bluuebunny/crossref_metadata_2025 huggingface dataset:
Embolization of parastomal and small bowel ectopic varices utilizing a transhepatic antegrade approach: A case series
Authors: Nadeem Ibrahim Mohammad , Badar Zain , Giglio Victoria , Stella Steffan Frosi , Markose George , Nair Sabarinath
Published: July 2022

Background

The ideal approach to managing parastomal and small bowel ectopic varices (EVs) is yet to be established.

Purpose

To evaluate outcomes following percutaneous antegrade transhepatic venous obliteration (PATVO) in patients presenting with bleeding from parastomal or small bowel EVs.

Material and Methods

A case series of 12 patients presenting with active or recurrent bleeding from parastomal or small bowel EVs who underwent 17 PATVO interventions at our tertiary care institution was performed. Data extraction from electronic medical records included baseline characteristics and procedural details. Endpoints included technical success, early clinical success, and re-bleeding.

Results

Technical success was 100% ( n = 17), and early clinical success was 82.3% ( n = 14). No patient experienced any intra- or post-operative complications. Rebleed rates after initial PATVO in patients who achieved early clinical success was as follows: 3-month, 0% ( n = 0); 6-month, 20% ( n = 2); 12-month, 20% ( n = 2). Rebleed rates after all PATVO procedures (including patients undergoing repeat procedures) that achieved early clinical success were as follows: 3-month, 0% ( n = 0); 6-month, 14% ( n = 2; 12-month, 14% ( n = 2). All patients with re-bleeding required reintervention with either PATVO, transjugular intrahepatic portosystemic shunt (TIPS) or both.

Conclusion

PATVO can be safely performed to treat bleeding from parastomal and small bowel EVs. In patients who present with recurrent bleeding despite PATVO, TIPS with/without embolization of bleeding varices remains a valid option as described by the literature.
Comparison Between Femoral Neck Systems and Cannulated Cancellous Screws in Treating Femoral Neck Fractures: A Meta-Analysis
Authors: Tian Peng , Kuang Lan , Li Zhi-jun , Xu Gui-jun , Fu Xin
Published: July 2022

Background

We performed a meta-analysis to compare the efficacy and safety of the femoral neck system (FNS) with cannulated cancellous screws (CCSs) in treating femoral neck fractures (FNFs) in controlled clinical trials.

Methods

Eligible scientific articles published prior to September 2021 were retrieved from the PubMed, Web of Science, Springer, ScienceDirect and Cochrane Library databases. The statistical analysis was performed with RevMan 5.1.

Results

Seven retrospective studies met the inclusion criteria. Meta-analysis showed that there were significant differences in perioperative blood loss, the postoperative Harris score, healing time, fluoroscopy frequency, total complications, femoral head necrosis, femoral neck shortening and screw cutout. No significant differences were found regarding operation time, length of hospital stay or nonunion between the two groups.

Conclusion

Compared with CCSs, the FNS showed better clinical efficacy and fewer complications in treating FNFs. Due to the limited quality and data of the currently available evidence, more high-quality randomized controlled trials are needed.
“Sorosoids”: Dehumanization and open society in contemporary Bulgaria
Authors: Terziev Lubomir
Published: July 2022

This text elucidates some of the uses and connotations of the word “sorosoid,” which has recently permeated the public discourse in Bulgaria, used to refer to individuals and organizations affiliated with Soros’ Open Society Foundation. I am particularly interested in the inflection “-oid,” which seeks to echo the word “humanoid.” In other words, my specific concern is with strategies of dehumanization of neoliberals in Bulgaria, whereby the fundamental values of open society in this country are challenged. The paper provides a glimpse of some key ideological attitudes in one of Europe’s post-communist democracies.
Vitamin K antagonist versus novel oral anticoagulants for management of cervical artery dissection: Interactive systematic review and meta-analysis
Authors: Essibayi Muhammed Amir , Lanzino Giuseppe , Keser Zafer
Published: July 2022

Purpose:

Cervical artery dissection (CAD) represents a unique clinical entity with a high risk of ischemic stroke. Vitamin K antagonists (VKA) showed good efficacy in CAD management but are cumbersome to use with potentially higher bleeding rates. Novel oral anticoagulants (NOAC) are easier to use and may have similar effects but lower hemorrhagic risk. In this systematic review, we compare the efficacy of NOAC to VKA as a potential alternative treatment.

Methods:

The literature was searched on Pubmed, PMC, and Embase via API through the Nested Knowledge AutoLit software in February 2022 for studies evaluating both NOAC and VKA. Baseline characteristics, clinical and radiographic outcomes, and hemorrhagic and ischemic complications were collected for single and double-arm studies and analyzed using random-effect subgroup meta-analysis.

Findings:

Overall, 11 studies were included with 699 patients treated with VKA and 53 treated with NOAC (from three studies; two were head-to-head comparative studies). There was no statistical difference in the baseline characteristics of VKA and NOAC patients. The rates of TIA/stroke in VKA and NOAC groups were 12.3% (95% CI; 0%, 28.6%) and 5.7% (95% CI; 0%, 12.2%), respectively. Major bleeding or intracranial bleeding were comparable between groups. Lesions treated with VKA showed angiographic recanalization with a rate of 51.4% (95% CI; 35.6%, 67.1%) and for those treated with NOAC was 58.4% (95% CI; 23.9%, 93.9%). The rates of good clinical outcomes were 79.9% (95% CI; 67.6%, 92.2%) in the VKA group and 91.4% (95% CI; 78.1%, 100%) in NOAC. No statistical difference was noted among any of the outcomes between the two treatment groups.

Discussion and conclusion:

We highlighted comparable efficacy and safety of NOAC to VKA for stroke prevention in CAD. Further head-to-head studies are warranted to validate these results.
The involvement of microRNAs in HCV and HIV infection
Authors: Joshi Nicky , Chandane Tak Madhuri , Mukherjee Anupam
Published: July 2022

Approximately 2.3 million people are suffering from human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection worldwide. Faster disease progression and increased mortality rates during the HIV/HCV co-infection have become global health concerns. Effective therapeutics against co-infection and complete infection eradication has become a mandatory requirement. The study of small non-coding RNAs in cellular processes and viral infection has so far been beneficial in various terms. Currently, microRNAs are an influential candidate for disease diagnosis and treatment. Dysregulation in miRNA expression can lead to unfavorable outcomes; hence, this exact inevitable nature has made various studies a focal point. A considerable improvement in comprehending HIV and HCV mono-infection pathogenesis is seen using miRNAs. The prominent reason behind HIV/HCV co-infection is seen to be their standard route of transmission, while some pieces of evidence also suspect viral interplay between having a role in increased viral infection. This review highlights the involvement of microRNAs in HIV/HCV co-infection, along with their contribution in HIV mono- and HCV mono-infection. We also discuss miRNAs that carry the potentiality of becoming a biomarker for viral infection and early disease progression.
Are instructional practices different between East and West? An analysis of Grade 8 TIMSS 2019 data
Authors: Bokhove Christian
Published: July 2022

After each round of International Large-scale Assessments such as the Trends in International Mathematics and Science Study (TIMSS) and the Programme for International Student Assessment (PISA), excellent achievements by countries in East Asia are explained in terms of their instructional practices. However, instructional practices are not easily captured in self-reported scales. In addition, speculations on what approaches lead to the highest mathematics achievement are often combined and conflated with discussions on how mathematical content needs to be taught. This article reports on a secondary analysis of TIMSS 2019 Grade 8 data from 46 jurisdictions of teacher-reported answers on instructional practices. Using a data-driven exploratory factor analysis, three instructional scales are compiled and supplemented with variables on barriers to instruction and instructional time. Multilevel models of all countries are created for students and teachers, in which the relationship between these instructional practices and mathematics achievement is explored. Across countries, the results show that the three new scales for instructional practice work in limited and different ways, but that barriers toward instruction, and to a lesser extent, instructional time, predict mathematics achievement. However, there is no consistent pattern of instructional practices across all countries, and also not among East Asian countries.
Translation of cytoplasmic UBA1 contributes to VEXAS syndrome pathogenesis
Authors: Ferrada Marcela A. , Savic Sinisa , Cardona Daniela Ospina , Collins Jason C. , Alessi Hugh , Gutierrez-Rodrigues Fernanda , Kumar Dinesh Babu Uthaya , Wilson Lorena , Goodspeed Wendy , Topilow James S. , Paik Julie J. , Poulter James A. , Kermani Tanaz A. , Koster Matthew J. , Warrington Kenneth J. , Cargo Catherine , Tattersall Rachel S. , Duncan Christopher J. A. , Cantor Anna , Hoffmann Patrycja , Payne Elspeth M. , Bonnekoh Hanna , Krause Karoline , Cowen Edward W. , Calvo Katherine R. , Patel Bhavisha A. , Ombrello Amanda K. , Kastner Daniel L. , Young Neal S. , Werner Achim , Grayson Peter C. , Beck David B.
Published: July 2022

Somatic mutations in UBA1 cause vacuoles, E1 ubiquitin-activating enzyme, X-linked, autoinflammatory somatic (VEXAS) syndrome, an adult-onset inflammatory disease with an overlap of hematologic manifestations. VEXAS syndrome is characterized by a high mortality rate and significant clinical heterogeneity. We sought to determine independent predictors of survival in VEXAS and to understand the mechanistic basis for these factors. We analyzed 83 patients with somatic pathogenic variants in UBA1 at p.Met41 (p.Met41Leu/Thr/Val), the start codon for translation of the cytoplasmic isoform of UBA1 (UBA1b). Patients with the p.Met41Val genotype were most likely to have an undifferentiated inflammatory syndrome. Multivariate analysis showed ear chondritis was associated with increased survival, whereas transfusion dependence and the p.Met41Val variant were independently associated with decreased survival. Using in vitro models and patient-derived cells, we demonstrate that p.Met41Val variant supports less UBA1b translation than either p.Met41Leu or p.Met41Thr, providing a molecular rationale for decreased survival. In addition, we show that these 3 canonical VEXAS variants produce more UBA1b than any of the 6 other possible single-nucleotide variants within this codon. Finally, we report a patient, clinically diagnosed with VEXAS syndrome, with 2 novel mutations in UBA1 occurring in cis on the same allele. One mutation (c.121 A>T; p.Met41Leu) caused severely reduced translation of UBA1b in a reporter assay, but coexpression with the second mutation (c.119 G>C; p.Gly40Ala) rescued UBA1b levels to those of canonical mutations. We conclude that regulation of residual UBA1b translation is fundamental to the pathogenesis of VEXAS syndrome and contributes to disease prognosis.
Protective role of trametenolic acid B against sevoflurane-induced cognitive impairments by its different regulatory modalities of mir-329-3p in neurons and microglia
Authors: Chen Jun , Feng Shuo , Li Linyan , Qiu Shujie , Jin Yanwu , Sun Yingui
Published: July 2022

Background

Postoperative cognitive dysfunction induced by anesthetics commonly occurs in elderly patients. This study aimed to evaluate the protective role of trametenolic acid B (TAB) in sevoflurane-induced cognitive impairments, and explore the underlying mechanisms.

Methods

Animal and cell experiments were performed in rats, differentiated PC12 and HAPI cells by exposing to 2% sevoflurane for 5 h. Different concentration (20, 40 and 80 µg/mL) of TAB was administrated in rats and cells. The cognitive function of rats was evaluated using the Morris water maze test and fear conditioning test. The cell proliferation and apoptosis were investigated using a CCK-8 assay and the flow cytometry. Pro-inflammatory cytokines in microglia were measured using ELISA kits. A miRNA microarray assay was conducted to screen differentially expressed miRNAs by TAB in both PC12 and HAPI cells. The luciferase reporter assay and western blot assay were used to assess the E2F1/CCNA2 and NF-κB pathways.

Results

TAB significantly alleviated sevoflurane-induced cognitive impairments in rats, improved PC12 cell viability, and inhibited the neuroinflammation of HAPI cells. miR-329-3p was downregulated in PC12 cells but upregulated in HAPI cells by TAB treatment, which mediated the effects of TAB on neurotoxicity and neuroinflammation. E2F1 and NF-κB P65 were two targets of miR-329-3p, and the E2F1/CCNA2 and NF-κB pathways were inhibited by miR-329-3p in PC12 and HAPI cells, respectively.

Conclusions

All the results provide evidence for the protective role of TAB against sevoflurane-induced cognitive impairments, which was achieved by alleviating neurotoxicity and neuroinflammation through differentially regulating miR-329-3p in neurons and microglia.
Assessment of deep learning and transfer learning for cancer prediction based on gene expression data
Authors: Hanczar Blaise , Bourgeais Victoria , Zehraoui Farida
Published: July 2022

Background

Machine learning is now a standard tool for cancer prediction based on gene expression data. However, deep learning is still new for this task, and there is no clear consensus about its performance and utility. Few experimental works have evaluated deep neural networks and compared them with state-of-the-art machine learning. Moreover, their conclusions are not consistent.

Results

We extensively evaluate the deep learning approach on 22 cancer prediction tasks based on gene expression data. We measure the impact of the main hyper-parameters and compare the performances of neural networks with the state-of-the-art. We also investigate the effectiveness of several transfer learning schemes in different experimental setups.

Conclusion

Based on our experimentations, we provide several recommendations to optimize the construction and training of a neural network model. We show that neural networks outperform the state-of-the-art methods only for very large training set size. For a small training set, we show that transfer learning is possible and may strongly improve the model performance in some cases.
Exploring deep learning methods for recognizing rare diseases and their clinical manifestations from texts
Authors: Segura-Bedmar Isabel , Camino-Perdones David , Guerrero-Aspizua Sara
Published: July 2022

Background and objective

Although rare diseases are characterized by low prevalence, approximately 400 million people are affected by a rare disease. The early and accurate diagnosis of these conditions is a major challenge for general practitioners, who do not have enough knowledge to identify them. In addition to this, rare diseases usually show a wide variety of manifestations, which might make the diagnosis even more difficult. A delayed diagnosis can negatively affect the patient’s life. Therefore, there is an urgent need to increase the scientific and medical knowledge about rare diseases. Natural Language Processing (NLP) and Deep Learning can help to extract relevant information about rare diseases to facilitate their diagnosis and treatments.

Methods

The paper explores several deep learning techniques such as Bidirectional Long Short Term Memory (BiLSTM) networks or deep contextualized word representations based on Bidirectional Encoder Representations from Transformers (BERT) to recognize rare diseases and their clinical manifestations (signs and symptoms).

Results

BioBERT, a domain-specific language representation based on BERT and trained on biomedical corpora, obtains the best results with an F1 of 85.2% for rare diseases. Since many signs are usually described by complex noun phrases that involve the use of use of overlapped, nested and discontinuous entities, the model provides lower results with an F1 of 57.2%.

Conclusions

While our results are promising, there is still much room for improvement, especially with respect to the identification of clinical manifestations (signs and symptoms).
A retrospective analysis of maternal complications and newborn outcomes of general anesthesia for cesarean delivery in a single tertiary hospital in China
Authors: Bao Yang , Zhang Ting , Li Ling , Zhou Changqing , Liang Minxian , Zhou Jie , Wang Chunling
Published: July 2022

Background

Either neuraxial anesthesia or general anesthesia can be performed for cesarean delivery. Generally, neuraxial anesthesia is the first choice with the risk and benefit balance for both the mother and fetus. However, general anesthesia is also applicable most commonly in the emergent setting. This study analyzed maternal complications associated with general anesthesia for cesarean delivery and suggested lowering pregnancy-related maternal and newborn adverse outcomes.

Methods

With the approval of the Institutional Ethics Review Board (No: 2017016), data on cesarean delivery and related anesthesia were collected from the Electronic Health Record System from 1/1/2013 to 12/31/2016. Statistical software STATA version 15.1 was used for data analyses. All statistical tests were two-sided, and a level significance of 0.05 was assumed.

Results

The rate of general anesthesia for cesarean delivery increased steadily during 2013–2016, 3.71% in 2013 to 10.23% in 2016 (p < 0.001). Repeat cesarean delivery among general anesthesia group increased significantly from 16.22% in 2013 to 54.14% in 2016 (p < 0.001). Morbidly adherent placenta (MAP) was the first reason among pregnancy-related complications, which accounted for 33% in total in general anesthesia group (38% in 2013 to 44% in 2016). The laryngeal mask airway (LMA) was used in airway management, and the proportion of LMA increased from 28.38% in 2013 to 92.99% in 2016 (p < 0.001). There were significant differences in newborn outcomes between general anesthesia and neuraxial anesthesia groups, including newborn weight, newborn Apgar score at 1 min and 5 min and newborn admission to the NICU (p < 0.001).

Conclusions

The growing incidence of general anesthesia was consistent with the trend of rising repeat cesarean delivery and MAP. low newborn Apgar score and high newborn admission to the NICU in general anesthesia group compared with neuraxial anesthesia group. The LMA was performed safely for airway management with enough fasting and careful gastric volume evaluation.
Assessing equity and quality indicators for older people – Adaptation and validation of the Assessing Care of Vulnerable Elders (ACOVE) checklist for the Portuguese care context
Authors: Taveira Adriana , Macedo Ana Paula , Rego Nazaré , Crispim José
Published: July 2022

Background

Development has promoted longer and healthier lives, but the rise in the proportion of older adults poses new challenges to health systems. Susceptibilities of older persons resulting from lower knowledge about services availability, health illiteracy, lower income, higher mental decline, or physical limitations need to be identified and monitored to assure the equity and quality of health care. The aim of this study was to develop equity indicators for the Assessing Care of Vulnerable Elders (ACOVE)-3 checklist and perform the first cross-cultural adaptation and validation of this checklist into Portuguese.

Methods

A scoping literature review of determinants or indicators of health (in)equity in the care of older people was performed. A total of 5 language experts and 18 health professionals were involved in the development and validation of the equity and quality indicators through expert opinion and focus groups. Data collected from focus groups was analyzed through directed or conventional content analysis. The usefulness of the indicators was assessed by analyzing the clinical records of 30 patients.

Results

The literature review revealed that there was a worldwide gap concerning equity indicators for older people primary health care. A structured and complete checklist composed of equity and quality indicators was obtained, validated and assessed. A significant number of non-screened quality or equity related potential occurrences that could have been avoided if the proposed indicators were implemented were detected. The percentage of non-registered indicators was 76.6% for quality and 96.7% for equity.

Conclusions

Applying the proposed checklist will contribute to improve the monitoring of the clinical situation of vulnerable older people and the planning of medical and social actions directed at this group.
A predictive model for recurrence after upfront surgery in patients with resectable pancreatic ductal adenocarcinoma (PDAC) by using preoperative clinical data and CT characteristics
Authors: Tian Ningzi , Wu Dong , Zhu Lei , Zeng Mengsu , Li Jianke , Wang Xiaolin
Published: July 2022

Background

The overall survival for patients with resectable PDAC following curative surgical resection hasn’t been improved significantly, as a considerable proportion of patients develop recurrence within a year. The purpose of this study was to develop and validate a predictive model to assess recurrence risk in patients with PDAC after upfront surgery by using preoperative clinical data and CT characteristics.

Methods

The predictive model was developed based on a retrospective set of 141 pancreatic cancer patients after surgery. A separate set of 77 patients was used to validate model. Between January 2017 and December 2019, all patients underwent multidetector pancreatic CT and upfront surgery. Univariable and multivariate Cox regression was used to determine the risk factors related to recurrence and then establish a nomogram to estimate the 1-year recurrence probability. The Harrell C-index was employed in evaluating the discrimination and calibration of the model.

Results

A total of 218 patients in this retrospective cohort. A recurrence model in nomogram form was developed with predictors including tumor size (hazard ratio [HR], 1.277; 95% CI 1.098, 1.495; P = 0.002), tumor density in the portal vein phase (HR, 0.598; 95% CI 0.424, 0.844; P = 0.003), peripancreatic infiltration (HR, 4.151; 95% CI 2.077, 8.298; P < 0.001), suspicious metastatic lymph node (HR, 2.561; 95% CI 1.653, 3.967; P < 0.001), Neutrophils/Lymphocytes ratio (HR, 1.111; 95% CI 1.016, 1.215; P = 0.020). The predictive nomogram had good discrimination capability with these predictors with an area under curve at 1 year of 0.84 (95%CI 0.77, 0.91) in the development set and 0.82 (95% CI 0.72, 0.92) and 0.84 (95% CI 0.74, 0.94) in the validation set for two radiologists reading respectively.

Conclusions

The model developed based on preoperative clinical data and CT characteristics of resectable pancreatic ductal adenocarcinoma patients, which can helpfully estimate the recurrence-free survival. It may be a useful tool for clinician to select optimal candidates for upfront surgery or neoadjuvant therapy.
A systematic review of health sciences students’ online learning during the COVID-19 pandemic
Authors: Abdull Mutalib Abdull Assyaqireen , Md. Akim Abdah , Jaafar Mohamad Hasif
Published: July 2022

Background

This study aims to analyse the effectiveness of distance learning during the COVID-19 pandemic among undergraduate health sciences students using systematic review. Online learning has been chosen as the best approach to continue offering education in this pandemic era. Method: The screening process was done using Scopus, ScienceDirect and PubMed based on the eligibility criteria. Out of 1486 studies, 1269 were screened. A total of 64 eligible studies obtained were included in the quantitative analysis. Results were categorized into i) student attitudes (perceptions/satisfactions/engagements), and ii) student learning outcomes, and compared to the Kirkpatrick model.

Results

Although facing difficulties, 50% of the studies was moderately satisfied with distance learning, while 36% was highly satisfied and 17% dissatisfied. Most studies (26%) reported flexibility in online learning. Internet issues (19%) and low interaction between learners and instructors (19%) were the most prevalent problems mentioned. Online education engages students better than traditional learning. The learning outcome was assessed using two categories: i) academic performance and ii) skill development. Most studies (72%) stated that online learning improves academic performance, 14% reported a drop, and 14% stated no effect, while an increase in clinical skills and communication skills were reported. Kirkpatrick evaluation revealed 80% of the studies obtained was evaluated at level 1 (reaction), 8% at level 2 (learning), 12% at level 3 (behaviour) and none at level 4 (results).

Conclusion

Overall, this systematic review found that the online learning performed better than expected during COVID-19, but the data gained is insufficient to say it is beneficial when compared to other types of teaching approaches.
Autonomous modeling of repetitive movement for rehabilitation exercise monitoring
Authors: Jatesiktat Prayook , Lim Guan Ming , Kuah Christopher Wee Keong , Anopas Dollaporn , Ang Wei Tech
Published: July 2022

Background

Insightful feedback generation for daily home-based stroke rehabilitation is currently unavailable due to the inefficiency of exercise inspection done by therapists. We aim to produce a compact anomaly representation that allows a therapist to pay attention to only a few specific sections in a long exercise session record and boost their efficiency in feedback generation.

Methods

This study proposes a data-driven technique to model a repetitive exercise using unsupervised phase learning on an artificial neural network and statistical learning on principal component analysis (PCA). After a model is built on a set of normal healthy movements, the model can be used to extract a sequence of anomaly scores from a movement of the same prescription.

Results

The method not only works on a standard marker-based motion capture system but also performs well on a more compact and affordable motion capture system based-on Kinect V2 and wrist-worn inertial measurement units that can be used at home. An evaluation of four different exercises shows its potential in separating anomalous movements from normal ones with an average area under the curve (AUC) of 0.9872 even on the compact motion capture system.

Conclusions

The proposed processing technique has the potential to help clinicians in providing high-quality feedback for telerehabilitation in a more scalable way.
Dengue and COVID-19: two sides of the same coin
Authors: Malavige Gathsaurie Neelika , Jeewandara Chandima , Ogg Graham S.
Published: July 2022

Background

Many countries in Asia and Latin America are currently facing a double burden of outbreaks due to dengue and COVID-19. Here we discuss the similarities and differences between the two infections so that lessons learnt so far from studying both infections will be helpful in further understanding their immunopathogenesis and to develop therapeutic interventions.

Main body

Although the entry routes of the SARS-CoV-2 and the dengue virus (DENV) are different, both infections result in a systemic infection, with some similar clinical presentations such as fever, headache, myalgia and gastrointestinal symptoms. However, while dengue is usually associated with a tendency to bleed, development of micro and macrothrombi is a hallmark of severe COVID-19. Apart from the initial similarities in the clinical presentation, there are further similarities between such as risk factors for development of severe illness, cytokine storms, endothelial dysfunction and multi-organ failure. Both infections are characterised by a delayed and impaired type I IFN response and a proinflammatory immune response. Furthermore, while high levels of potent neutralising antibodies are associated with protection, poorly neutralising and cross-reactive antibodies have been proposed to lead to immunopathology by different mechanisms, associated with an exaggerated plasmablast response. The virus specific T cell responses are also shown to be delayed in those who develop severe illness, while varying degrees of endothelial dysfunction leads to increased vascular permeability and coagulation abnormalities.

Conclusion

While there are many similarities between dengue and SARS-CoV-2 infection, there are also key differences especially in long-term disease sequelae. Therefore, it would be important to study the parallels between the immunopathogenesis of both infections for development of more effective vaccines and therapeutic interventions.
Expanded geographic distribution and host preference of Anopheles gibbinsi (Anopheles species 6) in northern Zambia
Authors: Gebhardt Mary E. , Krizek Rachel S. , Coetzee Maureen , Koekemoer Lizette L. , Dahan-Moss Yael , Mbewe David , Lupiya James Sichivula , Muleba Mbanga , Stevenson Jennifer C. , Moss William J. , Norris Douglas E. ,   For the Southern Africa International Centers of Excellence for Malaria Research
Published: July 2022

Background

Nchelenge District in northern Zambia suffers from holoendemic malaria transmission despite a decade of yearly indoor residual spraying (IRS) and insecticide-treated net (ITN) distributions. One hypothesis for this lack of impact is that some vectors in the area may forage in the early evening or outdoors. Anopheles gibbinsi specimens were identified in early evening mosquito collections performed in this study area, and further insight was gleaned into this taxon, including characterizing its genetic identity, feeding preferences, and potential role as a malaria vector.

Methods

Mosquitoes were collected in July and August 2019 by CDC light traps in Nchelenge District in indoor sitting rooms, outdoor gathering spaces, and animal pens from 16:00–22:00. Host detection by PCR, COI and ITS2 PCR, and circumsporozoite (CSP) ELISA were performed on all samples morphologically identified as An. gibbinsi, and a subset of specimens were selected for COI and ITS2 sequencing. To determine risk factors for increased abundance of An. gibbinsi, a negative binomial generalized linear mixed-effects model was performed with household-level variables of interest.

Results

Comparison of COI and ITS2 An. gibbinsi reference sequences to the NCBI database revealed > 99% identity to “Anopheles sp. 6” from Kenya. More than 97% of specimens were morphologically and molecularly consistent with An. gibbinsi. Specimens were primarily collected in animal pen traps (59.2%), followed by traps outdoors near where humans gather (24.3%), and traps set indoors (16.5%). Host DNA detection revealed a high propensity for goats, but 5% of specimens with detected host DNA had fed on humans. No specimens were positive for Plasmodium falciparum sporozoites. Animal pens and inland households > 3 km from Lake Mweru were both associated with increased An. gibbinsi abundance.

Conclusions

This is the first report of An. gibbinsi in Nchelenge District, Zambia. This study provided a species identity for unknown “An. sp. 6” in the NCBI database, which has been implicated in malaria transmission in Kenya. Composite data suggest that this species is largely zoophilic and exophilic, but comes into contact with humans and the malaria parasites they carry. This species should continue to be monitored in Zambia and neighbouring countries as a potential malaria vector.
Towards a framework for systematic reviews of the prevalence of exposure to environmental and occupational risk factors
Authors: Pega Frank , Momen Natalie C. , Bero Lisa , Whaley Paul
Published: July 2022

Exposure prevalence studies (as here defined) record the prevalence of exposure to environmental and occupational risk factors to human health. Applying systematic review methods to the synthesis of these studies would improve the rigour and transparency of normative products produced based on this evidence (e.g., exposure prevalence estimates). However, a dedicated framework, including standard methods and tools, for systematically reviewing exposure prevalence studies has yet to be created. We describe the need for this framework and progress made towards it through a series of such systematic reviews that the World Health Organization and the International Labour Organization conducted for their WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury (WHO/ILO Joint Estimates).

We explain that existing systematic review frameworks for environmental and occupational health cannot be directly applied for the generation of exposure prevalence estimates because they seek to synthesise different types of evidence (e.g., intervention or exposure effects on health) for different purposes (e.g., identify intervention effectiveness or exposure toxicity or carcinogenicity). Concepts unique to exposure prevalence studies (e.g., “expected heterogeneity”: the real, non-spurious variability in exposure prevalence due to exposure changes over space and/or time) also require new assessment methods. A framework for systematic reviews of prevalence of environmental and occupational exposures requires adaptation of existing methods (e.g., a standard protocol) and development of new tools or approaches (e.g., for assessing risk of bias and certainty of a body of evidence, including exploration of expected heterogeneity).

As part of the series of systematic reviews for the WHO/ILO Joint Estimates, the World Health Organization collaborating with partners has created a preliminary framework for systematic reviews of prevalence studies of exposures to occupational risk factors. This included development of protocol templates, data extraction templates, a risk of bias assessment tool, and an approach for assessing certainty of evidence in these studies. Further attention and efforts are warranted from scientific and policy communities, especially exposure scientists and policy makers, to establish a standard framework for comprehensive and transparent systematic reviews of studies estimating prevalence of exposure to environmental and occupational risk factors, to improve estimates, risk assessments and guidelines.
Establishment and evaluation of glucose-modified nanocomposite liposomes for the treatment of cerebral malaria
Authors: Tian Ya , Zheng Zhongyuan , Wang Xi , Liu Shuzhi , Gu Liwei , Mu Jing , Zheng Xiaojun , Li Yujie , Shen Shuo
Published: July 2022

Cerebral malaria (CM) is a life-threatening neurological complication caused by Plasmodium falciparum. About 627,000 patients died of malaria in 2020. Currently, artemisinin and its derivatives are the front-line drugs used for the treatment of cerebral malaria. However, they cannot target the brain, which decreases their effectiveness. Therefore, increasing their ability to target the brain by the nano-delivery system with brain-targeted materials is of great significance for enhancing the effects of antimalarials and reducing CM mortality. This study used glucose transporter 1 (GLUT1) on the blood–brain barrier as a target for a synthesized cholesterol-undecanoic acid–glucose conjugate. The molecular dynamics simulation found that the structural fragment of glucose in the conjugate faced the outside the phospholipid bilayers, which was conducive to the recognition of brain-targeted liposomes by GLUT1. The fluorescence intensity of the brain-targeted liposomes (na-ATS/TMP@lipoBX) in the mouse brain was significantly higher than that of the non-targeted liposomes (na-ATS/TMP@lipo) in vivo (P < 0.001) after intranasal administration. The infection and recurrence rate of the mice receiving na-ATS/TMP@lipoBX treatment were significantly decreased, which had more advantages than those of other administration groups. The analysis of pharmacokinetic data showed that na-ATS/TMP@lipoBX could enter the brain in both systemic circulation and nasal-brain pathway to treat malaria. Taken together, these results in this study provide a new approach to the treatment of cerebral malaria.

Graphical Abstract
A cellulose nanofibril-reinforced hydrogel with robust mechanical, self-healing, pH-responsive and antibacterial characteristics for wound dressing applications
Authors: Yang Guihua , Zhang Zhikun , Liu Kefeng , Ji Xingxiang , Fatehi Pedram , Chen Jiachuan
Published: July 2022

Background

Bacterial infection in wounds has become a major threat to human life and health. With the growth use of synthetic antibiotics and the elevated evolution of drug resistant bacteria in human body cells requires the development of novel wound curing strategies. Herein, a novel pH-responsive hydrogel (RPC/PB) was fabricated using poly(vinyl alcohol)-borax (PB) and natural antibiotic resveratrol grafted cellulose nanofibrils (RPC) for bacterial-infected wound management.

Results

In this hydrogel matrix, RPC conjugate was interpenetrated in the PB network to form a semi-interpenetrating network that exhibited robust mechanical properties (fracture strength of 149.6 kPa), high self-healing efficiency (> 90%), and excellent adhesion performance (tissue shear stress of 54.2 kPa). Interestingly, the induced RPC/PB hydrogel showed pH-responsive drug release behavior, the cumulative release amount of resveratrol in pH 5.4 was 2.33 times than that of pH 7.4, which was adapted well to the acidic wound microenvironment. Additionally, this RPC/PB hydrogel exhibited excellent biocompatibility and antioxidant effect. Moreover, in vitro and in vivo results revealed that such RPC/PB hydrogel had excellent antibacterial, skin tissue regeneration and wound closure capabilities.

Conclusion

Therefore, the generated RPC/PB hydrogel could be an excellent wound dressing for bacteria-infected wound healing.
Autophagy activation mediates resistance to FLT3 inhibitors in acute myeloid leukemia with FLT3-ITD mutation
Authors: Xu Dan , Chen Yishan , Yang Ying , Yin Zhao , Huang Changfen , Wang Qiang , Jiang Ling , Jiang Xuejie , Yin Changxin , Liu Qifa , Yu Guopan
Published: July 2022

Background

Autophagy plays a critical role in drug resistance in acute myeloid leukemia (AML), including the subtype with FLT3-ITD mutation. Yet how autophagy is activated and mediates resistance to FLT3 inhibitors in FLT3-ITD-positive AML remains unsure.

Methods

We detected the expression of autophagy markers in FLT3-ITD-positive leukemic cells after vs. before acquired resistance to FLT3 inhibitors; tested the stimulative effect of acquired D835Y mutation and bone marrow micro-environment (BME) on autophagy; explored the mechanism of autophagy mediating FLT3 inhibitor resistance.

Results

Sorafenib-resistant cells markedly overpresented autophagy markers in comparison with sorafenib-sensitive cells or the cells before sorafenib treatment. Both acquired D835Y mutation and BME activated cytoprotective autophagy to mediate FLT3 inhibitor resistance. Autophagy activation decreased the suppression efficacy of FLT3 inhibitors on FLT3 downstream signaling and then weakened their anti-leukemia effect. Inhibition of autophagy with CQ significantly enhanced the suppressive effect of FLT3 inhibitor on FLT3 downstream signaling, in the end overcame resistance to FLT3 inhibitors.

Conclusions

Autophagy might be stimulated by acquired mutation or BME, and bypass activate FLT3 downstream signaling to mediate FLT3 inhibitor resistance in FLT3-ITD-positive AML. Targeting autophagy could be a promising strategy to overcome resistance.
Low potassium disrupt intestinal barrier and result in bacterial translocation
Authors: Wu Haishan , Huang Rong , Fan Jinjin , Luo Ning , Yang Xiao
Published: July 2022

Background

Bacterial translocation was observed in critical illness and patients with chronic diseases such as liver cirrhosis and chronic kidney disease (CKD). Hypokalemia is a common complication in these diseases. Whether low potassium diet may increase intestinal permeability and result in bacterial translocation lack of evidence. The present study was aimed to investigate the potential effects of LK on intestinal permeability.

Methods

Grade 8-week-old male Bal B/C mice were randomly placed either on a normal potassium (NK) mouse chow or a low potassium (LK) diet for 28 days. Intestinal permeability and expression of tight junction proteins were compared between the two groups.

Results

Compared with the NK group, the mice in LK group had significantly lower serum potassium level, increased levels of plasmas endotoxin and plasma d-lactate. The bacterial translocation was higher and in occurred mainly in mesenteric lymph nodes (MLN), liver and spleen. The pathologic change of small intestine was obvious with thinner villus lamina propria, shorter crypt depth and thinner intestinal wall. Slight increases in the expression of proteins and mRNA levels of both claudin-1 and claudin-2 were observed in LK group.

Conclusions

Low potassium diet could increase intestinal permeability and thereby lead to bacterial translocation, which was suspected to result from impaired intestinal epithelial barrier and biological barrier.
Asafoetida exerts neuroprotective effect on oxidative stress induced apoptosis through PI3K/Akt/GSK3β/Nrf2/HO-1 pathway
Authors: Huang Qianqian , Zhang Chen , Dong Shi , Han Junwen , Qu Sihao , Xie Tianshu , Zhao Haibin , Shi Yuanyuan
Published: July 2022

Background

Alzheimer's Disease (AD) is a serious neurodegenerative disease and there is currently no effective treatment for AD progression. The use of TCM as a potential treatment strategy for AD is an evolving field of investigation. Asafoetida (ASF), an oleo-gum-resin isolated from Ferula assa-foetida root, has been proven to possess antioxidative potential and neuroprotective effects, which is closely associated with the neurological disorders. However, the efficacy and further mechanisms of ASF in AD experimental models are still unclear.

Methods

A cognitive impairment of mouse model induced by scopolamine was established to determine the neuroprotective effects of ASF in vivo, as shown by behavioral tests, biochemical assays, Nissl staining, TUNEL staining, Immunohistochemistry, western blot and qPCR. Furthermore, the PC12 cells stimulated by H2O2 were applied to explore the underlying mechanisms of ASF-mediated efficacy. Then, the UPLCM analysis and integrated network pharmacology approach was utilized to identified the main constitutes of ASF and the potential target of ASF against AD, respectively. And the main identified targets were validated in vitro by western blot, qPCR and immunofluorescence staining.

Results

In vivo, ASF treatment significantly ameliorated cognitive impairment induced by scopolamine, as evidenced by improving learning and memory abilities, and reducing neuronal injury, cholinergic system impairment, oxidative stress and apoptosis in the hippocampus of mice. In vitro, our results validated that ASF can dose-dependently attenuated H2O2-induced pathological oxidative stress in PC12 cells by inhibiting ROS and MDA production, as well as promoting the activities of SOD, CAT, GSH. We also found that ASF can significantly suppressed the apoptosis rate of PC12 cells increased by H2O2 exposure, which was confirmed by flow cytometry analysis. Moreover, treatment with ASF obviously attenuated H2O2-induced increase in caspase-3 and Bax expression levels, as well as decrease in Bcl-2 protein expression. KEGG enrichment analysis indicated that the PI3K/Akt/GSK3β/Nrf2 /HO-1pathway may be involved in the regulation of cognitive impairment by ASF. The results of western blot, qPCR and immunofluorescence staining of vitro assay proved it.

Conclusions

Collectively, our work first uncovered the significant neuroprotective effect of ASF in treating AD in vivo. Then, we processed a series of vitro experiments to clarify the biological mechanism action. These data demonstrate that ASF can inhibit oxidative stress induced neuronal apoptosis to foster the prevention of AD both in vivo and in vitro, and it may exert the function of inhibiting AD through PI3K/Akt/GSK3β/Nrf2/HO-1pathway.
Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application
Authors: Zhang Fusheng , Liu Haiyang , Duan Meiqi , Wang Guang , Zhang Zhenghou , Wang Yutian , Qian Yiping , Yang Zhi , Jiang Xiaofeng
Published: July 2022

The tumor microenvironment (TME), which is regulated by intrinsic oncogenic mechanisms and epigenetic modifications, has become a research hotspot in recent years. Characteristic features of TME include hypoxia, metabolic dysregulation, and immunosuppression. One of the most common RNA modifications, N6-methyladenosine (m6A) methylation, is widely involved in the regulation of physiological and pathological processes, including tumor development. Compelling evidence indicates that m6A methylation regulates transcription and protein expression through shearing, export, translation, and processing, thereby participating in the dynamic evolution of TME. Specifically, m6A methylation-mediated adaptation to hypoxia, metabolic dysregulation, and phenotypic shift of immune cells synergistically promote the formation of an immunosuppressive TME that supports tumor proliferation and metastasis. In this review, we have focused on the involvement of m6A methylation in the dynamic evolution of tumor-adaptive TME and described the detailed mechanisms linking m6A methylation to change in tumor cell biological functions. In view of the collective data, we advocate treating TME as a complete ecosystem in which components crosstalk with each other to synergistically achieve tumor adaptive changes. Finally, we describe the potential utility of m6A methylation-targeted therapies and tumor immunotherapy in clinical applications and the challenges faced, with the aim of advancing m6A methylation research.