bluuebunny/crossref_metadata_2025 huggingface dataset:
Information extraction from free text for aiding transdiagnostic psychiatry: constructing NLP pipelines tailored to clinicians’ needs
Authors: Turner Rosanne J. , Coenen Femke , Roelofs Femke , Hagoort Karin , Härmä Aki , Grünwald Peter D. , Velders Fleur P. , Scheepers Floortje E.
Published: June 2022

Background

Developing predictive models for precision psychiatry is challenging because of unavailability of the necessary data: extracting useful information from existing electronic health record (EHR) data is not straightforward, and available clinical trial datasets are often not representative for heterogeneous patient groups. The aim of this study was constructing a natural language processing (NLP) pipeline that extracts variables for building predictive models from EHRs. We specifically tailor the pipeline for extracting information on outcomes of psychiatry treatment trajectories, applicable throughout the entire spectrum of mental health disorders (“transdiagnostic”).

Methods

A qualitative study into beliefs of clinical staff on measuring treatment outcomes was conducted to construct a candidate list of variables to extract from the EHR. To investigate if the proposed variables are suitable for measuring treatment effects, resulting themes were compared to transdiagnostic outcome measures currently used in psychiatry research and compared to the HDRS (as a gold standard) through systematic review, resulting in an ideal set of variables. To extract these from EHR data, a semi-rule based NLP pipeline was constructed and tailored to the candidate variables using Prodigy. Classification accuracy and F1-scores were calculated and pipeline output was compared to HDRS scores using clinical notes from patients admitted in 2019 and 2020.

Results

Analysis of 34 questionnaires answered by clinical staff resulted in four themes defining treatment outcomes: symptom reduction, general well-being, social functioning and personalization. Systematic review revealed 242 different transdiagnostic outcome measures, with the 36-item Short-Form Survey for quality of life (SF36) being used most consistently, showing substantial overlap with the themes from the qualitative study. Comparing SF36 to HDRS scores in 26 studies revealed moderate to good correlations (0.62—0.79) and good positive predictive values (0.75—0.88). The NLP pipeline developed with notes from 22,170 patients reached an accuracy of 95 to 99 percent (F1 scores: 0.38 – 0.86) on detecting these themes, evaluated on data from 361 patients.

Conclusions

The NLP pipeline developed in this study extracts outcome measures from the EHR that cater specifically to the needs of clinical staff and align with outcome measures used to detect treatment effects in clinical trials.
A prediction model for xerostomia in locoregionally advanced nasopharyngeal carcinoma patients receiving radical radiotherapy
Authors: Li Minying , Zhang Jingjing , Zha Yawen , Li Yani , Hu Bingshuang , Zheng Siming , Zhou Jiaxiong
Published: June 2022

Background

This study was to evaluate the predictors of xerostomia and Grade 3 xerostomia in locoregionally advanced nasopharyngeal carcinoma (NPC) patients receiving radical radiotherapy and establish prediction models for xerostomia and Grade 3 xerostomia based on the predictors.

Methods

Totally, 365 patients with locoregionally advanced NPC who underwent radical radiotherapy were randomly divided into the training set (n = 255) and the testing set (n = 110) at a ratio of 7:3. All variables were included in the least absolute shrinkage and selection operator regression to screen out the potential predictors for xerostomia as well as the Grade 3 xerostomia in locoregionally advanced NPC patients receiving radical radiotherapy. The random forest (RF), a decision tree classifier (DTC), and extreme-gradient boosting (XGB) models were constructed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the curve (AUC) and accuracy were analyzed to evaluate the predictive performance of the models.

Results

In the RF model for predicting xerostomia, the sensitivity was 1.000 (95%CI 1.000–1.000), the PPV was 0.990 (95%CI 0.975–1.000), the NPV was 1.000 (95%CI 1.000–1.000), the AUC was 0.999 (95%CI 0.997–1.000) and the accuracy was 0.992 (95%CI 0.981–1.000) in the training set. The sensitivity was 0.933 (95%CI 0.880–0.985), the PPV was 0.933 (95%CI 0.880–0.985), and the AUC was 0.915 (95%CI 0.860–0.970) in the testing set. Hypertension, age, total radiotherapy dose, dose at 50% of the left parotid volume, mean dose to right parotid gland, mean dose to oral cavity, and course of induction chemotherapy were important variables associated with the risk of xerostomia in locoregionally advanced NPC patients receiving radical radiotherapy. The AUC of DTC model for predicting xerostomia was 0.769 (95%CI 0.666–0.872) in the testing set. The AUC of the XGB model for predicting xerostomia was 0.834 (0.753–0.916) in the testing set. The RF model showed the good predictive ability with the AUC of 0.986 (95%CI 0.972–1.000) in the training set, and 0.766 (95%CI 0.626–0.905) in the testing set for identifying patients who at high risk of Grade 3 xerostomia in those with high risk of xerostomia.

Conclusions

An RF model for predicting xerostomia in locoregionally advanced NPC patients receiving radical radiotherapy and an RF model for predicting Grade 3 xerostomia in those with high risk of xerostomia showed good predictive ability.
Learning from errors? The impact of erroneous example elaboration on learning outcomes of medical statistics in Chinese medical students
Authors: Wang Chengwei , Li Junyi , Li Haiyan , Xia Yijing , Wang Xiaoyu , Xie Yufei , Wu Jinyang
Published: June 2022

Background

Constructivism theory has suggested that constructing students’ own meaning is essential to successful learning. The erroneous example can easily trigger learners’ confusion and metacognition, which may “force” students to process the learning material and construct meaning deeply. However, some learners exhibit a low level of elaboration activity and spend little time on each example. Providing instructional scaffolding and elaboration training may be an efficient method for addressing this issue. The current study conducted a randomized controlled trial to examine the effectiveness of erroneous example elaboration training on learning outcomes and the mediating effects of metacognitive load for Chinese students in medical statistics during the COVID-19 pandemic.

Methods

Ninety-one third-year undergraduate medical students were randomly assigned to the training group (n = 47) and the control group (n = 44). Prerequisite course performance and learning motivation were collected as covariates. The mid-term exam and final exam were viewed as posttest and delayed-test to make sure the robustness of the training effect. The metacognitive load was measured as a mediating variable to explain the relationship between the training and academic performance.

Results

The training significantly improved both posttest and delayed-test performance compared with no training (Fposttest = 26.65, p < 0.001, Partial η2 = 0.23; Fdelayed test = 38.03, p < 0.001, Partial η2 = 0.30). The variation trend in metacognitive load in the two groups was significantly different (F = 2.24, p < 0.05, partial η2 = 0.20), but metacognitive load could not explain the positive association between the treatment and academic performance (β = − 0.06, se = 0.24, 95% CI − 0.57 to 0.43).

Conclusions

Erroneous example learning and metacognitive demonstrations are effective for academic performance in the domain of medical statistics, but their underlying mechanism merits further study.
Evaluation of an experiential clinical learning option during pandemic teaching suspensions
Authors: Canfield Jules , Truong Ve , Bereznicka Agata , Lunze Karsten
Published: June 2022

Background

As students’ direct patient contact was suspended because of COVID-19-related restrictions, we revised our clinical addiction medicine curriculum for students to learn about the different multidisciplinary clinical models delivered at our hospital and in community settings. Our aim was to provide an overview of clinical modalities and familiarize learners with clinician and patient experiential perspectives.

Methods

We implemented a multi-pronged approach, offering an overview of clinical care programs through remote panels involving care providers at the clinics where students had previously been scheduled for in-person rotations. This included inpatient and office-based addiction services, addiction treatment program for adolescents and young adults, integrated addiction care and HIV primary care clinic, and opioid use urgent care clinic. Beyond having them join outpatient telehealth clinic visits, students also participated in an online panel involving patients in recovery to gain familiarity with their care perspectives; and joined a panel with recovery coaches to get further insights into patient challenges in clinical settings. Students further participated in remote opioid treatment trainings and observed clinical rounds of inpatient addiction consults and adolescent clinic team meetings.

Results

With this revised curriculum, students learned about the variety of clinical modalities at the height of our hospital’s COVID-19 pandemic burden. The evaluation suggested that students appreciated the authenticity of accounts from patients and providers about their challenges and satisfaction related to clinical care. While in a remote learning setting, students overall wished for more personal interaction with patients and providers. They also noted a lack of group cohesion and connection that they felt would otherwise have been met in an in-person program.

Conclusions

Remote learning allowed our program to connect trainees to the multidisciplinary field of addiction medicine despite the COVID-19 pandemic. In future program iterations, we will consider hybrid formats of in-person learning experiences with direct patient and faculty contact where possible, combined with online provider and patient panels possibly, in addition to virtual breakout formats to facilitate more personal student-patient and student-faculty interactions.
Dysferlinopathy misdiagnosed with juvenile polymyositis in the pre-symptomatic stage of hyperCKemia: a case report and literature review
Authors: Contreras-Cubas Cecilia , Barajas-Olmos Francisco , Frayre-Martínez Maria Inés , Siordia-Reyes Georgina , Guízar-Sánchez Claudia C. , García-Ortiz Humberto , Orozco Lorena , Baca Vicente
Published: June 2022

Background

Dysferlinopathy encompasses a group of rare muscular dystrophies caused by recessive mutations in the DYSF gene. The phenotype ranges from asymptomatic elevated serum creatine kinase (hyperCKemia) to selective and progressive involvement of the proximal and/or distal muscles of the limbs. Bohan and Peter criteria are the most widely used for the diagnosis of polymyositis, but they have limitations and can misclassify muscular dystrophies with inflammation as polymyositis. Most dysferlinopathy patients have muscle biopsies with inflammation and thus are vulnerable to misdiagnosis with polymyositis and inappropriate treatment with steroids and immunosuppressors.

Case presentation

We describe a 14 years-old male patient who was referred for assessment of asymptomatic hyperCKemia (26,372 IU/L). An X-linked dystrophinopathy initially was ruled out by direct genetic testing. Juvenile polymyositis was considered based on muscle biopsy, creatine kinase levels, and electromyography changes. Corticosteroid treatment triggered proximal lower limb muscular weakness, and no full muscular strength recovery was observed after corticosteroid withdrawal. Based on these observations, a limb-girdle muscular dystrophy (LGMD) was suspected, and LGMDR2 was confirmed by whole exome sequencing.

Conclusion

We report a dysferlinopathy patient who was misdiagnosed with juvenile polymyositis and explore in a literature review how common such misdiagnoses are. With diagnosis based only on routine clinicopathological examinations, distinguishing an inflammatory myopathy from dysferlinopathy is quite difficult. We suggest that before establishing a diagnosis of “definite” or “probable” juvenile polymyositis, according to Bohan and Peter or current ACR/EULAR criteria, a muscular dystrophy must first be ruled out.
Blood gene expression risk profiles and interstitial lung abnormalities: COPDGene and ECLIPSE cohort studies
Authors: Moll Matthew , Hobbs Brian D. , Menon Aravind , Ghosh Auyon J. , Putman Rachel K. , Hino Takuya , Hata Akinori , Silverman Edwin K. , Quackenbush John , Castaldi Peter J. , Hersh Craig P. , McGeachie Michael J. , Sin Don D. , Tal-Singer Ruth , Nishino Mizuki , Hatabu Hiroto , Hunninghake Gary M. , Cho Michael H.
Published: June 2022

Background

Interstitial lung abnormalities (ILA) are radiologic findings that may progress to idiopathic pulmonary fibrosis (IPF). Blood gene expression profiles can predict IPF mortality, but whether these same genes associate with ILA and ILA outcomes is unknown. This study evaluated if a previously described blood gene expression profile associated with IPF mortality is associated with ILA and all-cause mortality.

Methods

In COPDGene and ECLIPSE study participants with visual scoring of ILA and gene expression data, we evaluated the association of a previously described IPF mortality score with ILA and mortality. We also trained a new ILA score, derived using genes from the IPF score, in a subset of COPDGene. We tested the association with ILA and mortality on the remainder of COPDGene and ECLIPSE.

Results

In 1469 COPDGene (training n = 734; testing n = 735) and 571 ECLIPSE participants, the IPF score was not associated with ILA or mortality. However, an ILA score derived from IPF score genes was associated with ILA (meta-analysis of test datasets OR 1.4 [95% CI: 1.2–1.6]) and mortality (HR 1.25 [95% CI: 1.12–1.41]). Six of the 11 genes in the ILA score had discordant directions of effects compared to the IPF score. The ILA score partially mediated the effects of age on mortality (11.8% proportion mediated).

Conclusions

An ILA gene expression score, derived from IPF mortality-associated genes, identified genes with concordant and discordant effects on IPF mortality and ILA. These results suggest shared, and unique biologic processes, amongst those with ILA, IPF, aging, and death.
Identification and functional characterization of the first deep intronic GLA mutation (IVS4+1326C>T) causing renal variant of Fabry disease
Authors: Dai Xuantong , Zong Xue , Pan Xiaoxia , Lu Wei , Jiang Geng-Ru , Lin Fujun
Published: June 2022

Background

Fabry disease (FD, OMIM #301500) is an X-linked lysosomal disorder caused by the deficiency of α-galactosidase A (α-GalA), encoded by the GLA gene. Among more than 1100 reported GLA mutations, few were deep intronic mutations which have been linked to classic and cardiac variants of FD.

Methods and results

We report a novel hemizygous deep intronic GLA mutation (IVS4+1326C>T) in a 33-year-old Chinese man with a mild α-GalA deficiency phenotype involving isolated proteinuria and predominant globotriaosylceramide deposits in podocytes. IVS4+1326C>T, which appears to be the first deep intronic GLA mutation associated with renal variant of FD, was identified by Sanger sequencing the entire GLA genomic DNA sequence of the patient’s peripheral mononuclear blood lymphocytes (PBMCs). Further sequencing of cDNA from PBMCs of the patient revealed a minor full-length GLA transcript accounting for about 25% of total GLA transcript, along with two major aberrantly spliced GLA transcripts encoding mutant forms of α-GalA with little enzyme activity characterized by in vitro α-GalA overexpression system in the HEK293T cells. Thus, the combined clinical phenotype, genetic analysis and functional studies verified the pathogenicity of IVS4+1326C>T.

Conclusions

The identification of IVS4+1326C>T establishes a link between deep intronic GLA mutation and the renal variant of FD, which extends the mutation spectrum in GLA gene and justifies further study of how IVS4+1326C>T and potentially other deep intronic GLA mutations contribute to Fabry podocytopathy through aberrant splicing. Future studies should also assess the true incidence of IVS4+1326C>T in patients with different variants of FD, which may improve early genetic diagnosis to allow timely treatment that can prevent disease progression and improve survival.
Assessing the impact of a novel house design on the incidence of malaria in children in rural Africa: study protocol for a household-cluster randomized controlled superiority trial
Authors: Mshamu Salum , Mmbando Arnold , Meta Judith , Bradley John , Bøjstrup Thomas Chevalier , Day Nicholas P. J. , Mukaka Mavuto , Okumu Fredros , Olotu Ally , Pell Christopher , Deen Jacqueline , Knudsen Jakob , Lindsay Steven W. , von Seidlein Lorenz
Published: June 2022

Background

Traditional rural housing in hot, humid regions of sub-Saharan Africa usually consists of single-level, poorly ventilated dwellings. Houses are mostly poorly screened against malaria mosquitoes and limited airflow discourages the use of bednets resulting in high indoor transmission. This study aims to determine whether living in a novel design house with elevated bedrooms and permeable screened walls reduces malaria, respiratory tract infections, and diarrhoea among children in rural Tanzania.

Methods/study design

This is a household-randomized, controlled study in 60 villages in Mtwara, Tanzania. A total of 550 households are randomly selected, 110 of which are allocated a novel design house and 440 households continue to reside in traditional houses. A dynamic cohort of about 1650 children under 13 years will be enrolled and followed for 3 years, approximately 330 living in novel design houses and 1320 in traditional rural houses. The primary endpoint is the incidence of malaria; secondary endpoints are incidences of acute respiratory tract infections and diarrhoea diseases detected by passive and active surveillance. Exposure to malaria vectors will be assessed using light traps in all study houses. Structural, economic, and social science studies will assess the durability, cost-effectiveness, and acceptability of the new houses compared with traditional housing. Environmental data will be collected indoors and outdoors in study homes to assess the differences between house typologies.

Discussion

This is the first randomized controlled trial to assess the protective efficacy of a new house design targeting malaria in sub-Saharan Africa. The findings of this study could influence the future construction of homes in hot and humid zones of Africa.

Trial registration

ClinicalTrials.govNCT04529434. Registered on August 27, 2020
Parasternal After Cardiac Surgery (PACS): a prospective, randomised, double-blinded, placebo-controlled trial study protocol for evaluating a continuous bilateral parasternal block with lidocaine after open cardiac surgery through sternotomy
Authors: Larsson Mark , Sartipy Ulrik , Franco-Cereceda Anders , Öwall Anders , Jakobsson Jan
Published: June 2022

Background

Multimodal analgesia that provides optimal pain treatment with minimal side effects is important for optimal recovery after open cardiac surgery. Regional anaesthesia can be used to block noxious nerve signals. Because sternotomy causes considerable pain that lasts several days, a continuous nerve block is advantageous. Previous studies on continuous sternal wound infusion or parasternal blocks with long-acting local anaesthetics have shown mixed results. This study aims to determine whether a continuous bilateral parasternal block with lidocaine, which is a short-acting local anaesthetic that has a favourable safety/toxicity profile, results in effective analgesia. We hypothesise that a 72-hour continuous parasternal block with 0.5% lidocaine at a rate of 7 ml/hour on each side provides effective analgesia and reduces opioid requirement. We will evaluate whether recovery is enhanced.

Methods

In a prospective, randomised, double-blinded manner, 45 patients will receive a continuous parasternal block with either 0.5% lidocaine or saline. The primary endpoint is cumulated intravenous morphine by patient-controlled analgesia at 72 hours. Secondary end-points include the following: (1) the cumulated numerical rating scale (NRS) score recorded three times daily at 72 hours; (2) the cumulated NRS score after two deep breaths three times daily at 72 hours; (3) the NRS score at rest and after two deep breaths at 2, 4, 8 and 12 weeks after surgery; (4) oxycodone requirement at 2, 4, 8 and 12 weeks after surgery; (5) Quality of Recovery-15 score preoperatively compared with that at 24, 48 and 72 hours, and at 2, 4, 8 and 12 weeks after surgery; (6) preoperative peak expiratory flow compared with postoperative daily values for 3 days; and (7) serum concentrations of interleukin-6 and lidocaine at 1, 24, 48 and 72 hours postoperatively compared with preoperative values.

Discussion

Adequate analgesia is important for quality of care and vital to a rapid recovery after cardiac surgery. This study aims to determine whether a continuous parasternal block with a short-acting local anaesthetic improves analgesia and recovery after open cardiac procedures.

Trial registration

The study was registered in the European Clinical Trials Database on 27/9/2019 (registration number: 2018-004672-35).
Metabolomics with severity of radiographic knee osteoarthritis and early phase synovitis in middle-aged women from the Iwaki Health Promotion Project: a cross-sectional study
Authors: Sasaki Eiji , Yamamoto Hiroyuki , Asari Toru , Matsuta Rira , Ota Seiya , Kimura Yuka , Sasaki Shizuka , Ishibashi Kyota , Yamamoto Yuji , Kami Kenjiro , Ando Masataka , Tsuda Eiichi , Ishibashi Yasuyuki
Published: June 2022

Background

Osteoarthritis (OA) is one of the costliest and most disabling forms of arthritis, and it poses a major public health burden; however, its detailed etiology, pathophysiology, and metabolism remain unclear. Therefore, the purpose of this study was to investigate the key plasma metabolites and metabolic pathways, especially focusing on radiographic OA severity and synovitis, from a large sample cohort study.

Methods

We recruited 596 female volunteers who participated in the Iwaki Health Promotion Project in 2017. Standing anterior-posterior radiographs of the knee were classified by the Kellgren-Lawrence (KL) grade. Radiographic OA was defined as a KL grade of ≥ 2. Individual effusion-synovitis was scored according to the Whole-Organ Magnetic Resonance Imaging Scoring System. Blood samples were collected, and metabolites were extracted from the plasma. Metabolome analysis was performed using capillary electrophoresis time-of-flight mass spectrometry. To investigate the relationships among metabolites, the KL grade, and effusion-synovitis scores, partial least squares with rank order of groups (PLS-ROG) analyses were performed.

Results

Among the 82 metabolites examined in this assay, PLS-ROG analysis identified 42 metabolites that correlated with OA severity. A subsequent metabolite set enrichment analysis using the significant metabolites showed the urea cycle and tricarboxylic acid cycle as key metabolic pathways. Moreover, further PLS-ROG analysis identified cystine (p= 0.009), uric acid (p= 0.024), and tyrosine (p= 0.048) as common metabolites associated with both OA severity and effusion-synovitis. Receiver operating characteristic analyses showed that cystine levels were moderately associated with radiographic OA (p< 0.001, area under the curve 0.714, odds ratio 3.7).

Conclusion

Large sample metabolome analyses revealed that cystine, an amino acid associated with antioxidant activity and glutamate homeostasis, might be a potential metabolic biomarker for radiographic osteoarthritis and early phase synovitis.
Isolation of high-quality RNA for high throughput applications from secondary metabolite-rich Crocus sativus L.
Authors: Wani Umer Majeed , Wani Zubair Ahmad , Koul Aabid M. , Amin Asif , Shah Basit Amin , Farooq Faizah , Qadri Raies A.
Published: June 2022

Objective

Isolating high-quality RNA is a basic requirement while performing high throughput sequencing, microarray, and various other molecular investigations. However, it has been quite challenging to isolate RNA with absolute purity from plants likeCrocus sativusthat are rich in secondary metabolites, polysaccharides, and other interfering compounds which often irreversibly co-precipitate with the RNA. While many methods have been proposed for RNA extraction including CTAB, TriZol, and SDS-based methods, which invariably yield less and poor quality RNA and hence it necessitated the isolation of high-quality RNA suitable for high throughput applications.

Results

In the present study we made certain adjustments to the available protocols including modifications in the extraction buffer itself and the procedure employed. Our method led to the isolation of clear and non-dispersive total RNA with an RNA Integrity Number (RIN) value greater than 7.5. The quality of the RNA was further assessed by qPCR-based amplification of mRNA and mature miRNAs such as Cs-MIR166c and Cs-MIR396a.
A long-term anti-inflammation markedly alleviated high-fat diet-induced obesity by repeated administrations of overexpressing IL10 human umbilical cord-derived mesenchymal stromal cells
Authors: Wang Liudi , Gao Tianyun , Li Yu , Xie Yuanyuan , Zeng Sheng , Tai Chenxu , Feng Yirui , Shen Pingping , Wang Bin
Published: June 2022

Objectives

Obesity is a chronic process and could activate various inflammatory responses, which in turn aggravates obesity and related metabolic syndrome. Here we explored whether long-term inhibition of inflammation could successfully alleviate high-fat diet (HFD)-induced obesity.

Methods

We constructed stable overexpressing interleukin 10 (IL10) human umbilical cord-derived mesenchymal stromal cells (HUCMSCs) which repeatedly were applied to obesity mice with HFD feeding to obtain a long-term anti-inflammation based on the prominent anti-inflammation effects of IL10 and immunomodulatery effects of HUCMSCs. Then we monitored the features of obesity including body weight, serum ALT, AST, and lipids. In addition, glucose homeostasis was determined by glucose tolerance and insulin sensitivity tests. The infiltrated macrophages in adipose tissues and hepatic lipid accumulation were detected, and the expressions of adipogenesis and inflammatory genes in adipose tissues were examined by real-time (RT) PCR and western blot analysis.

Results

Compared with HUCMSCs, IL10-HUCMSCs treatment had much better anti-obesity effects including body weight reduction, less hepatic lipids accumulation, lower amount and size of adipocyte, greater glucose tolerance, less systemic insulin resistance, and less adipose tissue inflammation in HFD feeding mice. Finally, IL10-HUCMSCs could decrease the activation of MAPK JNK of adipose tissue induced by HFD. The inhibition of MAPK JNK signal pathway by a small chemical molecule SP600125 in 3T3-L1 cells, a preadipocyte line, reduced the differentiation of adipocytes and lipid droplet accumulation.

Conclusion

A lasting anti-inflammation based on gene modified stem cell therapy is an effective strategy in preventing diet-induced obesity and obesity-related metabolic syndrome.
Glutamate regulates gliosis of BMSCs to promote ENS regeneration through α-KG and H3K9/H3K27 demethylation
Authors: Fan Mengke , Shi Huiying , Yao Hailing , Wang Weijun , Zhang Yurui , Jiang Chen , Lin Rong
Published: June 2022

Background

There is a lack of effective therapies for enteric nervous system (ENS) injury. Our previous study showed that transplanted bone marrow-derived mesenchymal stem cells (BMSCs) play a “glia-like cells” role in initiating ENS regeneration in denervated mice. Cellular energy metabolism is an important factor in maintaining the biological characteristics of stem cells. However, how cellular energy metabolism regulates the fate of BMSCs in the ENS-injured microenvironment is unclear.

Methods

The biological characteristics, energy metabolism, and histone methylation levels of BMSCs following ENS injury were determined. Then, glutamate dehydrogenase 1 (Glud1) which catalyzes the oxidative deamination of glutamate to α-KG was overexpressed (OE) in BMSCs. Further, OE-Glud1 BMSCs were targeted–transplanted into the ENS injury site of denervated mice to determine their effects on ENS regeneration.

Results

In vitro, in the ENS-injured high-glutamate microenvironment, the ratio of α-ketoglutarate (α-KG) to succinate (P < 0.05), the histone demethylation level (P < 0.05), the protein expression of glial cell markers (P < 0.05), and the gene expression of Glud1 (P < 0.05) were significantly increased. And the binding of H3K9me3 to the GFAP, S100B, and GDNF promoter was enhanced (P < 0.05). Moreover, α-KG treatment increased the monomethylation and decreased the trimethylation on H3K9 (P < 0.01) and H3K27 (P < 0.05) in BMSCs and significantly upregulated the protein expression of glial cell markers (P < 0.01), which was reversed by the α-KG competitive inhibitor D-2-hydroxyglutarate (P < 0.05). Besides, overexpression of Glud1 in BMSCs exhibited increases in monomethylation and decreases in trimethylation on H3K9 (P < 0.05) and H3K27 (P < 0.05), and upregulated protein expression of glial cell markers (P < 0.01). In vivo, BMSCs overexpressing Glud1 had a strong promotion effect on ENS regeneration in denervated mice through H3K9/H3K27 demethylation (P < 0.05), and upregulating the expression of glial cell protein (P < 0.05).

Conclusions

BMSCs overexpressing Glud1 promote the expression of glial cell markers and ENS remodeling in denervated mice through regulating intracellular α-KG and H3K9/H3K27 demethylation.
Graphical structure of double controlled metric-like spaces with an application
Authors: Hammad Hasanen A. , Aydi Hassen , De la Sen Manuel
Published: June 2022

The aim of the manuscript is to present the concept of a graphical double controlled metric-like space (for short, GDCML-space). The structure of an open ball of the proposed space is also discussed, and the newly presented ideas are explained with a new technique by depicting appropriately directed graphs. Moreover, we present some examples in a graph structure to prove that our results are sharp compared to those in the previous papers. Further, the existence of a solution to the boundary value problem originating from the transverse oscillations of a homogeneous bar (TOHB) is obtained theoretically.
Detection range of two acoustic transmitters in four reservoir habitat types using passive receivers
Authors: Fincel Mark , Goble Cameron , Gravenhof Dylan , Morey Hilary
Published: June 2022

Background

Recently, South Dakota Department of Game, Fish, and Parks (SDGFP), has undertaken a suite of rigorous acoustic telemetry studies. The goals and scope of the individual research projects vary but all use the same receiver array throughout Lake Sharpe in central South Dakota. Prior to initiating the telemetry studies, we sought to describe the detection probability of receivers from a representation of habitats within Lake Sharpe, South Dakota. We used both a V9-2H transmitter and a V13-1L transmitter in combination with VR2W 69 kHz passive receivers [all from Innovasea (Vemco)] to determine detection probability in four novel habitats of Lake Sharpe. Both transmitter and receiver were moored at fixed distances (200 m 400, and 600 m) for multiple consecutive days and detection probability compared between transmitter type, distance, site, and diel period using ANOVA following arcsine square-root transformation.

Results

We found significant differences in detection probability between the four habitat types for both the V9 and V13 transmitters. Sites protected from wind and wave action, and with little boat traffic, had larger detection ranges compared to areas that were wind exposed and host more boat traffic. The site immediately downstream from a hydroelectric dam that is exposed to both high wind fetch and is popular for boating, exhibited the poorest detection probability at all distances for both transmitter types. V13 transmitters consistently exhibited greater detection probability relative to V9 transmitters and this difference was greater at further distances. In general, detection probability was higher at nighttime compared to daytime and these differences were significant dependent on transmitter, site, and distance.

Conclusions

Using the information presented, SDGFP has modified their receiver array to maximize the ability to detect acoustic transmitters in the novel habitats of Lake Sharpe. Specifically, receiver spacing was reduced and/or expanded dependent on the distance, where 50% detection probability was attained. More work is needed to identify those factors that influence detection probability of acoustic telemetry systems.
MiR-1248: a new prognostic biomarker able to identify supratentorial hemispheric pediatric low-grade gliomas patients associated with progression
Authors: Catanzaro Giuseppina , Besharat Zein Mersini , Carai Andrea , Jäger Natalie , Splendiani Elena , Colin Carole , Po Agnese , Chiacchiarini Martina , Citarella Anna , Gianno Francesca , Cacchione Antonella , Miele Evelina , Diomedi Camassei Francesca , Gessi Marco , Massimi Luca , Locatelli Franco , Jones David T. W. , Figarella-Branger Dominique , Pfister Stefan M. , Mastronuzzi Angela , Giangaspero Felice , Ferretti Elisabetta
Published: June 2022

Background

Pediatric low-grade gliomas (pLGGs), particularly incompletely resected supratentorial tumours, can undergo progression after surgery. However to date, there are no predictive biomarkers for progression. Here, we aimed to identify pLGG-specific microRNA signatures and evaluate their value as a prognostic tool.

Methods

We identified and validated supratentorial incompletey resected pLGG-specific microRNAs in independent cohorts from four European Pediatric Neuro-Oncology Centres.

Results

These microRNAs demonstrated high accuracy in differentiating patients with or without progression. Specifically, incompletely resected supratentorial pLGGs with disease progression showed significantly higher miR-1248 combined with lower miR-376a-3p and miR-888-5p levels than tumours without progression. A significant (p < 0.001) prognostic performance for miR-1248 was reported with an area under the curve (AUC) of 1.00. We also highlighted a critical oncogenic role for miR-1248 in gliomas tumours. Indeed, high miR-1248 levels maintain low its validated target genes (CDKN1A (p21)/FRK/SPOP/VHL/MTAP) and consequently sustain the activation of oncogenic pathways.

Conclusions

Altogether, we provide a novel molecular biomarker able to successfully identify pLGG patients associated with disease progression that could support the clinicians in the decision-making strategy, advancing personalized medicine.
The use of three implants to support a fixed prosthesis in the management of the edentulous mandible: a systematic review
Authors: Hirani Murtaza , Devine Maria , Obisesan Olamide , Bryant Cathy
Published: June 2022

Background

Dental implants have been widely utilised as a treatment modality for prosthetic rehabilitation. The aim of this study was to evaluate the implant and prosthetic survival rate, changes in marginal bone level, and patient satisfaction outcomes with the use of three implants to support a fixed prosthesis in the edentulous mandible.

Methods

A comprehensive electronic search was performed in the MEDLINE, Embase and Cochrane databases to retrieve studies that met the selection criteria. Sixteen articles were selected which consisted of two randomised controlled trials, eight prospective cohort studies, five retrospective studies and one case series.

Results

A total of 2055 implants were placed in 685 patients with a mean age of 62.2 years. The mean cumulative implant survival rate was 96.2% over a mean follow-up period of 3.35 years. Mean marginal bone loss recorded was 1.25 mm and high patient satisfaction rates were reported across the studies.

Conclusion

The use of three implants to support a fixed prosthesis appears to be a successful approach to restoring the edentulous mandible in the short-to-medium term. Further longitudinal comparative studies are required to support longer-term success, and to guide minimum implant dimension requirements for the technique.
Spatio-temporal variation in the root-associated microbiota of orchard-grown apple trees
Authors: Becker Maximilian Fernando , Hellmann Manfred , Knief Claudia
Published: June 2022

Background

The root-associated microbiome has been of keen research interest especially in the last decade due to the large potential for increasing overall plant performance in agricultural systems. Studies about spatio-temporal variation of the root-associated microbiome focused so far primarily on community-compositional changes of annual plants, while little is known about their perennial counterparts. The aim of this work was to get deep insight into the spatial patterns and temporal dynamics of the root associated microbiota of apple trees.

Results

The bacterial community structure in rhizospheric soil and endospheric root material from orchard-grown apple trees was characterized based on 16S rRNA gene amplicon sequencing. At the small scale, the rhizosphere and endosphere bacterial communities shifted gradually with increasing root size diameter (PERMANOVA R2-values up to 0.359). At the larger scale, bulk soil heterogeneity introduced variation between tree individuals, especially in the rhizosphere microbiota, while the presence of a root pathogen was contributing to tree-to-tree variation in the endosphere microbiota. Moreover, the communities of both compartments underwent seasonal changes and displayed year-to-year variation (PERMANOVA R2-values of 0.454 and 0.371, respectively).

Conclusions

The apple tree root-associated microbiota can be spatially heterogeneous at field scale due to soil heterogeneities, which particularly influence the microbiota in the rhizosphere soil, resulting in tree-to-tree variation. The presence of pathogens can contribute to this variation, though primarily in the endosphere microbiota. Smaller-scale spatial heterogeneity is observed in the rhizosphere and endosphere microbiota related to root diameter, likely influenced by root traits and processes such as rhizodeposition. The microbiota is also subject to temporal variation, including seasonal effects and annual variation. As a consequence, responses of the tree root microbiota to further environmental cues should be considered in the context of this spatio-temporal variation.
The natural history and ecology of melanism in red wolf and coyote populations of the southeastern United States – evidence for Gloger’s rule
Authors: Hinton Joseph W. , West Kyla M. , Sullivan Daniel J. , Frair Jacqueline L. , Chamberlain Michael J.
Published: June 2022

Background

Gloger’s rule postulates that animals should be darker colored in warm and humid regions where dense vegetation and dark environments are common. Although rare inCanispopulations, melanism in wolves is more common in North America than other regions globally and is believed to follow Gloger’s rule. In the temperate forests of the southeastern United States, historical records of red wolf (Canis rufus) and coyote (Canis latrans) populations document a consistent presence of melanism. Today, the melanistic phenotype is extinct in red wolves while occurring in coyotes and red wolf-coyote hybrids who occupy the red wolf's historical range. To assess if Gloger’s rule could explain the occurrence and maintenance of melanistic phenotypes inCanistaxa, we investigated differences in morphology, habitat selection, and survival associated with pelage color using body measurements, GPS tracking data, and long-term capture-mark-recapture and radio-telemetry data collected on coyotes and hybrids across the southeastern United States.

Results

We found no correlation between morphometrics and pelage color forCanistaxa. However, we observed that melanistic coyotes and hybrids experienced greater annual survival than did their gray conspecifics. Furthermore, we observed that melanistic coyotes maintained larger home ranges and exhibited greater selection for areas with dense canopy cover and wetlands than did gray coyotes.

Conclusions

In the southeastern United States, pelage color influenced habitat selection by coyotes and annual survival of coyotes and hybrids providing evidence that Gloger’s rule is applicable to canids inhabiting regions with dense canopy cover and wetlands. Greater annual survival rates observed in melanisticCanismay be attributed to better concealment in areas with dense canopy cover such as coastal bottomland forests. We suggest that the larger home range sizes of melanistic coyotes may reflect the trade-off of reduced foraging efficiency in lower quality wetland habitat for improved survival. Larger home ranges and differential use of land cover by melanistic coyotes may facilitate weak assortative mating in eastern coyote populations, in which melanistic animals may have lower success of finding compatible mates in comparison to gray conspecifics. We offer that our observations provide a partial explanation for why melanism is relatively low (< 10%) but consistent within coyote populations throughout southeastern parts of their range.
Fruit and vegetable consumption during the COVID-19 lockdown in Sri Lanka: an online survey
Authors: Sooriyaarachchi Piumika , Francis Tormalli V. , Jayawardena Ranil
Published: June 2022

Purpose

The COVID-19 pandemic has drastically altered the dietary patterns of individuals. This study aimed to investigate the changes in the purchase and consumption of fruit and vegetables in Sri Lanka during the COVID-19 pandemic.

Methods

An online cross-sectional survey assessed the self-reported changes in fruit and vegetable consumption and purchase using Google forms. Logistic regression analyses were performed to assess the association between decreased consumption of imported fruits and increased home-grown food intake with socio-demographic variables.

Results

Among the 3621 survey respondents, 63.0% and 43.3% reported a decreased intake of imported and local fruits purchased from the market, respectively. Although the overall vegetable consumption has declined, the leafy vegetable consumption has increased by 40.7%. Imported fruit intake has significantly reduced among youngsters, males, respondents living in municipal areas, employed, and those with lower monthly incomes. Among the respondent, 48.9% declared an increased consumption of home-grown fruits or vegetables. Responders living away from Colombo and rural areas were more likely to report a higher intake of home-grown fruits and vegetables (OR 2.021; 95% CI, 1.762–2.318, P < 0.001). Employed males residing in municipal areas were less likely to report an increased intake (OR 0.689; 95% CI, 0.574–0.827, P < 0.001).

Conclusion

Purchase of imported and local fruits from the market has reduced. Although the overall vegetable consumption was decreased, there has been an increase in the consumption of leafy vegetables. Furthermore, consumption of home-grown fruits and vegetables has increased considerably. Well-established food distribution programs are essential in future pandemics to promote healthy eating.
Efficacy of the bacterium Lysobacter enzymogenes strain ch3B10 as a new biocontrol agent on the pathogenic fungi Alternaria solani and Fusarium oxysporum under laboratory conditions
Authors: Alharbi Asmaa Ahmed
Published: June 2022

Background

The plant pathogenic fungi, Alternaria solani and Fusarium oxysporum, are considered among the fungal pathogens which cause severe damages to tomato plants. The application of chemicals fungicides reduced fungal infection and entails great risks to human health and to the environment. Using biological control agents is considered one of the most effective techniques which suppress fungal pathogens and preserve the environment. The beneficial bacterium, Lysobacter enzymogenes, is applied as a biocontrol agent against different plant pathogens.

Results

The present work was carried out, under laboratory conditions, to investigate the efficacy of L. enzymogenes different concentrations of the strain ch3B10 on controlling the linear growth of A. solani and F. oxysporum compared to using the fungicide Benlate®. Treatment with Benlate® and the highest concentration (2 × 108 CFU/ml) of L. enzymogenes strain ch3B10 showed the highest inhibition of 70.6–94.0% on linear growth of all the tested fungi. Also, treatments with two concentrations (2 × 106 and 2 × 107 CFU/ml) of L. enzymogenes strain ch3B10 inhibited linear growth of all tested fungi by means of 47.1–69.7%. The low concentration of 2 × 103 CFU/ml of the strain ch3B10 resulted in the lowest linear growth inhibition 19.8–28.1% in all tested than the check treatment.

Conclusion

Further experiments under both greenhouse and field conditions are needed to approve the efficacy of the strain ch3B10 as an effective bioagent and ecologically safer approach than chemical treatments.
Planning for resilience in screening operations using discrete event simulation modeling: example of HPV testing in Peru
Authors: Rositch Anne F. , Singh Aditya , Lahrichi Nadia , Paz-Soldan Valerie A. , Kohler-Smith Anna , Gravitt Patti , Gralla Erica
Published: June 2022

Background

The World Health Organization (WHO) has called for the elimination of cervical cancer. Unfortunately, the implementation of cost-effective prevention and control strategies has faced significant barriers, such as insufficient guidance on best practices for resource and operations planning. Therefore, we demonstrate the value of discrete event simulation (DES) in implementation science research and practice, particularly to support the programmatic and operational planning for sustainable and resilient delivery of healthcare interventions. Our specific example shows how DES models can inform planning for scale-up and resilient operations of a new HPV-based screen and treat program in Iquitos, an Amazonian city of Peru.

Methods

Using data from a time and motion study and cervical cancer screening registry from Iquitos, Peru, we developed a DES model to conduct virtual experimentation with “what-if” scenarios that compare different workflow and processing strategies under resource constraints and disruptions to the screening system.

Results

Our simulations show how much the screening system’s capacity can be increased at current resource levels, how much variability in service times can be tolerated, and the extent of resilience to disruptions such as curtailed resources. The simulations also identify the resources that would be required to scale up for larger target populations or increased resilience to disruptions, illustrating the key tradeoff between resilience and efficiency. Thus, our results demonstrate how DES models can inform specific resourcing decisions but can also highlight important tradeoffs and suggest general “rules” for resource and operational planning.

Conclusions

Multilevel planning and implementation challenges are not unique to sustainable adoption of cervical cancer screening programs but represent common barriers to the successful scale-up of many preventative health interventions worldwide. DES represents a broadly applicable tool to address complex implementation challenges identified at the national, regional, and local levels across settings and health interventions—how to make effective and efficient operational and resourcing decisions to support program adaptation to local constraints and demands so that they are resilient to changing demands and more likely to be maintained with fidelity over time.