bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiologic IGFBP7 levels prolong IGF1R activation in acute lymphoblastic leukemia
Authors: Artico Leonardo Luís , Laranjeira Angelo Brunelli Albertoni , Campos Livia Weijenborg , Corrêa Juliana Ronchi , Zenatti Priscila Pini , Carvalheira José Barreto Campello , Brambilla Sandra Regina , Nowill Alexandre Eduardo , Brandalise Silvia Regina , Yunes José Andrés
Published: August 2021

Insulin and insulin-like growth factors (IGFs) are mitogenic and prosurvival factors to many different cell types, including acute lymphoblastic leukemia (ALL). Circulating IGFs are bound by IGF binding proteins (IGFBPs) that regulate their action. IGFBP7 is an IGFBP-related protein (IGFBP-rP) that in contrast to other IGFBPs/IGFBP-rPs features higher affinity for insulin than IGFs and was shown to bind the IGF1 receptor (IGF1R) as well. The role of IGFBP7 in cancer is controversial: on some tumors, it functions as an oncogene, whereas in others, it functions as a tumor suppressor. In childhood ALL, higher IGFBP7 expression levels were associated with worse prognosis. Here we show that IGFBP7 exerts mitogenic and prosurvival autocrine effects on ALL cells that were dependent on insulin/IGF. IGFBP7 knockdown or antibody-mediated neutralization resulted in significant attenuation of ALL cell viability in vitro and leukemia progression in vivo. IGFBP7 was shown to prolong the surface retention of the IGF1R under insulin/IGF1 stimulation, resulting in sustained IGF1R, insulin receptor substrate 1 (IRS-1), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK) phosphorylation. Conversely, the insulin receptor was readily internalized and dephosphorylated on insulin stimulation, despite IGFBP7 addition. The affinity of homodimeric IGF1R for insulin is reportedly >100 times lower than for IGF1. In the presence of IGFBP7, however, 25 ng/mL insulin resulted in IGF1R activation levels equivalent to that of 5 ng/mL IGF1. In conclusion, IGFBP7 plays an oncogenic role in ALL by promoting the perdurance of IGF1R at the cell surface, prolonging insulin/IGF stimulation. Preclinical data demonstrate that IGFBP7 is a valid target for antibody-based therapeutic interventions in ALL.
In-hospital and midterm post-discharge complications of adults hospitalised with respiratory syncytial virus infection in France, 2017–2019: an observational study
Authors: Descamps Alexandre , Lenzi Nezha , Galtier Florence , Lainé Fabrice , Lesieur Zineb , Vanhems Philippe , Amour Sélilah , L'Honneur Anne-Sophie , Fidouh Nadhira , Foulongne Vincent , Lagathu Gisèle , Duval Xavier , Merle Corinne , Lina Bruno , Carrat Fabrice , Launay Odile , Loubet Paul
Published: August 2021

Objectives

The purpose of this study was to describe the clinical characteristics and in-hospital and post-discharge outcomes of respiratory syncytial virus (RSV) infection among adults hospitalised with influenza-like illness (ILI) and compared against patients admitted for influenza.

Methods

Adults hospitalised with ILI were prospectively included from five French university hospitals over two consecutive winter seasons (2017/2018 and 2018/2019). RSV and influenza virus were detected by multiplex reverse transcription PCR on nasopharyngeal swabs. RSV-positive patients were compared to RSV-negative and influenza-positive hospitalised patients. Poisson regression models were used to estimate the adjusted prevalence ratio (aPR) associated with in-hospital and post-discharge outcomes between RSV and influenza infections. The in-hospital outcome was a composite of the occurrence of at least one complication, length of stay ≥7 days, intensive care unit admission, use of mechanical ventilation and in-hospital death. Post-discharge outcome included 30- and 90-day all-cause mortality and 90-day readmission rates.

Results

Overall, 1428 hospitalised adults with ILI were included. RSV was detected in 8% (114 of 1428) and influenza virus in 31% (437 of 1428). Patients hospitalised with RSV were older than those with influenza (mean age 73.0versus68.8 years, p=0.015) with a higher frequency of chronic respiratory or cardiac disease (52%versus39%, p=0.012, and 52%versus41%, p=0.039, respectively) and longer hospitalisation duration (median stay 8versus6 days, p<0.001). Anti-influenza therapies were less prescribed among RSV patients than influenza patients (20%versus66%, p<0.001). In-hospital composite outcome was poorer in RSV patients (aPR 1.5, 95% CI 1.1–2.1) than in those hospitalised with influenza. No difference was observed for the post-discharge composite outcome (aPR 1.1, 95% CI 0.8–1.6).

Conclusion

RSV infection results in serious respiratory illness, with worse in-hospital outcomes than influenza and with similar midterm post-discharge outcomes.
VEGF-C/VEGFR-3 signalling in macrophages ameliorates acute lung injury
Authors: Yamashita Masahiro , Niisato Miyuki , Kawasaki Yasushi , Karaman Sinem , Robciuc Marius R. , Shibata Yuji , Ishida Yoji , Nishio Ryosuke , Masuda Tomoyuki , Sugai Tamotsu , Ono Masao , Tuder Rubin M. , Alitalo Kari , Yamauchi Kohei
Published: August 2021

Background

Successful recovery from acute lung injury requires inhibition of neutrophil influx and clearance of apoptotic neutrophils. However, the mechanisms underlying recovery remain unclear. We investigated the ameliorative effects of vascular endothelial growth factor (VEGF)-C/VEGF receptor 3 (VEGFR-3) signalling in macrophages in lipopolysaccharide (LPS)-induced lung injury.

Methods

LPS was intranasally injected into wild-type and transgenic mice. Gain and loss of VEGF-C/VEGFR-3 signalling function experiments employed adenovirus-mediated intranasal delivery of VEGF-C (Ad-VEGF-C vector) and soluble VEGFR-3 (sVEGFR-3) or anti-VEGFR-3 blocking antibodies and mice with a deletion of VEGFR-3 in myeloid cells.

Results

The early phase of lung injury was significantly alleviated by the overexpression of VEGF-C with increased levels of bronchoalveolar lavage (BAL) fluid interleukin-10 (IL-10), but worsened in the later phase by VEGFR-3 inhibition upon administration of Ad-sVEGFR-3 vector. Injection of anti-VEGFR-3 antibodies to mice in the resolution phase inhibited recovery from lung injury. The VEGFR-3-deleted mice had a shorter survival time than littermates and more severe lung injury in the resolution phase. Alveolar macrophages in the resolution phase digested most of the extrinsic apoptotic neutrophils and VEGF-C/VEGFR-3 signalling increased efferocytosisviaupregulation of integrin αvin the macrophages. We also found that incubation with BAL fluid from acute respiratory distress syndrome (ARDS) patients, but not from controls, decreased VEGFR-3 expression and the efficiency of IL-10 expression and efferocytosis in human monocyte-derived macrophages.

Conclusions

VEGF-C/VEGFR-3 signalling in macrophages ameliorates experimental lung injury. This mechanism may also provide an explanation for ARDS resolution.
Identification of asthma-associated microRNAs in bronchial biopsies
Authors: Roffel Mirjam P. , Boudewijn Ilse M. , van Nijnatten Jos L.L. , Faiz Alen , Vermeulen Corneel J. , van Oosterhout Antoon J. , Affleck Karen , Timens Wim , Bracke Ken R. , Maes Tania , Heijink Irene H. , Brandsma Corry-Anke , van den Berge Maarten
Published: August 2021

Background

Changes in microRNA (miRNA) expression can contribute to the pathogenesis of many diseases, including asthma. We aimed to identify miRNAs that are differentially expressed between asthma patients and healthy controls, and explore their association with clinical and inflammatory parameters of asthma.

Methods

Differentially expressed miRNAs were determined by small RNA sequencing on bronchial biopsies of 79 asthma patients and 82 healthy controls using linear regression models. Differentially expressed miRNAs were associated with clinical and inflammatory asthma features. Potential miRNA–mRNA interactions were analysed using mRNA data available from the same bronchial biopsies, and enrichment of pathways was identified with Enrichr and g:Profiler.

Results

In total, 78 differentially expressed miRNAs were identified in bronchial biopsies of asthma patients compared with controls, of which 60 remained differentially expressed after controlling for smoking and inhaled corticosteroid treatment. We identified several asthma-associated miRNAs, including miR-125b-5p and miR-223-3p, based on a significant association with multiple clinical and inflammatory asthma features and their negative correlation with genes associated with the presence of asthma. The most enriched biological pathway(s) affected by miR-125b-5p and miR-223-3p were inflammatory response and cilium assembly/organisation. Of interest, we identified that lower expression of miR-26a-5p was linked to more severe eosinophilic inflammation as measured in blood, sputum as well as bronchial biopsies.

Conclusion

Collectively, we identified miR-125b-5p, miR-223-3p and miR-26a-5p as potential regulators that could contribute to the pathogenesis of asthma.
Blood leukocyte transcriptomes in Gram-positive and Gram-negative community-acquired pneumonia
Authors: Pereverzeva Liza , Uhel Fabrice , Peters Sengers Hessel , Butler Joe , van Vught Lonneke A. , Burnham Katie L. , Davenport Emma E. , Knight Julian C. , Cremer Olaf L. , Schultz Marcus J. , Bonten Marc M.J. , Scicluna Brendon P. , van der Poll Tom
Published: August 2021

Background

Gram-positive and Gram-negative bacteria are the most common causative pathogens in community-acquired pneumonia (CAP) on the intensive care unit (ICU). The aim of this study was to determine whether the host immune response differs between Gram-positive and Gram-negative CAP upon ICU admission.

Methods

16 host response biomarkers providing insight into pathophysiological mechanisms implicated in sepsis and blood leukocyte transcriptomes were analysed in patients with CAP upon ICU admission in two tertiary hospitals in the Netherlands.

Results

309 patients with CAP with a definite or probable likelihood (determined by predefined criteria) were included. A causative pathogen was determined in 74.4% of admissions. Patients admitted with Gram-positive CAP (n=90) were not different from those admitted with Gram-negative CAP (n=75) regarding demographics, chronic comorbidities, severity of disease and mortality. Host response biomarkers reflective of systemic inflammation, coagulation activation and endothelial cell function, as well as blood leukocyte transcriptomes, were largely similar between Gram-positive and Gram-negative CAP. Blood leukocyte transcriptomes were also similar in Gram-positive and Gram-negative CAP in two independent validation cohorts. On a pathogen-specific level,Streptococcus pneumoniaeandEscherichia coliinduced the most distinct host immune response.

Conclusion

Outcome and host response are similar in critically ill patients with CAP due to Gram-positive bacteria compared with Gram-negative bacteria.
Exhaled volatile organic compounds and lung microbiome in COPD: a pilot randomised controlled trial
Authors: Mohan Divya , Keir Holly R. , Richardson Hollian , Mayhew David , Boyer Joseph , van der Schee Marc P. , Allsworth Max D. , Miller Bruce E. , Tal-Singer Ruth , Chalmers James D.
Published: August 2021

Background

Breath analysis is a burgeoning field, with interest in volatile organic compounds (VOCs) as a noninvasive diagnostic tool or an outcome measure, but no randomised controlled trials (RCTs) have yet evaluated this technology in a clinical trial longitudinally. In a pilot RCT, our exploratory objectives were feasibility of measuring VOCsviamultiple techniques, assessing relationships between VOCs andHaemophiluscolonisation and whether CXCR2 antagonism with danirixin altered lung microbiome composition in individuals with COPD.

Method

43 participants had VOCs and sputum biomarkers evaluated. VOCs and induced sputum were collected after 6 h of fasting at screening and at days 1, 7 and 14. VOCs were analysedviagas chromatography mass spectrometry (GC-MS), field asymmetric ion mobility spectrometry (FAIMS) and eNose. The primary outcome for these analyses was the relationship between VOCs andHaemophilusabundance determined by 16S rRNA sequencing.

Results

A joint-effects model demonstrated a modest relationship between four exhaled VOCs andHaemophilusrelative abundance (R2=0.55) measured only by GC-MS, but not as measured using gas chromtaography FAIMS or eNose. There was considerable variability in absolute quantities of individual VOCs longitudinally.

Conclusions

VOC measurement in clinical trials to identify subsets of COPD is feasible, but assessment of new VOC technologies must include concurrent GC-MS validation. Further work to standardise collection of VOCs and measuring a background or “housekeeper” VOC is required to understand and normalise individual VOC quantities.
Methacholine challenges: comparison of different tidal breathing challenge methods
Authors: Dean James , Jackson Natalie , Keidel-Morgan Brett , Hamer Daniel , Singh Dave
Published: August 2021

Tidal-breathing methacholine challenges are now recommended by guidelines, to avoid the bronchoprotective effects of deep inhalation. This study compared different tidal breathing methacholine challenge methods; assessed the agreement between tidal dosimetric and continuous output challenges; and assessed challenge repeatability with different methods.

15 asthma patients performed dosimetric challenges and a continuous-output breath-actuated challenge, all ≥3 days apart. All subjects had a pre-bronchodilator forced expiratory volume in 1 s (FEV1) ≥65% predicted, and a cumulative dose causing a 20% reduction in FEV1(PD20) <1.2 mg.

Of the dosimetric challenges, one method increased methacholine concentration (standard dosimetric challenge), and one adjusted nebuliser output time to increase dose (adjusted dosimetric challenge). The adjusted dosimetric and continuous output challenges were performed twice on separate days to assess for repeatability. All challenges were matched for dose at each dose step. The mean PD20ratio of the standard dosimetric challenge to the adjusted dosimetric challenge was 0.90 (95% CI 0.66–1.23, p=0.49) and intraclass correlation coefficient (ICC) was 0.82. Repeated adjusted dosimetric challenges had an ICC 0.62 for PD20. Repeated continuous output challenges had an ICC 0.74 for PD20. The adjusted dosimetric and continuous output challenges correlated (r=0.69, p=0.0043; ICC 0.65), but PD20was higher for the adjusted dosimetric challenge (mean PD20ratio 2.31, 95% CI 1.57–3.40; p=0.0004).

Tidal dosimetric methacholine challenge using adjustment of nebuliser output produces results with good repeatability. The results of this adjusted dosimetric method differed from the continuous output method, underscoring that the results of different methacholine challenge methodologies may not be directly comparable.
The angiostatic peptide endostatin enhances mortality risk prediction in pulmonary arterial hypertension
Authors: Simpson Catherine E. , Griffiths Megan , Yang Jun , Nies Melanie K. , Vaidya R. Dhananjay , Brandal Stephanie , Martin Lisa J. , Pauciulo Michael W. , Lutz Katie A. , Coleman Anna W. , Austin Eric D. , Ivy D. Dunbar , Nichols William C. , Everett Allen D. , Hassoun Paul M. , Damico Rachel L.
Published: August 2021

Currently available noninvasive markers for assessing disease severity and mortality risk in pulmonary arterial hypertension (PAH) are unrelated to fundamental disease biology. Endostatin, an angiostatic peptide known to inhibit pulmonary artery endothelial cell migration, proliferation and survivalin vitro, has been linked to adverse haemodynamics and shortened survival in small PAH cohorts. This observational cohort study sought to assess: 1) the prognostic performance of circulating endostatin levels in a large, multicentre PAH cohort; and 2) the added value gained by incorporating endostatin into existing PAH risk prediction models.

Endostatin ELISAs were performed on enrolment samples collected from 2017 PAH subjects with detailed clinical data, including survival times. Endostatin associations with clinical variables, including survival, were examined using multivariable regression and Cox proportional hazards models. Extended survival models including endostatin were compared to null models based on the REVEAL risk prediction tool and European Society of Cardiology/European Respiratory Society (ESC/ERS) low-risk criteria using likelihood ratio tests, Akaike and Bayesian information criteria and C-statistics.

Higher endostatin was associated with higher right atrial pressure, mean pulmonary arterial pressure and pulmonary vascular resistance, and with shorter 6-min walk distance (p<0.01). Mortality risk doubled for each log higher endostatin (hazard ratio 2.3, 95% CI 1.6–3.4, p<0.001). Endostatin remained an independent predictor of survival when incorporated into existing risk prediction models. Adding endostatin to REVEAL-based and ESC/ERS criteria-based risk assessment strategies improved mortality risk prediction.

Endostatin is a robust, independent predictor of mortality in PAH. Adding endostatin to existing PAH risk prediction strategies improves PAH risk assessment.
Breastfeeding and risk of childhood asthma: a systematic review and meta-analysis
Authors: Xue Mike , Dehaas Emily , Chaudhary Nagendra , O'Byrne Paul , Satia Imran , Kurmi Om P.
Published: August 2021

Objective

To investigate the relationship between breastfeeding and the development of paediatric asthma.

Methods

A systematic review and meta-analysis was conducted with MEDLINE, Embase, CINAHL and ProQuest Nursing and Allied Health source databases. Retrospective/prospective cohorts in children aged <18 years with breastfeeding exposure reported were included. The primary outcome was a diagnosis of asthma by a physician or using a guideline-based criterion. A secondary outcome was asthma severity.

Results

42 studies met inclusion criteria. 37 studies reported the primary outcome of physician-/guideline-diagnosed asthma, and five studies reported effects on asthma severity. Children with longer duration/more breastfeeding compared to shorter duration/less breastfeeding have a lower risk of asthma (OR 0.84, 95% CI 0.75–0.93; I2 = 62.4%). Similarly, a lower risk of asthma was found in children who had more exclusive breastfeedingversusless exclusive breastfeeding (OR 0.81, 95% CI 0.72–0.91; I2=44%). Further stratified analysis of different age groups demonstrated a lower risk of asthma in the 0–2-years age group (OR 0.73, 95% CI 0.63–0.83) and the 3–6-years age group (OR 0.69, 95% CI 0.55–0.87); there was no statistically significant effect on the ≥7-years age group.

Conclusion

The findings suggest that the duration and exclusivity of breastfeeding are associated with a lower risk of asthma in children aged <7 years.
An Adaptive Nonsingular Fast Terminal Sliding Mode Control for Yaw Stability Control of Bus Based on STI Tire Model
Authors: Sun Xiaoqiang , Wang Yujun , Cai Yingfeng , Wong Pak Kin , Chen Long
Published: August 2021

Due to the bus characteristics of large quality, high center of gravity and narrow wheelbase, the research of its yaw stability control (YSC) system has become the focus in the field of vehicle system dynamics. However, the tire nonlinear mechanical properties and the effectiveness of the YSC control system are not considered carefully in the current research. In this paper, a novel adaptive nonsingular fast terminal sliding mode (ANFTSM) control scheme for YSC is proposed to improve the bus curve driving stability and safety on slippery roads. Firstly, the STI (Systems Technologies Inc.) tire model, which can effectively reflect the nonlinear coupling relationship between the tire longitudinal force and lateral force, is established based on experimental data and firstly adopted in the bus YSC system design. On this basis, a more accurate bus lateral dynamics model is built and a novel YSC strategy based on ANFTSM, which has the merits of fast transient response, finite time convergence and high robustness against uncertainties and external disturbances, is designed. Thirdly, to solve the optimal allocation problem of the tire forces, whose objective is to achieve the desired direct yaw moment through the effective distribution of the brake force of each tire, the robust least-squares allocation method is adopted. To verify the feasibility, effectiveness and practicality of the proposed bus YSC approach, the TruckSim-Simulink co-simulation results are finally provided. The co-simulation results show that the lateral stability of bus under special driving conditions has been significantly improved. This research proposes a more effective design method for bus YSC system based on a more accurate tire model.
Association between height-related polymorphism rs17081935 and reduced handgrip strength in relation to status of atherosclerosis: a cross-sectional study
Authors: Shimizu Yuji , Kawashiri Shin-Ya , Arima Kazuhiko , Noguchi Yuko , Yamanashi Hirotomo , Nobusue Kenichi , Nonaka Fumiaki , Nakamichi Seiko , Nagata Yasuhiro , Maeda Takahiro
Published: August 2021

Background

Aging is a process that increases oxidative stress. Increased oxidative stress leads to the development of atherosclerosis and mitochondrial dysfunction. Mitochondria contribute to energy production that might have a beneficial influence on maintaining muscle strength. Therefore, the height-related single nucleotide polymorphism (SNP) rs17081935, which is also reported to be associated with mitochondrial metabolism, might be associated with reduced muscle strength and this association might be affected by atherosclerosis status. To clarify those associations, a cross-sectional study of 1374 elderly Japanese individuals aged 60–89 years was conducted.

Methods

Logistic regression was used to clarify the association between rs17081935 and reduced handgrip strength. Since atherosclerosis might affect handgrip strength, participants were stratified by atherosclerosis status. Reduced handgrip strength was defined as being in the lowest quintile of handgrip strength (< 25.6 kg for men and < 16.1 kg for women).

Results

No significant associations were found between a minor allele of rs17081935 and reduced handgrip strength among elderly participants without atherosclerosis. A significant inverse association was observed among elderly participants with atherosclerosis. After adjusting for known cardiovascular risk factors and height, the adjusted odd ratio (OR) and 95% confidence interval (CI) for reduced handgrip strength and a minor allele of rs17081935 were 1.13 (0.86, 1.43) for elderly participants without atherosclerosis and 0.55 (0.36, 0.86) for those with atherosclerosis, respectively.

Conclusion

A minor allele of the height-related SNP rs17081935 was significantly inversely associated with reduced handgrip strength among older individuals with atherosclerosis, but not among those without atherosclerosis.
Assessment of the correlation of commonly used laboratory tests with clinical activity, renal involvement and treatment of systemic small-vessel vasculitis with the presence of ANCA antibodies
Authors: Mosakowska Magdalena , Kania Dorota Brodowska , Szamotulska Katarzyna , Rymarz Aleksandra , Niemczyk Stanisław
Published: August 2021

Background

The aim of the study was to assess the correlation of commonly used laboratory tests with clinical activity, degree of kidney involvement and treatment of systemic small-vessel vasculitis with the presence of ANCA antibodies.

Methods

The study included 28 patients with active AAV (BVAS ≥ 3). The following tests were performed: MPO-ANCA, PR3-ANCA, peripheral blood count, ESR, CRP, procalcitonin, creatinine, GFR, urea, albumin, fibrinogen, d-dimer, components of the C3 and C4 complement systems, urinalysis with sediment evaluation and diurnal proteinuria. The assessments were conducted twice: at study entry (A0) and after 6 months (A6) (BVAS = 0).

Results

At the time of inclusion in the study, the mean creatinine concentration was 3.39 mg/dl (GFR 33.17 ml/min/1.73 m²), after achieving remission in 11 patients (39.3 %) GFR remained below 30 ml/min/1.73 m², 4 patients (14.3 %) continued renal replacement therapy, and 3 patients (10.7 %) with advanced renal failure died. Microscopic hematuria occurred in 80.9 % of the studied population, withdrew in most patients, strongly correlated with renal involvement p < 0.001 and was not related to disease severity p = 0.147. CRP, ESR, fibrinogen, d-dimer, albumin and hemoglobin in the peripheral blood showed a strong correlation with the clinical activity of AAV and well identified severe patients. High procalcitonin concentrations correlated with a severe form of the disease, pulmonary involvement with respiratory failure and alveolar hemorrhage (mean 3.41 ng/ml, median 0.91 ng/ml, SD 7.62, p = 0.000), and were associated with the occurrence of infectious complications and the need to administer antibiotic therapy. ANCA antibodies were useful in the evaluation of patients with AAV, the amount of antibodies did not correlate with the severity of vasculitis (p = 0.685) and the results in many patients did not match the expected assumptions.

Conclusions

CRP, ESR, fibrinogen, d-dimers, albumin and hemoglobin in the peripheral blood correlate well with the activity of vasculitis and identify severe patients. The resolution of microscopic hematuria suggests remission of the disease in the renal area. Procalcitonin may be slightly increased in patients with active AAV without infection, high concentrations are strongly associated with infectious complications. ANCA antibodies should always be interpreted in the context of the observed clinical symptoms.
Nasopalatine duct cyst with sebaceous differentiation: a rare case report with literature review
Authors: Yeom Han-Gyeol , Kang Jae-Hyun , Yun Sun-Ung , Yoon Jung-Hoon
Published: August 2021

Background

The aim of this study was to report a rare case of nasopalatine duct cyst with sebaceous differentiation. Further, a systematic search of the literature was performed to identify studies reporting patients with intraosseous jaw cysts with sebaceous differentiation.

Case presentation

A 55-year-old Korean man was referred to our hospital because of a cystic lesion of the anterior maxilla. Radiologic examination revealed a well-circumscribed radiolucent lesion in the anterior maxilla. Histology showed a respiratory columnar and cuboidal epithelium-lined cyst. Transition from the ciliated columnar epithelium to stratified squamous epithelium with sebaceous differentiation was observed. Based on these findings, the final diagnosis was nasopalatine duct cyst with sebaceous differentiation. A systematic search of the literature was performed to identify studies reporting patients with intraosseous jaw cysts with sebaceous differentiation. There were 24 cases of sebaceous differentiation in the epithelium of the cysts including 2 odontogenic keratocysts, 8 orthokeratinized odontogenic cysts, 8 dentigerous cysts, 1 radicular cyst, and 2 glandular odontogenic cysts. However, no case reports describing the occurrence of nasopalatine duct cysts with sebaceous differentiation have been reported.

Conclusion

This first case report of nasopalatine duct cysts with sebaceous differentiation could provide insight into the diagnostic process of cystic lesions with sebaceous differentiation.
Factors affecting the grieving process after perinatal loss
Authors: Kishimoto Makiko , Yamaguchi Arisa , Niimura Marina , Mizumoto Miki , Hikitsuchi Tatsuo , Ogawa Kohei , Ozawa Nobuaki , Tachibana Yoshiyuki
Published: August 2021

Background

Factors associated with the grief process in response to perinatal loss have been investigated. However, few studies focused on the intrapersonal factors, such as developmental and personality traits. Hence, this study aimed to investigate medical and psychosocial risk factors, including inter- and intrapersonal factors for the development of complicated grief following perinatal loss, while considering emotional support.

Methods

A total of 50 patients who were treated for grief due to perinatal loss at the National Center for Child Health and Development were divided into two groups according to the treatment period (< 6 months: n = 28; ≥ 6 months: n = 22). We compared medical and psychosocial variables between the two groups using the χ2 test and t test. All data were further analyzed using a logistic regression model to adjust for confounding effects.

Results

Patients who had traits of developmental/personality disorders (adjusted odds ratio [OR]: 7.21, 95% confidence interval (CI): 1.21–42.9, P = .030), and those treated with psychoactive drugs (adjusted OR: 5.77, 95% CI 1.09–30.5, P = .039) required a longer treatment period (≥ 6 months).

Conclusions

Patients with personality/developmental traits and those with active psychiatric symptoms required a more extended treatment period in response to loss, suggesting the accumulation of negative factors in these patients; thus, more intensive and specialized care is necessary for these patients. Precise analysis of the coping style, attachment style, communication skills, and life history including relationship with the original family of the patients may have implications on the approach toward patients with complicated grief after perinatal loss. Studies with larger sample size are required to increase the reliability of the present findings, and future research should address the effects of the differential attachment and coping styles of patients with developmental/personality traits on the grief process.
Examining the association of social risk with heart failure readmission in the Veterans Health Administration
Authors: Wray Charlie M. , Vali Marzieh , Walter Louise C. , Christensen Lee , Chapman Wendy , Austin Peter C. , Byers Amy L. , Keyhani Salomeh
Published: August 2021

Background

Previous research has found that social risk factors are associated with an increased risk of 30-day readmission. We aimed to assess the association of 5 social risk factors (living alone, lack of social support, marginal housing, substance abuse, and low income) with 30-day Heart Failure (HF) hospital readmissions within the Veterans Health Affairs (VA) and the impact of their inclusion on hospital readmission model performance.

Methods

We performed a retrospective cohort study using chart review and VA and Centers for Medicare and Medicaid Services (CMS) administrative data from a random sample of 1,500 elderly (≥ 65 years) Veterans hospitalized for HF in 2012. Using logistic regression, we examined whether any of the social risk factors were associated with 30-day readmission after adjusting for age alone and clinical variables used by CMS in its 30-day risk stratified readmission model. The impact of these five social risk factors on readmission model performance was assessed by comparing c-statistics, likelihood ratio tests, and the Hosmer-Lemeshow goodness-of-fit statistic.

Results

The prevalence varied among the 5 risk factors; low income (47 % vs. 47 %), lives alone (18 % vs. 19 %), substance abuse (14 % vs. 16 %), lacks social support (2 % vs. <1 %), and marginal housing (< 1 % vs. 3 %) among readmitted and non-readmitted patients, respectively. Controlling for clinical factors contained in CMS readmission models, a lack of social support was found to be associated with an increased risk of 30-day readmission (OR 4.8, 95 %CI 1.35–17.88), while marginal housing was noted to decrease readmission risk (OR 0.21, 95 %CI 0.03–0.87). Living alone (OR: 0.9, 95 %CI 0.64–1.26), substance abuse (OR 0.91, 95 %CI 0.67–1.22), and having low income (OR 1.01, 95 %CI 0.77–1.31) had no association with HF readmissions. Adding the five social risk factors to a CMS-based model (age and comorbid conditions; c-statistic 0.62) did not improve model performance (c-statistic: 0.62).

Conclusions

While a lack of social support was associated with 30-day readmission in the VA, its prevalence was low. Moreover, the inclusion of some social risk factors did not improve readmission model performance. In an integrated healthcare system like the VA, social risk factors may have a limited effect on 30-day readmission outcomes.
Unexpected organellar locations of ESCRT machinery in Giardia intestinalis and complex evolutionary dynamics spanning the transition to parasitism in the lineage Fornicata
Authors: Pipaliya Shweta V. , Santos Rui , Salas-Leiva Dayana , Balmer Erina A. , Wirdnam Corina D. , Roger Andrew J. , Hehl Adrian B. , Faso Carmen , Dacks Joel B.
Published: August 2021

Background

Comparing a parasitic lineage to its free-living relatives is a powerful way to understand how that evolutionary transition to parasitism occurred. Giardia intestinalis (Fornicata) is a leading cause of gastrointestinal disease world-wide and is famous for its unusual complement of cellular compartments, such as having peripheral vacuoles instead of typical endosomal compartments. Endocytosis plays an important role in Giardia’s pathogenesis. Endosomal sorting complexes required for transport (ESCRT) are membrane-deforming proteins associated with the late endosome/multivesicular body (MVB). MVBs are ill-defined in G. intestinalis, and roles for identified ESCRT-related proteins are not fully understood in the context of its unique endocytic system. Furthermore, components thought to be required for full ESCRT functionality have not yet been documented in this species.

Results

We used genomic and transcriptomic data from several Fornicata species to clarify the evolutionary genome streamlining observed in Giardia, as well as to detect any divergent orthologs of the Fornicata ESCRT subunits. We observed differences in the ESCRT machinery complement between Giardia strains. Microscopy-based investigations of key components of ESCRT machinery such as GiVPS36 and GiVPS25 link them to peripheral vacuoles, highlighting these organelles as simplified MVB equivalents. Unexpectedly, we show ESCRT components associated with the endoplasmic reticulum and, for the first time, mitosomes. Finally, we identified the rare ESCRT component CHMP7 in several fornicate representatives, including Giardia and show that contrary to current understanding, CHMP7 evolved from a gene fusion of VPS25 and SNF7 domains, prior to the last eukaryotic common ancestor, over 1.5 billion years ago.

Conclusions

Our findings show that ESCRT machinery in G. intestinalis is far more varied and complete than previously thought, associates to multiple cellular locations, and presents changes in ESCRT complement which pre-date adoption of a parasitic lifestyle.
Bioconversion of sago processing wastewater into biodiesel: Optimization of lipid production by an oleaginous yeast, Candida tropicalis ASY2 and its transesterification process using response surface methodology
Authors: Thangavelu Kiruthika , Sundararaju Pugalendhi , Srinivasan Naganandhini , Uthandi Sivakumar
Published: August 2021

Background

Biodiesel is an eco-friendly and renewable energy source and a valuable substitute for petro-diesel. Sago processing wastewater (SWW), a by-product of the cassava processing industry, has starch content ranging from 4 to 7 g L–1 and serves as an outstanding source for producing microbial lipids by the oleaginous microorganisms. In the present study, Candida tropicalis ASY2 was employed to optimize single-cell oil (SCO) production using SWW and subsequent transesterification by response surface methodology. Variables such as starch content, yeast extract, airflow rate, pH, and temperature significantly influenced lipid production in a preliminary study. The lipid production was scaled up to 5 L capacity airlift bioreactor and its optimization was done by response surface methodology. The dried yeast biomass obtained under optimized conditions from 5 L bioreactor was subjected to a direct transesterification process. Biomass: methanol ratio, catalyst concentration, and time were the variables used to attain higher FAME yield in the transesterification optimization process.

Results

Under optimized conditions, the highest lipid yield of 2.68 g L–1 was obtained with 15.33 g L–1 of starch content, 0.5 g L–1 of yeast extract, and 5.992 L min–1 of airflow rate in a bioreactor. The optimized direct transesterification process yielded a higher FAME yield of 86.56% at 1:20 biomass: methanol ratio, 0.4 M catalyst concentration, and a time of 6.85 h.

Conclusions

Thus, this optimized process rendered the microbial lipids derived from C. tropicalis ASY2 as potentially alternative oil substitutes for sustainable biodiesel production to meet the rising energy demands.
Higher titer hepatitis B core antibody predicts a higher risk of liver metastases and worse survival in patients with colorectal cancer
Authors: Li Ziyao , Li Shaofei , Tao Hangbo , Zhan Yixiang , Ni Kemin , Gong Jianfeng , Li Guoxun
Published: August 2021

Background

There have been controversial voices on if hepatitis B virus infection decreases the risk of colorectal liver metastases or not. This study aims to the find the association between HBV infection and postoperative survival of colorectal cancer and the risk of liver metastases in colorectal cancer patients.

Methods

Patients who underwent curative surgical resection for colorectal cancer between January 2011 and December 2012 were included. Patients were grouped according to anti-HBc. Differences in overall survival, time to progress, and hepatic metastasis-free survival between groups and significant predictors were analyzed.

Results

Three hundred twenty-seven colorectal cancer patients were comprised of 202 anti-HBc negative cases and 125 anti-HBc positive cases, and anti-HBc positive cases were further divided into high-titer anti-HBc group (39) and low-titer anti-HBc group (86). The high-titer anti-HBc group had significantly worse overall survival (5-Yr, 65.45% vs. 80.06%; P < .001), time to progress (5-Yr, 44.26% vs. 84.73%; P < .001), and hepatic metastasis-free survival (5-Yr, 82.44% vs. 94.58%; P = .029) than the low-titer group. Multivariate model showed anti-HBc ≥ 8.8 S/CO was correlated with poor overall survival (HR, 3.510; 95% CI, 1.718–7.17; P < .001), time to progress (HR, 5.747; 95% CI, 2.789–11.842; P < .001), and hepatic metastasis-free survival (HR, 3.754; 95% CI, 1.054–13.369; P = .041) in the anti-HBc positive cases.

Conclusions

Higher titer anti-HBc predicts a potential higher risk of liver metastases and a worse survival in anti-HBc positive colorectal cancer patients.
Tunneling a crosstown highway: a natural experiment testing the longitudinal effect on physical activity and active transport
Authors: Stappers Nicole E. H. , Schipperijn Jasper , Kremers Stef P. J. , Bekker Marleen P. M. , Jansen Maria W. J. , de Vries Nanne K. , Van Kann Dave H. H.
Published: August 2021

Background

In the city of Maastricht in the Netherlands, a highway crossing several deprived neighborhoods was tunneled in 2016. The vacant space on top of this tunnel was redesigned and prioritized for pedestrians and cyclists. The aim of this study was to evaluate the effect of this major infrastructural change, named the Green Carpet, on total and transport-based physical activity (PA) levels.

Methods

Participants (≥18 years) were part of one of three area-based exposure groups. The maximal exposure group lived in neighborhoods directly bordering the Green Carpet. The minimal exposure group consisted of individuals living at the other side of the city, and the no exposure group consisted of individuals living in a nearby city. Actual use of the new infrastructure was incorporated as a second measure of exposure. Data were collected before and 3-15 months after the opening of the Green Carpet. Device-based measurements were conducted to obtain PA levels and collect location data. Changes in PA over time and intervention effects were determined using linear mixed models.

Results

PA levels in the Green Carpet area increased for the maximal and minimal exposure groups, but did not lead to an increase in total or transport-based PA. For the no exposure group, transport-based MVPA decreased and transport-based SB increased. The significant interaction (time x exposure) for transport-based SB, indicated differences in trends between the no exposure and maximal exposure group (B=-3.59, 95% CI - 7.15; -0.02) and minimal exposure group (B= -4.02, 95% CI -7.85, -0.19). Trends in the results based on analyses focusing on actual use and non-use of the new infrastructure were similar to those of the area-based analyses.

Conclusions

Results suggest that the Green Carpet led to more PA in this specific area, but did not increase the total volume of PA. The area-based differences might reflect the differences between users and non-users, but we should be careful when interpreting these results, due to possible interference of selective mobility bias. This paper reflects that the relationship between infrastructure and PA is not unambiguous.

Trial registration

This research was retrospectively registered at the Netherlands Trial Register (NL8108).
Advanced baseline immunosuppression is associated with elevated levels of plasma markers of fungal translocation and inflammation in long-term treated HIV-infected Tanzanians
Authors: Barabona Godfrey , Mahiti Macdonald , Toyoda Mako , Kamori Doreen , Masoud Salim , Judicate George P. , Sunguya Bruno , Lyamuya Eligius , Ueno Takamasa
Published: August 2021

Background

For over a decade, antiretroviral therapy (ART) in resource-limited countries was only recommended for patients with advanced HIV disease. We investigated this group of patients in order to determine any relationship between degree of immunosuppression during treatment initiation and the subsequent levels of inflammatory biomarkers, reservoir size and plasma marker of fungal translocation after achieving long-term virological control.

Methods

We analyzed 115 virally suppressed (female 83.5%) and 40 untreated (female 70%) subjects from Dar es Salaam, Tanzania. The size of HIV latent reservoir (proviral DNA copy) was determined using quantitative PCR. Inflammatory biomarkers; IL-6, IL-10, and soluble CD14 (sCD14), were measured using multiplex cytometric beads array. Antibody titers for Cytomegalovirus (CMV) and Epstein Barr virus (EBV), plasma level of 1-3-beta-d-Glucan (BDG) was measured using ELISA. High-sensitivity C-reactive protein (hsCRP) was measured using nephelometric method.

Results

The median age was 36 (IQR 32-44) and 47 (IQR 43–54) years in untreated and virally suppressed patients respectively. Median duration of treatment for virally suppressed patients was 9 years (IQR 7–12) and median baseline CD4 count was 147 cells/mm3 (IQR 65–217). Virally suppressed patients were associated with significantly lower plasma levels of IL-10, sCD14 and BDG (P < 0.05) when compared to untreated patients. However, plasma level of IL-6 was similar between the groups. Baseline advanced level of immunosuppression (CD4 < 100cells/cm3) was associated with significantly higher plasma level of IL-6 (P = 0.02), hsCRP (P = 0.036) and BDG (P = 0.0107). This relationship was not seen in plasma levels of other tested markers. Degree of baseline immunosuppression was not associated with the subsequent proviral DNA copy. In addition, plasma levels of inflammatory marker were not associated with sex, CMV or EBV antibody titers, treatment duration or regimen.

Conclusions

Our data suggest that advanced immunosuppression at ART initiation is associated with severity of inflammation and elevated fungal translocation marker despite long term virological control. Further studies are needed to evaluate the potential increased burden of non-AIDS comorbidities that are linked to elevated inflammatory and fungal translocation markers as a result of the policy of HIV treatment at CD4 count < 200 cells/cm3 implemented for over a decade in Tanzania.
Advancing sustainable development goals through immunization: a literature review
Authors: Decouttere Catherine , De Boeck Kim , Vandaele Nico
Published: August 2021

Background

Immunization directly impacts health (SDG3) and brings a contribution to 14 out of the 17 Sustainable Development Goals (SDGs), such as ending poverty, reducing hunger, and reducing inequalities. Therefore, immunization is recognized to play a central role in reaching the SDGs, especially in low- and middle-income countries (LMICs). Despite continuous interventions to strengthen immunization systems and to adequately respond to emergency immunization during epidemics, the immunization-related indicators for SDG3 lag behind in sub-Saharan Africa. Especially taking into account the current Covid19 pandemic, the current performance on the connected SDGs is both a cause and a result of this.

Methods

We conduct a literature review through a keyword search strategy complemented with handpicking and snowballing from earlier reviews. After title and abstract screening, we conducted a qualitative analysis of key insights and categorized them according to showing the impact of immunization on SDGs, sustainability challenges, and model-based solutions to these challenges.

Results

We reveal the leveraging mechanisms triggered by immunization and position them vis-à-vis the SDGs, within the framework of Public Health and Planetary Health. Several challenges for sustainable control of vaccine-preventable diseases are identified: access to immunization services, global vaccine availability to LMICs, context-dependent vaccine effectiveness, safe and affordable vaccines, local/regional vaccine production, public-private partnerships, and immunization capacity/capability building. Model-based approaches that support SDG-promoting interventions concerning immunization systems are analyzed in light of the strategic priorities of the Immunization Agenda 2030.

Conclusions

In general terms, it can be concluded that relevant future research requires (i) design for system resilience, (ii) transdisciplinary modeling, (iii) connecting interventions in immunization with SDG outcomes, (iv) designing interventions and their implementation simultaneously, (v) offering tailored solutions, and (vi) model coordination and integration of services and partnerships. The research and health community is called upon to join forces to activate existing knowledge, generate new insights and develop decision-supporting tools for Low-and Middle-Income Countries’ health authorities and communities to leverage immunization in its transformational role toward successfully meeting the SDGs in 2030.