bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissociating the effects of distraction and proactive interference on object memory through tests of novelty preference
Authors: Landreth K. , Simanaviciute U. , Fletcher J. , Grayson B. , Grant R. A. , Harte M. H. , Gigg J.
Published: April 2021

Encoding information into memory is sensitive to distraction while retrieving that memory may be compromised by proactive interference from pre-existing memories. These two debilitating effects are common in neuropsychiatric conditions, but modelling them preclinically to date is slow as it requires prolonged operant training. A step change would be the validation of functionally equivalent but fast, simple, high-throughput tasks based on spontaneous behaviour. Here, we show that spontaneous object preference testing meets these requirements in the subchronic phencyclidine rat model for cognitive impairments associated with schizophrenia. Subchronic phencyclidine rats show clear memory sensitivity to distraction in the standard novel object recognition task. However, due to this, standard novel object recognition task cannot assess proactive interference. Therefore, we compared subchronic phencyclidine performance in standard novel object recognition task to that using the continuous novel object recognition task, which offers minimal distraction, allowing disease-relevant memory deficits to be assessed directly. We first determined that subchronic phencyclidine treatment did not affect whisker movements during object exploration. Subchronic phencyclidine rats exhibited the expected distraction standard novel object recognition task effect but had intact performance on the first continuous novel object recognition task trial, effectively dissociating distraction using two novel object recognition task variants. In remaining continuous novel object recognition task trials, the cumulative discrimination index for subchronic phencyclidine rats was above chance throughout, but, importantly, their detection of object novelty was increasingly impaired relative to controls. We attribute this effect to the accumulation of proactive interference. This is the first demonstration that increased sensitivity to distraction and proactive interference, both key cognitive impairments in schizophrenia, can be dissociated in the subchronic phencyclidine rat using two variants of the same fast, simple, spontaneous object memory paradigm.
Astrocytes in schizophrenia
Authors: Notter Tina
Published: April 2021

Schizophrenia is a severe and clinically heterogenous mental disorder affecting approximately 1% of the population worldwide. Despite tremendous achievements in the field of schizophrenia research, its precise aetiology remains elusive. Besides dysfunctional neuronal signalling, the pathophysiology of schizophrenia appears to involve molecular and functional abnormalities in glial cells, including astrocytes. This article provides a concise overview of the current evidence supporting altered astrocyte activity in schizophrenia, which ranges from findings obtained from post-mortem immunohistochemical analyses, genetic association studies and transcriptomic investigations, as well as from experimental investigations of astrocyte functions in animal models. Integrating the existing data from these research areas strongly suggests that astrocytes have the capacity to critically affect key neurodevelopmental and homeostatic processes pertaining to schizophrenia pathogenesis, including glutamatergic signalling, synaptogenesis, synaptic pruning and myelination. The further elucidation of astrocytes functions in health and disease may, therefore, offer new insights into how these glial cells contribute to abnormal brain development and functioning underlying this debilitating mental disorder.
Physicochemical Variation in Nanogold-Based Ayurved Medicine Suvarna Bhasma Produced by Various Manufacturers Lead to Different In Vivo Bioaccumulation Profiles
Authors: Biswas Snehasis , Chawda Mukesh , Thakur Kapil , Gudi Ramacharya , Bellare Jayesh
Published: April 2021

Suvarna Bhasma (SB) is a gold particle-based medicine that is used in Ayurved to treat tuberculosis, arthritis and nervous diseases. Traditionally, the Ayurved preparation processes of SB do exist, but they are all long, tedious and involve several steps. Due to this, there is a possibility of bypassing the necessary Ayurved processes or non-adherence to all steps or use of synthetic gold particles. Our aim is to characterize 5 commercial SB preparations from 5 different manufacturers. A comparative physicochemical, pharmacokinetic (PK) and bioaccumulation study was carried out on all the 5 SB preparations. The general appearance such as color and texture of these 5 samples were different from each other. The size, shape and gold concentration (from 32-98 wt%) varied among all the 5 SBs. The accumulation of ionic gold in zebrafish and gold concentration profiles in rat blood were found to be significantly different for all the 5 SBs. Non-compartmental PK model obtained from the concentration-time profile showed significant differences in various PK parameters such as peak concentration (Cmax), half-life (t1/2) and terminal elimination slope (λz) for all the 5 SB preparations. SB-B showed the highest Cmax (8.55 μg/L), whereas SB-D showed the lowest Cmax (4.66 μg/L). The dissolution of ionic gold from SBs in zebrafish tissue after the oral dose had a 5.5-fold difference between the highest and lowest ionic gold concentrations. All the 5 samples showed distinct physicochemical and biological properties. Based on characteristic microscopic morphology, it was found that 2 preparations among them were suspected of being manufactured by non-adherence to the mentioned Ayurved references.
Characterization of Brazilian palygorskite (Guadalupe region) and adsorptive behaviour for solvatochromic dyes
Authors: de Souza Cristiane Gimenes , de Jesus Tammy Caroline Lima , dos Santos Rafael Cavalcante , Bomfim Lívia Melo , Bertolino Luiz Carlos , de Andrade Débora França , d´Avila Luiz Antonio , Spinelli Luciana S.
Published: April 2021

This work presents the results of the physical characterization of palygorskite and its adsorptive behaviour for three solvatochromic dyes (Nile blue chloride (NBC), methylene blue (MTB) and dithizone (DTZ)). Adsorption isotherms were used to determine the maximum adsorption of the solvatochromic dyes on the palygorskite. The characterization of palygorskite was carried out via mineralogical and chemical analysis with X-ray diffraction, X-ray fluorescence, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy, surface-charge measurement (ζ-potential), thermogravimetric analysis, textural analysis and cation-exchange capacity analysis. The material consists of palygorskite and quartz and its chemistry is dominated by SiO2, MgO and Fe2O3. The specific surface area and cation-exchange capacity of the palygorskite are 142 m2 g–1 and 41 cmol(+) kg–1, respectively. The SEM and TEM analyses showed a fibrous structure with fibres 20–100 nm long. The thermogravimetric analysis showed three endothermic events at 57.3°C, 171.8°C and 439.6°C. The adsorption capacities of the palygorskite for NBC (basic pH), MTB (basic pH) and DTZ (neutral pH) were 0.082, 0.013 and 0.102 g g–1, respectively. The adsorptions of NBC and MTB were fitted with the Langmuir isotherm model and the adsorption of DTZ was fitted with the Sips model.
MondoA drives malignancy in B-ALL through enhanced adaptation to metabolic stress
Authors: Sipol Alexandra , Hameister Erik , Xue Busheng , Hofstetter Julia , Barenboim Maxim , Öllinger Rupert , Jain Gaurav , Prexler Carolin , Rubio Rebeca Alba , Baldauf Michaela C. , Franchina Davide G. , Petry Andreas , Schmäh Juliane , Thiel Uwe , Görlach Agnes , Cario Gunnar , Brenner Dirk , Richter Günther H. S. , Grünewald Thomas G. P. , Rad Roland , Wolf Elmar , Ruland Jürgen , Sorensen Poul H. , Burdach Stefan E. G.
Published: April 2021

Cancer cells are in most instances characterized by rapid proliferation and uncontrolled cell division. Hence, they must adapt to proliferation-induced metabolic stress through intrinsic or acquired antimetabolic stress responses to maintain homeostasis and survival. One mechanism to achieve this is reprogramming gene expression in a metabolism-dependent manner. MondoA (also known as Myc-associated factor X–like protein X-interacting protein [MLXIP]), a member of the MYC interactome, has been described as an example of such a metabolic sensor. However, the role of MondoA in malignancy is not fully understood and the underlying mechanism in metabolic responses remains elusive. By assessing patient data sets, we found that MondoA overexpression is associated with worse survival in pediatric common acute lymphoblastic leukemia (ALL; B-precursor ALL [B-ALL]). Using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) and RNA-interference approaches, we observed that MondoA depletion reduces the transformational capacity of B-ALL cells in vitro and dramatically inhibits malignant potential in an in vivo mouse model. Interestingly, reduced expression of MondoA in patient data sets correlated with enrichment in metabolic pathways. The loss of MondoA correlated with increased tricarboxylic acid cycle activity. Mechanistically, MondoA senses metabolic stress in B-ALL cells by restricting oxidative phosphorylation through reduced pyruvate dehydrogenase activity. Glutamine starvation conditions greatly enhance this effect and highlight the inability to mitigate metabolic stress upon loss of MondoA in B-ALL. Our findings give novel insight into the function of MondoA in pediatric B-ALL and support the notion that MondoA inhibition in this entity offers a therapeutic opportunity and should be further explored.
Medication overuse and drug addiction: a narrative review from addiction perspective
Authors: Takahashi Tatiane Teru , Ornello Raffaele , Quatrosi Giuseppe , Torrente Angelo , Albanese Maria , Vigneri Simone , Guglielmetti Martina , Maria De Marco Cristiano , Dutordoir Camille , Colangeli Enrico , Fuccaro Matteo , Di Lenola Davide , Spuntarelli Valerio , Pilati Laura , Di Marco Salvatore , Van Dycke Annelies , Abdullahi Ramla Abuukar , Maassen van den Brink Antoinette , Martelletti Paolo ,   on behalf of the European Headache Federation School of Advanced Studies (EHF-SAS)
Published: April 2021

Chronic headache is particularly prevalent in migraineurs and it can progress to a condition known as medication overuse headache (MOH). MOH is a secondary headache caused by overuse of analgesics or other medications such as triptans to abort acute migraine attacks. The worsening of headache symptoms associated with medication overuse (MO) generally ameliorates following interruption of regular medication use, although the primary headache symptoms remain unaffected. MO patients may also develop certain behaviors such as ritualized drug administration, psychological drug attachment, and withdrawal symptoms that have been suggested to correlate with drug addiction. Although several reviews have been performed on this topic, to the authors best knowledge none of them have examined this topic from the addiction point of view. Therefore, we aimed to identify features in MO and drug addiction that may correlate. We initiate the review by introducing the classes of analgesics and medications that can cause MOH and those with high risk to produce MO. We further compare differences between sensitization resulting from MO and from drug addiction, the neuronal pathways that may be involved, and the genetic susceptibility that may overlap between the two conditions. Finally, ICHD recommendations to treat MOH will be provided herein.
Headache service quality evaluation: implementation of quality indicators in primary care in Europe
Authors:   on behalf of European Headache Federation and Lifting The Burden: the Global Campaign against Headache, Lenz B. , Katsarava Z. , Gil-Gouveia R. , Karelis G. , Kaynarkaya B. , Meksa L. , Oliveira E. , Palavra F. , Rosendo I. , Sahin M. , Silva B. , Uludüz D. , Ural Y. Z. , Varsberga-Apsite I. , Zengin S. T. , Zvaune L. , Steiner T. J.
Published: April 2021

Background

Lifting The Burden (LTB) and European Headache Federation (EHF) have developed a set of headache service quality indicators, successfully tested in specialist headache centres. Their intended application includes all levels of care. Here we assess their implementation in primary care.

Methods

We included 28 primary-care clinics in Germany (4), Turkey (4), Latvia (5) and Portugal (15). To implement the indicators, we interviewed 111 doctors, 92 nurses and medical assistants, 70 secretaries, 27 service managers and 493 patients, using the questionnaires developed by LTB and EHF. In addition, we evaluated 675 patients’ records. Enquiries were in nine domains: diagnosis, individualized management, referral pathways, patient education and reassurance, convenience and comfort, patient satisfaction, equity and efficiency of headache care, outcome assessment and safety.

Results

The principal finding was that Implementation proved feasible and practical in primary care. In the process, we identified significant quality deficits. Almost everywhere, histories of headache, especially temporal profiles, were captured and/or assessed inaccurately. A substantial proportion (20%) of patients received non-specific ICD codes such as R51 (“headache”) rather than specific headache diagnoses. Headache-related disability and quality of life were not part of routine clinical enquiry. Headache diaries and calendars were not in use. Waiting times were long (e.g., about 60 min in Germany). Nevertheless, most patients (> 85%) expressed satisfaction with their care. Almost all the participating clinics provided equitable and easy access to treatment, and follow-up for most headache patients, without unnecessary barriers.

Conclusions

The study demonstrated that headache service quality indicators can be used in primary care, proving both practical and fit for purpose. It also uncovered quality deficits leading to suboptimal treatment, often due to a lack of knowledge among the general practitioners. There were failures of process also. These findings signal the need for additional training in headache diagnosis and management in primary care, where most headache patients are necessarily treated. More generally, they underline the importance of headache service quality evaluation in primary care, not only to identify-quality failings but also to guide improvements.

This study also demonstrated that patients’ satisfaction is not, on its own, a good indicator of service quality.
Co-occurring hydrocephalus in autism spectrum disorder: a Danish population-based cohort study
Authors: Munch Tina Nørgaard , Hedley Paula Louise , Hagen Christian Munch , Bækvad-Hansen Marie , Bybjerg-Grauholm Jonas , Grove Jakob , Nordentoft Merete , Børglum Anders Dupont , Mortensen Preben Bo , Werge Thomas Mears , Melbye Mads , Hougaard David Michael , Christiansen Michael
Published: April 2021

Background

The association between autism spectrum disorder and hydrocephalus is not well understood, despite demonstrated links between autism spectrum disorder and cerebrospinal fluid abnormalities. Based on the hypothesis that autism spectrum disorder and hydrocephalus may, at least in some cases, be two manifestations of a shared congenital brain pathology, we investigated the potential association between autism spectrum disorder and hydrocephalus in a large Danish population-based cohort.

Methods

Patients and controls were obtained from the Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH2012 case-cohort, which includes all patients with selected psychiatric disorders born in Denmark 1981–2005 along with randomly selected population controls (end of follow-up, December 31, 2016). The associations between individual psychiatric disorders and hydrocephalus were estimated using binary logistic regression with adjustment for age and sex.

Results

The cohort consisted of 86,571 individuals, of which 14,654 were diagnosed with autism spectrum disorder, 28,606 were population controls, and the remaining were diagnosed with other psychiatric disorders. We identified 201 hydrocephalus cases; 68 among autism spectrum disorder patients and 40 among controls (OR 3.77, 95% CI 2.48–5.78), which corresponds to an absolute risk of 0.46 % (i.e. approximately one in 217 children with autism spectrum disorder had co-occurring hydrocephalus). The autism spectrum disorder-hydrocephalus association was significant over the entire subgroup spectrum of autism spectrum disorder.

Conclusions

Given the considerable risk of hydrocephalus among patients with autism spectrum disorder, we suggest that patients with autism spectrum disorder should be evaluated for co-occurring hydrocephalus on a routine basis as timely neurosurgical intervention is important. Likewise, attention must be paid to traits of autism spectrum disorder in children with hydrocephalus. The results of this study call for future investigations on a potential shared aetiology between hydrocephalus and autism spectrum disorder, including the role abnormal CSF dynamics in the pathogenesis of autism spectrum disorder.
Two VQ Proteins are Substrates of the OsMPKK6-OsMPK4 Cascade in Rice Defense Against Bacterial Blight
Authors: Li Na , Yang Zeyu , Li Juan , Xie Wenya , Qin Xiaofeng , Kang Yuanrong , Zhang Qinglu , Li Xianghua , Xiao Jinghua , Ma Haigang , Wang Shiping
Published: April 2021

Background

The plant-specific valine-glutamine (VQ) protein family with the conserved motif FxxxVQxLTG reportedly functions with the mitogen-activated protein kinase (MAPK) in plant immunity. However, the roles of VQ proteins in MAPK-mediated resistance to disease in rice remain largely unknown.

Results

In this study, two rice VQ proteins OsVQ14 and OsVQ32 were newly identified to function as the signaling components of a MAPK cascade, OsMPKK6-OsMPK4, to regulate rice resistance to Xanthomonas oryzae pv. oryzae (Xoo). Both OsVQ14 and OsVQ32 positively regulated rice resistance to Xoo. In vitro and in vivo studies revealed that OsVQ14 and OsVQ32 physically interacted with and were phosphorylated by OsMPK4. OsMPK4 was highly phosphorylated in transgenic plants overexpressing OsMPKK6, which showed enhanced resistance to Xoo. Meanwhile, phosphorylated OsVQ14 and OsVQ32 were also markedly accumulated in OsMPKK6-overexpressing transgenic plants.

Conclusions

We discovered that OsVQ14 and OsVQ32 functioned as substrates of the OsMPKK6-OsMPK4 cascade to enhance rice resistance to Xoo, thereby defining a more complete signal transduction pathway for induced defenses.
Variants at the ASIP locus contribute to coat color darkening in Nellore cattle
Authors: Trigo Beatriz B. , Utsunomiya Adam T. H. , Fortunato Alvaro A. A. D. , Milanesi Marco , Torrecilha Rafaela B. P. , Lamb Harrison , Nguyen Loan , Ross Elizabeth M. , Hayes Ben , Padula Rômulo C. M. , Sussai Thayla S. , Zavarez Ludmilla B. , Cipriano Rafael S. , Caminhas Maria M. T. , Lopes Flavia L. , Pelle Cassiano , Leeb Tosso , Bannasch Danika , Bickhart Derek , Smith Timothy P. L. , Sonstegard Tad S. , Garcia José F. , Utsunomiya Yuri T.
Published: April 2021

Background

Nellore cattle (Bos indicus) are well-known for their adaptation to warm and humid environments. Hair length and coat color may impact heat tolerance. The Nellore breed has been strongly selected for white coat, but bulls generally exhibit darker hair ranging from light grey to black on the head, neck, hump, and knees. Given the potential contribution of coat color variation to the adaptation of cattle populations to tropical and sub-tropical environments, our aim was to map positional and functional candidate genetic variants associated with darkness of hair coat (DHC) in Nellore bulls.

Results

We performed a genome-wide association study (GWAS) for DHC using data from 432 Nellore bulls that were genotyped for more than 777 k single nucleotide polymorphism (SNP) markers. A single major association signal was detected in the vicinity of the agouti signaling protein gene (ASIP). The analysis of whole-genome sequence (WGS) data from 21 bulls revealed functional variants that are associated with DHC, including a structural rearrangement involving ASIP (ASIP-SV1). We further characterized this structural variant using Oxford Nanopore sequencing data from 13 Australian Brahman heifers, which share ancestry with Nellore cattle; we found that this variant originates from a 1155-bp deletion followed by an insertion of a transposable element of more than 150 bp that may impact the recruitment of ASIP non-coding exons.

Conclusions

Our results indicate that the variant ASIP sequence causes darker coat pigmentation on specific parts of the body, most likely through a decreased expression of ASIP and consequently an increased production of eumelanin.
SMALF: miRNA-disease associations prediction based on stacked autoencoder and XGBoost
Authors: Liu Dayun , Huang Yibiao , Nie Wenjuan , Zhang Jiaxuan , Deng Lei
Published: April 2021

Background

Identifying miRNA and disease associations helps us understand disease mechanisms of action from the molecular level. However, it is usually blind, time-consuming, and small-scale based on biological experiments. Hence, developing computational methods to predict unknown miRNA and disease associations is becoming increasingly important.

Results

In this work, we develop a computational framework called SMALF to predict unknown miRNA-disease associations. SMALF first utilizes a stacked autoencoder to learn miRNA latent feature and disease latent feature from the original miRNA-disease association matrix. Then, SMALF obtains the feature vector of representing miRNA-disease by integrating miRNA functional similarity, miRNA latent feature, disease semantic similarity, and disease latent feature. Finally, XGBoost is utilized to predict unknown miRNA-disease associations. We implement cross-validation experiments. Compared with other state-of-the-art methods, SAMLF achieved the best AUC value. We also construct three case studies, including hepatocellular carcinoma, colon cancer, and breast cancer. The results show that 10, 10, and 9 out of the top ten predicted miRNAs are verified in MNDR v3.0 or miRCancer, respectively.

Conclusion

The comprehensive experimental results demonstrate that SMALF is effective in identifying unknown miRNA-disease associations.
Shifting the microbiome of a coral holobiont and improving host physiology by inoculation with a potentially beneficial bacterial consortium
Authors: Zhang Ying , Yang Qingsong , Ling Juan , Long Lijuan , Huang Hui , Yin Jianping , Wu Meilin , Tang Xiaoyu , Lin Xiancheng , Zhang Yanying , Dong Junde
Published: April 2021

Background

The coral microbiome plays a key role in host health by being involved in energy metabolism, nutrient cycling, and immune system formation. Inoculating coral with beneficial bacterial consortia may enhance the ability of this host to cope with complex and changing marine environments. In this study, the coral Pocillopora damicornis was inoculated with a beneficial microorganisms for corals (BMC) consortium to investigate how the coral host and its associated microbial community would respond.

Results

High-throughput 16S rRNA gene sequencing revealed no significant differences in bacterial community α-diversity. However, the bacterial community structure differed significantly between the BMC and placebo groups at the end of the experiment. Addition of the BMC consortium significantly increased the relative abundance of potentially beneficial bacteria, including the genera Mameliella and Endozoicomonas. Energy reserves and calcification rates of the coral host were also improved by the addition of the BMC consortium. Co-occurrence network analysis indicated that inoculation of coral with the exogenous BMC consortium improved the physiological status of the host by shifting the coral-associated microbial community structure.

Conclusions

Manipulating the coral-associated microbial community may enhance the physiology of coral in normal aquarium conditions (no stress applied), which may hypothetically contribute to resilience and resistance in this host.
Timeliness of contact tracing among flight passengers during the COVID-19 epidemic in Vietnam
Authors: Pham Thai Quang , Hoang Ngoc-Anh , Quach Ha-Linh , Nguyen Khanh Cong , Colquhoun Samantha , Lambert Stephen , Duong Luong Huy , Tran Quang Dai , Ha Duc Anh , Phung Dinh Cong , Ngu Nghia Duy , Tran Tu Anh , La Quang Ngoc , Nguyen Tai Trong , Le Quynh Mai Thi , Tran Duong Nhu , Vogt Florian , Dang Duc-Anh
Published: April 2021

Background

International air travel plays an important role in the global spread of SARS-CoV-2, and tracing of close contacts is an integral part of the public health response to COVID-19. We aimed to assess the timeliness of contact tracing among airline passengers arriving in Vietnam on flights containing COVID-19 cases and investigated factors associated with timeliness of contact tracing.

Methods

We included data from 2228 passengers on 22 incoming flights between 2 and 19 March 2020. Contact tracing duration was assessed separately for the time between the date of index case confirmation and date of contact tracing initiation (interval I), and the date of contact tracing initiation and completion (interval II). We used log-rank tests and multivariable Poisson regression models to identify factors associated with timeliness.

Results

The median duration of interval I and interval II was one (IQR: 1–2) and 3 days (IQR: 2–5), respectively. The contact tracing duration was shorter for passengers from flights where the index case was identified through mandatory testing directly upon arrival (median = 4; IQR: 3–5) compared to flights with index case detection through self-presentation at health facilities after arrival (median = 7; IQR: 5–8) (p-value = 0.018). Cumulative hazards for successful tracing were higher for Vietnamese nationals compared to non-Vietnamese nationals (p < 0.001).

Conclusions

Contact tracing among flight passengers in the early stage of the COVID-19 epidemic in Vietnam was timely though delays occurred on high workload days. Mandatory SARS-CoV-2 testing at arrival may reduce contact tracing duration and should be considered as an integrated screening tool for flight passengers from high-risk areas when entering low-transmission settings with limited contact tracing capacity. We recommend a standardized risk-based contact tracing approach for flight passengers during the ongoing COVID-19 epidemic.
Locoregional recurrence via mucus-mediated extension following lung resection for mucinous tumors
Authors: Kawaguchi Yo , Hanaoka Jun , Ohshio Yasuhiko , Okamoto Keigo , Kaku Ryosuke , Hayashi Kazuki , Shiratori Takuya , Akazawa Akira , Ishida Mitsuaki
Published: April 2021

Background

Clinically, locoregional recurrences following mucinous tumor resection are often experienced. However, it remains unclear whether mucinous tumors directly affect local recurrence or not, and if so, the mechanism is not known. Therefore, we investigated whether mucinous tumors are associated with locoregional recurrence after pulmonary resection and whether mucus extension is a risk factor for locoregional recurrence.

Methods

The data of 152 patients who underwent pulmonary resection for metastases were reviewed. When mucus was partially or wholly present in the tumor based on macro- or microscopic identification, we assigned the tumor as mucinous. In mucinous tumors, when mucus was identified within the air spaces in the normal lung parenchyma, beyond the edge of the tumor, we assigned the tumor as positive for “mucus extension.”

Results

The 5-year cumulative incidence of locoregional recurrence in patients with mucinous tumors was 48.1%, which was significantly higher than that observed in those with non-mucinous tumors (14.9%). Within the mucinous tumor, the presence of mucus extension beyond the tumor edge was an independent risk factor for locoregional recurrence after pulmonary resection (hazard ratio, 5.52; P = 0.019).

Conclusions

During the resection of mucinous cancer, surgeons should maintain sufficient distance from the tumor edge to prevent locoregional recurrences.
Bidirectional association of neurodevelopment with growth: a prospective cohort study
Authors: Wei Xiaotong , Hu Jiajin , Yang Liu , Gao Ming , Li Lin , Ding Ning , Ma Yanan , Wen Deliang
Published: April 2021

Background

The study aims to use the cross-lagged model and utilize data from the Born in Shenyang Cohort Study to characterize the bidirectional associations of the term-born infants’ neurodevelopment in five domains and physical growth in early life.

Method

This study consists of 688 mother-child dyads from the Born in Shenyang Cohort Study. Infants’ anthropometric (weight and length) and development in neurological outcomes (Gesell Development Scale) were measured at the age of 6 and 12 months. Cross-lagged analyses and multiple linear regression analyses were used to explore the longitudinal relationships in both directions.

Results

In terms of longitudinal studies, the inverse associations between infants’ two skills (gross motor and social behavior) at the age of 6 months with BMI Z -scores at the age of 12 months (gross motor: aβ = − 0.20, 95% CI: − 0.31 to- 0.09; social behavior: aβ = − 0.23, 95% CI: − 0.33 to- 0.13) were found. Conversely, a higher infant Z -scored BMI at the age of 6 months predicted a lower gross motor at the age of 12 months (aβ = − 0.08, 95% CI: − 0.12 to- 0.04). In cross-lagged analyses, an adverse association in both directions between gross motor and Z -scored BMI was observed.

Conclusion

We found bidirectional relationships between infants’ neurodevelopment of gross motor with physical growth and suggested the term-born infants, who are on the edge of the developmental danger, should not be overlooked.
Experimental observation of the sequence of tibial plateau chondrocyte and matrix degeneration in spontaneous osteoarthritis in Guinea pigs
Authors: Wang Xiao-jian , Wei Lei , Xue Yan , Li Rong-shan
Published: April 2021

Background

To observe the sequence of chondrocyte degeneration and matrix degradation in the superficial surface cartilage of the tibial plateau in guinea pigs with spontaneous knee osteoarthritis (OA).

Methods

Sixty guinea pigs were euthanized at the ages of 8 months (n = 20),10 months (n = 20) and 12 months (n = 20) respectively. The degree of degeneration of the tibial plateau cartilage was evaluated by Osteoarthritis Research Society International (OARSI) score. The levels of Aggrecan,CollagenX,MMP-13 and Caspase-3 in the chondrocytes were detected by immunohistochemistry (IHC). The serum concentration of CTX-II was measured and compared. Western blot analysis was used to detect the levels of Aggrecan,CollagenX,MMP-13 and Caspase-3 in the cartilage tissue.

Results

The OARSI scores both in 8-month-old group and 10-month-old group were lower than that in the 12-month-old group. The levels of Aggrecan in articular chondrocyte were higher both in 8-month-old group and 10-month-old group than that in 12-month-old group. The level of Collagen X increased with the age of guinea pigs. And the levels of MMP-13 and caspase-3 both in 10-month-old group and 12-month-old group were higher than those in 8-month-old group. The concentration of CTX-II in serum increased significantly in 12 months old group.

Conclusion

The superficial chondrocytes of the tibial plateau first appeared to be hypertrophic and then apoptotic, and the matrix was further degraded when spontaneous knee osteoarthritis occurred in guinea pigs. Changes in the physiological state of chondrocytes are the initiating factors in the pathogenesis of knee OA.
Estimating the effectiveness of routine asymptomatic PCR testing at different frequencies for the detection of SARS-CoV-2 infections
Authors:   The SAFER Investigators and Field Study Team, Hellewell Joel ,   The Crick COVID-19 Consortium,   CMMID COVID-19 working group, Russell Timothy W. , Beale Rupert , Kelly Gavin , Houlihan Catherine , Nastouli Eleni , Kucharski Adam J.
Published: April 2021

Background

Routine asymptomatic testing using RT-PCR of people who interact with vulnerable populations, such as medical staff in hospitals or care workers in care homes, has been employed to help prevent outbreaks among vulnerable populations. Although the peak sensitivity of RT-PCR can be high, the probability of detecting an infection will vary throughout the course of an infection. The effectiveness of routine asymptomatic testing will therefore depend on testing frequency and how PCR detection varies over time.

Methods

We fitted a Bayesian statistical model to a dataset of twice weekly PCR tests of UK healthcare workers performed by self-administered nasopharyngeal swab, regardless of symptoms. We jointly estimated times of infection and the probability of a positive PCR test over time following infection; we then compared asymptomatic testing strategies by calculating the probability that a symptomatic infection is detected before symptom onset and the probability that an asymptomatic infection is detected within 7 days of infection.

Results

We estimated that the probability that the PCR test detected infection peaked at 77% (54–88%) 4 days after infection, decreasing to 50% (38–65%) by 10 days after infection. Our results suggest a substantially higher probability of detecting infections 1–3 days after infection than previously published estimates. We estimated that testing every other day would detect 57% (33–76%) of symptomatic cases prior to onset and 94% (75–99%) of asymptomatic cases within 7 days if test results were returned within a day.

Conclusions

Our results suggest that routine asymptomatic testing can enable detection of a high proportion of infected individuals early in their infection, provided that the testing is frequent and the time from testing to notification of results is sufficiently fast.
Prognostic value of SH3PXD2B (Tks4) in human hepatocellular carcinoma: a combined multi-omics and experimental study
Authors: Kui Xiang , Wang Yan , Zhang Cheng , Li Hai , Li Qingfeng , Ke Yang , Wang Lin
Published: April 2021

Background

Hepatocellular carcinoma (HCC) is one of the most common and fatal cancers worldwide. HCC invasion and metastasis are crucial for its poor prognosis. SH3PXD2B is a scaffold protein and critical for intravascular and extravascular invasion and metastasis of various types of tumors. However, the role of SH3PXD2B in HCC progression remains unclear.

Methods

The levels of SH3PXD2B mRNA transcripts in the TCGA database and SH3PXD2B protein expression in the Human Protein Atlas were analyzed. Furthermore, the levels of SH3PXD2B expression in clinical samples were analyzed by quantitative RT-PCR and immunohistochemistry. The potential association of the levels of SH3PXD2B expression with clinicopathological characteristics, overall survival (OS), and recurrence-free survival (RFS) of HCC patients was analyzed. The impact of SH3PXD2B silencing by shRNA-based lentivirus transduction on the proliferation and invasion of human HCC Hep3B and Huh7 cells was determined.

Results

SH3PXD2B expression was up-regulated in HCC tissues in the TCGA and Human Protein Atlas as well as clinical samples, relative to that of non-tumor liver samples. The levels of SH3PXD2B expression in HCC tissues were significantly associated with higher HBV infection rate, higher HCC grades and TNM stages, higher Ki-67 expression, higher serum α-fetoprotein (AFP), a shorter OS and RFS of HCC patients. Functionally, SH3PXD2B silencing significantly inhibited the formation and function of invadopodia and the invasion of Hep3B and Huh7 cells, but did not affect their proliferation in vitro.

Conclusions

Our data suggest that SH3PXD2B may promote the invasion and metastasis of HCC and be a valuable therapeutic target and biomarker for treatment and prognosis of HCC.
RhoA: a dubious molecule in cardiac pathophysiology
Authors: Kilian Lucia Sophie , Voran Jakob , Frank Derk , Rangrez Ashraf Yusuf
Published: April 2021

The Ras homolog gene family member A (RhoA) is the founding member of Rho GTPase superfamily originally studied in cancer cells where it was found to stimulate cell cycle progression and migration. RhoA acts as a master switch control of actin dynamics essential for maintaining cytoarchitecture of a cell. In the last two decades, however, RhoA has been coined and increasingly investigated as an essential molecule involved in signal transduction and regulation of gene transcription thereby affecting physiological functions such as cell division, survival, proliferation and migration. RhoA has been shown to play an important role in cardiac remodeling and cardiomyopathies; underlying mechanisms are however still poorly understood since the results derived from in vitro and in vivo experiments are still inconclusive. Interestingly its role in the development of cardiomyopathies or heart failure remains largely unclear due to anomalies in the current data available that indicate both cardioprotective and deleterious effects. In this review, we aimed to outline the molecular mechanisms of RhoA activation, to give an overview of its regulators, and the probable mechanisms of signal transduction leading to RhoA activation and induction of downstream effector pathways and corresponding cellular responses in cardiac (patho)physiology. Furthermore, we discuss the existing studies assessing the presented results and shedding light on the often-ambiguous data. Overall, we provide an update of the molecular, physiological and pathological functions of RhoA in the heart and its potential in cardiac therapeutics.
Integrated analysis of potential pathways by which aloe-emodin induces the apoptosis of colon cancer cells
Authors: Jiang Dongxiao , Ding Shufei , Mao Zhujun , You Liyan , Ruan Yeping
Published: April 2021

Background

Colon cancer is a malignant gastrointestinal tumour with high incidence, mortality and metastasis rates worldwide. Aloe-emodin is a monomer compound derived from hydroxyanthraquinone. Aloe-emodin produces a wide range of antitumour effects and is produced by rhubarb, aloe and other herbs. However, the mechanism by which aloe-emodin influences colon cancer is still unclear. We hope these findings will lead to the development of a new therapeutic strategy for the treatment of colon cancer in the clinic.

Methods

We identified the overlapping targets of aloe-emodin and colon cancer and performed protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. In addition, we selected apoptosis pathways for experimental verification with cell viability, cell proliferation, caspase-3 activity, DAPI staining, cell cycle and western blotting analyses to evaluate the apoptotic effect of aloe-emodin on colon cancer cells.

Results

The MTT assay and cell colony formation assay showed that aloe-emodin inhibited cell proliferation. DAPI staining confirmed that aloe-emodin induced apoptosis. Aloe-emodin upregulated the protein level of Bax and decreased the expression of Bcl-2, which activates caspase-3 and caspase-9. Furthermore, the protein expression level of cytochrome C increased in a time-dependent manner in the cytoplasm but decreased in a time-dependent manner in the mitochondria.

Conclusion

These results indicate that aloe-emodin may induce the apoptosis of human colon cancer cells through mitochondria-related pathways.
Perceptions and prevention practices on malaria among the indigenous Orang Asli community in Kelantan, Peninsular Malaysia
Authors: Munajat Mohd Bakhtiar , Rahim Mohd Amirul Fitri A. , Wahid Wathiqah , Seri Rakna Mohd Ikhwan Mukmin , Divis Paul C. S. , Chuangchaiya Sriwipa , Lubis Inke Nadia D. , Osman Emelia , Mohd Kasri Muhd Rafiq , Idris Zulkarnain Md
Published: April 2021

Background

Malaysia is on track towards malaria elimination. However, several cases of malaria still occur in the country. Contributing factors and communal aspects have noteworthy effects on any malaria elimination activities. Thus, assessing the community’s knowledge, attitudes and practices (KAP) towards malaria is essential. This study was performed to evaluate KAP regarding malaria among the indigenous people (i.e. Orang Asli) in Peninsular Malaysia.

Methods

A household-based cross-sectional study was conducted in five remote villages (clusters) of Orang Asli located in the State of Kelantan, a central region of the country. Community members aged six years and above were interviewed. Demographic, socio-economic and KAP data on malaria were collected using a structured questionnaire and analysed using descriptive statistics.

Results

Overall, 536 individuals from 208 households were interviewed. Household indoor residual spraying (IRS) coverage and bed net ownership were 100% and 89.2%, respectively. A majority of respondents used mosquito bed nets every night (95.1%), but only 50.2% were aware that bed nets were used to prevent malaria. Nevertheless, almost all of the respondents (97.9%) were aware that malaria is transmitted by mosquitoes. Regarding practice for managing malaria, the most common practice adopted by the respondents was seeking treatment at the health facilities (70.9%), followed by self-purchase of medication from a local shop (12.7%), seeking treatment from a traditional healer (10.5%) and self-healing (5.9%). Concerning potential zoonotic malaria, about half of the respondents (47.2%) reported seeing monkeys from their houses and 20.1% reported entering nearby forests within the last 6 months.

Conclusion

This study found that most populations living in the villages have an acceptable level of knowledge and awareness about malaria. However, positive attitudes and practices concerning managing malaria require marked improvement.
Practical implications of naloxone knowledge among suburban people who use opioids
Authors: Schneider Kristin E. , Urquhart Glenna J. , Rouhani Saba , Park Ju Nyeong , Morris Miles , Allen Sean T. , Sherman Susan G.
Published: April 2021

Background

Naloxone distribution programs have been a cornerstone of the public health response to the overdose crisis in the USA. Yet people who use opioids (PWUO) continue to face a number of barriers accessing naloxone, including not knowing where it is available.

Methods

We used data from 173 PWUO from Anne Arundel County, Maryland, which is located between Baltimore City and Washington, DC. We assessed the prevalence of recently (past 6 months) receiving naloxone and currently having naloxone, the type(s) of the naloxone kits received, and the perceived ease/difficultly of accessing naloxone. We also assessed participants knowledge of where naloxone was available in the community.

Results

One third (35.7%) of participants had recently received naloxone. Most who had received naloxone received two doses (72.1%), nasal naloxone (86.9%), and education about naloxone use (72.1%). Most currently had naloxone in their possession (either on their person or at home; 78.7%). One third (34.4%) believed naloxone was difficult to obtain in their community. Only half (56.7%) knew of multiple locations where they could get naloxone. The health department was the most commonly identified naloxone source (58.0%). Identifying multiple sources of naloxone was associated with being more likely to perceive that naloxone is easy to access.

Discussion

Our results suggest that additional public health efforts are needed to make PWUO aware of the range of sources of naloxone in their communities in order to ensure easy and continued naloxone access to PWUO.
Transplantation of mesenchymal stem cells for spinal cord injury: a systematic review and network meta-analysis
Authors: Chen Wei-can , Liu Wei-feng , Bai Yu-yan , Zhou Ying-ying , Zhang Yan , Wang Cong-mei , Lin Shu , He He-fan
Published: April 2021

Spinal cord injury (SCI) is a severe traumatic disease of the central nervous system, with a global prevalence of 236–4187 per million people. This meta-analysis aimed to evaluate the safety and efficacy of mesenchymal stem cells (MSCs) in treating patients with SCI as well as the optimal source and transplantation method of MSCs. PubMed, OVID, Cochrane, Web of Science, and China Biomedical Database were searched up until April 01, 2021. The study was conducted for five endpoints: American Spinal Injury Association (ASIA) motor and sensory score, ASIA grade improvement, Barthel Index (BI), and adverse reactions. Standard meta-analysis and network meta-analysis were performed using Stata 14.0. Eighteen studies with a total of 949 patients, were included in the meta-analysis. Standard meta-analysis showed that MSCs significantly improved ASIA motor score (P < 0.001), sensory score (P < 0.001), ASIA grade (P < 0.001), and BI (P < 0.001) compared to rehabilitation. In addition, in the network meta-analysis, autologous MSCs significantly improved the ASIA motor [MD = 8.01, 95% CI (4.27, 11.76)], sensory score [MD = 17.98, 95% CI (10.04, 25.91)], and BI [MD = 7.69, 95% CI (2.10, 13.29)] compared to rehabilitation. Similarly, compared to rehabilitation, intrathecal injection (IT) of MSCs significantly improved the ASIA motor [MD = 7.97, 95% CI (4.40, 11.53)] and sensory score [MD = 19.60, 95% CI (9.74, 29.46)]. Compared to rehabilitation, however, only the IL of MSCs was associated with more adverse reactions [OR = 17.82, 95% CI (2.48, 128.22)]. According to the results of SUCRA, both autologous MSCs and IT transplantation approaches most improved the neurological function in SCI patients. Cell transplantation using MSCs is effective in patients with SCI and IT of autologous MSCs may be more beneficial.
Establishment and evaluation of a rat model of extracorporeal membrane oxygenation (ECMO) thrombosis using a 3D-printed mock-oxygenator
Authors: Umei Nao , Lai Angela , Miller Jennifer , Shin Suji , Roberts Kalliope , AI Qatarneh Saif , Ichiba Shingo , Sakamoto Atsuhiro , Cook Keith E.
Published: April 2021

Background

Extracorporeal membrane oxygenation (ECMO) research using large animals requires a significant amount of resources, slowing down the development of new means of ECMO anticoagulation. Therefore, this study developed and evaluated a new rat ECMO model using a 3D-printed mock-oxygenator.

Methods

The circuit consisted of tubing, a 3D-printed mock-oxygenator, and a roller pump. The mock-oxygenator was designed to simulate the geometry and blood flow patterns of the fiber bundle in full-scale oxygenators but with a low (2.5 mL) priming volume. Rats were placed on arteriovenous ECMO at a 1.9 mL/min flow rate at two different heparin doses (n = 3 each): low (15 IU/kg/h for eight hours) versus high (50 IU/kg/h for one hour followed by 25 IU/kg/h for seven hours). The experiment continued for eight hours or until the mock-oxygenator failed. The mock-oxygenator was considered to have failed when its blood flow resistance reached three times its baseline resistance.

Results

During ECMO, rats maintained near-normal mean arterial pressure and arterial blood gases with minimal hemodilution. The mock-oxygenator thrombus weight was significantly different (p < 0.05) between the low (0.02 ± 0.006 g) and high (0.003 ± 0.001 g) heparin delivery groups, and blood flow resistance was also larger in the low anticoagulation group.

Conclusions

This model is a simple, inexpensive system for investigating new anticoagulation agents for ECMO and provides low and high levels of anticoagulation that can serve as control groups for future studies.