bluuebunny/crossref_metadata_2025 huggingface dataset:
Implant Removal Versus Implant Retention Following Posterior Surgical Stabilization of Thoracolumbar Burst Fractures: A Systematic Review and Meta-Analysis
Authors: Kweh Barry Ting Sheen , Tan Terence , Lee Hui Qing , Hunn Martin , Liew Susan , Tee Jin Wee
Published: April 2021

Study Design:

Systematic review and meta-analysis.

Objectives:

To compare biomechanical and functional outcomes between implant removal and implant retention following posterior surgical fixation of thoracolumbar burst fractures.

Methods:

A search of the MEDLINE, EMBASE, Google Scholar and Cochrane Databases was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.

Results:

Of the 751 articles initially retrieved, 13 published articles pooling 673 patients were included. Meta-analysis revealed there was a statistically significant improvement in sagittal Cobb Angle by 16.48 degrees (9.13-23.83, p < 0.01) after surgical stabilization of thoracolumbar burst fractures. This correction decremented to 9.68 degrees (2.02-17.35, p < 0.01) but remained significant at the time of implant removal approximately 12 months later. At final follow-up, the implant removal group demonstrated a 10.13 degree loss (3.00-23.26, p = 0.13) of reduction, while the implant retention group experienced a 10.17 degree loss (1.79-22.12, p = 0.10). There was no statistically significant difference in correction loss between implant retention and removal cohorts (p = 0.97). Pooled VAS scores improved by a mean of 3.32 points (0.18 to 6.45, p = 0.04) in the combined removal group, but by only 2.50 points (-1.81 to 6.81, p = 0.26) in the retention group. Oswestry Disability Index scores also improved after implant removal by 7.80 points (2.95-12.64, p < 0.01) at 1 year and 11.10 points (5.24-16.96, p < 0.01) at final follow-up.

Conclusions:

In younger patients with thoracolumbar burst fractures who undergo posterior surgical stabilization, planned implant removal results in superior functional outcomes without significant difference in kyphotic angle correction loss compared to implant retention.
Human decellularized adipose tissue hydrogels as a culture platform for human adipose-derived stem cell delivery
Authors: Pu Wenwen , Han Yan , Yang Mingyong
Published: April 2021

Adipose-derived stem cells (ADSCs) have been widely researched and used as a drug therapy in many fields like disease treatment and tissue engineering. However, ADSCs are susceptible to the surrounding environment. The emergence of acellular extracellular matrix provides a solution, which can serve as biomaterial scaffold as well as original ecological niche for the stem cells. Therefore, we propose the hypothesis that human decellularized adipose tissues (hDAT) are processed into injectable hydrogels and then mixed evenly with ADSCs. So that the ADSCs embedded-hydrogels could directly carry the stem cells to the appropriate sites. The hDAT hydrogel could provide microenvironmental protection for ADSCs. In this study, we successfully made human decellularized adipose tissue hydrogel (hDAT-gel), which was temperature-sensitive, liquid at 4°C and semi-solid at 37°C. When the ADSCs were embedded in hDAT-gel, they survived well and continued to grow well in layers. When the pre-gel containing ADSCs was injected subcutaneously into nude mice, the sample results after 15 min showed gelation occurred in situ. These results suggested that hDAT-gel could provide a culture platform for ADSCs delivery.
Book review: D. N. Sansanwal, Research Methodology and Applied Statistics
Authors: Majid Ishfaq , Kouser Shazia
Published: April 2021

D. N. Sansanwal, Research Methodology and Applied Statistics. New Delhi: Shipra Publications, 2020, pp. 302, ₹395, ISBN: 978-93-88691-55-0..
Macroeconomic State Variables and Stock Market Performance: A Systematic Review and Future Research Agenda
Authors: Lone Umer Mushtaq , Darzi Mushtaq Ahmad , Bhat Suhail Ahmad
Published: April 2021

The current study presents a systematic review of macroeconomic risk factors and stock market performance under the broader theme of multi-factor asset pricing or the Arbitrage Pricing Theory (APT). Based on the review of relevant literature, the study summarizes key findings of different research works and identifies significant research gaps that need to be addressed by future research. It assesses the state of published work in the domain of asset pricing by systematically analyzing 116 research articles. The research works whose focal point has been asset pricing have been retrieved from leading databases and journals related to financial economics for the period 1976–2019. The study provides a comprehensive look at the conceptual, theoretical, and methodological (or empirical) developments and patterns prevalent at the aggregate level. The implications of the study hold key importance for academia or future researchers, policy-makers and most importantly the investors for guiding their investment decisions efficiently.
Vitamin D Intoxication Presenting as Subacute Encephalopathy—A Case Report
Authors: Tripty Naik , Tushar Jagzape , Sunil Jondhale
Published: April 2021

Vitamin D intoxication is uncommon in children and is more commonly suspected in the setting of ingestion of high doses of vitamin D. Its manifestations can be non specific and varied ranging from mild like constipation and vomiting to life threatening like arrhythmias and encephalopathy. Here we present a 14 month female who presented with loss of milestones, floppiness, and poor interaction with mother. She was detected to have hypercalcemia and was subsequently diagnosed with vitamin D intoxication. She was successfully treated with hydration, furosemide, prednisolone and frequent monitoring of electrolytes, electrocardiography and volume status. Subsequently as her serum calcium levels normalized with therapy, she became alert, conscious and started achieving developmental milestones.
Correlation between Insulin-Like Growth Factor I and Skeletal Maturity Indicators
Authors: Carelli Julia , Mattos Camila , Morais Nathaly D. , Scariot Rafaela , Brancher João Armando , Baratto-Filho Flares , Kuchler Erika Calvano , Moro Alexandre
Published: April 2021

Objective: The purpose of this study was to evaluate the correlation between the growth maturity indicators in orthodontic patients. Design: This cross-sectional study was performed on 37 orthodontic patients (17 males and 20 females). An anamnesis, clinical and image examination, and blood sample collection were performed. The inclusion criteria were non-syndromic Class II patients of both gender, age ranging between 10 to 16 years. The lateral cephalometric radiographs were evaluated using 6-stage cervical vertebrae maturation (CVM) technique. The hand-wrist radiographs were staged using the 11-stage skeletal maturation indicator (SMI) technique. Blood was collected in the same week of the images to quantify IGF-1 levels in serum. Data were tested for normality by Shapiro–Wilk test. The Pearson test was used to determine the correlation strength between the variables (alpha of 5%). Results: A strong correlation was observed only between SMI stages and CVM stages in the total sample (r=0.864; p<0.0001) and according to the gender (r=0.793; p<0.0001 for females; and r=0.753; p<0.0001 for males). IGF-1 was only moderately correlated with SMI stages and CVM stages. Conclusion: Hand-wrist and cervical vertebral stages were strongly correlated among them, however, IGF-1 was only moderately correlated with both skeletal maturity indicators.
College-Going in the Era of High Expectations: Racial/Ethnic Disparities in College Enrollment, 2006 to 2015
Authors: Villalobos Amber D.
Published: April 2021

Adolescents with high educational expectations are more likely to enroll in college. Although most adolescents today report high educational expectations, there remains important racial/ethnic heterogeneity in college enrollment patterns. In particular, at every level of socioeconomic status, minority youth have higher educational expectations than their white peers yet enroll in college at lower rates. The rapidly increasing size and college enrollment of the Hispanic population motivate renewed examination of the expectation-enrollment relationship. Using data from the Education Longitudinal Study (ELS) and the High School Longitudinal Study (HSLS), the author examines whether the relationship between adolescent educational expectations and enrollment in a four-year college within two years of high school graduation differs by race/ethnicity and whether this relationship changed over time. The author finds that the expectation-enrollment relationship is positive for all students but is smaller for black and Hispanic students in the ELS cohort. However, by the HSLS cohort, the gaps have largely closed.
Two Cases of Tuberous Sclerosis With Multiple Rhabdomyoma Succumbing to Sudden Cardiac Death
Authors: Mahadevappa Manjappa , Patil Vikram , Poornima K.S. , Velamala Sowmya , Guruprasad B.V.
Published: April 2021

Tuberous sclerosis complex is an autosomal dominant condition with variable penetrance. It is characterized by tuberose deposits in various organ systems. Although clinical features predominate neurocutaneous manifestations, cardiac, kidney, and lung involvement are common. Cardiac involvement is marked by the presence of multiple rhabdomyomas and in some cases arrhythmias. In the absence of symptoms, rhabdomyomas require no specific treatment. However, cardiac arrhythmias are unpredictable and may be the cause of sudden cardiac death in some cases. Although treatment is mainly symptomatic, drugs like rapamycin have shown promise in the regression of astrocytomas and angiofibromas. Here, we are reporting two cases of tuberous sclerosis of which one succumbed to arrhythmias and the other to possible sudden cardiac death.
Responsibility inoculation: Constructing ‘good parent’ accounts when accessing child mental health services
Authors: O’Reilly Michelle , Kiyimba Nikki
Published: April 2021

With the prevalence of child mental health conditions rising, the role of the initial mental health assessment is crucial in determining need. Utilising a critical discursive analytic framework, we explored the ways in which parents during these mental health assessments constructed the child’s difficulties as medicalised and doctorable as opposed to systemic and familial. Through this discursive positioning, we examined the ways in which parents mitigated blame and accounted for the child’s behaviours and emotions. Parents engaged in three accounting practices to construct the child’s problems as dispositional and to mitigate against an alternative familial system interpretation. First, they drew upon normative cultural repertoires of parenting. Second, they mediated ways whereby normative practices were deviated from in the best interest of the child. Third, they rhetorically positioned overcoming systemic difficulties by illustrating cooperative parenting in separated families. Our findings have implications for how parents build a case for the need for medical intervention in assessment settings.
Development of an Emergency Revisit Score for Patients With Drug-Related Problems
Authors: Ruiz Ramos Jesus , Gras-Martin Laura , Juanes Borrego Ana María , Blazquez-Andion Marta , Puig Campmany Mireia , Mangues-Bafalluy Maria Antonia
Published: April 2021

Background: Drug-related problems (DRPs) are a frequent reason for emergency departments (EDs) visits. However, data about the risk factors associated with EDs revisits are limited. Objective: To develop and validate a predictive model indicating the risk factors associated with EDs revisit within 30 days of the first visit. Methods: A retrospective cohort study was conducted involving patients who attended an ED for DRPs related to cardiovascular drugs. A 30-day prediction model was created in a derivation cohort by logistic regression. An integer score proportional to the regression coefficient was assigned to the variables with P < .100 in the multivariate analysis. Results: 581 patients (mean age: 80.0 [12.6] years) were included, 133 (22.9%) revisited the ED within 30 days from discharge. Six factors (chronic kidney disease, chronic heart failure, visit to an ED in the preceding 3 months, high anticholinergic burden, DRPs associated with heparin, and safety-related DRPs) were identified as risk factors and combined into a final score, termed the DREAMER score. The model reached an area under the receiver operating curve values of 0.72 (95% confidence interval [CI] = 0.67-0.77) in the referral cohort and 0.71 (95% CI = 0.65-0.74) in the validation cohort ( P = .273). Three risk categories were generated, with the following scores and estimated risks: low risk (0-8 points): 11.6%; intermediate risk (9-14 points): 21.3%; and high risk (>14 points): 41.2%. Conclusion and Relevance: The DREAMER score identifies patients at high risk for ED revisit within 30 days from the first visit for a DRPs, being a useful tool to prioritize interventions on discharge.
Microwave-Assisted Chitosan-Functionalized Graphene Oxide as Controlled Intracellular Drug Delivery Nanosystem for Synergistic Antitumour Activity
Authors: Shu Mengjun , Gao Feng , Zeng Min , Yu Chulang , Wang Xue , Huang Renhua , Yang Jianhua , Su Yanjie , Hu Nantao , Zhou Zhihua , Liu Ke , Yang Zhi , Tan Hongtao , Xu Lin
Published: April 2021

To achieve better antitumour efficacy, it is urgent to improve anticancer drug delivery efficiency in targeting cancer cells. In this work, chitosan-functionalized graphene oxide (ChrGO) nanosheets were fabricated via microwave-assisted reduction, which were employed to the intracellular delivery nanosystem for anticancer drug agent in breast cancer cells. Drug loading and release research indicated that adriamycin can be efficiently loaded on and released from the ChrGO nanosheets. Less drug release during delivery and better biocompatibility of ChrGO/adriamycin significantly improve its safety and therapeutic efficacy in HER2-overexpressing BT-474 cells. Furthermore, ChrGO/adriamycin in combination with trastuzumab exhibited synergistic antitumour activity in BT-474 cells, which demonstrated superior therapeutic efficacy compared with each drug alone. Cells treated with trastuzumab (5 μg/mL) or equivalent ChrGO/adriamycin (5 μg/mL) each elicited 54.5% and 59.5% cell death, respectively, while the combination treatment with trastuzumab and ChrGO/adriamycin resulted in a dramatic 88.5% cell death. The dual-targeted therapy displayed higher apoptosis, indicating superior therapeutic efficacy due to the presence of different mechanisms of action. The combined treatment of ChrGO/adriamycin and trastuzumab in BT-474 cells induced cell cycle arrest and apoptosis, which ultimately led to the death of augmented cancer cells. This work has provided a facile microwave-assisted fabrication of ChrGO as a controlled and targeted intracellular drug delivery nanosystem, which is expected to be a novel promising therapy for treating HER2-overexpressing breast cancer cells.
Hypokalaemic paralysis and metabolic alkalosis in a patient with Sjögren syndrome: a case report and literature review
Authors: Ranaweerage Rasika , Perera Shehan , Gunapala Aruna
Published: April 2021

Background

Acquired Gitelman syndrome is a very rare disorder reported in association with autoimmune disorders, mostly Sjögren syndrome. It is characterized by the presence of hypokalaemic metabolic alkalosis, hypocalciuria, hypomagnesaemia and hyper-reninaemia, in the absence of typical genetic mutations associated with inherited Gitelman syndrome.

Case presentation

A 20 year old woman who was previously diagnosed with primary Sjögren syndrome and autoimmune thyroiditis presented with two week history of lower limb weakness and salt craving. Examination revealed upper limb and lower limb muscle weakness with muscle power of 3/5 on MRC scale and diminished deep tendon reflexes. On evaluation, she had hypokalaemia with high trans-tubular potassium gradient, metabolic alkalosis and hypocalciuria, features suggestive of Gitelman syndrome. New onset hypokalaemic alkalosis in a previously normokalaemic patient with Sjögren syndrome strongly favored a diagnosis of acquired Gitelman syndrome. Daily potassium supplementation and spironolactone resulted in complete clinical recovery.

Conclusions

Acquired Gitelman syndrome associated with Sjögren syndrome is rare. It should be considered as a differential diagnosis during evaluation of acute paralysis and hypokalaemic metabolic alkalosis in patients with autoimmune disorders, especially Sjögren syndrome.
Identification of key pseudogenes in nasopharyngeal carcinoma based on RNA-Seq analysis
Authors: Zhang Xiujuan , Song Xiaole , Lai Yuting , Zhu Bijun , Luo Jiqin , Yu Hongmeng , Yu Yiqun
Published: April 2021

Background

Nasopharyngeal carcinoma (NPC) is a malignant head and neck tumor, and more than 70% of new cases are in East and Southeast Asia. However, association between NPC and pseudogenes playing important roles in genesis of multiple tumor types is still not clear and needs to be investigated.

Methods

Using RNA-Sequencing (RNA-seq) technology, we analyzed pseudogene expression in 13 primary NPC and 6 recurrent NPC samples as well as their paracancerous counterparts. Quantitative PCR was used to validate the differentially expressed pseudogenes.

Results

We found 251 differentially expressed pseudogenes including 73 up-regulated and 178 down-regulated ones between primary NPC and paracancerous tissues. Enrichment analysis of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were conducted to filter out the key pseudogenes. We reported that pseudogenes from cytochrome P450 (CYP) family, such as CYP2F2P, CYP2G1P, CYP4F24P, CYP2B7P and CYP2G2P were significantly down-regulated in NPC compared to paracancerous tissues, while IGHV1OR15–2, IGHV3–11, FCGR1CP and IGHV3–69-1 belonging to Fc gamma receptors were significantly up-regulated. CYP2B7P, CYP2F2P and CYP4F26P were enriched in arachidonic acid metabolism pathway. The qRT-PCR analysis validated the lower expression of pseudogenes CYP2F2P and CYP2B7P in NPC tissues and cell lines compared to paracancerous tissues and normal human nasopharyngeal epithelial cell line. CYP2B7P overexpression weakened migratory and invasive capacity of NPC cell line. Moreover, the expression pattern of those pseudogenes in recurrent NPC tissues was different from the primary NPC.

Conclusion

This study suggested the role of pseudogenes in tumorigenesis and progression, potentially functioning as therapeutic targets to NPC.
Modified technique of closing the port site after multiport thoracoscopic surgery using the shingled suture technique: a single centre experience
Authors: Xu Haitao , Ren Shuai , She Tianyu , Zhang Jingyu , Zhang Lianguo , Jia Teng , Zhang Qingguang
Published: April 2021

Background

Due to improvements in operative techniques and medical equipment, video-assisted thoracoscopic surgery has become a mainstay of thoracic surgery. Nevertheless, in multiport thoracoscopic surgery, there have been no substantial advances related to the improvement of the esthetics of the site of the chest tube kept for postoperative drainage of intrathoracic fluid and decompression of air leak after thoracoscopic surgery. Leakage of fluid and air around the site of the chest tube can be extremely bothersome to patients.

Methods

From March 2019 to April 2020, we used a modified technique of closing the port site in 67 patients and the traditional method in 51 patients undergoing multiport thoracoscopic surgery due to lung disease or mediastinal disease. We recorded patients’ age, gender, body mass index, surgical method, postoperative drainage time, and postoperative complications.The NRS pain scale was used to score the pain in each patient on the day of extubation.The PSAS and the OSAS were used for the assessment of scars one month after surgery.

Results

In the modified technique group, only one patient (1.49%) had pleural effusion leakage, compared with five patients (9.80%) in the traditional method group (P < 0.05). There were no significant differences in the pain of extubating and wound dehiscence between the two groups. However,the incidence rates of wound dehiscence in the modified technique group were lower than in the traditional method group. There were no post-removal pneumothorax and wound infection in either of the groups. Significant differences in the PSAS and OSAS were observed between the groups,where the modified technique group was superior to the traditional method group.

Conclusions

The modified technique of port site closure is a leak-proof method of fixation of the chest tube after multiport thoracoscopic surgery. Moreover, it is effective and preserves the esthetic appearance of the skin.
Hyperspectral Imaging (HSI) as a new diagnostic tool in free flap monitoring for soft tissue reconstruction: a proof of concept study
Authors: Kohler Lukas H. , Köhler Hannes , Kohler Simon , Langer Stefan , Nuwayhid Rima , Gockel Ines , Spindler Nick , Osterhoff Georg
Published: April 2021

Objectives

Free flap surgery is an essential procedure in soft tissue reconstruction. Complications due to vascular compromise often require revision surgery or flap removal. We present hyperspectral imaging (HSI) as a new tool in flap monitoring to improve sensitivity compared to established monitoring tools.

Methods

We performed a prospective observational cohort study including 22 patients. Flap perfusion was assessed by standard clinical parameters, Doppler ultrasound, and HSI on t0 (0 h), t1 (16–28 h postoperatively), and t2 (39–77 h postoperatively). HSI records light spectra from 500 to 1000 nm and provides information on tissue morphology, composition, and physiology. These parameters contain tissue oxygenation (StO2), near-infrared perfusion- (NIR PI), tissue hemoglobin- (THI), and tissue water index (TWI).

Results

Total flap loss was seen in n = 4 and partial loss in n = 2 cases. Every patient with StO2 or NIR PI below 40 at t1 had to be revised. No single patient with StO2 or NIR PI above 40 at t1 had to be revised. Significant differences between feasable (StO2 = 49; NIR PI = 45; THI = 16; TWI = 56) and flaps with revision surgery [StO2 = 28 (p < 0.001); NIR PI = 26 (p = 0.002); THI = 56 (p = 0.002); TWI = 47 (p = 0.045)] were present in all HSI parameters at t1 and even more significant at t2 (p < 0.0001).

Conclusion

HSI provides valuable data in free flap monitoring. The technique seems to be superior to the gold standard of flap monitoring. StO2 and NIR PI deliver the most valuable data and 40 could be used as a future threshold in surgical decision making. Clinical Trial Register This study is registered at the German Clinical Trials Register (DRKS) under the registration number DRKS00020926.
Investigating the prevalence of primary thyroid dysfunction in obese and overweight individuals: Tehran thyroid study
Authors: Mahdavi Mahdi , Amouzegar Atieh , Mehran Ladan , Madreseh Elham , Tohidi Maryam , Azizi Fereidoun
Published: April 2021

Background

Due to the increasing worldwide prevalence of obesity, it is essential to determine the prevalence of obesity-related thyroid dysfunctions. The purpose of this study was to investigate the prevalence of thyroid dysfunctions, namely hypothyroidism and hyperthyroidism, and their association with BMI among adult Iranian overweight and obese individuals.

Method

This cross-sectional study was carried out within the framework of the Tehran Thyroid Study (TTS); 5353 participants (57.5% female) entered our study. Anthropometric measurements were performed. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) were assayed. We categorized individuals into 3 BMI groups (normal-weight, overweight and obese), then calculated prevalence rate, odds ratio (OR), and 95% confidence interval (CI) for outcomes in overweight and obese groups. The normal-weight group was used as the control group.

Results

We found a higher prevalence of hypothyroidism (11.6% vs 8.2% Total, 4.0% vs 1.1% overt and 7.6% vs 7.1% subclinical, P < 0.001) and TPOAb positivity (17.3% vs 11.6%, P < 0.001) in obese participants compared with normal-weight participants. Hyperthyroidism’s overall prevalence was 4.2, 5.7, and 4.9% in obese, overweight, and normal-weight groups, respectively. Obesity was associated with higher odds of overt hypothyroidism (OR: 2.0, 95% CI: 1.15–3.49, P < 0.05) and TPOAb positivity (OR: 1.29, 95% CI: 1.04–1.60, P < 0.05) after adjusting for confounding variables. In contrast, no association was observed between the overweight group and the odds of hypothyroidism and TPOAb positivity in the adjusted results.

Conclusions

Obesity was associated with an increased risk of overt hypothyroidism and TPOAb positivity.
Web-based formative assessment through clinical cases: role in pathophysiology teaching
Authors: Fernández Ros Nerea , Lucena Felipe , Iñarrairaegui Mercedes , Landecho Manuel F. , Sunsundegui Patricia , Jordán-Iborra Carlota , Pineda Iñigo , Quiroga Jorge , Herrero Jose Ignacio
Published: April 2021

Background

Active learning strategies such as formative assessment through clinical cases may help to get a deeper learning. We have studied the effect of this kind of online formative assessment in pathophysiology teaching.

Methods

Seven brief clinical cases were used to give formative assessment in the first semester of a pathophysiology course. To evaluate its effect on learning, we analyzed the proportion of students that passed the end of semester exam with a score above 60 over 100. We also analyzed the effect of the intervention according to the students’ previous academic performance.

Results

Ninety-six students participated in the study and sat the exam. Sixty-five of them passed it. Students that passed the exam had a higher previous academic performance and had done a higher number of exercises of formative assessment, both in univariate and multivariate analysis. The participants were divided in three groups, according to their previous academic performance. In the intermediate group, the number of cases done by the students who passed the exam was significantly higher than in those who did not pass it (median: 4 versus 0; P = 0.009).

Conclusion

Formative assessment through web-based clinical cases was followed by an improvement of the academic results in pathophysiology, mainly in students with intermediate performance.
Identification of significant climatic risk factors and machine learning models in dengue outbreak prediction
Authors: Yavari Nejad Felestin , Varathan Kasturi Dewi
Published: April 2021

Background

Dengue fever is a widespread viral disease and one of the world’s major pandemic vector-borne infections, causing serious hazard to humanity. The World Health Organisation (WHO) reported that the incidence of dengue fever has increased dramatically across the world in recent decades. WHO currently estimates an annual incidence of 50–100 million dengue infections worldwide. To date, no tested vaccine or treatment is available to stop or prevent dengue fever. Thus, the importance of predicting dengue outbreaks is significant. The current issue that should be addressed in dengue outbreak prediction is accuracy. A limited number of studies have conducted an in-depth analysis of climate factors in dengue outbreak prediction.

Methods

The most important climatic factors that contribute to dengue outbreaks were identified in the current work. Correlation analyses were performed in order to determine these factors and these factors were used as input parameters for machine learning models. Top five machine learning classification models (Bayes network (BN) models, support vector machine (SVM), RBF tree, decision table and naive Bayes) were chosen based on past research. The models were then tested and evaluated on the basis of 4-year data (January 2010 to December 2013) collected in Malaysia.

Results

This research has two major contributions. A new risk factor, called the TempeRain factor (TRF), was identified and used as an input parameter for the model of dengue outbreak prediction. Moreover, TRF was applied to demonstrate its strong impact on dengue outbreaks. Experimental results showed that the Bayes Network model with the new meteorological risk factor identified in this study increased accuracy to 92.35% for predicting dengue outbreaks.

Conclusions

This research explored the factors used in dengue outbreak prediction systems. The major contribution of this study is identifying new significant factors that contribute to dengue outbreak prediction. From the evaluation result, we obtained a significant improvement in the accuracy of a machine learning model for dengue outbreak prediction.
Traumatic brain injury does not disrupt costimulatory blockade-induced immunological tolerance to glial-restricted progenitor allografts
Authors: Wang Rui , Chu Chengyan , Wei Zhiliang , Chen Lin , Xu Jiadi , Liang Yajie , Janowski Miroslaw , Stevens Robert D. , Walczak Piotr
Published: April 2021

Background

Cell transplantation-based treatments for neurological disease are promising, yet graft rejection remains a major barrier to successful regenerative therapies. Our group and others have shown that long-lasting tolerance of transplanted stem cells can be achieved in the brain with systemic application of monoclonal antibodies blocking co-stimulation signaling. However, it is unknown if subsequent injury and the blood-brain barrier breach could expose the transplanted cells to systemic immune system spurring fulminant rejection and fatal encephalitis. Therefore, we investigated whether delayed traumatic brain injury (TBI) could trigger graft rejection.

Methods

Glial-restricted precursor cells (GRPs) were intracerebroventricularly transplanted in immunocompetent neonatal mice and co-stimulation blockade (CoB) was applied 0, 2, 4, and 6 days post-grafting. Bioluminescence imaging (BLI) was performed to monitor the grafted cell survival. Mice were subjected to TBI 12 weeks post-transplantation. MRI and open-field test were performed to assess the brain damage and behavioral change, respectively. The animals were decapitated at week 16 post-transplantation, and the brains were harvested. The survival and distribution of grafted cells were verified from brain sections. Hematoxylin and eosin staining (HE) was performed to observe TBI-induced brain legion, and neuroinflammation was evaluated immunohistochemically.

Results

BLI showed that grafted GRPs were rejected within 4 weeks after transplantation without CoB, while CoB administration resulted in long-term survival of allografts. BLI signal had a steep rise following TBI and subsequently declined but remained higher than the preinjury level. Open-field test showed TBI-induced anxiety for all animals but neither CoB nor GRP transplantation intensified the symptom. HE and MRI demonstrated a reduction in TBI-induced lesion volume in GRP-transplanted mice compared with non-transplanted mice. Brain sections further validated the survival of grafted GRPs and showed more GRPs surrounding the injured tissue. Furthermore, the brains of post-TBI shiverer mice had increased activation of microglia and astrocytes compared to post-TBI wildtype mice, but infiltration of CD45+ leukocytes remained low.

Conclusions

CoB induces sustained immunological tolerance towards allografted cerebral GRPs which is not disrupted following TBI, and unexpectedly TBI may enhance GRPs engraftment and contribute to post-injury brain tissue repair.
Simultaneous enterovirus EV-D68 and CVA6 infections causing acute respiratory distress syndrome and hand, foot and mouth disease
Authors: de Sousa Ivanildo Pedro , Giamberardino Heloísa Ihle , Raboni Sonia Mara , Debur Maria Carmo , de Lourdes Aguiar Oliveira Maria , Burlandy Fernanda Marcicano , da Silva Edson Elias
Published: April 2021

Background

Although most enterovirus (EV) infections can be asymptomatic, these viral agents can cause serious conditions associated with central nervous system, respiratory disease and uncommon manifestations of hand, foot and mouth disease (HFMD). EV-coinfections have been rarely reported with development of complications and severe clinical outcome. An atypical case of a child presenting HFMD and severe acute respiratory syndrome, co-infected with EV-D68 and CVA6, is reported herein.

Case presentation

A 3-year-old boy was admitted in the emergency department unit showing fever, abdominal pain and tachycardia. Twenty-four hours after hospitalization the child developed severe clinical symptoms associated with HFMD and was discharged after recovery. Two days later, the child was readmitted with fever, cough and respiratory distress. RT-PCR and Sanger sequencing confirmed positivity for EV-D68 and CVA6 in oro and nasopharynges swabs and vesicles fluid, respectively. Phylogenetic analysis based on VP1 gene sequences suggested that CVA6 was closely related with HFMD viruses circulating in Turkey, while EV-D68 was genetically related to a Chinese strain.

Conclusions

To the best of our knowledge, this case is the first report of a double infection caused by CVA6 and EV-D68, which shed light on the pathogenesis of enterovirus infections. Further studies must be conducted to ascertain the role and clinical significance of EV co-infections, as well as a potential synergistic pathway between these viruses.
FMRP attenuates activity dependent modifications in the mitochondrial proteome
Authors: Bülow Pernille , Zlatic Stephanie A. , Wenner Peter A. , Bassell Gary J. , Faundez Victor
Published: April 2021

Homeostatic plasticity is necessary for the construction and maintenance of functional neuronal networks, but principal molecular mechanisms required for or modified by homeostatic plasticity are not well understood. We recently reported that homeostatic plasticity induced by activity deprivation is dysregulated in cortical neurons from Fragile X Mental Retardation protein (FMRP) knockout mice (Bulow et al. in Cell Rep 26: 1378-1388 e1373, 2019). These findings led us to hypothesize that identifying proteins sensitive to activity deprivation and/or FMRP expression could reveal pathways required for or modified by homeostatic plasticity. Here, we report an unbiased quantitative mass spectrometry used to quantify steady-state proteome changes following chronic activity deprivation in wild type and Fmr1−/y cortical neurons. Proteome hits responsive to both activity deprivation and the Fmr1−/y genotype were significantly annotated to mitochondria. We found an increased number of mitochondria annotated proteins whose expression was sensitive to activity deprivation in Fmr1−/y cortical neurons as compared to wild type neurons. These findings support a novel role of FMRP in attenuating mitochondrial proteome modifications induced by activity deprivation.
Ablation of interleukin-19 improves motor function in a mouse model of amyotrophic lateral sclerosis
Authors: Komiya Hiroyasu , Takeuchi Hideyuki , Ogawa Yuki , Suzuki Kosuke , Ogasawara Akihiro , Takahashi Keita , Azuma Yasu-Taka , Doi Hiroshi , Tanaka Fumiaki
Published: April 2021

Neuroinflammation by activated microglia and astrocytes plays a critical role in progression of amyotrophic lateral sclerosis (ALS). Interleukin-19 (IL-19) is a negative-feedback regulator that limits pro-inflammatory responses of microglia in an autocrine and paracrine manner, but it remains unclear how IL-19 contributes to ALS pathogenesis. We investigated the role of IL-19 in ALS using transgenic mice carrying human superoxide dismutase 1 with the G93A mutation (SOD1G93A Tg mice). We generated IL-19–deficient SOD1G93A Tg (IL-19−/−/SOD1G93A Tg) mice by crossing SOD1G93A Tg mice with IL-19−/− mice, and then evaluated disease progression, motor function, survival rate, and pathological and biochemical alternations in the resultant mice. In addition, we assessed the effect of IL-19 on glial cells using primary microglia and astrocyte cultures from the embryonic brains of SOD1G93A Tg mice and IL-19−/−/SOD1G93A Tg mice. Expression of IL-19 in primary microglia and lumbar spinal cord was higher in SOD1G93A Tg mice than in wild-type mice. Unexpectedly, IL-19−/−/SOD1G93A Tg mice exhibited significant improvement of motor function. Ablation of IL-19 in SOD1G93A Tg mice increased expression of both neurotoxic and neuroprotective factors, including tumor necrosis factor-α (TNF-α), IL-1β, glial cell line–derived neurotrophic factor (GDNF), and transforming growth factor β1, in lumbar spinal cord. Primary microglia and astrocytes from IL-19−/−/SOD1G93A Tg mice expressed higher levels of TNF-α, resulting in release of GDNF from astrocytes. Inhibition of IL-19 signaling may alleviate ALS symptoms.
ALG3 contributes to stemness and radioresistance through regulating glycosylation of TGF-β receptor II in breast cancer
Authors: Sun Xiaoqing , He Zhenyu , Guo Ling , Wang Caiqin , Lin Chuyong , Ye Liping , Wang Xiaoqing , Li Yue , Yang Meisongzhu , Liu Sailan , Hua Xin , Wen Wen , Lin Chao , Long Zhiqing , Zhang Wenwen , Li Han , Jian Yunting , Zhu Ziyuan , Wu Xianqiu , Lin Huanxin
Published: April 2021

Background

Radiotherapy is a conventional and effective local treatment for breast cancer. However, residual or recurrent tumors appears frequently because of radioresistance. Novel predictive marker and the potential therapeutic targets of breast cancer radioresistance needs to be investigated.

Methods

In this study, we screened all 10 asparagine-linked glycosylation (ALG) members in breast cancer patients’ samples by RT-PCR. Cell viability after irradiation (IR) was determined by CCK-8 assay and flow cytometry. The radiosensitivity of cell lines with different ALG3 expression was determined with the colony formation assay by fitting the multi-target single hit model to the surviving fractions. Cancer stem-like traits were assessed by RT-PCR, Western blot, and flow cytometry. The mechanisms of ALG3 influencing radiosensitivity was detected by Western blot and immunoprecipitation. And the effect of ALG3 on tumor growth after IR was verified in an orthotopic xenograft tumor models. The association of ALG3 with prognosis of breast cancer patients was confirmed by immunohistochemistry.

Results

ALG3 was the most significantly overexpressing gene among ALG family in radioresistant breast cancer tissue. Overexpression of ALG3 predicted poor clinicopathological characteristics and overall survival (OS), and early local recurrence-free survival (LRFS) in breast cancer patients. Upregulating ALG3 enhanced radioresistance and cancer stemness in vitro and in vivo. Conversely, silencing ALG3 increased the radiosensitivity and repressed cancer stemness in vitro, and more importantly inhibition of ALG3 effectively increased the radiosensitivity of breast cancer cells in vivo. Mechanistically, our results further revealed ALG3 promoted radioresistance and cancer stemness by inducing glycosylation of TGF-β receptor II (TGFBR2). Importantly, both attenuation of glycosylation using tunicamycin and inhibition of TGFBR2 using LY2109761 differentially abrogated the stimulatory effect of ALG3 overexpression on cancer stemness and radioresistance. Finally, our findings showed that radiation played an important role in preventing early recurrence in breast cancer patients with low ALG3 levels, but it had limited efficacy in ALG3-overexpressing breast cancer patients.

Conclusion

Our results suggest that ALG3 may serve as a potential radiosensitive marker, and an effective target to decrease radioresistance by regulating glycosylation of TGFBR2 in breast cancer. For patients with low ALG3 levels, radiation remains an effective mainstay therapy to prevent early recurrence in breast cancer.
ZBTB28 induces autophagy by regulation of FIP200 and Bcl-XL facilitating cervical cancer cell apoptosis
Authors: Li Li , Gong Yijia , Xu Ke , Chen Weihong , Xia Jiuyi , Cheng Zhaobo , Li Lili , Yu Renjie , Mu Junhao , Le Xin , Xiang Qin , Peng Weiyan , Tang Junying , Xiang Tingxiu
Published: April 2021

Background

Among the common preventable cancers of women, cervical cancer has the highest morbidity. It is curable if detected at an early stage. However, reliable diagnostic and prognostic markers, which relate to physiologic and pathologic regulation of cervical cancer, are not available. In this study, one such potential marker, ZBTB28, was evaluated for its potential usefulness in cervical cancer assessment.

Methods

Public database analysis, reverse-transcription polymerase chain reaction (PCR), and methylation-specific PCR were employed to analyze ZBTB28 expression and promoter methylation. The importance of ZBTB28 in cervical cancer cells was assessed by cellular and molecular analysis in vitro and in vivo.

Results

This study assessed the anti-tumor effects of the transcription factor, ZBTB28, which is often silenced in cervical cancer due to CpG methylation of its promoter. We found ZBTB28 to directly affect cervical cancer cell proliferation, apoptosis, autophagy, and tumorigenesis. Also, it increased cancer cell chemosensitivity to Paclitaxel, Cisplatin, and 5-fluorouracil. Ectopic ZBTB28 expression inhibited the growth of cervical cancer xenografts in nude mice. Furthermore, electron microscopy demonstrated ZBTB28 to induce autophagosomes in cervical cancer cells. ZBTB28 induced cellular autophagy by the degradation of Bcl-XL, reduction of the Bcl-XL-BECN1 complex, and by interaction with the autophagy-related gene FIP200. ZBTB28-induced autophagy of cervical cancer cells was shown to mediate cellular apoptosis through the regulation of FIP200.

Conclusion

These findings identify ZBTB28 as a tumor suppressor gene that can induce autophagy-related apoptosis in cervical cancer cells. As such, ZBTB28 may be a target for the treatment of uterine-cervical carcinoma. Further, ZBTB28 promoter methylation analysis may offer a new objective strategy for cervical cancer screening.
MARS: leveraging allelic heterogeneity to increase power of association testing
Authors: Hormozdiari Farhad , Jung Junghyun , Eskin Eleazar , J. Joo Jong Wha
Published: April 2021

In standard genome-wide association studies (GWAS), the standard association test is underpowered to detect associations between loci with multiple causal variants with small effect sizes. We propose a statistical method, Model-based Association test Reflecting causal Status (MARS), that finds associations between variants in risk loci and a phenotype, considering the causal status of variants, only requiring the existing summary statistics to detect associated risk loci. Utilizing extensive simulated data and real data, we show that MARS increases the power of detecting true associated risk loci compared to previous approaches that consider multiple variants, while controlling the type I error.
Seroepidemiological study of toxoplasmosis in women referred to a pre-marriage counseling center in Alborz Province, Iran
Authors: Shahighi Melica , Heidari Aliehsan , Keshavarz Hossein , Bairami Amir , Shojaee Saeedeh , Sezavar Monireh , Salimi Mahboobeh , Teimouri Aref
Published: April 2021

Objectives

The aim of the current study was to assess prevalence of Toxoplasma infection and its associated risk factors in women of childbearing-age in central Iran.

Results

Of 400 serum samples assessed for anti-T. gondii antibodies, 81 (20.25%) samples were positive for anti-T. gondii antibodies, including 74 positive samples (91.3%) for anti-T. gondii IgG and seven positive samples (8.7%) for IgG and IgM. Of seven IgG and IgM positive samples, five and two samples were high and low in IgG avidity, respectively. Based on PCR analysis, Toxoplasma infection was detected in one sample with anti-T. gondii IgM and low IgG avidity. The Chi-square test showed significant correlations of T. gondii seropositivity with history of undercooked meat consumption and contacts with cats (p < 0.05). In the present study, 79.75% of the participants were negative for IgG against T. gondii infection. Furthermore, recently acquired Toxoplasma infection was found using IgG avidity and PCR assays among women of childbearing-age in the study area, which would increase the risk of their fetus becoming infected. Educational program and antenatal screening of childbearing-age women for T. gondii infection may be important primary prevention strategies and help reduce the risk of congenital toxoplasmosis in this population.
Correlation of 4′-[methyl-11C]-thiothymidine PET with Gd-enhanced and FLAIR MRI in patients with newly diagnosed glioma
Authors: Norikane Takashi , Mitamura Katsuya , Yamamoto Yuka , Maeda Yukito , Tanaka Kenichi , Hatakeyama Tetsuhiro , Miyake Keisuke , Toyohara Jun , Nishiyama Yoshihiro
Published: April 2021

Purpose

To elucidate the biological association between tumor proliferation, tumor infiltration and neovascularization, we analyzed the association between volumetric information of 4′-[methyl-11C]thiothymidine (4DST) positron emission tomography (PET) and fluid-attenuated inversion recovery (FLAIR) and T1-weighted gadopentetate dimeglumine (Gd)-enhanced magnetic resonance imaging (MRI), in patients with newly diagnosed glioma.

Methods

A total of 23 patients with newly diagnosed glioma who underwent both 4DST PET/CT and Gd-enhanced MRI before therapy were available for a retrospective analysis of prospectively collected data. The maximum standardized uptake value (SUVmax) for tumor (T) and the mean SUV for normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined. Proliferative tumor volume (PTV) from 4DST PET and the volume of Gd enhancement (GdV) and hyperintense region on FLAIR (FLAIRV) from MRI were calculated.

Results

All gliomas but 3 diffuse astrocytomas and one anaplastic astrocytoma had 4DST uptake and Gd enhancement on MRI. There was no significant difference between PTV and GdV although the exact edges of the tumor differed in each modality. The FLAIRV was significantly larger than PTV (P < 0.001). Significant correlations between PTV and GdV (ρ = 0.941, P < 0.001) and FLAIRV (ρ = 0.682, P < 0.001) were found.

Conclusion

These preliminary results indicate that tumor proliferation assessed by 4DST PET is closely associated with tumor-induced neovascularization determined by Gd-enhanced MRI in patients with newly diagnosed glioma.