleton and in the location,
number and shape of focal adhesions. From our findings we identify that the cells can be categorised into different regimes based on their spreading and adhesion behaviour on nanopillars. A quantitative analysis suggests that cells seeded on dense nanopillar arrays are suspended on top of the pillars with focal adhesions forming closer to the cell periphery compared to flat surfaces or sparse pillar arrays. This change is analogous to similar responses for cells seeded on soft substrates.

Results

In this work, we explore how U2OS cells are affected by arrays of polymer nanopillars fabricated on flat glass surfaces. We focus on describing changes to the organisation of the actin cytoskeleton and in the location, number and shape of focal adhesions. From our findings we identify that the cells can be categorised into different regimes based on their spreading and adhesion behaviour on nanopillars. A quantitative analysis suggests that cells seeded on dense nanopillar arrays are suspended on top of the pillars with focal adhesions forming closer to the cell periphery compared to flat surfaces or sparse pillar arrays. This change is analogous to similar responses for cells seeded on soft substrates.

Conclusion

Overall, we show that the combination of high throughput nanofabrication, advanced optical microscopy, molecular biology tools to visualise cellular processes and data analysis can be used to investigate how cells interact with nanostructured surfaces and will in the future help to create culture substrates that induce particular cell function.

Graphic Abstract
Recurrent acute pancreatitis during a ketogenic diet—a case report and literature review
Authors: Choi Joseph , Young Tayler L. , Chartier Lucas B.
Published: September 2021

Background

The ketogenic (“keto”) diet has been gaining more attention lately in the medical literature and the lay media as a potentially effective method for weight control and management of type 2 diabetes. Though rare, there have been case reports of serious side effects. Here, we present a peculiar case of pancreatitis presumably associated with the ketogenic diet.

Case presentation

A 35-year-old man on a calorie-restricted ketogenic diet presented to the emergency department with weekly abdominal pain on Monday mornings, each time after dietary indiscretions (“cheat days”) on the weekend. It was found that he had a clinical presentation consistent with acute pancreatitis with no associated alcohol use, hypertriglyceridemia, pancreatic obstruction, or other anatomic abnormalities. The patient’s symptoms resolved with conservative management and progressive reintroduction of a standard diet.

Conclusion

This case indicates that the ketogenic diet could lower the threshold for acute pancreatitis, and that an episodic stressor may trigger an acute attack in the absence of traditional risk factors.
Brain-derived neurotrophic factor gene variants and obesity in former smokers
Authors: Yang Shan-shan , He Yao , Xu Lin , Jin Yali , Zhang Wei-sen , Jiang Chao-qiang , Cheng Kar Keung , Lam Tai Hing
Published: September 2021

Objective

From genome-wide association studies, brain-derived neurotrophic factor (BDNF) locus on chromosome 11 was the only SNP associated with both smoking and body mass index (BMI) in European, African and Asian population. This study aims to explore the unique genetic predisposition to obesity in former smokers by examining the effects of BDNF on BMI and waist circumference (WC).

Methods

The study design is case-control study with a cohort validation in supplementary. We included 15,072 ethnic Chinese participants in the Guangzhou Biobank Cohort Study (GBCS) with data of four BDNF SNPs related to both BMI and smoking behavior. We used baseline smoke exposure data in 2003–2007 and follow-up outcomes of general obesity (by BMI) and central obesity (WC) in 2008–2012. Odds ratios (ORs) and 95% confidence intervals (CIs) for general obesity and central obesity associated with these SNPs were derived from logistic regression.

Results

Of 15,072 participants (3169 men and 11,903 women), 1664 (11.0%) had general and 7868 (52.2%) had central obesity. In 1233 former smokers, the rs6265 GG, versus AA, genotype was associated with higher risks of general obesity (OR = 1.79, 95% CI = 1.06–3.01) and central obesity (OR = 2.08, 95% CI = 1.47–2.92) after adjustment. These associations were not significant in never or current smokers. In former heavy (≥20 cigarettes/day) smokers, the rs6265 GG genotype showed a higher odds for general obesity (OR = 2.15, 95% CI = 1.05–4.40), while no association was found in former light (1–9 cigarettes/day) smokers. Similar results were found for the association of rs6265 with central obesity and for the associations of other two BDNF SNPs (rs4923457 and rs11030104) with both general and central obesity.

Conclusions

We firstly identified the genetic predisposition (BDNF SNPs) to general and central obesity in former smokers, particularly in former heavy smokers. The different associations of the SNPs for general/central obesity in different smoke exposure groups may be related to the competitive performance of the sites and epigenetic modification, which needs further study.
Predictive value of CHADS2 and CHA2DS2-VASc scores for coronary artery lesions and in-hospital prognosis of patients with acute ST-segment elevation myocardial infarction
Authors: Li Xiaoli , Zeng Zhen , Yang Xinchun , Wang Hongjiang
Published: September 2021

Objective

To evaluate the predictive value of CHADS2 and CHA2DS2-VASc scores for coronary artery lesions and in-hospital prognosis of patients with acute ST-segment elevation myocardial infarction (STEMI).

Methods

A total of 524 patients who were diagnosed with STEMI from January 2016 to August 2017 were retrospectively reviewed. The correlation between CHADS2 and CHA2DS2-VASc scores with the patients’ clinical data, number of coronary lesions, Gensini scores, the target vessel and hospitalization time and in-hospital adverse events (AEs) was analyzed.

Results

The number of coronary lesions in STEMI patients was mainly single and double lesions. The CHADS2 and CHA2DS2-VASc scores were not meaningful for predicting the number of coronary lesions. However, for left main coronary artery lesion, CHADS2 score was significantly increased when the number increased (P < 0.05), but CHA2DS2-VASc score showed no statistical difference (P > 0.05). The incidence of target lesions in STMEI patients was mainly left anterior descending coronary artery (LAD) and right coronary artery (RCA). The two scores were not meaningful for predicting target lesions (P > 0.05). For the severity of coronary lesions, there was positive correlation between CHADS2 score with Gensini score (P < 0.05), but no exact correlation between CHA2DS2-VASc score and Gensini score (P > 0.05). The stratifications of CHADS2 score and CHA2DS2-VASc score were significantly associated with hospitalization time and adverse events during hospitalization (P < 0.05). The high score group had longer hospitalization time and more AEs during hospitalization than the low score group and the middle group statistically (P < 0.05).

Conclusion

CHADS2 score had a certain value to predict the severity of coronary lesion and the presence of left main coronary artery in STEMI. The CHA2DS2-VASc score had no predictive ability to do it. There was no significant value in predicting the number of coronary lesions and the location of the target lesions in STEMI patients. However, both scores had the predictive ability for patient hospitalization and AEs during hospitalization.
eIF5B regulates the expression of PD-L1 in prostate cancer cells by interacting with Wig1
Authors: Li Qi , Xiao Mulun , Shi Yibo , Hu Jinhao , Bi Tianxiang , Wang Chaoliang , Yan Liang , Li Xiaoyan
Published: September 2021

Background

Eukaryotic translation initiation factors (eIFs) are the key factors to synthesize translation initiation complexes during the synthesis of eukaryotic proteins. Besides, eIFs are especially important in regulating the immune function of tumor cells. However, the effect mechanism of eIFs in prostate cancer remains to be studied, which is precisely the purpose of this study.

Methods

In this study, three groups of prostate cancer cells were investigated. One group had its eIF5B gene knocked down; another group had its Programmed death 1 (PD-L1) overexpressed; the final group had its Wild-type p53-induced gene 1 (Wig1) overexpressed. Genetic alterations of the cancer cells were performed by plasmid transfection. The expression of PD-L1 mRNA was detected by quantitative real-time PCR (qRT-PCR), and the expressions of PD-L1 and eIF5B proteins were observed by western blot assays. Cell Counting Kit-8 (CCK-8), flow cytometry, Transwell and Transwell martrigel were used to investigated cell proliferation, apoptosis, migration and invasion, respectively. The effect of peripheral blood mononuclear cells (PBMCs) on tumor cells was observed, and the interaction between eIF5B and Wig1 was revealed by co-immunoprecipitation (CoIP) assay. Finally, the effects of interference with eIF5B expression on the growth, morphology, and immunity of the tumor, as well as PD-L1 expression in the tumor, were verified by tumor xenograft assays in vivo.

Results

Compared with normal prostate epithelial cells, prostate cancer cells revealed higher expressions of eIF5B and PD-L1 interference with eIF-5B expression can inhibit the proliferation, migration, invasion and PD-L1 expression of prostate cancer cells. Meanwhile, the cancer cell group with interference with eIF5B expression also demonstrated greater, apoptosis and higher vulnerability to PBMCs. CoIP assays showed that Wig1 could bind to eIF5B in prostate cancer cells, and its overexpression can inhibit the proliferation, migration, invasion and PD-L1 expression of cancer cells while promoting apoptosis. Moreover, interference with eIF5B expression can inhibit tumor growth, destroy tumor morphology, and suppress the proliferation of tumor cells.

Conclusion

eIF5B can promote the expression of PD-L1 by interacting with Wig1. Besides, interference with eIF5B expression can inhibit the proliferation, migration, invasion and immunosuppressive response of prostate cancer cells. This study proposes a new target, eIF5B, for immunotherapy of prostate cancer.
Complete reversal of bilateral optic nerve infiltration from lymphoblastic leukemia using chemotherapy without adjuvant radiotherapy
Authors: da Costa Douglas Rodrigues , Fernandes Rodrigo Dahia , Susanna Fernanda Nicolela , da Silva Neto Epitácio Dias , Monteiro Mario Luiz Ribeiro
Published: September 2021

Background

Leukemic involvement of the eyes is rare, therefore, treatment relies on previous case reports. The treatment of ocular complications poses additional difficulties, because the eye is considered as a pharmacological “sanctuary” for patients with acute lymphoblastic leukemia (ALL). Therefore, radiotherapy is the main therapeutic choice; however, it might lead to many important side effects. To the best of our knowledge, this is the first case report of a bilateral leukemic optic nerve infiltration that remitted with chemotherapy without adjuvant radiotherapy.

Case presentation

A 30-year-old female patient with previous history of remitted ALL presented with a one-week history of floaters in her right eye. Her ophthalmological exam showed remarkable optic disc swelling, in both eyes. She was diagnosed with ALL relapse presenting as a bilateral optic nerve leukemic infiltration. Local radiotherapy was planned for both eyes, however, due to efficient recovery with chemotherapy, it was cancelled. Allogenic bone marrow transplantation was subsequently performed. The patient is being followed up and ALL remitted.

Conclusion

Leukemia relapse on central nervous system, despite rare, is a sign of poor prognosis and requires prompt treatment. Its occurrence on ocular tissues is even rarer. It is hypothesized that the blood-brain barrier limits the delivery of chemotherapeutic drugs to the eye and infiltration of the optic nerve by leukemic cells might prejudice the flow of cerebrospinal fluid between the cranial space and the optic disc.
Bidirectional associations between sedentary time and sleep duration among 12- to 14-year-old adolescents
Authors: Verloigne Maïté , Van Oeckel Veerle , Brondeel Ruben , Poppe Louise
Published: September 2021

Background

The aim of this study was to investigate bidirectional associations between (prolonged) sitting time and sleep duration in 12- to 14-year-old adolescents using a between-subjects and within-subjects analyses approach.

Methods

Observational data were used from 108 adolescents (53% girls; mean age 12.9 (SD 0.7) years) from six schools in Flanders, Belgium. The Axivity AX3 triaxial accelerometer, worn on the thigh, was used to assess daily total sitting time and daily time spent in sedentary bouts of ≥30 min (as a proxy for prolonged sitting time). The Fitbit Charge 3 was used to assess nightly sleep duration. Both monitors were worn on schooldays only (ranging from 4 to 5 days). Linear mixed models were conducted to analyse the associations, resulting in four models. In each model, the independent variable (sleep duration, sitting time or prolonged sitting time) was included as within- as well as between-subjects factor.

Results

Within-subjects analyses showed that when the adolescents sat more and when the adolescents spent more time sitting in bouts of ≥30 min than they usually did on a given day, they slept less during the following night (p = 0.01 and p = 0.05 (borderline significant), respectively). These associations were not significant in the other direction. Between-subjects analyses showed that adolescents who slept more on average, spent less time sitting (p = 0.006) and less time sitting in bouts of ≥30 min (p = 0.004) compared with adolescents who slept less on average. Conversely, adolescents who spent more time sitting on average and adolescents who spent more time sitting in bouts of ≥30 min on average, slept less (p = 0.02 and p = 0.003, respectively).

Conclusions

Based on the between-subjects analyses, interventions focusing on reducing or regularly breaking up sitting time could improve adolescents’ sleep duration on a population level, and vice versa. However, the within-subjects association was only found in one direction and suggests that to sleep sufficiently during the night, adolescents might limit and regularly break up their sitting time the preceding day.

Trial registration

Data have been used from our trial registered at ClinicalTrials.gov (NCT04327414; registered on March 11, 2020).
Modeling count data for health care utilization: an empirical study of outpatient visits among Vietnamese older people
Authors: Le Duc Dung , Gonzalez Roberto Leon , Matola Joseph Upile
Published: September 2021

Background

Vietnam is undergoing a fast-aging process that poses potential critical issues for older people and central among those is demand for healthcare utilization. However, healthcare utilization, here measured as count data, creates challenges for modeling because such data typically has distributions that are skewed with a large mass at zero. This study compares empirical econometric strategies for the modeling of healthcare utilization (measured as the number of outpatient visits in the last 12 months) and identifies the determinants of healthcare utilization among Vietnamese older people based on the best-fitting model identified.

Methods

Using the Vietnam Household Living Standard Survey in 2006 (N = 2426), nine econometric regression models for count data were examined to identify the best-fitting one. We used model selection criteria, statistical tests and goodness-of-fit for in-sample model selection. In addition, we conducted 10-fold cross-validation checks to examine reliability of the in-sample model selection. Finally, we utilized marginal effects to identify the factors associated with the number of outpatient visits among Vietnamese older people based on the best-fitting model identified.

Results

We found strong evidence in favor of hurdle negative binomial model 2 (HNB2) for both in-sample selection and 10-fold cross-validation checks. The marginal effect results of the HNB2 showed that ethnicity, region, household size, health insurance, smoking status, non-communicable diseases, and disability were significantly associated with the number of outpatient visits. The predicted probabilities for each count event revealed the distinct trends of healthcare utilization among specific groups: at low count events, women and people in the younger age group used more healthcare utilization than did men and their counterparts in older age groups, but a reverse trend was found at higher count events.

Conclusions

The high degree of skewness and dispersion that typically characterizes healthcare utilization data affects the appropriateness of the econometric models that should be used in modeling such data. In the case of Vietnamese older people, our study findings suggest that hurdle negative binomial models should be used in the modeling of healthcare utilization given that the data-generating process reflects two different decision-making processes.
The value of innovation: association between improvements in survival of advanced and metastatic non-small cell lung cancer and targeted and immunotherapy
Authors: Ramagopalan Sreeram , Leahy Thomas P. , Ray Joshua , Wilkinson Samantha , Sammon Cormac , Subbiah Vivek
Published: September 2021

Background

Significant improvements in mortality among patients with non-small cell lung cancer (NSCLC) in the USA over the past two decades have been reported based on Surveillance, Epidemiology, and End Results (SEER) data. The timing of these improvements led to suggestions that they result from the introduction of new treatments; however, few studies have directly investigated this. The aim of this study was to investigate the extent to which population level improvements in survival of advanced and/or metastatic NSCLC (admNSCLC) patients were associated with changes in treatment patterns.

Methods

We utilized a de-identified database to select three cohorts of patients with admNSCLC: (1) patients with non-oncogene (EGFR/ALK/ROS1/BRAF) positive tumors, (2) patients with ALK-positive (ALK+) tumors, and (3) patients with EGFR-positive (EGFR+) tumors. All patients were diagnosed with admNSCLC between 2012 and 2019. Multivariable Cox models adjusting for baseline characteristics and receipt of targeted and immunotherapy were utilized to explore the relationship between these variables and changes in the hazard of death by calendar year in each cohort.

Results

We included 28,154 admNSCLC patients with non-oncogene positive tumors, 598 with ALK+ tumors, and 2464 with EGFR+ tumors eligible for analysis. After adjustment for differences in baseline characteristics, the hazard of death in patients who had non-oncogene positive tumors diagnosed in 2015, 2016, 2017, 2018 ,and 2019 was observed to be 12%, 11%, 17%, 20%, and 21% lower respectively than that for those diagnosed in 2012. Upon additionally adjusting for receipt of first line or second line immunotherapy, the decrease in the hazard of death by calendar year was no longer observed, suggesting improvements in survival observed over time may be explained by the introduction of these treatments. Similarly, decreases in the hazard of death were only observed in patients with ALK+ tumors diagnosed between 2017 and 2019 relative to 2012 but were no longer observed following adjustment for the use of 1st and later generation ALK inhibitors. Among patients with EGFR+ tumors, the hazard of death did not improve significantly over time.

Conclusion

Our findings expand on the SEER data and provide additional evidence suggesting improvements in survival of patients with advanced and metastatic NSCLC over the past decade could be explained by the change in treatment patterns over this period.
Decolonizing health in Canada: A Manitoba first nation perspective
Authors: Eni Rachel , Phillips-Beck Wanda , Achan Grace Kyoon , Lavoie Josée G. , Kinew Kathi Avery , Katz Alan
Published: September 2021

Introduction & Background

Global persistence of health inequities for Indigenous peoples is evident in ongoing discrepancies in health and standards of living. International literature suggests the key to transformation lies in Indigenous efforts to control Indigenous health and healthcare. Previous authors have focused upon participation, structural transformation, and culturally appropriate healthcare recognized as a political right as fundamental tenets of Indigenous control. Contextualizing Indigenous health and wellness falls within a growing discussion on decolonization – a resituating of expertise that privileges Indigenous voice and interests.

Methods

The study is a qualitative, grounded theory analysis, which is a constructivist approach to social research allowing for generation of theory in praxis, through interactions and conversations between researchers and participants. One hundred eighty-three interviews with additional focus groups were held between 2013-15 in eight Manitoba First Nation communities representing different models of health delivery, geographies, accessibilities, and Indigenous language groups. Community research assistants and respected Elders participated in data collection, analysis and interpretation. Line-by-line coding and constant comparative method led to the discovery of converging themes.

Findings

Ultimately four main themes arose: 1) First Nation control of healthcare; 2) traditional medicine and healing activities; 3) full and meaningful community participation; and 4) cleaning up impacts of colonization. Joint analyses and interpretation of findings revealed substantial evidence that communities were looking profoundly into problems of improperly delivered services and health inequities. Issues were consistent with those highlighted by international commissions on reconciliation, health, Indigenous rights and liberties. To those documents, these findings add ground upon which to build the transformative agenda.

Results & Discussion

Communities discussed the need for creation of protocols, constitution and laws to ensure growth of a decolonizing agenda. Inclusive to the concept are holistic, preventative, traditional health perspectives, and Indigenous languages. Colonization impacts were of critical concern and in need of undoing. Sharing of social and political efforts is seen as pivotal to change and includes all members of communities.
How equitable are the distributions of the physical activity and accessibility benefits of bicycle infrastructure?
Authors: Standen Christopher , Crane Melanie , Greaves Stephen , Collins Andrew T. , Rissel Chris
Published: September 2021

Background

Cycling for transport provides many health and social benefits – including physical activity and independent access to jobs, education, social opportunities, health care and other services (accessibility). However, some population groups have less opportunity to reach everyday destinations, and public transport stops, by bicycle – owing in part to their greater aversion to riding amongst motor vehicle traffic. Health equity can therefore be improved by providing separated cycleway networks that give more people the opportunity to access places by bicycle using traffic-free routes. The aim of this study was to assess the health equity benefits of two bicycle infrastructure development scenarios – a single cycleway, and a complete network of cycleways – by examining the distributions of physical activity and accessibility benefits across gender, age and income groups.

Methods

Travel survey data collected from residents in Sydney (Australia) were used to train a predictive transport mode choice model, which was then used to forecast the impact of the two intervention scenarios on transport mode choice, physical activity and accessibility. The latter was measured using a utility-based measure derived from the mode choice model. The distributions of the forecast physical activity and accessibility benefits were then calculated across gender, age and income groups.

Results

The modelled physical activity and accessibility measures improve in both intervention scenarios. However, in the single cycleway scenario, the benefits are greatest for the male, high-income and older age groups. In the complete network scenario, the benefits are more equally distributed. Forecast increases in cycling time are largely offset by decreases in walking time – though the latter is typically low-intensity physical activity, which confers a lesser health benefit than moderate-intensity cycling.

Conclusions

Separated cycleway infrastructure can be used to improve health equity by providing greater opportunities for transport cycling in population groups more averse to riding amongst motor vehicle traffic. Disparities in the opportunity to access services and economic/social activities by bicycle – and incorporate more physical activity into everyday travel – could be addressed with connected, traffic-free cycleway networks that cater to people of all genders, ages and incomes.
Treatment adequacy and remission of depression and anxiety disorders and quality of life in primary care older adults
Authors: Lamoureux-Lamarche Catherine , Berbiche Djamal , Vasiliadis Helen-Maria
Published: September 2021

Background

Studies on the long-term outcomes of receiving adequate treatment for depression and anxiety disorders are scarce. The aims of this study were to assess the association between adequacy of care and remission of common mental disorders (CMD) and change in quality of life among a population of older adults consulting in primary care.

Methods

The study was conducted among 225 older adults with a CMD who participated in the longitudinal ESA-Services study. Adequacy of care was assessed using administrative and self-reported data and was based on Canadian guidelines and relevant literature. CMD were measured at baseline and follow-up using self-reported measures (DSM-5 criteria) and physician diagnostic codes (International Classification of Diseases, 9thand 10threvisions) for depression and anxiety disorders. The remission of CMD was defined by the presence of at least one disorder at baseline and absence at follow-up. Quality of life was measured at baseline and follow-up using a visual analog scale and the Satisfaction With Life Scale. To estimate the probability to receive adequate/inadequate care, a propensity score was calculated, and analyses were weighted by the inverse probability. Weighted multivariable analyses were carried out to assess the remission of CMD and change in quality of life as a function of adequacy of care controlling for individual and health system factors.

Results

Results showed that 40% of older adults received adequate care for CMD and 55% were in remission at follow-up. Adequacy of care was associated with remission of CMD (AOR: 0.66; CI 0.45–0.97; p-value: 0.032). Participants receiving adequate care had an improvement between baseline and follow-up of 0.7 (beta: 0.69, CI 0.18; 1.20,p = 0.008) point on the Satisfaction With Life Scale, while a marginal association was observed with improvement in HRQOL (beta: 2.83, CI 0.12; 5.79,p = 0.060).

Conclusion

The findings contribute to the rare observational studies on the association between adequacy of care for CMD and long-term treatment effects. Future studies on population effectiveness should focus on patient indicators of quality of care which may better predict long-term outcomes for patients with depression and anxiety.
Light-intensity physical activity and mental ill health: a systematic review of observational studies in the general population
Authors: Felez-Nobrega Mireia , Bort-Roig Judit , Ma Ruimin , Romano Eugenia , Faires Matthew , Stubbs Brendon , Stamatakis Emmanuel , Olaya Beatriz , Haro Josep Maria , Smith Lee , Shin Jae Il , Kim Min Seo , Koyanagi Ai
Published: September 2021

Background

Most of theevidence has focused on examining the influence of moderate-to-vigorous intensity physical activity on mental health, but he role of light intensity physical activity (LIPA) is less understood. The purpose of this systematic review was to assess the relationship between time spent in LIPA and mental ill health across the lifespan.

Methods

Data were obtained from online databases (Medline, Embase, Scopus, PsychInfo and CINAHL). The search and collection of eligible studies was conducted up to May 28, 2020. Observational studies conducted in the general population and reporting on the association between LIPA (1.6–2.9 metabolic equivalents; either self-reported or device-based measured) and mental ill health were included.

Results

Twenty-two studies were included in the review (16 cross-sectional and 6 longitudinal). In older adults (≥ 65 years) and adults (18–64 years), the evidence examining the relationship between LIPA and depressive symptoms is mixed. Data on anxiety, psychological distress and overall mental health are scarce, and results are inconclusive. There is no evidence suggesting favorable associations between LIPA and anxiety in college students. Finally, very limited data was found in adolescents (11–17 years) (n = 2 studies) and children (6–10 years) (n = 2 studies), but the evidence suggests that LIPA does not influence mental health outcomes in these age groups.

Conclusions

This review provided mostly cross-sectional evidence indicating that LIPA may not be associated with mental health outcomes across age groups. Future research efforts employing prospective research designs are warranted to better understand the role of LIPA on mental ill health across age groups.