bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathognomonic macular ripples are revealed by polarized infrared retinal imaging
Authors: Ansari Darius , Borkar Poulami P , Davis Patricia L , Collison Frederick T , Wynne Niamh , Zangler Nicole , Fishman Gerald A , Carroll Joseph , Yao Xincheng , Grassi Michael A
Published: July 2021

A pathognomonic macular ripple sign has been reported with scanning laser ophthalmoscopy images in patients with foveal hypoplasia, though the optical basis of this sign is presently unknown. Here we present a case series of seven individuals with foveal hypoplasia (based on spectral domain optical coherence tomography). Each patient underwent infrared scanning laser ophthalmoscopy retinal imaging in both eyes, acquired with and without a polarization filter and assessment for a ripple-like effect in the fovea. On imaging, macular ripples were present in all eyes with foveal hypoplasia when using a polarization filter, but not when imaged without the filter. We conclude that the macular ripple sign is an imaging artifact attributable to the unique pattern of phase retardation of the Henle fiber layer in the setting of foveal hypoplasia. By utilizing a polarization filter with retinal photography, this feature can be exploited to promptly identify foveal hypoplasia in settings where OCT is not possible due to nystagmus.
A Novel Intraoperative Ultrasound Probe for Transsphenoidal Surgery: First-in-human study
Authors: Cabrilo Ivan , Delaunay Rémi , Heaysman Clare L. , Ourselin Sebastien , Vitiello Valentina , Vercauteren Tom , Marcus Hani J. , Dorward Neil L.
Published: July 2021

Background. Ultrasound has been explored as an alternative, less bulky, less time-consuming and less expensive means of intraoperative imaging in pituitary surgery. However, its use has been limited by the size of its probes relative to the transsphenoidal corridor. We developed a novel prototype that is more slender than previously reported forward-viewing probes and, in this report, we assess its feasibility and safety in an initial patient cohort. Method. The probe was integrated into the transsphenoidal approach in patients with pituitary adenoma, following a single-centre prospective proof of concept study design, as defined by the Innovation, Development, Exploration, Assessment and Long-Term Study (IDEAL) guidelines for assessing innovation in surgery (IDEAL stage 1 – Idea phase). Results. The probe was employed in 5 cases, and its ability to be used alongside the standard surgical equipment was demonstrated in each case. No adverse events were encountered. The average surgical time was 20 minutes longer than that of 30 contemporaneous cases operated without intraoperative ultrasound. Conclusion. We demonstrate the safety and feasibility of our novel ultrasound probe during transsphenoidal procedures to the pituitary fossa, and, as a next step, plan to integrate the device into a surgical navigation system (IDEAL Stage 2a – Development phase).
Why pioneer camps survived the collapse of the Soviet Union
Authors: Kozlova Anna
Published: July 2021

The article analyses the survival of the children’s centres, Artek and Orlyonok, during the post-socialist transformation. It is based on 50 interviews with employees who worked there starting in the late-Soviet era. Artek and Orlyonok were exemplary children’s camps, subordinated to the Central Committee of the Komsomol. Since the early 1960s, they have functioned as schools for distinguished teenagers who were considered ‘good examples’ for other children. In this article, I have made an ethnographic analysis of Artek and Orlyonok employees’ late-Soviet experiences. This analysis shows how the agency of Soviet counsellors and camp directors became a creative interpretation of the governmental order to raise the children as active Soviet citizens. Camp educators transformed it in line with the idea to base their agency on ‘common human values’, which was spread in the Soviet educational field in the post-Stalin era. As a result, the Soviet teaching experiences gained in these education centres were heterogeneous. When a child-centred paradigm was later introduced to the post-Soviet educational system, the camps adopted the most applicable practices from their Soviet experiences.
Impact of stroke center certification on rt-PA thrombolysis after acute ischemic stroke in South China from 2015 to 2020
Authors: Chen Yicong , Li Jiaoxing , Dang Chao , Tan Shuangquan , Ouyang Fubing , Li Jianle , Yu Jian , Zeng Jinsheng , Fan Yuhua
Published: July 2021

Background and purpose

In China, stroke center certification was launched in 2015, but little is known about its impact on intravenous thrombolysis. This study aimed to evaluate the effects of stroke center certification on the use of intravenous thrombolysis during a five-year period in South China.

Methods

We retrospectively collected data regarding the use of recombinant tissue plasminogen activator (rt-PA) in 21 cities of Guangdong from 2015 to 2020. The annual thrombolysis rate was defined as the number of patients who underwent intravenous rt-PA therapy divided by the number of those who had acute ischemic stroke within the same year. The density of stroke centers was calculated as the number of stroke centers divided by the corresponding residents. Spearman’s correlation analysis was used to determine the correlations between the annual thrombolysis rates and the number/density of stroke centers. Paired t-test was used to compare differences in growth in annual thrombolysis rates before and after having stroke centers.

Results

From 2015 to 2020, the annual rt-PA thrombolysis rates of Guangdong increased from 1.4% to 7.2%, which was accompanied by an increase in the number of stroke centers from 0 to 82 and density of stroke centers from 0.00 to 0.71 per million population. The average annual rt-PA use in stroke centers was higher than that in non-stroke centers from 2016 to 2020 (all P < 0.05). There was a positive correlation of annual thrombolysis rates with the number of stroke centers ( r = 1.00, P = 0.0028) and with the density of stroke centers in the 21 cities from 2018 to 2020 (all P < 0.05). The growth in annual thrombolysis rates significantly accelerated at the city-level after having stroke centers (1.55%/y vs. 0.77%/y, P < 0.001).

Conclusions

Stroke center certification may partially drive the increased use of rt-PA thrombolysis. Stroke center certification should be continually promoted to facilitate access to intravenous thrombolysis for patients with acute ischemic stroke.
Dynamic Changes, Correlation of Basophils, and the Therapeutic Effect in Patients With Allergic Rhinitis During Allergen-specific Immunotherapy
Authors: Huo Meixu , Tang Susu , Wang Daihua , Liu Xiaoqing , Liu Qianxu
Published: July 2021

Background

The role of basophils in allergic rhinitis (AR) has been studied extensively; however, there are very few reports on changes in basophils after allergen-specific immunotherapy (SIT).

Objective

To examine the changes and correlation of peripheral blood basophils and the therapeutic effect in patients with AR during allergen-SIT.

Methods

A total of 77 patients with AR who were allergic only to house dust mites received allergen-SIT. At 3 time points, patients underwent testing for the percentage and activation rate of basophils in peripheral blood, skin index (SI) measurement, visual analog scale (VAS) assessment, and rhinoconjunctivitis quality of life questionnaire (RQLQ) evaluation. The results were compared to a control group with congenital preauricular fistula.

Results

(1) Before treatment, the percentage and activation rate of basophils in patients with AR were significantly higher than those in controls. There was no significant difference in the percentages and activation rates of basophils at the 3 time points. (2) The SIs, VAS, and RQLQ scores of the patients immediately after treatment and 2 years posttreatment decreased significantly compared to those before treatment; the SI, VAS, and RQLQ scores of the patients 2 years posttreatment increased significantly compared with those immediately after treatment. (3) There was no correlation between the patients’ basophil activation rate and percentage and the SI, VAS, and RQLQ scores at all time points.

Conclusion

The percentage and activation rate of basophils were higher in patients with AR than in controls. The values did not change significantly after allergen-SIT and showed no correlation with treatment effectiveness. Therefore, the frequency and activation rate of basophils cannot be used as criteria for assessing the effectiveness of allergen-SIT for house dust mites. Allergen-SIT is effective for the management of AR, but the effect declines after the completion of therapy.
Novel integrative rehabilitation system for the upper extremity: Design and usability evaluation
Authors: Burdea Grigore , Kim Nam , Polistico Kevin , Kadaru Ashwin , Roll Doru , Grampurohit Namrata
Published: July 2021

Purpose

Design and test the usability of a novel virtual rehabilitation system for bimanual training of gravity supported arms, pronation/supination, grasp strengthening, and finger extension.

Methods

A robotic rehabilitation table, therapeutic game controllers, and adaptive rehabilitation games were developed. The rehabilitation table lifted/lowered and tilted up/down to modulate gravity loading. Arms movement was measured simultaneously, allowing bilateral training. Therapeutic games adapted through a baseline process. Four healthy adults performed four usability evaluation sessions each, and provided feedback using the USE questionnaire and custom questions. Participant’s game play performance was sampled and analyzed, and system modifications made between sessions.

Results

Participants played four sessions of about 50 minutes each, with training difficulty gradually increasing. Participants averaged a total of 6,300 arm repetitions, 2,200 grasp counts, and 2,100 finger extensions when adding counts for each upper extremity. USE questionnaire data averaged 5.1/7 rating, indicative of usefulness, ease of use, ease of learning, and satisfaction with the system. Subjective feedback on the custom evaluation form was 84% favorable.

Conclusions

The novel system was well-accepted, induced high repetition counts, and the usability study helped optimize it and achieve satisfaction. Future studies include examining effectiveness of the novel system when training patients acute post-stroke.
The Trend of Health Service Utilization and Challenges Faced During the COVID-19 Pandemic at Primary Units in Addis Ababa: A Mixed-Methods Study
Authors: Shimels Tariku
Published: July 2021

Introduction:

The COVID-19 pandemic has imposed an extraordinary challenge to the health and socio-economic facet of nations globally. Health facilities have encountered tremendous challenges to contain service delivery at all levels. This study aims to assess the trend of health service utilization and challenges faced during the COVID-19 pandemic at primary units in Addis Ababa, Ethiopia.

Method:

A multi-facility-based cross-sectional study was conducted in Addis Ababa between 1 and 30 of August 2020. A mixed-methods design was employed, and both quantitative and qualitative data were collected at 5 health centers. Facilities were selected randomly from 5 sub-cities while interviewees were recruited purposively. A structured questionnaire was used to collect quantitative data from the HMIS units of each facility. Qualitative data was collected using a semi-structured key-informant interview guide. Quantitative data were analyzed using Microsoft Excel, and a 10-month time-series trend was generated. For the qualitative data, qualitative data analysis (QDA-minor) software was used.

Results:

Time-series comparison of the pre-COVID-19 era loads with the COVID-19 period showed that there was an extensive disparity in the service delivery capacity of the health facilities. A huge drop in inpatient flow of some units such as PICT, VCT, FP services, and most sub-units of the OPDs has been recorded following the COVID-19 outbreak. The key-informant interview also revealed that such challenges, as fear of infection and stigma, poor infrastructure, challenges related to human resources, and challenges related to the supply of prevention and treatment inputs were prominently encountered at the health centers.

Conclusion:

The COVID-19 wave has negatively impacted many service delivery points in the study settings. The presence of weak infrastructure, lack of PPEs, fear of the infection and stigma, and staff workload have been mentioned as the predominant challenges faced during the outbreak. Health authorities should arrange multifaceted supports to ensure uninterrupted service delivery at primary healthcare units.
Thermal Injuries Caused by Water from Loose Garden Hoses
Authors: Uhrová Karolína , Böhm Pavel
Published: July 2021

This is a monitoring research, the purpose of which is to point out the danger of scalding with water from loose garden hoses. All the stated data are the result of this research, which occurred during the month of August. To adequately compare the maximum temperature that the water reaches in garden hoses exposed to sunlight, 2 different surfaces were chosen, namely grass and concrete. It has been found that water in garden hoses, which lie in a place exposed to sunlight, is able to reach temperatures at which, in case of contact with human skin, there is a risk of scalding. The results confirmed the assumption that the temperature in the grass will be lower in the hoses than in the concrete surface. At an air temperature of 35°C, the water in the hoses on the grass reached a temperature of up to 47.3°C. On a concrete surface at an air temperature of 28.5°C, the water in the hoses reached 49.8°C. There is a risk of scalding from such hot water contact with the skin, and especially with sensitive baby skin. The aim of this research is to provide valid data on the risk of spilling hyperthermic water in free-lying garden hoses exposed to sunlight. The threat of scalding can occur unknowingly or through negligence, the risk of scalding with such water increases during tropical days significantly.
Science Graduate Students’ Reports of Discrimination Due to Gender, Race, and Religion: Identifying Shared and Unique Predictors
Authors: Scheitle Christopher P. , Remsburg Taylor , Platt Lisa F.
Published: July 2021

Students from underrepresented groups face numerous challenges during their scientific education and training, including discrimination. Research tends to investigate student experiences with discrimination on the basis of a single characteristic, but an intersectional framework is necessary for understanding the complexity of discrimination. Using data from a survey of more than 1,300 U.S. graduate students in five natural and social science disciplines, the authors examine the predictors of reported discrimination across three different characteristics: gender, race, and religion. They find that nearly two thirds of students report discrimination on at least one characteristic, while almost 30 percent report discrimination along multiple characteristics. Multivariate analyses show that a student’s report of discrimination on any one characteristic is significantly associated with increased odds of reporting discrimination on each of the other two characteristics. This suggests that an individual’s experiences within one social location are often intertwined with and influence their experiences with in other social locations.
Convalescent plasma for COVID-19 in hospitalised patients: an open-label, randomised clinical trial
Authors: Sekine Leo , Arns Beatriz , Fabro Bruna R. , Cipolatt Murillo M. , Machado Rafael R.G. , Durigon Edison L. , Parolo Edino , Pellegrini José Augusto S. , Viana Marina V. , Schwarz Patrícia , Lisboa Thiago C. , Dora José Miguel S. , Portich Julia P. , Paz Alessandra A. , Silla Lucia , Balsan Almeri M. , Schirmer Felipe da-Silva , Franz Juliana P.M. , da-Silveira Luciana M. , Breunig Raquel C. , Petersen Viviana , Sosnoski Monalisa , Mesquita Nanci F. , Volpato Fabiana Caroline Z. , Sganzerla Daniel , Falavigna Maicon , Rosa Regis G. , Zavascki Alexandre P.
Published: July 2021

Background

The effects of convalescent plasma (CP) therapy in hospitalised patients with coronavirus disease 2019 (COVID-19) remain uncertain. This study investigates the effect of CP on clinical improvement in these patients.

Methods

This is an investigator-initiated, randomised, parallel arm, open-label, superiority clinical trial. Patients were randomly (1:1) assigned to two infusions of CP plus standard of care (SOC) or SOC alone. The primary outcome was the proportion of patients with clinical improvement 28 days after enrolment.

Results

A total of 160 (80 in each arm) patients (66.3% critically ill, 33.7% severely ill) completed the trial. The median (interquartile range (IQR)) age was 60.5 (48–68) years; 58.1% were male and the median (IQR) time from symptom onset to randomisation was 10 (8–12) days. Neutralising antibody titres >1:80 were present in 133 (83.1%) patients at baseline. The proportion of patients with clinical improvement on day 28 was 61.3% in the CP+SOC group and 65.0% in the SOC group (difference −3.7%, 95% CI −18.8–11.3%). The results were similar in the severe and critically ill subgroups. There was no significant difference between CP+SOC and SOC groups in pre-specified secondary outcomes, including 28-day mortality, days alive and free of respiratory support and duration of invasive ventilatory support. Inflammatory and other laboratory marker values on days 3, 7 and 14 were similar between groups.

Conclusions

CP+SOC did not result in a higher proportion of clinical improvement on day 28 in hospitalised patients with COVID-19 compared to SOC alone.
The long noncoding RNA MEG3 regulates Ras-MAPK pathway through RASA1 in trophoblast and is associated with unexplained recurrent spontaneous abortion
Authors: Zhang Jun , Liu Xinqiong , Gao Yali
Published: July 2021

Background

Maternally Expressed Gene 3 (MEG3) is expressed at low levels in placental villi during preeclampsia; however, its roles in unexplained recurrent spontaneous abortion (URSA) remain unclear. In this study, we aimed to explore the relationship betweenMEG3and URSA.

Methods

The differentially expressed lncRNAs (MEG3) and its downstream genes (RASA1) were identified using bioinformatics analysis of Genomic Spatial Event (GSE) database. The expression levels ofMEG3in embryonic villis (with gestational ages of 49–63 days) and primary trophoblasts were determined using quantitative RT-PCR assay. A mouse model of Embryo implantation, Cell Counting Kit-8 (CCK-8), flow cytometry, and Transwell migration assays were performed to determine the implantation, proliferative, apoptotic, and invasive capacities of trophoblast. The level of phosphorylated core proteins in the RAS-MAPK pathway were analyzed using Western blot assay. The mechanisms ofMEG3in the regulation ofRASA1were studied by RNA pulldown, RNA immunoprecipitation (RIP), DNA pulldown, and chromatin immunoprecipitation (ChIP) assays.

Results

MEG3had a low expression level in embryonic villis of 102 URSA patients compared with those of 102 normal pregnant women. MEG3 could promote proliferation and invasion, inhibit the apoptosis of primary trophoblast of URSA patients (PT-U cells), as well as promote embryo implantation of mouse. Besides, MEG3 also promoted the phosphorylation of rapidly accelerated fibrosarcoma (Raf), mitogen-activated protein kinase kinase (MEK), and extracellular-signal-regulated kinase (ERK) proteins. The results of RNA pull down and RIP assays showed that MEG3 bound with the enhancer of zeste homolog 2 (EZH2). The DNA pulldown assay revealed that MEG3 could bind to the promoter sequence of the RAS P21 Protein Activator 1 (RASA1) gene. Further, the ChIP assay showed that MEG3 promoted the binding of EZH2 to the promoter region of theRASA1gene.

Conclusions

The inactivation of MEG3 in embryonic villi association with URSA; MEG3 inhibited the expression ofRASA1by mediating the histone methylation of the promoter ofRASA1gene by EZH2, thereby activating the RAS-MAPK pathway and enhancing the proliferative and invasive capacities of trophoblasts.
The patients’ perspective on the burden of idiopathic intracranial hypertension
Authors: Witry Max , Kindler Christine , Weller Johannes , Linder Andreas , Wüllner Ullrich
Published: July 2021

Background

Idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure without evidence of a tumor or any other underlying cause. Headache and visual disturbances are frequent complaints of IIH patients, but little is known about other symptoms. In this study, we evaluated the patients’ perspective on the burden of IIH.

Methods

For this cross-sectional study, we developed an online survey for patients with IIH containing standardized evaluations of headache (HIT-6), sleep (PROMIS Sleep Disturbance Scale) and depression (MDI) in relation to BMI, lumbar puncture opening pressure (LP OP) and treatment.

Results

Between December 2019 and February 2020, 306 patients completed the survey. 285 (93 %) were female, mean age was 36.6 years (± 10.8), mean BMI 34.2 (± 7.3) and mean LP OP at diagnosis was 37.8 cmH2O (± 9.5). 219 (72 %) of the participants were obese (BMI ≥ 30); 251 (82 %) reported severe impacting headaches, 140 (46 %) were suffering from sleep disturbances and 169 (56 %) from depression. Higher MDI scores correlated with higher BMI and increased sleep disturbances. Patients with a normalized LP opening pressure reported less headaches, less sleep disturbances and less depression than those with a constantly elevated opening pressure.

Conclusions

In addition to headaches and visual disturbances, sleep disturbances and depression are frequent symptoms in IIH and contribute to the patients’ burden. Structured questionnaires can help to identify IIH patients’ needs and can lead to personalized and better treatment.
Phenome-wide analysis highlights putative causal relationships between self-reported migraine and other complex traits
Authors: García-Marín Luis M. , Campos Adrián I. , Martin Nicholas G. , Cuéllar-Partida Gabriel , Rentería Miguel E.
Published: July 2021

Background

Migraine is a complex neurological disorder that is considered the most common disabling brain disorder affecting 14 % of people worldwide. The present study sought to infer potential causal relationships between self-reported migraine and other complex traits, using genetic data and a hypothesis-free approach.

Methods

We leveraged available summary statistics from genome-wide association studies (GWAS) of 1,504 phenotypes and self-reported migraine and inferred pair-wise causal relationships using the latent causal variable (LCV) method.

Results

We identify 18 potential causal relationships between self-reported migraine and other complex traits. Hypertension and blood clot formations were causally associated with an increased migraine risk, possibly through vasoconstriction and platelet clumping. We observed that sources of abdominal pain and discomfort might influence a higher risk for migraine. Moreover, occupational and environmental factors such as working with paints, thinner or glues, and being exposed to diesel exhaust were causally associated with higher migraine risk. Psychiatric-related phenotypes, including stressful life events, increased migraine risk. In contrast, ever feeling unenthusiastic / disinterested for a whole week, a phenotype related to the psychological well-being of individuals, was a potential outcome of migraine.

Conclusions

Overall, our results suggest a potential vascular component to migraine, highlighting the role of vasoconstriction and platelet clumping. Stressful life events and occupational variables potentially influence a higher migraine risk. Additionally, a migraine could impact the psychological well-being of individuals. Our findings provide novel testable hypotheses for future studies that may inform the design of new interventions to prevent or reduce migraine risk and recurrence.
LncRNA UCA1 promotes development of gastric cancer via the miR-145/MYO6 axis
Authors: Yang An , Liu Xin , Liu Ping , Feng Yunzhang , Liu Hongbo , Gao Shen , Huo Limin , Han Xinyan , Wang Jurong , Kong Wei
Published: July 2021

Background

Long noncoding RNA (lncRNA), urothelial carcinoma-associated 1 (UCA1) is aberrantly expressed in multiple cancers and has been verified as an oncogene. However, the underlying mechanism of UCA1 in the development of gastric cancer is not fully understood. In the present study, we aimed to identify how UCA1 promotes gastric cancer development.

Methods

The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to analyze UCA1 and myosin VI (MYO6) expression in gastric cancer. Western blot and quantitative real-time PCR (QPCR) were performed to test the expression level of the UCA1/miR-145/MYO6 axis in gastric cancer cell lines and tissues. The roles of the UCA1/miR-145/MYO6 axis in gastric cancer in vitro and in vivo were investigated by CCK-8 assay, flow cytometry, siRNAs, immunohistochemistry, and a mouse xenograft model. The targeted relationship among UCA1, miR-145, and MYO6 was predicted using LncBase Predicted v.2 and TargetScan online software, and then verified by luciferase activity assay and RNA immunoprecipitation.

Results

UCA1 expression was higher but miR-145 expression was lower in gastric cancer cell lines or tissues, compared to the adjacent normal cell line or normal tissues. Function analysis verified that UCA1 promoted cell proliferation and inhibited cell apoptosis in the gastric cancer cells in vitro and in vivo. Mechanistically, UCA1 could bind directly to miR-145, and MYO6 was found to be a downstream target gene of miR-145. miR-145 mimics or MYO6 siRNAs could partly reverse the effect of UCA1 on gastric cancer cells.

Conclusions

UCA1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-145 to upregulate MYO6 expression in gastric cancer, indicating that the UCA1/miR-145/MYO6 axis may serve as a potential therapeutic target for gastric cancer.
Radiolabeling and PET–MRI microdosing of the experimental cancer therapeutic, MN-anti-miR10b, demonstrates delivery to metastatic lesions in a murine model of metastatic breast cancer
Authors: Le Fur Mariane , Ross Alana , Pantazopoulos Pamela , Rotile Nicholas , Zhou Iris , Caravan Peter , Medarova Zdravka , Yoo Byunghee
Published: July 2021

Background

In our earlier work, we identified microRNA-10b (miR10b) as a master regulator of the viability of metastatic tumor cells. This knowledge allowed us to design a miR10b-targeted therapeutic consisting of an anti-miR10b antagomir conjugated to ultrasmall iron oxide nanoparticles (MN), termed MN-anti-miR10b. In mouse models of breast cancer, we demonstrated that MN-anti-miR10b caused durable regressions of established metastases with no evidence of systemic toxicity. As a first step towards translating MN-anti-miR10b for the treatment of metastatic breast cancer, we needed to determine if MN-anti-miR10b, which is so effective in mice, will also accumulate in human metastases.

Results

In this study, we devised a method to efficiently radiolabel MN-anti-miR10b with Cu-64 (64Cu) and evaluated the pharmacokinetics and biodistribution of the radiolabeled product at two different doses: a therapeutic dose, referred to as macrodose, corresponding to 64Cu-MN-anti-miR10b co-injected with non-labeled MN-anti-miR10b, and a tracer-level dose of 64Cu-MN-anti-miR10b, referred to as microdose. In addition, we evaluated the uptake of 64Cu-MN-anti-miR10b by metastatic lesions using both in vivo and ex vivo positron emission tomography–magnetic resonance imaging (PET–MRI). A comparable distribution of the therapeutic was observed after administration of a microdose or macrodose. Uptake of the therapeutic by metastatic lymph nodes, lungs, and bone was also demonstrated by PET–MRI with a significantly higher PET signal than in the same organs devoid of metastatic lesions.

Conclusion

Our results demonstrate that PET–MRI following a microdose injection of the agent will accurately reflect the innate biodistribution of the therapeutic. The tools developed in the present study lay the groundwork for the clinical testing of MN-anti-miR10b and other similar therapeutics in patients with cancer.
Venom-gland transcriptomic, venomic, and antivenomic profiles of the spine-bellied sea snake (Hydrophis curtus) from the South China Sea
Authors: Zhao Hong-Yan , Wen Lin , Miao Yu-Feng , Du Yu , Sun Yan , Yin Yin , Lin Chi-Xian , Lin Long-Hui , Ji Xiang , Gao Jian-Fang
Published: July 2021

Background

A comprehensive evaluation of the -omic profiles of venom is important for understanding the potential function and evolution of snake venom. Here, we conducted an integrated multi-omics-analysis to unveil the venom-transcriptomic and venomic profiles in a same group of spine-bellied sea snakes (Hydrophis curtus) from the South China Sea, where the snake is a widespread species and might generate regionally-specific venom potentially harmful to human activities. The capacity of two heterologous antivenoms to immunocapture the H. curtus venom was determined for an in-depth evaluation of their rationality in treatment of H. curtus envenomation. In addition, a phylogenetic analysis by maximum likelihood was used to detect the adaptive molecular evolution of full-length toxin-coding unigenes.

Results

A total of 90,909,384 pairs of clean reads were generated via Illumina sequencing from a pooled cDNA library of six specimens, and yielding 148,121 unigenes through de novo assembly. Sequence similarity searching harvested 63,845 valid annotations, including 63,789 non-toxin-coding and 56 toxin-coding unigenes belonging to 22 protein families. Three protein families, three-finger toxins (3-FTx), phospholipase A2 (PLA2), and cysteine-rich secretory protein, were detected in the venom proteome. 3-FTx (27.15% in the transcriptome/41.94% in the proteome) and PLA2 (59.71%/49.36%) were identified as the most abundant families in the venom-gland transcriptome and venom proteome. In addition, 24 unigenes from 11 protein families were shown to have experienced positive selection in their evolutionary history, whereas four were relatively conserved throughout evolution. Commercial Naja atra antivenom exhibited a stronger capacity than Bungarus multicinctus antivenom to immunocapture H. curtus venom components, especially short neurotoxins, with the capacity of both antivenoms to immunocapture short neurotoxins being weaker than that for PLA2s.

Conclusions

Our study clarified the venom-gland transcriptomic and venomic profiles along with the within-group divergence of a H. curtus population from the South China Sea. Adaptive evolution of most venom components driven by natural selection appeared to occur rapidly during evolutionary history. Notably, the utility of commercial N. atra and B. multicinctus antivenoms against H. curtus toxins was not comprehensive; thus, the development of species-specific antivenom is urgently needed.
Characterization of resistance mechanisms of Enterobacter cloacae Complex co-resistant to carbapenem and colistin
Authors: Liu Shixing , Fang Renchi , Zhang Ying , Chen Lijiang , Huang Na , Yu Kaihang , Zhou Cui , Cao Jianming , Zhou Tieli
Published: July 2021

Background

The emergence of carbapenem-resistant and colistin-resistant ECC pose a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in Enterobacter cloacae Complex (ECC) strains.

Results

This study showed that the mechanisms of carbapenem resistance in this study are: 1. Generating carbapenemase (7 of 19); 2. The production of AmpC or ESBLs combined with decreased expression of out membrane protein (12 of 19). hsp60 sequence analysis suggested 10 of 19 the strains belong to colistin hetero-resistant clusters and the mechanism of colistin resistance is increasing expression of acrA in the efflux pump AcrAB-TolC alone (18 of 19) or accompanied by a decrease of affinity between colistin and outer membrane caused by the modification of lipid A (14 of 19). Moreover, an ECC strain co-harboring plasmid-mediated mcr-4.3 and blaNDM-1 has been found.

Conclusions

This study suggested that there is no overlap between the resistance mechanism of co-resistant ECC strains to carbapenem and colistin. However, the emergence of strain co-harboring plasmid-mediated resistance genes indicated that ECC is a potential carrier for the horizontal spread of carbapenems and colistin resistance.
Genome-wide analysis of MYB transcription factors and their responses to salt stress in Casuarina equisetifolia
Authors: Wang Yujiao , Zhang Yong , Fan Chunjie , Wei Yongcheng , Meng Jingxiang , Li Zhen , Zhong Chonglu
Published: July 2021

Background

MYB transcription factors are a kind of DNA binding protein that can specifically interact with the promoter region. Members of MYB TFs are widely involved in plant growth and development, secondary metabolism, stress response, and hormone signal transduction. However, there is no report of comprehensive bioinformatics analysis on the MYB family of Casuarina equisetifolia.

Results

In this study, bioinformatics methods were used to screen out 182 MYB transcription factors from the Casuarina equisetifolia genome database, including 69 1R-MYB, 107 R2R3-MYB, 4 R1R2R3-MYB, and 2 4R-MYB. The C. equisetifolia R2R3-MYB genes were divided into 29 groups based on the phylogenetic topology and the classification of the MYB superfamily in Arabidopsis thaliana, while the remaining MYB genes (1R-MYB, R1R2R3-MYB, and 4R-MYB) was divided into 19 groups. Moreover, the conserved motif and gene structure analysis shown that the members of the CeqMYBs were divided into the same subgroups with mostly similar gene structures. In addition, many conserved amino acids in the R2 and R3 domains of CeqMYBs by WebLogo analysis, especially tryptophan residues (W), with 3 conserved W in R2 repeat and 2 conserved W in R3 repeat. Combining promoter and GO annotation analysis, speculated on the various biological functions of CeqMYBs, thus 32 MYB genes were selected to further explore its response to salt stress by using qPCR analysis technique. Most CeqMYB genes were differentially regulated following multiple salt treatments.

Conclusions

Seven genes (CeqMYB164, CeqMYB4, CeqMYB53, CeqMYB32, CeqMYB114, CeqMYB71 and CeqMYB177) were assigned to the “response to salt stress” by GO annotation. Among them, the expression level of CeqMYB4 was up-regulated under various salt treatments, indicating CeqMYB4 might participated in the response to salt stress. Our results provide important information for the biological function of C. equisetifolia, as well as offer candidate genes for further study of salt stress mechanism.
A new likelihood model for analyses of pharmacoepidemiologic case–control studies which avoids decision rules for determining latent exposure status
Authors: Støvring Henrik , Pottegård Anton , Hallas Jesper
Published: July 2021

Background

Case–control studies based on pharmaco-epidemiological databases typically use decision rules to determine exposure status from information on dates of prescription redemptions, although this induces misclassification. The reverse Waiting Time Distribution has been suggested as a likelihood based model to estimate the latent exposure status, and we therefore suggest to extend this into a joint likelihood based model, which incorporates both the latent exposure status and the exposure-outcome association. This will achieve consistency and efficiency of the estimates, i.e. they can be expected to be asymptotically unbiased and have optimal precision.

Methods

We established a joint likelihood for the observed case–control status and last prescription redemption before the index date. The likelihood combines the ordinary logistic regression likelihood and the reverse Waiting Time Distribution, and allows inclusion of covariates in both parts to adjust for observed confounders. We conducted a simulation study of the new model and standard models based on decision rules for exposure and the probability of being exposed, respectively, to assess the relative bias and variability of estimates. Lastly, we applied the models to a case–control study on use of nonsteroidal anti-inflammatory drugs and risk of upper-gastrointestinal bleeding.

Results

In simulation studies the new model had low relative bias (< 1.4%) and largely retained nominal coverage probabilities (90.2% to 95.1% of nominal 95% confidence intervals), also when moderate misspecification was introduced. All standard methods generally had substantial bias (-21.1% to 17.0%) and low coverage probabilities (0.0% to 68.9%). When analyzing the empirical case–control study, the new method estimated the effect of nonsteroidal anti-inflammatory drugs on risk of with upper-gastrointestinal bleeding hospitalization to 2.52 (1.59 – 3.45), whereas the other methods had estimates ranging from 3.52 (2.19 – 5.65) to 5.17 (2.40 – 11.11).

Conclusions

Unlike standard methods, the proposed model gave nearly unbiased estimates with adequate coverage probabilities in simulation studies. The developed model demonstrates the potential for the reverse Waiting Time Distribution to be integrated with existing likelihood based analyses in pharmacoepidemiological studies.
Small intestinal follicular lymphoma induced by methotrexate: a case report
Authors: Osaki Yui , Kawaratani Hideto , Kachi Hiroki , Matsuura Kyohei , Tsuji Yuki , Ozutsumi Takahiro , Takagi Hirotetsu , Furukawa Masanori , Sawada Yasuhiko , Mitoro Akira , Yamao Junichi , Yoshiji Hitoshi
Published: July 2021

Background

Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a rare but critical complication that develops in patients treated with MTX. Although MTX-LPD has been recently reported, the incidence of follicular lymphoma in the intestine is very low.

Case presentation

A 73-year-old woman who had been receiving MTX for over 10 years visited our hospital complaining of postprandial abdominal pain and nausea. Upper and lower digestive tract endoscopies did not show any abnormal findings. A patency capsule was stagnated at the proximal part of the ileum with a mild dilation on the oral side. An oral balloon endoscopy revealed shallow ulcerative lesions in the jejunum. She was diagnosed with MTX-LPD based on histopathological findings. The symptoms did not improve with the discontinuation of MTX, and the patient required partial resection of the small intestine. The test result for Epstein-Barr virus-encoded small RNA was negative. She was diagnosed with follicular lymphoma based on the histology findings of a surgical specimen. Postoperative positron emission tomography-computed tomography and bone marrow aspiration did not show any findings of lymphoma. On follow-up, no recurrence was noted four years after the surgery.

Conclusions

Herein, we report the first case of follicular lymphoma that occurred in the small intestine, negative for Epstein-Barr virus-encoded small RNA. If intestinal symptoms occur during MTX administration, it is important to directly observe by endoscopy and perform histological examination.
Successful use of montelukast in eosinophilic gastroenteritis: a case report and a literature review
Authors: El-Alali Emran A. , Abukhiran Ibrahim M. , Alhmoud Tarik Z.
Published: July 2021

Background

Eosinophilic gastrointestinal disorders, also known as eosinophilic gastroenteritis, are rare inflammatory conditions characterized by eosinophilic infiltration of different parts of the gastrointestinal tract, along with peripheral eosinophilia in most cases. Other known causes for gut eosinophilic infiltration must be excluded to confirm the diagnosis of eosinophilic gastroenteritis. Symptoms of the disorder depend on the affected gastrointestinal tract segment and depth of involvement. Treatment includes systemic glucocorticoids and/or dietary therapy with an empiric elimination diet. Second line therapies include the leukotriene receptor antagonist montelukast, and other anti-allergy drugs such as mast cell stabilizers (including cromolyn and the H1-antihistamine ketotifen), suplatast tosilate which is a selective Th-2 cytokines (IL-4 and IL-5) inhibitor, and the monoclonal anti-IgE antibody omalizumab. We report a case of eosinophilic gastroenteritis who was successfully treated and achieved remission with montelukast as an initial monotherapy. Upon extensive literature review, this represents the second reported adult case of eosinophilic gastroenteritis who responds to montelukast alone as a first line therapy.

Case presentation

A 49-year-old female presented with recurrent abdominal pain, vomiting, diarrhea and unexplained eosinophilia. She was diagnosed with eosinophilic gastroenteritis and was successfully treated with montelukast monotherapy. After 7 days of therapy, the patient responded well and had complete resolution of her gastrointestinal symptoms and peripheral eosinophilia. Patient remained in remission on follow-up after 12 months. We reviewed the literature for leukotriene antagonist use in the treatment of eosinophilic gastroenteritis and included the cases treated with the leukotriene antagonist montelukast as an initial therapy or as a second line therapy for refractory disease.

Conclusion

Montelukast may be an effective treatment for eosinophilic gastroenteritis, either alone or in combination with systemic steroids or ketotifen. Our patient is the second reported adult case of eosinophilic gastroenteritis who responded to montelukast alone as a first line therapy. Further studies and clinical trials are required to confirm efficacy compared to standard therapy.
The increasing use of the WHO Safe Childbirth Checklist: lessons learned at the Yaoundé Gynaeco-Obstetric and Paediatric Hospital, Cameroon
Authors: Dohbit Julius Sama , Woks Namanou Ines Emma , Koudjine Carlin Héméry , Tafen Willy , Foumane Pascal , Bella Assumpta Lucienne , Ogu Rosemary Nkemdilim , Angwafo Fru Fobuzshi
Published: July 2021

Background

Safe childbirth remains a daunting challenge, particularly in low-middle income countries, where most pregnancy-related deaths occur. Cameroon’s maternal mortality rate, estimated at 529 per 100,000 live births in 2017, is significantly high. The WHO Safe Childbirth Checklist (SCC) was designed to improve the quality of care provided to pregnant women during childbirth. The SCC was implemented at the Yaoundé Gynaeco-Obstetric and Paediatric Hospital to improve the quality of care during childbirth.

Methods

This study was a retrospective study to determine the adoption rate of the SCC and its association with maternal (eclampsia, perineal tears, and postpartum haemorrhage) and neonatal (stillbirth, neonatal asphyxia and neonatal death) complications. Data were collected 6 months after the introduction of the SCC. Multivariate binary logistic regression was used to analyse the association between the use of the SCC and maternofoetal complications.

Results

Out of 1611 deliveries conducted, 1001 records were found, giving a retrieval rate of 62%. Twenty-five records were excluded. During the study period, the checklists were used in 828 of 976 clinical notes, with an adoption rate of 84.8% and a utilization rate of 93.9% at 6 months. Severe preeclampsia/eclampsia was associated with the non-use of the SCC (2.1 vs 5.4%, p = 0.041). Stillbirth, neonatal asphyxia, and neonatal death rates were not significantly different between the checklist and non-checklist groups. However, for all neonatal outcomes, the proportion of complications was lower when the checklist was used.

Conclusion

The use of the SCC was associated with significantly reduced pregnancy complications, especially for reducing the rates of severe pre-eclampsia/eclampsia. The use of the SCC increased to 93.9% of all deliveries within 6 months. We advocate for the use of the WHO Safe Childbirth Checklist in maternity units.
PTSD, depression and anxiety in Ebola virus disease survivors in Beni town, Democratic Republic of the Congo
Authors: Kaputu-Kalala-Malu Célestin , Musalu Eric Mafuta , Walker Tim , Ntumba-Tshitenge Olga , Ahuka-Mundeke Steve
Published: July 2021

Background

Ebola Virus Disease (EVD) is a deadly and feared infectious disease, which can be responsible of debilitating physical and psychological sequelae in survivors including depression and anxiety disorders. Unfortunately, there are scarce data on survivor sequelae in Democratic Republic of the Congo. So this study assessed PTSD, depression and anxiety symptoms among EVD survivors enrolled in the follow-up program of the psychosocial care team of Beni town’s general hospital.

Methods

A cross-sectional study used consecutive sampling to recruit 144 Ebola virus disease survivors who came for follow up from October 23 to November 13; 2019. Basic socio-demographic data, presence of headache and short-term memory function were assessed. The Post-traumatic Checklist Scale and Hospital Anxiety and Depression Scale were used to assess psychological burden among participants. Descriptive statistics were used to summarized data and Pearson’s or likelihood chi-square were used to test association between psychiatric disorders and associated factors.

Results

The prevalence of PTSD, depression and anxiety was 24.3, 24.3 and 33.3% respectively. Being male (OR = 0.42, 95% CI: 0.16, 0.95, p = 0.049), suffering from persistent headache (OR = 2.62, 95% CI: 1.12, 6.14, p = 0.014), losing a loved one because of EVD (OR: 2.60, 95% CI: 1.11, 6.15, p = 0. 015) and being young − 18-24 years - (OR: 0. 261, 95% CI: 0. 08, 0.82, p = 0,026) were statistically associated with PTSD diagnosis. Having short-term memory impairment and suffering from persistent headache were statistically associated with depression and anxiety diagnoses (OR = 2.44, 95% CI: 1.03, 5.82, p = 0.026); (OR = 2.24, 95% CI: 1.04, 4.85, p = 0.025); (OR = 2.62, 95% CI: 1.12, 6.14, p = 0.014); (OR = 2.31, 95% CI: 1.06, 5.01, p = 0.020).

Conclusion

The prevalence of PTSD, depression and anxiety is high among EVD survivors. Development of specialized psychiatric services to sustain psychiatric and psychological health amongst survivors in the cultural context of the Eastern part of the DRC should be considered by the teams fighting against EVD in the DRC.
Orthorexia Nervosa: differences between clinical and non-clinical samples
Authors: Novara C. , Maggio E. , Piasentin S. , Pardini S. , Mattioli S.
Published: July 2021

Background

Orthorexia Nervosa (ON) is a construct characterized by behaviors, emotions, and beliefs on eating healthy food and excessive attention to diet; moreover, dieting has been considered a risk factor in ON symptoms development. The principal aim of this study was to investigate the differences in clinical and non-clinical groups most at risk of ON. Aspects that could be associated with ON (Eating Disorders [EDs], obsessive-compulsive symptomatology, perfectionistic traits, anxiety, depression, Body Mass Index [BMI]) were investigated in all groups.

Methods

The sample consisted of 329 adults belonging to four different groups. Three were on a diet: Anorexia/Bulimia Nervosa group (N = 90), Obesity/Binge Eating Disorder group (N = 54), Diet group (N = 91). The Control group consisted of people who were not following a diet (N = 94). Participants completed several self-administered questionnaires (EHQ-21, EDI-3, OCI-R, MPS, BAI, BDI-II) to assess ON-related features in different groups.

Results

Analyses highlighted higher orthorexic tendencies in Anorexia/Bulimia Nervosa, Obesity/BED, and Diet groups than in the Control group. Moreover, results have shown that in the AN/BN group, eating disorders symptomatology and a lower BMI were related to ON and that in Obesity/Binge Eating Disorder and Diet groups, perfectionism traits are associated with ON.

Conclusion

Individuals who pursue a diet share some similarities with those who have an eating disorder regarding emotions, behaviors, and problems associated with orthorexic tendencies. Moreover, perfectionistic traits seem to predispose to higher ON tendencies. In general, these results confirm the ON as an aspect of the main eating disorders category.