bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular exploration of paediatric intracranial germinomas from multi-ethnic Singapore
Authors: Low Sharon Yin Yee , Cheng He , Zou Ruiyang , Ng Lee Ping , Kuick Chik Hong , Syed Sulaiman Nurfarhanah Bte , Chang Kenneth Tou En , Low David Chyi Yeu , Zhou Lihan , Seow Wan Tew
Published: November 2020

Background

Germinomas (IG) account for up to 50% of all intracranial germ cell tumours. These tumours are reputed to be more prevalent in Oriental populations in comparison to Western cohorts. Biological characteristics of IG in other ethnic groups are unknown. Singapore is a multi-ethnic country with diverse cultures. Owing to inter-racial heterogeneity, the authors hypothesize there are molecular differences between paediatric IG patients in our local population. The aims of this study are exploratory: firstly, to identify molecular characteristics in this tumour type and circulating CSF unique to different racial cohorts; and next, to corroborate our findings with published literature.

Methods

This is a single-institution, retrospective study of prospectively collected data. Inclusion criteria encompass all paediatric patients with histologically confirmed IG. Excess CSF and brain tumour tissues are collected for molecular analysis. Tumour tissues are subjected to a next generation sequencing (NGS) targeted panel forKIT and PDGRA. All CSF samples are profiled via a high-throughput miRNA multiplexed workflow. Results are then corroborated with existing literature and public databases.

Results

In our cohort of 14 patients, there areKITexon variants in the tumour tissues and CSF miRNAs corroborative with published studies. Separately, there are alsoKITexon variants and miRNAs not previously highlighted in IG. A subgroup analysis demonstrates differential CSF miRNAs between Chinese and Malay IG patients.

Conclusion

This is the first in-depth molecular study of a mixed ethnic population of paediatric IGs from a Southeast Asian cohort. Validation studies are required to assess the relevance of novel findings in our study.
Ovarian ependymoma presenting in pregnancy: a case report and literature review
Authors: Jin Bo , Jiang Jingjing , Peng Hongfa
Published: November 2020

Background

Ovarian ependymoma is a rare malignancy. Because of the extreme rarity, certain features of the neoplasm, including its clinical behaviour and optimal therapy, are incompletely characterized.

Case presentation

A 32-year-old pregnant woman at term presented with a left ovarian neoplasm that occurred in the early stage of pregnancy. She underwent left adnexectomy during the caesarean section, and the neoplasm was histologically and immunohistochemically identified to be ovarian ependymoma. Immunohistochemical staining with oestrogen receptors and progesterone receptors showed strong positive staining. According to reports in the literature, the pathological type of ovarian ependymoma in our patient was the extra-axial type. Interestingly, the foetus was also found to have bilateral ependymal cysts during pregnancy. The patient received no further surgical treatment or adjuvant therapy. She and her 14-month-old baby both have no evidence of disease at present. The follow-up of both mother and child is still continuing.

Conclusions

The case presented here illustrates high levels of oestrogen during pregnancy may stimulate viable malignant ependymal cells to proliferate. Hence, young women with extra-axial-type ependymomas may not be suitable for fertility preservation. Moreover, hormone-based therapies can be a potentially effective treatment for women with extra-axial ependymomas.
Racial discrimination and health: a prospective study of ethnic minorities in the United Kingdom
Authors: Hackett Ruth A. , Ronaldson Amy , Bhui Kamaldeep , Steptoe Andrew , Jackson Sarah E.
Published: November 2020

Background

Racism has been linked with poor health in studies in the United States. Little is known about prospective associations between racial discrimination and health outcomes in the United Kingdom (UK).

Methods

Data were from 4883 ethnic minority (i.e. non-white) participants in the UK Household Longitudinal Study. Perceived discrimination in the last 12 months on the basis of ethnicity or nationality was reported in 2009/10. Psychological distress, mental functioning, life satisfaction, self-rated health, physical functioning and reports of limiting longstanding illness were assessed in 2009/10 and 2011/12. Linear and logistic regression analyses adjusted for age, sex, income, education and ethnicity. Prospective analyses also adjusted for baseline status on the outcome being evaluated.

Results

Racial discrimination was reported by 998 (20.4%) of the sample. Cross-sectionally, those who reported racial discrimination had a greater likelihood on average of limiting longstanding illness (odds ratio (OR) = 1.78, 95% confidence interval (CI) 1.49; 2.13) and fair/poor self-rated health (OR = 1.50; 95% CI 1.24; 1.82) than those who did not report racial discrimination. Racial discrimination was associated with greater psychological distress (B = 1.11, 95% CI 0.88; 1.34), poorer mental functioning (B = − 3.61; 95% CI -4.29; − 2.93), poorer physical functioning (B = − 0.86; 95% CI -1.50; − 0.27), and lower life satisfaction (B = − 0.40, 95% CI -0.52; − 0.27). Prospectively, those who reported racial discrimination had a greater likelihood on average of limiting longstanding illness (OR = 1.31, 95% CI 1.01; 1.69) and fair/poor self-rated health (OR = 1.30; 95% CI 1.00; 1.69), than those who did not report racial discrimination. Racial discrimination was associated increased psychological distress (B = 0.52, 95% CI 0.20; 0.85) and poorer mental functioning (B = − 1.77; 95% CI -2.70; − 0.83) over two-year follow-up, adjusting for baseline scores.

Conclusions

UK adults belonging to ethnic minority groups who perceive racial discrimination experience poorer mental and physical health than those who do not. These results highlight the need for effective interventions to combat racial discrimination in order to reduce inequalities in health.
Selective thoracolumbar/lumbar fusion for Syringomyelia-associated scoliosis: a case-control study with Lenke 5C adolescent idiopathic scoliosis
Authors: Feng Fan , Shen Hongxing , Chen Xiuyuan , Liu Zude , Chen Jianwei , Li Quan , Lao Lifeng
Published: November 2020

Background

Selective thoracolumbar/lumbar fusion technique was introduced to treat adolescent idiopathic scoliosis (AIS) patients with major thoracolumbar/lumbar curves. Theoretically, this surgical strategy could also be applied to syringomyelia patients. No previous study has specifically addressed the effectiveness of selective thoracolumbar/lumbar fusion for patients with syringomyelia-associated scoliosis. The aim of the study was to investigate the effectiveness of selective thoracolumbar/lumbar fusion for the surgical treatment of patients with syringomyelia-associated scoliosis.

Methods

From February 2010 to September 2016, 14 syringomyelia-associated patients with major thoracolumbar/lumbar curves were retrospectively reviewed. Besides, 30 Lenke 5C AIS patients were enrolled as a control group. Posterior selective thoracolumbar/lumbar fusion was performed for both groups. Patients’ demographic, operative, radiological, and quality of life data were reviewed with follow-up. Intragroup comparisons were performed for each parameter.

Results

The two groups were matched by age, gender, curve characteristics, duration of follow-up, and all preoperative radiographic parameters except for thoracic kyphosis. After surgery, the average correction rate of the major thoracolumbar/lumbar curve was 82.2 ± 7.8% in the syringomyelia group, which was not significantly different from that of AIS group (82.5 ± 10.6%, P = 0.47). A similar improvement of unfused thoracic curve was observed between the two groups (50.1 ± 16.5% vs. 48.5 ± 26.9%, P = 0.29). During the follow-up, the correction effect of scoliosis was well maintained, without aggravation of the original neural symptoms or fresh permanent neurological deficits. Of note, the number of fusion levels was significantly larger in syringomyelia group than that in AIS group (7.6 ± 1.4 vs. 6.5 ± 1.2, P < 0.01). The average follow up was 47.6 months (36–81 months).

Conclusion

Similar to AIS cases, syringomyelia-associated scoliosis can be effectively and safely corrected by selective thoracolumbar/lumbar fusion with satisfactory surgical outcomes. However, the syringomyelia group, on average, required an additional fused segment for treatment as compared to the AIS group (7.6 versus 6.5 in the AIS group).
Validity and reliability of the self-rated fall risk questionnaire in older adults with osteoporosis
Authors: Kitcharanant Nitchanant , Vanitcharoenkul Ekasame , Unnanuntana Aasis
Published: November 2020

Background

Several risk assessments have been developed to evaluate fall risk in older adults, but it has not been conclusively established which of these tools is most effective for assessing fall risk in this vulnerable population. Recently, the U.S. Centers for Disease Control and Prevention (CDC) developed the self-rated Fall Risk Questionnaire (self-rated FRQ), a 12-item questionnaire designed to screen older adults who are at risk of falling and has been widely used in many centers. This study aimed to determine the validity and reliability of the self-rated FRQ in older adults with osteoporosis.

Methods

This prospective study was conducted at the Department of Orthopedic Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand from December 2019 to March 2020. Sixty-eight men or postmenopausal women aged > 65 years who were diagnosed with osteoporosis either by bone mineral density T-score or by occurrence of fragility fracture were evaluated with the self-rated FRQ, the Thai falls risk assessment test (Thai-FRAT), the timed get-up-and-go test (TUG test), the Berg Balance Scale (BBS), and the 5 times sit-to-stand test (5TSTS test). Validity of the self-rated FRQ was assessed by evaluating the correlations (r) between the self-rated FRQ score and the scores from the other four assessments. Reliability of the self-rated FRQ was evaluated by measuring test-retest reliability and internal consistency.

Results

The self-rated FRQ was moderately strongly correlated with the BBS, TUG test, and 5TSTS test (r = 0.535 to 0.690; p < 0.001), and fairly correlated with the Thai-FRAT (r = 0.487; p < 0.001). Test-retest reliability of the self-rated FRQ was high, with a Kappa of 1. Internal consistency of the self-rated FRQ was excellent (Cronbach’s alpha: 0.936).

Conclusions

The self-rated FRQ was found to be a valid and reliable tool for evaluating fall risk in older adults with osteoporosis. Since assessment of fall risk requires a multifaceted measurement tool, the self-rated FRQ is an appropriate tool that can be integrated into the fall risk assessment algorithm in older adults with osteoporosis.
In vivo imaging of injured cortical axons reveals a rapid onset form of Wallerian degeneration
Authors: Canty Alison Jane , Jackson Johanna Sara , Huang Lieven , Trabalza Antonio , Bass Cher , Little Graham , Tortora Maria , Khan Shabana , De Paola Vincenzo
Published: November 2020

Background

Despite the widespread occurrence of axon and synaptic loss in the injured and diseased nervous system, the cellular and molecular mechanisms of these key degenerative processes remain incompletely understood. Wallerian degeneration (WD) is a tightly regulated form of axon loss after injury, which has been intensively studied in large myelinated fibre tracts of the spinal cord, optic nerve and peripheral nervous system (PNS). Fewer studies, however, have focused on WD in the complex neuronal circuits of the mammalian brain, and these were mainly based on conventional endpoint histological methods. Post-mortem analysis, however, cannot capture the exact sequence of events nor can it evaluate the influence of elaborated arborisation and synaptic architecture on the degeneration process, due to the non-synchronous and variable nature of WD across individual axons.

Results

To gain a comprehensive picture of the spatiotemporal dynamics and synaptic mechanisms of WD in the nervous system, we identify the factors that regulate WD within the mouse cerebral cortex. We combined single-axon-resolution multiphoton imaging with laser microsurgery through a cranial window and a fluorescent membrane reporter. Longitudinal imaging of > 150 individually injured excitatory cortical axons revealed a threshold length below which injured axons consistently underwent a rapid-onset form of WD (roWD). roWD started on average 20 times earlier and was executed 3 times slower than WD described in other regions of the nervous system. Cortical axon WD and roWD were dependent on synaptic density, but independent of axon complexity. Finally, pharmacological and genetic manipulations showed that a nicotinamide adenine dinucleotide (NAD+)-dependent pathway could delay cortical roWD independent of transcription in the damaged neurons, demonstrating further conservation of the molecular mechanisms controlling WD in different areas of the mammalian nervous system.

Conclusions

Our data illustrate how in vivo time-lapse imaging can provide new insights into the spatiotemporal dynamics and synaptic mechanisms of axon loss and assess therapeutic interventions in the injured mammalian brain.
Platelet activation in adult HIV-infected patients on antiretroviral therapy: a systematic review and meta-analysis
Authors: Nkambule Bongani B. , Mxinwa Vuyolwethu , Mkandla Zibusiso , Mutize Tinashe , Mokgalaboni Kabelo , Nyambuya Tawanda M. , Dludla Phiwayinkosi V.
Published: November 2020

Background

Antiretroviral therapy (ART) alters platelet reactivity, and as a consequence, patients living with HIV may be at an increased risk of cardiovascular disease (CVD). The current evidence on platelet activation levels in patients with HIV remains inconclusive. We therefore aimed to systematically synthesise evidence on the association of platelet activation in HIV-infected patients on successful treatment.

Methods

Electronic databases were searched from inception until November 2019. Studies were included if the primary or secondary outcome of the study was to assess platelet activation in HIV-infected patients on ART. The primary outcome of this review included the levels of platelet activation. The pooled effect estimates were calculated using a random-effects meta-analysis model.

Results

We identified 30 studies comprising of 2325 participants. The pooled estimates showed elevated levels of platelet activation in treatment-naïve HIV-infected patients compared to uninfected controls (Hedges’ g 2.00 [95%CI 1.05, 2.94]; z = 4.12, p < 0.0001). These remained elevated despite successful ART (Hedges’ g 2.05 [95%CI 0.58, 3.52]; z = 2.71, p = 0.0067).

Conclusion

The levels of platelet activation are elevated in treatment-naïve HIV-infected patients, and these persist during successful ART. Further studies should assess the clinical relevance of monitoring the levels of platelet activation in HIV-infected patients on ART.
Mutational profiling of micro-dissected pre-malignant lesions from archived specimens
Authors: Nachmanson Daniela , Steward Joseph , Yao Huazhen , Officer Adam , Jeong Eliza , O’Keefe Thomas J. , Hasteh Farnaz , Jepsen Kristen , Hirst Gillian L. , Esserman Laura J. , Borowsky Alexander D. , Harismendy Olivier
Published: November 2020

Background

Systematic cancer screening has led to the increased detection of pre-malignant lesions (PMLs). The absence of reliable prognostic markers has led mostly to over treatment resulting in potentially unnecessary stress, or insufficient treatment and avoidable progression. Importantly, most mutational profiling studies have relied on PML synchronous to invasive cancer, or performed in patients without outcome information, hence limiting their utility for biomarker discovery. The limitations in comprehensive mutational profiling of PMLs are in large part due to the significant technical and methodological challenges: most PML specimens are small, fixed in formalin and paraffin embedded (FFPE) and lack matching normal DNA.

Methods

Using test DNA from a highly degraded FFPE specimen, multiple targeted sequencing approaches were evaluated, varying DNA input amount (3–200 ng), library preparation strategy (BE: Blunt-End, SS: Single-Strand, AT: A-Tailing) and target size (whole exome vs. cancer gene panel). Variants in high-input DNA from FFPE and mirrored frozen specimens were used for PML-specific variant calling training and testing, respectively. The resulting approach was applied to profile and compare multiple regions micro-dissected (mean area 5 mm2) from 3 breast ductal carcinoma in situ (DCIS).

Results

Using low-input FFPE DNA, BE and SS libraries resulted in 4.9 and 3.7 increase over AT libraries in the fraction of whole exome covered at 20x (BE:87%, SS:63%, AT:17%). Compared to high-confidence somatic mutations from frozen specimens, PML-specific variant filtering increased recall (BE:85%, SS:80%, AT:75%) and precision (BE:93%, SS:91%, AT:84%) to levels expected from sampling variation. Copy number alterations were consistent across all tested approaches and only impacted by the design of the capture probe-set. Applied to DNA extracted from 9 micro-dissected regions (8 PML, 1 normal epithelium), the approach achieved comparable performance, illustrated the data adequacy to identify candidate driver events (GATA3 mutations, ERBB2 or FGFR1 gains, TP53 loss) and measure intra-lesion genetic heterogeneity.

Conclusion

Alternate experimental and analytical strategies increased the accuracy of DNA sequencing from archived micro-dissected PML regions, supporting the deeper molecular characterization of early cancer lesions and achieving a critical milestone in the development of biology-informed prognostic markers and precision chemo-prevention strategies.
Lower serum 25-hydroxycholecalciferol is associated with depressive symptoms in older adults in Southern Brazil
Authors: Ceolin Gilciane , Matsuo Luísa Harumi , Confortin Susana Cararo , D’Orsi Eleonora , Rieger Débora Kurrle , Moreira Júlia Dubois
Published: November 2020

Background

Older adults are one of the most susceptible populations to depression, especially those living in low- and middle-income countries. As well, they are also considering a risk group for vitamin D deficiency. Low serum vitamin D has been associated with an increased risk of brain neuropsychiatry disorders. We aimed to investigate the association between serum 25-hydroxycholecalciferol concentrations and depressive symptoms in adults aged 60 years and over from southern Brazil.

Methods

A cross-sectional analysis was performed using data collected during 2013–2014 from the populational-based longitudinal EpiFloripa Aging Study (n = 1197). Serum 25-hydroxycholecalciferol concentrations were analyzed and classified according to the Endocrine Society reference values [sufficiency (≥ 30 ng/mL), insufficiency (21–29 ng/mL), and deficiency (≤ 20 ng/mL)]. Depressive symptoms were evaluated using the Geriatric Depression Scale (15-item GDS). Logistic regression was performed to assess depressive symptoms in each vitamin D category. The analysis was adjusted for sex, age, skin color, family income, leisure-time physical activities, social or religious groups attendance, morbidities, cognitive impairment, and dependence in activities of daily living.

Results

A total of 557 participants with complete data for exposure and outcome were enrolled in the analysis. Most of the sample participants were female (63.1%), age-range 60–69 years (42.2%), white skin color (85.1%), and vitamin D serum level samples were collected in autumn (50.7%). Depressive symptoms were present in 15.8% of the participants, and the prevalence was higher in individuals classified as deficient in vitamin D (23.2, 95% confidence interval [CI] = 15.6;32.9) and insufficiency (17.2, 95%CI = 11.0;25.9). The crude analysis showed that vitamin D deficient participants had 3.08 (CI = 1.53;6.20) times higher odds to present depressive symptoms compared to vitamin D sufficiency. After adjusting, the association was maintained [OR 2.27 (95%CI = 1.05;4.94).

Conclusions

Serum 25-hydroxycholecalciferol deficiency was positively associated with depressive symptoms in older adults from southern Brazil.
Cytoplasm protein GFAP magnetic beads construction and application as cell separation target for brain tumors
Authors: Zhao Yang , Jiang Feng , Wang Qinhua , Wang Baocheng , Han Yipeng , Yang Jian , Wang Jiajia , Wang Kai , Ao Junping , Guo Xunxiang , Liang Xiaofei , Ma Jie
Published: November 2020

Background

It is very important to develop a highly efficient cerebrospinal fluid (CSF) detection system with diagnosis and prediction function, for which the detection of circulating tumor cells (CTCs) in CSF is a good choice. In contrast to the past use of epithelial EpCAM as CTCs separation target, a cytoplasm protein of GFAP antibody was first selected to construct highly-sensitive immunomagnetic liposome beads (IMLs). The validation and efficiency of this system in capturing CTCs for brain tumors were measured both in vitro and in vivo. The associations between the numbers of CTCs in patients with their clinical characteristics were further analyzed.

Results

Our data show that CTCs can be successfully isolated from CSF and blood samples from 32 children with brain tumors. The numbers of CTCs in CSF were significantly higher than those in blood. The level of CTCs in CSF was related to the type and location of the tumor rather than its stage. The higher the CTCs number is, the more possibly the patient will suffer from poor prognosis. Genetic testing in GFAP CTC-DNA by sanger sequencing, q-PCR and NGS methods indicated that the isolated CTCs (GFAP+/EGFR+) are the related tumor cell. For example, the high expression of NPR3 gene in CSF CTCs was consistent with that of tumor tissue.

Conclusions

The results indicated that GFAP-IML CTCs isolation system, combined with an EGFR immunofluorescence assay of antitumor marker, can serve as a brand-new method for the identification of CTCs for brain tumors. Via lumbar puncture, a minimally invasive procedure, this technique may play a significant role in the clinical diagnosis and drug evaluation of brain tumors.
Effect of silica-coated magnetic nanoparticles on rigidity sensing of human embryonic kidney cells
Authors: Ketebo Abdurazak Aman , Shin Tae Hwan , Jun Myeongjun , Lee Gwang , Park Sungsu
Published: November 2020

Background

Nanoparticles (NPs) can enter cells and cause cellular dysfunction. For example, reactive oxygen species generated by NPs can damage the cytoskeleton and impair cellular adhesion properties. Previously, we reported that cell spreading and protrusion structures such as lamellipodia and filopodia was reduced when cells are treated with silica-coated magnetic nanoparticles incorporating rhodamine B isothiocyanate (MNPs@SiO2(RITC)), even at 0.1 μg/μL. These protruded structures are involved in a cell’s rigidity sensing, but how these NPs affect rigidity sensing is unknown.

Results

Here, we report that the rigidity sensing of human embryonic kidney (HEK293) cells was impaired even at 0.1 μg/μL of MNPs@SiO2(RITC). At this concentration, cells were unable to discern the stiffness difference between soft (5 kPa) and rigid (2 MPa) flat surfaces. The impairment of rigidity sensing was further supported by observing the disappearance of locally contracted elastomeric submicron pillars (900 nm in diameter, 2 μm in height, 24.21 nN/μm in stiffnessk) under MNPs@SiO2(RITC) treated cells. A decrease in the phosphorylation of paxillin, which is involved in focal adhesion dynamics, may cause cells to be insensitive to stiffness differences when they are treated with MNPs@SiO2(RITC).

Conclusions

Our results suggest that NPs may impair the rigidity sensing of cells even at low concentrations, thereby affecting cell adhesion and spreading.
Plasma level of lipocalin 2 is increased in neovascular age-related macular degeneration patients, particularly those with macular fibrosis
Authors: Chen Mei , Yang Nan , Lechner Judith , Toth Levente , Hogg Ruth , Silvestri Giuliana , Chakravarthy Usha , Xu Heping
Published: November 2020

Background

Previously, we and others have reported higher populations of circulating neutrophils in patients with neovascular age-related macular degeneration (nAMD). Neutrophil gelatinase-associated lipocalin (NGAL, also known as lipocalin-2, LCN2), an important innate immune mediator, is known to be critically involved in sterile inflammation-mediated organ failure, fibrosis, cancer progression and retinal degeneration. This study investigated the plasma levels of LCN2, matrix metalloproteinase 9 (MMP9) and LCN2/MMP9 complex in different types of nAMD and examined whether the levels were related to patients’ responsiveness to anti-VEGF therapy.

Results

One hundred and seventy-four nAMD patients, including 108 with choroidal neovascularisation (CNV), 32 with retinal angiomatous proliferation (RAP), 23 with polypoidal choroidal vasculopathy (PCV) and 11 unclassified patients, and 43 healthy controls were recruited to this case-control study. Fifty-eight nAMD patients had macular fibrosis and 110 patients did not. Out of the 174 nAMD patients, 80 patients responded completely, 90 responded partially, and 4 did not respond to the anti-VEGF therapy. The plasma levels of LCN2 in nAMD patients (181.46 ± 73.62 ng/ml) was significantly higher than that in healthy controls (152.24 ± 49.55 ng/ml, P = 0.047). However, the difference disappeared after adjusting for age. A positive correlation between plasma level of LCN2 and age was observed in nAMD patients (r = 0.29, P = 0.0002) but not in healthy controls. The plasma level of LCN2 was also positively correlated with circulating neutrophils in nAMD patients (r = 0.34, p = 0.0007) but not in healthy controls (r = 0.057, p = 0.77). No correlation was observed between age and circulating neutrophils. Further analysis of nAMD subtypes uncovered a significantly higher level of LCN2 in patients with macular fibrosis even after adjusting for age. No relationship was observed between plasma levels of LCN2 and patients’ responsiveness to anti-VEGF therapy. The plasma levels of MMP9 and LCN2/MMP9 complex were comparable between nAMD and controls.

Conclusions

Our results suggest that higher plasma levels of LCN2 in nAMD are related to ageing and increased population of circulating neutrophils. Our results also suggest that higher levels of LCN2 may increase the risk of macular fibrosis in nAMD.
An anti-CD6 monoclonal antibody (itolizumab) reduces circulating IL-6 in severe COVID-19 elderly patients
Authors: Saavedra Danay , Añé-Kourí Ana Laura , Sánchez Naivy , Filgueira Lázaro Manuel , Betancourt Julio , Herrera Carlos , Manso Leniel , Chávez Elibet , Caballero Armando , Hidalgo Carlos , Lorenzo Geydi , Cepeda Meylan , Valenzuela Carmen , Ramos Mayra , León Kalet , Mazorra Zaima , Crombet Tania
Published: November 2020

Background

Since the COVID-19 outbreak an unprecedented challenge for healthcare systems around the world has been placed. In Cuba, the first case of COVID-19 was reported on March 11. Elderly with multiple comorbidities have been the most risky population. Although most patients present a mild to moderate disease, some have developed severe symptoms. One of the possible mechanisms underlying rapid disease progression is a cytokine storm, in which interleukin (IL) -6 seems to be a major mediator. Itolizumab is a humanized recombinant anti-CD6 monoclonal antibody (MAb), with the ability of reducing serum interferon gamma (INF-γ), tumour necrosis factor alpha (TNFα) and IL-6. Based on these previous results in patients with psoriasis and rheumatoid arthritis, an expanded access clinical trial was approved by the Cuban regulatory agency for COVID-19 critically, severely and moderately ill patients.

Results

We show here a short kinetic of IL-6 serum concentration in the first 24 COVID-19 patients treated with itolizumab. Most of patients were elderly with multiple comorbidities. We found that with one itolizumab dose, the circulating IL-6 decreased in critically and severely ill patients, whereas in moderately ill patients the values didn’t rise as compared to their low baseline levels.

Conclusion

These findings suggest that itolizumab could be an attractive therapeutic option to decrease the negative outcome of the cytokine storm in COVID-19 patients.

Trial registration

CECMED IIC RD-EC 179, RPCEC00000311. Registered 4 May 2020 - Retrospectively registered, http://rpcec.sld.cu/ensayos/RPCEC00000311-Sp or http://rpcec.sld.cu/trials/RPCEC00000311-En
First report of Plum bark necrosis stem pitting-associated virus infecting grapevine in China
Authors: Yang Yang , Sun Yifan , Li Qingliang , Wu Yufeng , Wang Deya
Published: November 2020

Background

Virus disease is one of the main diseases in grapevine, and there has been no report on Plum bark necrosis and stem pitting-associated virus infecting grapevine in China.

Objective

The leaf samples of grapevine cultivar 'Cabernet Gernischt' were collected from Shandong province, which the leaves suffered from viral-like symptoms with spotting and crinkle.

Methods

Small RNA-seq combined with reverse transcription PCR (RT-PCR) were performed to detect the potential viruses in these field samples. Phylogenetic tree was constructed using the neighbor joining method in MEGA 5.1

Conclusions

This is the first report of PBNSPaV infecting grapevine in China, contributing to a better understanding of the epidemiology and host range distribution of this pathogen.
Poor sensitivity of "AccuPower SARS-CoV-2 real time RT-PCR kit (Bioneer, South Korea)"
Authors: Freire-Paspuel Byron , Garcia-Bereguiain Miguel Angel
Published: November 2020

Background

Several molecular kits are available for SARS-CoV-2 diagnosis, mostly lacking of proper clinical evaluation due to the emergency caused by COVID19 pandemia, particularly at developing countries like Ecuador.

Objective

We carried out an evaluation of the clinical performance of "AccuPower SARS-CoV-2 Real Time RT-PCR kit" (Bioneer, South Korea) for SARS-CoV-2 diagnosis using 2019-nCoV CDC EUA kit (IDT, USA) as a gold standard.

Results

48 clinical specimens were included on the study, 38 tested SARS-CoV-2 positive and 10 SARS-CoV-2 negative for 2019-nCoV CDC EUA kit. For "AccuPower SARS-CoV-2 Real Time RT-PCR kit", only 30 were SARS-CoV-2 positive, indicating a low clinical performance with sensitivity of 78.9%. Moreover, the limit of detection for "AccuPower SARS-CoV-2 Real Time RT-PCR kit" was estimated to be higher than 40,000 viral RNA copies/mL of sample.

Conclusions

Proper clinical performance evaluation studies from government agencies at developing countries should be mandatory prior to clinical use authorization of SARS-CoV-2 diagnosis kits, particularly when those kits lack of either FDA or its country of origin clinical use authorization, to prevent the distribution of low quality products that may have a negative impact of COVID19 surveillance at developing countries.
Estimated prevalence of mucopolysaccharidoses from population-based exomes and genomes
Authors: Borges Pâmella , Pasqualim Gabriela , Giugliani Roberto , Vairo Filippo , Matte Ursula
Published: November 2020

Background

In this study, the prevalence of different types of mucopolysaccharidoses (MPS) was estimated based on data from the exome aggregation consortium (ExAC) and the genome aggregation database (gnomAD). The population-based allele frequencies were used to identify potential disease-causing variants on each gene related to MPS I to IX (except MPS II).

Methods

We evaluated the canonical transcripts and excluded homozygous, intronic, 3′, and 5′ UTR variants. Frameshift and in-frame insertions and deletions were evaluated using the SIFT Indel tool. Splice variants were evaluated using SpliceAI and Human Splice Finder 3.0 (HSF). Loss-of-function single nucleotide variants in coding regions were classified as potentially pathogenic, while synonymous variants outside the exon–intron boundaries were deemed non-pathogenic. Missense variants were evaluated by five in silico prediction tools, and only those predicted to be damaging by at least three different algorithms were considered disease-causing.

Results

The combined frequencies of selected variants (ranged from 127 in GNS to 259 in IDUA) were used to calculate prevalence based on Hardy–Weinberg's equilibrium. The maximum estimated prevalence ranged from 0.46 per 100,000 for MPSIIID to 7.1 per 100,000 for MPS I. Overall, the estimated prevalence of all types of MPS was higher than what has been published in the literature. This difference may be due to misdiagnoses and/or underdiagnoses, especially of the attenuated forms of MPS. However, overestimation of the number of disease-causing variants by in silico predictors cannot be ruled out. Even so, the disease prevalences are similar to those reported in diagnosis-based prevalence studies.

Conclusion

We report on an approach to estimate the prevalence of different types of MPS based on publicly available population-based genomic data, which may help health systems to be better prepared to deal with these conditions and provide support to initiatives on diagnosis and management of MPS.
Promoting the co-utilisation of glucose and xylose in lignocellulosic ethanol fermentations using a data-driven feed-back controller
Authors: Lopez Pau Cabaneros , Abeykoon Udugama Isuru , Thomsen Sune Tjalfe , Bayer Christoph , Junicke Helena , Gernaey Krist V.
Published: November 2020

Background

The diauxic growth of Saccharomyces cerevisiae on glucose and xylose during cellulose-to-ethanol processes extends the duration of the fermentation and reduces productivity. Despite the remarkable advances in strain engineering, the co-consumption of glucose and xylose is still limited due to catabolite repression. This work addresses this challenge by developing a closed-loop controller that is capable of maintaining the glucose concentration at a steady set-point during fed-batch fermentation. The suggested controller uses a data-driven model to measure the concentration of glucose from ‘real-time’ spectroscopic data. The concentration of glucose is then automatically controlled using a control scheme that consists of a proportional, integral, differential (PID) algorithm and a supervisory layer that manipulates the feed-rates to the reactor accounting for the changing dynamics of fermentation.

Results

The PID parameters and the supervisory layer were progressively improved throughout four fed-batch lignocellulosic-to-ethanol fermentations to attain a robust controller able of maintaining the glucose concentration at the pre-defined set-points. The results showed an increased co-consumption of glucose and xylose that resulted in volumetric productivities that are 20–33% higher than the reference batch processes. It was also observed that fermentations operated at a glucose concentration of 10 g/L were faster than those operated at 4 g/L, indicating that there is an optimal glucose concentration that maximises the overall productivity.

Conclusions

Promoting the simultaneous consumption of glucose and xylose in S. cerevisiae is critical to increase the productivity of lignocellulosic ethanol processes, but also challenging due to the strong catabolite repression of glucose on the uptake of xylose. Operating the fermentation at low concentrations of glucose allows reducing the effects of the catabolite repression to promote the co-consumption of the two carbon sources. However, S. cerevisiae is very sensitive to changes in the glucose concentration and deviations from a set-point result in notable productivity losses. The controller structure developed and implemented in this work illustrates how combining data-driven measurements of the glucose concentration and a robust yet effective PID-based supervisory control allowed tight control of the concentration of glucose to adjust it to the metabolic requirements of the cell culture that can unlock tangible gains in productivities.
Evaluating the impact of biannual school-based and community-wide treatment on urogenital schistosomiasis in Niger
Authors: Phillips Anna E. , Tohon Zilahatou , Dhanani Neerav A. , Sofo Boubacar , Gnandou Issa , Sidikou Boubacar , Noma Adamou Garba , Madougou Bassirou , Alto Oumarou , Sebangou Hannatou , Halilou Kader M. , Andia Roumanatou , Garba Amadou , Fenwick Alan , Hamidou Amina A.
Published: November 2020

Background

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) coordinated a five-year study implemented in several countries, including Niger, to provide an evidence-base for programmatic decisions regarding cost-effective approaches to preventive chemotherapy for schistosomiasis control.

Methods

This was a cluster-randomised trial investigating six possible combinations of annual or biannual community-wide treatment (CWT), school-based treatment (SBT), and holidays from mass treatment over four years. The most intense arm involved two years of annual CWT followed by 2 years of biannual CWT, while the least intensive arm involved one year of annual SBT followed by a year without treatment and two more years of annual SBT. The primary outcome of interest was prevalence and intensity of Schistosoma haematobium among 100 children aged 9–12 years sampled each year. In addition, 100 children aged 5–8 years in their first year of school and 50 adults (aged 20–55 years) were tested in the first and final fifth year of the study.

Results

In total, data were collected from 167,500 individuals across 225 villages in nine districts within the Niger River valley, Western Niger. Overall, the prevalence of S. haematobium decreased from baseline to Year 5 across all study arms. The relative reduction of prevalence was greater in biannual compared with annual treatment across all arms; however, the only significant difference was seen in areas with a high starting prevalence. Although adults were not targeted for treatment in SBT arms, a statistically significant decrease in prevalence among adults was seen in moderate prevalence areas receiving biannual (10.7% to 4.8%) SBT (P < 0.001). Adults tested in the annual SBT group also showed a decrease in prevalence between Year 1 and Year 5 (12.2% to 11.0%), but this difference was not significant.

Conclusions

These findings are an important consideration for schistosomiasis control programmes that are considering elimination and support the idea that scaling up the frequency of treatment rounds, particularly in areas of low prevalence, will not eliminate schistosomiasis. Interestingly, the finding that prevalence decreased among adults in SBT arms suggests that transmission in the community can be reduced, even where only school children are being treated, which could have logistical and cost-saving implications for the national control programmes.

Graphical Abstract
Evaluating survey designs for targeting preventive chemotherapy against Schistosoma haematobium and Schistosoma mansoni across sub-Saharan Africa: a geostatistical analysis and modelling study
Authors: Fornace Kimberly M , Fronterrè Claudio , Fleming Fiona M. , Simpson Hope , Zoure Honorat , Rebollo Maria , Mwinzi Pauline , Vounatsou Penelope , Pullan Rachel L.
Published: November 2020

Background

Schistosomiasis control programmes primarily use school-based surveys to identify areas for mass drug administration of preventive chemotherapy. However, as the spatial distribution of schistosomiasis can be highly focal, transmission may not be detected by surveys implemented at districts or larger spatial units. Improved mapping strategies are required to accurately and cost-effectively target preventive chemotherapy to remaining foci across all possible spatial distributions of schistosomiasis.

Methods

Here, we use geostatistical models to quantify the spatial heterogeneity of Schistosoma haematobium and S. mansoni across sub-Saharan Africa using the most comprehensive dataset available on school-based surveys. Applying this information to parameterise simulations, we assess the accuracy and cost of targeting alternative implementation unit sizes across the range of plausible schistosomiasis distributions. We evaluate the consequences of decisions based on survey designs implemented at district and subdistrict levels sampling different numbers of schools. Cost data were obtained from field surveys conducted across multiple countries and years, with cost effectiveness evaluated as the cost per correctly identified school.

Results

Models identified marked differences in prevalence and spatial distributions between countries and species; however, results suggest implementing surveys at subdistrict level increase the accuracy of treatment classifications across most scenarios. While sampling intensively at the subdistrict level resulted in the highest classification accuracy, this sampling strategy resulted in the highest costs. Alternatively, sampling the same numbers of schools currently recommended at the district level but stratifying by subdistrict increased cost effectiveness.

Conclusions

This study provides a new tool to evaluate schistosomiasis survey designs across a range of transmission settings. Results highlight the importance of considering spatial structure when designing sampling strategies, illustrating that a substantial proportion of children may be undertreated even when an implementation unit is correctly classified. Control programmes need to weigh the increased accuracy of more detailed mapping strategies against the survey costs and treatment priorities.

Graphical Abstract
Contralateral tension pneumothorax during video-assisted thoracic surgery for lung cancer in a patient with obesity and rib fractures: a case report and review of the literature
Authors: Kumata Sakiko , Matsuoka Katsunari , Nagai Shinjiro , Ueda Mitsuhiro , Okada Yoshinori , Miyamoto Yoshihiro
Published: November 2020

Background

Intraoperative contralateral pneumothorax during one-lung ventilation is a rare but life-threatening complication. Although the exact incidence is unknown, only 14 cases with this complication have been reported until now.

Case presentation

A 67-year-old Japanese man with a weight of 80 kg, height of 162.2 cm, and body mass index of 30.4 kg/m2underwent three-port video-assisted thoracic surgery for lung cancer with one-lung ventilation. He had suffered from traumatic right rib fractures 6 weeks before the referral. Fifteen minutes before the end of the surgery, the systolic blood pressure suddenly dropped to about 50 mmHg, which was immediately recovered by intravenous injection of phenylephrine. This episode occurred during chest closure after the completion of the left upper lobectomy, and one-lung ventilation was soon switched to two-lung ventilation. Contralateral tension pneumothorax was noted by the postoperative chest x-ray. As the patient was complicated with obesity and a past history of rib fractures, increased airway pressure during one-lung ventilation related to obesity together with the persistent compression of the visceral pleura by the fractured ends of the ribs was considered to be the factors responsible for this critical complication.

Conclusions

Patient backgrounds such as obesity and past history of rib fractures should be noted carefully as risk factors for intraoperative contralateral pneumothorax during one-lung ventilation. We present the clinical course and discuss the mechanism of development of this potentially life-threatening complication in the present case with a review of the literature.
Development of pre-syrinx state and syringomyelia following a minor injury: a case report
Authors: Kleindienst Andrea , Engelhorn Tobias , Roeckelein Verena , Buchfelder Michael
Published: November 2020

Background

A generally accepted rule is that posttraumatic syringomyelia (PTS) results from spinal cord injury (SCI).

Case presentation

Here, we report the development of syringomyelia without SCI in a 54-year-old Caucasian man following a mild motor vehicle accident. The computed tomography on admission excluded an injury of the spine. Because of neck and back pain, magnetic resonance imaging was performed on day 3 post-injury and demonstrated minimal changes from a ligamentous strain at the cervicothoracic transition. Any traumatic affection of the bone, vertebral discs, intraspinal compartment, or spinal cord were excluded. Some limb weakness and neurogenic bladder dysfunction started manifesting within the following weeks. Repeated MRIs following the accident demonstrated arachnoid adhesions at the C1–2 level and spinal cord edema equivalent to a pre-syrinx state at 12 months and syrinx formation at 24 months. Because of further deterioration, decompression was performed at 36 months.

Conclusions

We conclude that even after a minor trauma PTS can occur and that medullary edema (pre-syrinx state) may precede syrinx formation.
Economic analysis of sugammadex versus neostigmine for reversal of neuromuscular blockade for laparoscopic surgery in China
Authors: Ren Maodong , Wang Ying , Luo Yan , Fang Jia , Lu Yongji , Xuan Jianwei
Published: November 2020

Background

Neuromuscular blockade and pneumoperitoneum (PP) are important factors to ensure successful laparoscopic surgery. However, residual neuromuscular blockade (rNMB) and PP are associated with many unfavorable complications. The aim of this study is to compare the cost-effectiveness of using sugammadex versus neostigmine in laparoscopic surgery in China.

Methods

A decision tree model was developed with a time horizon based on laparoscopic surgery related hospitalization duration. 2000 patients using sugammadex or neostigmine were simulated within the model. The model outcomes included incidence of rNMB and PP related complications and their treatment costs. Data on clinical efficacy, safety and cost were collected from published literature and interviews of physicians.

Results

The model projected that treatment with sugammadex instead of neostigmine would lead to 673 fewer total complications, including rNMB/PP related complications, hospitalization, and other AEs (621 events versus 1294 events, respectively). Use of sugammadex was associated with an incremental medication cost of ¥1,360,410. However, 93.6% of the increased medication cost can be off-set by the reduced costs attributable to treatment of rNMB related complications, PP related complications, hospitalization and other adverse events in sugammadex group. In aggregate, the sugammadex group incurred an incremental cost of ¥86,610 to prevent 673 complications, (¥128.56 per one rNMB/PP related complications prevention). One-way sensitivity analysis confirmed the robustness of the model.

Conclusions

Use of sugammadex in replacement of neostigmine would result in significantly lower rNMB/PP related complications but at a substantially higher medication cost. Upon accounting for the costs associated with treatment of rNMB/PP related complications, 93.6% of medication cost is projected to be offset. In balance, sugammadex appears to offer good value for reversal of neuromuscular blockade for laparoscopic surgery in China.