bluuebunny/crossref_metadata_2025 huggingface dataset:
Response to pembrolizumab in a patient with primary lung adenocarcinoma originated from indium lung
Authors: Sekine Yasuharu , Ichimura Hideo , Ueda Sho , Kobayashi Keisuke , Nawa Takeshi , Amata Atsuko , Chonan Tatsuya , Sakata Akiko , Komatsu Yoji , Sato Yukio
Published: March 2021

Background

Indium is a metal used as a compound called indium-tin oxide for liquid crystal display. Its inhalation causes lung toxicity, resulting in a new occupational lung disease called indium lung. Although the carcinogenicity of indium has been reported in an animal model, its carcinogenicity in humans is unknown.

Case presentation

This is the first reported case of a primary lung cancer originating from indium lung. In this report, we describe a 46-year-old man with interstitial pneumonia-type indium lung diagnosed 16 years ago. The initial symptom was left chest pain, and computed tomography showed a mass adjacent to the aorta with left pleural effusion. Specimens collected using video-assisted thoracoscopy revealed an adenocarcinoma with a high expression of programmed cell death-ligand 1 (cT4N0M1a stage IVA). Although the lesions showed a remarkable aggressive nature, the patient benefited from pembrolizumab, a monoclonal antibody against programmed cell death 1, which was used as second-line therapy for 2 years.

Conclusions

It is important for clinicians to be aware of lung cancer development in indium-exposed workers or in patients with indium lung, as this could have an aggressive behavior. Treatment with immune checkpoint inhibitors is an option even in patients with interstitial pneumonia-type indium lung.
Phytochemical analysis, in-vitro anti-proliferative, anti-oxidant, anti-diabetic, and anti-obesity activities of Rumex rothschildianus Aarons. extracts
Authors: Jaradat Nidal , Hawash Mohammed , Dass Gada
Published: March 2021

Background

Rumex rothschildianus is the sole member of a unique section of the genus Rumex, in the family Polygonaceae. This species is a very rare small dioecious annual, endemic to Palestine that is traditionally used as food and for the treatment of various diseases. Therefore, the current investigation aimed to screen the chemical constituents, antioxidants, anti-α-amylase, anti-α-glucosidase, antilipase, and cytotoxic effects of four solvents fractions of R. rothschildianus leaves.

Methods

Dried powder of R. rothschildianus leaves was extracted in four solvents with different polarities. Several qualitative and quantitative phytochemical tests were performed to determine the components of the extracts. The colorimetric analysis was used for the quantitative determination of phenols, flavonoids, and tannins. In-vitro assays were performed to evaluate the extracts for antioxidant, anti-α-amylase, anti-α-glucosidase, and antilipase inhibitory activities, as well as cytotoxicity by MTS assay against cervical carcinoma cells line (HeLa) and breast cancer cell line (MCF7).

Results

The acetone fraction of R. rothschildianus leaves showed the most significant antioxidant activity, due to having the highest content of flavonoids and phenolics, with an IC50 value of 6.3 ± 0.4 μg/ml, compared to 3.1 ± 0.9 μg/ml for Trolox, and regarding lipase inhibition activity the acetone fraction showed the most potent activity with an IC50 value of 26.3 ± 0.6 μg/ml, in comparison with orlistat positive control IC50 12.3 μg/ml. The same extract was the most potent inhibitor of α-amylase and α-glucosidase, with IC50 values of 19.1 ± 0.7 μg/ml and 54.9 ± 0.3 μg/ml, respectively, compared to 28.8, 37.1 ± 0.3 μg/ml of acarbose, respectively. The hexane fraction showed 99.9% inhibition of HeLa cells and 97.4% inhibition for MCF7 cells.

Conclusion

The acetone fraction of R. rothschildianus leaves might provide a source of bioactive compounds for the treatment of oxidative stress. Similarly, the hexane fraction indicates the promising antitumor potential of R. rothschildianus. Clearly, these initial indications need further purification of potentially active compounds, and ultimately, in-vivo studies to determine their effectiveness.
Predicting unplanned medical visits among patients with diabetes: translation from machine learning to clinical implementation
Authors: Selya Arielle , Anshutz Drake , Griese Emily , Weber Tess L. , Hsu Benson , Ward Cheryl
Published: March 2021

Background

Diabetes is a medical and economic burden in the United States. In this study, a machine learning predictive model was developed to predict unplanned medical visits among patients with diabetes, and findings were used to design a clinical intervention in the sponsoring healthcare organization. This study presents a case study of how predictive analytics can inform clinical actions, and describes practical factors that must be incorporated in order to translate research into clinical practice.

Methods

Data were drawn from electronic medical records (EMRs) from a large healthcare organization in the Northern Plains region of the US, from adult (≥ 18 years old) patients with type 1 or type 2 diabetes who received care at least once during the 3-year period. A variety of machine-learning classification models were run using standard EMR variables as predictors (age, body mass index (BMI), systolic blood pressure (BP), diastolic BP, low-density lipoprotein, high-density lipoprotein (HDL), glycohemoglobin (A1C), smoking status, number of diagnoses and number of prescriptions). The best-performing model after cross-validation testing was analyzed to identify strongest predictors.

Results

The best-performing model was a linear-basis support vector machine, which achieved a balanced accuracy (average of sensitivity and specificity) of 65.7%. This model outperformed a conventional logistic regression by 0.4 percentage points. A sensitivity analysis identified BP and HDL as the strongest predictors, such that disrupting these variables with random noise decreased the model’s overall balanced accuracy by 1.3 and 1.4 percentage points, respectively. These recommendations, along with stakeholder engagement, behavioral economics strategies, and implementation science principles helped to inform the design of a clinical intervention targeting behavioral changes.

Conclusion

Our machine-learning predictive model more accurately predicted unplanned medical visits among patients with diabetes, relative to conventional models. Post-hoc analysis of the model was used for hypothesis generation, namely that HDL and BP are the strongest contributors to unplanned medical visits among patients with diabetes. These findings were translated into a clinical intervention now being piloted at the sponsoring healthcare organization. In this way, this predictive model can be used in moving from prediction to implementation and improved diabetes care management in clinical settings.
Effectiveness of self-re-learning using video recordings of advanced life support on nursing students’ knowledge, self-efficacy, and skills performance
Authors: Jang Kyeongmin , Kim Sung Hwan , Oh Ja Young , Mun Ji Yeon
Published: March 2021

Background

Nurses are presumably the first to see an in-hospital cardiac arrest patient. This study proposed measuring nursing students’ knowledge, self-efficacy, and skills performance in advanced life support (ALS), 6 months after training, by sending videos taken during their final skills test after the ALS training.

Methods

This is an experimental study using a randomised control group design. This study was conducted from June to December 2018, and the subjects of the study were 4th year students, recruited through a bulletin board at a nursing university. The participants’ knowledge, self-efficacy, and skill performance in ALS were evaluated immediately after the training, and participants were videotaped during the final skills test. Thereafter, the videos were sent to the experimental group through a mobile phone messenger application, once a month, from the third month after training. Approximately six months after training day, a follow-up test was conducted for the measured variables using a blinded method. The paired t-test and Wilcoxon signed-rank test were used to compare the two groups pre-and post-intervention. The statistical significance level was set at p < .05.

Results

Six months after the ALS training, knowledge scores decreased significantly in both groups (p < 0.001). Self-efficacy decreased by about 3 points from 50.55 to 47.18 in the experimental group (p = 0.089), while it decreased by 10 points in the control group, from 50.67 to 39 (p < 0.001). The skills performance decreased from 27.5 to 26.68 in the experimental group, while it decreased significantly from 27.95 to 16.9 in the control group (p < 0.001).

Conclusion

Self-study with videos taken during an ALS skills test helps enhance the sustainable effects of training such as knowledge, self-efficacy, and skills performance.
Understanding HPV-positive women’s needs and experiences in relation to patient-provider communication issues: a qualitative study
Authors: Qaderi Kowsar , Geranmayeh Mehrnaz , Farnam Farnaz , Sheikh Hasani Shahrzad , Mirmolaei Seyedeh Tahereh
Published: March 2021

Background

HPV testing has been integrated in cervical cancer screening program. Patient-providers relationship is extremely important to improve cervical cancer screening outcomes. This qualitative study aims to understand HPV-positive women’s needs and preferences about HCPs and patient-provider communication based on their experiences of accessing primary and specialized care.

Methods

We conducted 40 semi-structured interviews with HPV-positive women. Recorded interviews transcribed and analyzed using conventional content analysis approach.

Results

The analysis of the data led to the extraction of three main categories, including: provider’s communication and counseling skills, commitment to professional principles, and knowledgeable and competent provider. Women needed understandable discussion about HPV, emotional support and acceptance, receiving HPV-related guidance and advice, and some considerations during clinical appointments. Women needed HCPs to treat them respectfully, gently and with non-judgmental attitude. “Precancerous” and “high-risk” words and watching colposcopy monitor during procedure had made women anxious. Weak referral system and limited interactions among gynecologists and other HCPs highlighted by participants.

Conclusion

The results of this study, based on the experiences and perceptions of HPV women receiving health care, contain messages and practical tips to healthcare providers at the primary and specialized levels of care to facilitate patient-provider communication around HPV. Providers need to approach the discussion of HPV with sensitivity and take individual needs and preferences into account to improve the HPV-positive women’s healthcare experience.
Scores based on neutrophil percentage and lactate dehydrogenase with or without oxygen saturation predict hospital mortality risk in severe COVID-19 patients
Authors: Fan Xiude , Zhu Bin , Nouri-Vaskeh Masoud , Jiang Chunguo , Feng Xiaokai , Poulsen Kyle , Baradaran Behzad , Fang Jiansong , Ade Erfan Ahmadi , Sharifi Akbar , Zhao Zhigang , Han Qunying , Zhang Yong , Zhang Liming , Liu Zhengwen
Published: March 2021

Background

Risk scores are needed to predict the risk of death in severe coronavirus disease 2019 (COVID-19) patients in the context of rapid disease progression.

Methods

Using data from China (training dataset, n = 96), prediction models were developed by logistic regression and then risk scores were established. Leave-one-out cross validation was used for internal validation and data from Iran (test dataset, n = 43) was used for external validation.

Results

A NSL model (area under the curve (AUC) 0.932) and a NL model (AUC 0.903) were developed based on neutrophil percentage and lactate dehydrogenase with and without oxygen saturation (SaO2) using the training dataset. AUCs of the NSL and NL models in the test dataset were 0.910 and 0.871, respectively. The risk scoring systems corresponding to these two models were established. The AUCs of the NSL and NL scores in the training dataset were 0.928 and 0.901, respectively. At the optimal cut-off value of NSL score, the sensitivity and specificity were 94% and 82%, respectively. The sensitivity and specificity of NL score were 94% and 75%, respectively.

Conclusions

These scores may be used to predict the risk of death in severe COVID-19 patients and the NL score could be used in regions where patients' SaO2 cannot be tested.
Association of spectroscopically determined leaf nutrition related traits and breeding selection in Sassafras tzumu
Authors: Liu Jun , Sun Yang , Liu Wenjian , Tan Zifeng , Jiang Jingmin , Li Yanjie
Published: March 2021

Background

Plant traits related to nutrition have an influential role in tree growth, tree production and nutrient cycling. Therefore, the breeding program should consider the genetics of the traits. However, the measurement methods could seriously affect the progress of breeding selection program. In this study, we tested the ability of spectroscopy to quantify the specific leaf nutrition traits including anthocyanins (ANTH), flavonoids (FLAV) and nitrogen balance index (NBI), and estimated the genetic variation of these leaf traits based on the spectroscopic predicted data. Fresh leaves of Sassafras tzumu were selected for spectral collection and ANTH, FLAV and NBI concentrations measurement by standard analytical methods. Partial least squares regression (PLSR), five spectra pre-processing methods, and four variable selection algorisms were conducted for the optimal model selection. Each trait model was simulated 200 times for error estimation.

Results

The standard normal variate (SNV) to the ANTH model and 1st derivatives to the FLAV and NBI models, combined with significant Multivariate Correlation (sMC) algorithm variable selection are finally regarded as the best performance models. The ANTH model produced the highest accuracy of prediction with a mean R2 of 0.72 and mean RMSE of 0.10%, followed by FLAV and NBI model (mean R2 of 0.58, mean RMSE of 0.11% and mean R2 of 0.44, mean RMSE of 0.04%). High heritability was found for ANTH, FLAV and NBI with h2 of 0.78, 0.58 and 0.61 respectively. It shows that it is beneficial and possible for breeding selection to the improvement of leaf nutrition traits.

Conclusions

Spectroscopy can successfully characterize the leaf nutrition traits in living tree leaves and the ability to simultaneous multiple plant traits provides a promising and high-throughput tool for the quick analysis of large size samples and serves for genetic breeding program.
Comparison of new hyperspectral index and machine learning models for prediction of winter wheat leaf water content
Authors: Zhang Juanjuan , Zhang Wen , Xiong Shuping , Song Zhaoxiang , Tian Wenzhong , Shi Lei , Ma Xinming
Published: March 2021

Background

The leaf water content estimation model is established by hyperspectral technology, which is crucial and provides technical reference for precision irrigation.

Methods

In this study, two consecutive years of field experiments (different irrigation times and seven wheat varieties) in 2018–2020 were performed to obtain the canopy spectra reflectance and leaf water content (LWC) data. The characteristic bands related to LWC were extracted from correlation coefficient method (CA) and x-Loading weight method (x-Lw). Five modeling methods, spectral index and four other methods (Partial Least-Squares Regression (PLSR), Random Forest Regression (RFR), Extreme Random Trees (ERT), and K-Nearest Neighbor (KNN)) based characteristic bands, were employed to construct LWC estimation models.

Results

The results showed that the canopy spectral reflectance increased with the increase of irrigation times, especially in the near-infrared band (750–1350 nm). The prediction accuracy of the newly developed differential spectral index DVI (R1185, R1307) was higher than that of the existing spectral index, with R2 of 0.85 and R2 of 0.78 for the calibration and validation, respectively. Due to a large amount of hyperspectral data, the correlation coefficient method (CA) and x-Loading weight (x-Lw) were used to select the water characteristic bands (100 and 28 characteristic bands, respectively) from the full spectrum. We found that the accuracy of the model based on the characteristic bands was not significantly lower than that of the full spectrum-based models. Among these models, the ERT- x-Lw model performed the best (R2 and RMSE of 0.88 and 1.46; 0.84 and 1.62 for the calibration and validation, respectively). In addition, the accuracy of the LWC estimation model constructed by ERT-x-Lw was higher than that of DVI (R1185, R1307).

Conclusion

The two models based on ERT-x-Lw and DVI (R1185, R1307) can effectively predict wheat leaf water content. The results provide a technical reference and a basis for crop water monitoring and diagnosis under similar production conditions.
Assessment of fluralaner as a treatment in controlling Dermanyssus gallinae infestation on commercial layer farms and the potential for resulting benefits of improved bird welfare and productivity
Authors: Petersen Ivo , Johannhörster Katharina , Pagot Eric , Escribano Damian , Zschiesche Eva , Temple Déborah , Thomas Emmanuel
Published: March 2021

Background

Poultry red mite (PRM) (Dermanyssus gallinae) infestations are a cause of anaemia, impaired productivity and stress-related behaviours linked to reduced hen welfare. A study investigated the potential health, welfare and productivity benefits following fluralaner treatment to eliminate PRM from infested hens.

Methods

A PRM-infested layer house was selected on a free-range farm (5400 hens) and an aviary farm (42,400 hens). Fluralaner (Exzolt®; 0.5 mg/kg body weight) was administered twice, 7 days apart (Weeks 0 and 1), via drinking water. Mite populations were monitored by traps. Cameras recorded nighttime hen behaviours weekly, pre- and post-treatment. On the free-range farm, daytime behaviours were also recorded weekly. For pre- and post-treatment corticosterone assessments, eggs were randomly collected on both farms, and blood samples were collected from 50 randomly selected aviary farm hens. Production parameters were assessed using farm records.

Results

Throughout the post-treatment period, fluralaner efficacy against PRM was > 99% on both farms. On the aviary and free-range farms, treatment was followed by significant nighttime increases in the proportion of resting hens (P < 0.0001; P = 0.0175, respectively). Significant post-treatment versus pre-treatment nighttime reductions were observed in head shaking (aviary, P < 0.0001; free-range P = 0.0233) and preening (P = 0.0032; P = 0.0018) and on the aviary farm in bouts of body shaking (P = 0.0108), vertical wing shaking (P = 0.0002), head scratching (P = 0.0335), and gentle feather pecking (P < 0.0001). On the free-range farm there were significant daytime reductions in head scratching (P < 0.0001), head shaking (P = 0.0492) and preening (P = 0.0012). Relative to standard production parameters, no differences were detected on the aviary farm, but on the free-range farm the laying rate decline with increasing age was less than expected and the increase in egg weight greater than expected. Post-treatment increases in egg and plasma corticosterone were suggestive of stress factors in addition to mite infestation. Red blood cell counts and haematocrit increased following treatment.

Conclusion

Fluralaner treatment eliminated mite challenge, leading to improved hen welfare and health, based on reductions in stress-related behaviours and restoration of the anaemia-inducing effects of mite blood feeding.

Graphical Abstract
Glioblastoma stem cell (GSC)-derived PD-L1-containing exosomes activates AMPK/ULK1 pathway mediated autophagy to increase temozolomide-resistance in glioblastoma
Authors: Zheng Yong , Liu Liang , Wang Yan , Xiao Shan , Mai Rongkang , Zhu Zifeng , Cao Yiyao
Published: March 2021

Temozolomide (TMZ)-resistance hampers the therapeutic efficacy of this drug for glioblastoma (GBM) treatment in clinic, and emerging evidences suggested that exosomes from GBM-derived stem cells (GSCs) contributed to this process, but the detailed mechanisms are still largely unknown. In the present study, we reported that GSCs derived programmed death-ligand 1 (PD-L1) containing exosomes activated AMPK/ULK1 pathway mediated protective autophagy enhanced TMZ-resistance in GBM in vitro and in vivo. Specifically, we noticed that continuous low-dose TMZ stimulation promoted GSCs generation and PD-L1 containing exosomes (PD-L1-ex) secretion in GBM cells, and that PD-L1-ex inhibited cell apoptosis and promoted cell autophagy to increased TMZ-resistance in GBM cells, which were reversed by co-treating cells with the autophagy inhibitor 3-methyladenine (3-MA). Consistently, upregulation of PD-L1 also increased TMZ-resistance in TS-GBM cells, and silencing of PD-L1 sensitized TR-GBM cells to TMZ. In addition, PD-L1-ex activated AMPK/ULK1 pathway to induce autophagy in TMZ treated GBM cells, and the inhibitors for AMPK (compound C) and ULK1 (SBI-0206965) promoted cell apoptosis in GBM cells co-treated with PD-L1-ex and high-dose TMZ. Finally, we evidenced that PD-L1-ex promoted tumor growth and Ki67 protein expressions to increase TMZ-resistance in GBM in vivo. Collectively, we concluded that GSCs-derived PD-L1-ex activated AMPK1/ULK1 signaling cascade mediated autophagy to increase TMZ-resistance in GBM, and this study provided potential strategies to improve the therapeutic efficacy of TMZ in GBM.
Modes of transmission and attack rates of group A Streptococcal infection: a protocol for a systematic review and meta-analysis
Authors: Barth Dylan D. , Daw Jessica , Xu Ruomei , Enkel Stephanie , Pickering Janessa , McRae Tracy , Engel Mark E. , Carapetis Jonathan , Wyber Rosemary , Bowen Asha C.
Published: March 2021

Background

Group A Streptococcus (Strep A) is an important cause of mortality and morbidity globally. This bacterium is responsible for a range of different infections and post-infectious sequelae. Summarising the current knowledge of Strep A transmission to humans will address gaps in the evidence and inform prevention and control strategies. The objective of this study is to evaluate the modes of transmission and attack rates of group A streptococcal infection in human populations.

Methods

This systematic review protocol was prepared according to the Preferred Reporting Items for Systematic reviews and Meta-analysis Protocols (PRISMA-P) 2015 Statement. Using a comprehensive search strategy to identify any transmission studies that have been published in English since 1980, full-text articles will be identified and considered for inclusion against predefined criteria. We will include all studies reporting on Strep A transmission, who have identified a mode of transmission, and who reported attack rates. Risk of bias will be appraised using an appropriate tool. Our results will be described narratively and where feasible and appropriate, a meta-analysis utilizing the random-effects model will be used to aggregate the incidence proportions (attack rates) for each mode of transmission. In addition, we will also evaluate the emm genotype variants of the M protein causing Strep A infection and the association with transmission routes and attack rates, if any, by setting, socioeconomic background and geographical regions.

Discussion

We anticipate that this review will contribute to elucidating Strep A modes of transmission which in turn, will serve to inform evidence-based strategies including environmental health activities to reduce the transmission of Strep A in populations at risk of severe disease.

Trial registration

Systematic review registration: PROSPERO (CRD42019138472).
Stability of a generalized n-variable mixed-type functional equation in fuzzy modular spaces
Authors: Ramdoss Murali , Pachaiyappan Divyakumari , Park Choonkil , Lee Jung Rye
Published: March 2021

This research paper deals with general solution and the Hyers–Ulam stability of a new generalizedn-variable mixed type of additive and quadratic functional equations in fuzzy modular spaces by using the fixed point method.
Fluorescence polarization assay improves the rapid detection of human brucellosis in China
Authors: Dong Shuai-Bing , Xiao Di , Liu Jing-Yao , Bi Hui-Mei , Zheng Zun-Rong , Wang Li-Da , Yang Xiao-Wen , Tian Guo-Zhong , Zhao Hong-Yan , Piao Dong-Ri , Xing Zhi-Feng , Jiang Hai
Published: March 2021

Background

Brucellosis is an infectious-allergic zoonotic disease caused by bacteria of the genus Brucella. Early diagnosis is the key to preventing, treating, and controlling brucellosis. Fluorescence polarization immunoassay (FPA) is a new immunoassay for relatively rapid and accurate detection of antibodies or antigens based on antigen–antibody interaction. However, there is no report on FPA-based detection of human brucellosis in China. Therefore, this study is to evaluate the value of FPA for the diagnosis of human brucellosis in China.

Methods

We recruited 320 suspected brucellosis cases who had the clinical symptoms and epidemiological risk factors between January and December, 2019. According to China Guideline for Human Brucellosis Diagnosis, the Rose Bengal test (RBT) was used for the screening test, and the serum agglutination test (SAT) was used as the confirmatory test. Brucellosis was confirmed only if the results of both tests were positive. Additionally, FPA and enzyme linked immune sorbent assay (ELISA) were compared with SAT, and their sensitivity, specificity, coincidence rate and consistency coefficient (Kappa value) as diagnostic tests were analyzed individually and in combination. The optimal cut-off value of FPA was also determined using the receiver operator characteristic (ROC) curve.

Results

The optimum cut-off value of FPA was determined to be 88.5 millipolarization (mP) units, with a sensitivity of 94.5% and specificity of 100.0%. Additionally, the coincidence rate with the SAT test was 96.6%, and the Kappa value (0.9) showed excellent consistency. The sensitivity and specificity of FPA and ELISA combined were higher at 98.0% and 100.0% respectively.

Conclusions

When the cut-off value of FPA test is set at 88.5 mP, it has high value for the diagnosis of brucellosis. Additionally, when FPA and ELISA are combined, the sensitivity of diagnosis is significantly improved. Thus, FPA may have potential in the future as a diagnostic method for human brucellosis in China.

Graphic abstract
Behavior of magmatic components in fumarolic gases related to the 2018 phreatic eruption at Ebinokogen Ioyama volcano, Kirishima Volcanic Group, Kyushu, Japan
Authors: Ohba Takeshi , Yaguchi Muga , Tsunogai Urumu , Ito Masanori , Shingubara Ryo
Published: March 2021

Direct sampling and analysis of fumarolic gas was conducted at Ebinokogen Ioyama volcano, Japan, between December 2015 and July 2020. Notable changes in the chemical composition of gases related to volcanic activity included a sharp increase in SO2 and H2 concentrations in May 2017 and March 2018. The analyses in March 2018 immediately preceded the April 2018 eruption at Ioyama volcano. The isotopic ratios of H2O in fumarolic gas revealed the process of formation. Up to 49% high-enthalpy magmatic vapor mixed with 51% of cold local meteoric water to generate coexisting vapor and liquid phases at 100–160 °C. Portions of the vapor and liquid phases were discharged as fumarolic gases and hot spring water, respectively. The CO2/SO2 ratio of the fumarolic gas was higher than that estimated for magmatic vapor due to SO2 hydrolysis during the formation of the vapor phase. When the flux of the magmatic vapor was high, effects of hydrolysis were small resulting in low CO2/SO2 ratios in fumarolic gases. The high apparent equilibrium temperature defined for reactions involving SO2, H2S, H2 and H2O, together with low CO2/SO2 and H2S /SO2 ratios were regarded to be precursor signals to the phreatic eruption at Ioyama volcano. The apparent equilibrium temperature increased rapidly in May 2017 and March 2018 suggesting an increased flux of magmatic vapor. Between September 2017 and January 2018, the apparent equilibrium temperature was low suggesting the suppression of magmatic vapor flux. During this period, magmatic eruptions took place at Shinmoedake volcano 5 km away from Ioyama volcano. We conclude that magma sealing and transport to Shinmoedake volcano occurred simultaneously in the magma chamber beneath Ioyama volcano.
Initial experience with HydroPearl microspheres for uterine artery embolization for the treatment of symptomatic uterine fibroids
Authors: Patetta Matthew A. , Isaacson Ari J. , Stewart Jessica K.
Published: March 2021

Background

Uterine Artery Embolization (UAE) is a minimally invasive procedure used to treat symptomatic uterine fibroids. The HydroPearl Microsphere (Terumo Interventional Systems) is an embolic agent approved for UAE and other embolization procedures. The purpose of this article is to describe our initial experience with HydroPearl for UAE in patients with symptomatic uterine fibroids. Twenty-one patients who underwent UAE using HydroPearl Microspheres at a single institution from May 1, 2018 to December 31, 2019 were included in the study. The electronic medical record (EMR) was reviewed for documentation of short- and long-term complications, as well as improvements in menorrhagia and bulk-type symptoms. We also describe unique attributes of the HydroPearl Microsphere that should be considered when utilizing this embolization particle for UAE.

Results

Of the 21 patients, 18 had a 3-month or later post-procedure follow-up documented in the EMR and were included in the analysis. The average time between the UAE procedure and the most recent clinical note was 145 days. Sixteen patients reported symptoms of menorrhagia and 13 reported bulk symptoms prior to the UAE procedure. On follow-up, 13/16 patients (81%) and 12/13 patients (92%) experienced improvement in menorrhagia and bulk symptoms, respectively. The only recorded complication was amenorrhea in 4 patients (22%) who had an average age of 51 years.

Conclusions

Several characteristics of HydroPearl Microsphere may prove helpful when considering these embolic particles for use in UAE. Our initial experience with this embolic agent suggest that the reatment response for menorrhagia and bulk symptoms are largely similar to success rates reported in the literature for other embolic agents. Larger studies are needed to evaluate the safety and efficacy of this embolic particle for this indication.
3D-printed microplate inserts for long term high-resolution imaging of live brain organoids
Authors: Oksdath Mansilla Mariana , Salazar-Hernandez Camilo , Perrin Sally L. , Scheer Kaitlin G. , Cildir Gökhan , Toubia John , Sedivakova Kristyna , Tea Melinda N. , Lenin Sakthi , Ponthier Elise , Yeo Erica C. F. , Tergaonkar Vinay , Poonnoose Santosh , Ormsby Rebecca J. , Pitson Stuart M. , Brown Michael P. , Ebert Lisa M. , Gomez Guillermo A.
Published: March 2021

Background

Organoids are a reliable model used in the study of human brain development and under pathological conditions. However, current methods for brain organoid culture generate tissues that range from 0.5 to 2 mm of size, which need to be constantly agitated to allow proper oxygenation. The culture conditions are, therefore, not suitable for whole-brain organoid live imaging, required to study developmental processes and disease progression within physiologically relevant time frames (i.e. days, weeks, months).

Results

Here we designed 3D-printed microplate inserts adaptable to standard 24 multi-well plates, which allow the growth of multiple organoids in pre-defined and fixed XYZ coordinates. This innovation facilitates high-resolution imaging of whole-cerebral organoids, allowing precise assessment of organoid growth and morphology, as well as cell tracking within the organoids, over long periods. We applied this technology to track neocortex development through neuronal progenitors in brain organoids, as well as the movement of patient-derived glioblastoma stem cells within healthy brain organoids.

Conclusions

This new bioengineering platform constitutes a significant advance that permits long term detailed analysis of whole-brain organoids using multimodal inverted fluorescence microscopy.
Quorum sensing-mediated inter-specific conidial anastomosis tube fusion between Colletotrichum gloeosporioides and C. siamense
Authors: Mehta Nikita , Baghela Abhishek
Published: March 2021

Many plant pathogenic filamentous fungi undergo fusion of conidia through conidial anastomosis tubes (CATs), which is believed to facilitate horizontal gene transfer between species. We discovered a remarkable inter-specific CAT fusion between two important plant fungal pathogensColletotrichum gloeosporioidesandC. siamense. In an invitro assay, under no selection pressure, the inter-specific CAT fusion was preferred with higher frequency (25% ± 5%) than intra-specific CAT fusion (11% ± 3.6%). Different stages of CAT fusion viz. CAT induction, homing, and fusion were observed during this inter-specific CAT fusion. The CAT fusion was found to be higher in absence of nutrients and under physiological stresses. This CAT fusion involved a quorum sensing phenomenon, wherein the CAT induction was dependent on conidial density and the putative quorum sensing molecule was extractable in chloroform. Movement of nuclei, mitochondria, and lipid droplets were observed during the CAT fusion. Post CAT fusion, the resulting conidia gave rise to putative heterokaryotic progenies with variable colony characteristics as compared to their parental strains. Few heterokaryons showed variable AFLP banding pattern compared to their parental strains, thereby suggesting a possible genetic exchange between the two species through CAT fusion. The heterokaryotic progenies exhibited varied fitness under different stress conditions. Our study illustrated a possible role of inter-specific CAT fusion in generation of genetic and phenotypic diversity in these fungal pathogens.
Mutational analysis of p53 gene in cervical cancer and useful polymorphic variants in exons 3 and 4
Authors: Gbadegesin Michael A. , Omotoso Olabode E. , Oluwasola Timothy A. O. , Okolo Clement A. , Soremekun Opeyemi , Ogun Gabriel O. , Oluwasola Abideen O. , Odunola Oyeronke A.
Published: March 2021

Background

Factors contributing to the pathogenesis and progression of cervical cancer include poor attitude to screening and health intervention, late presentation, among others. Mutations in p53 gene have been attributed to several cancer cases. The present study was designed to find relationships between the mutation patterns in p53 gene and cervical carcinoma staging. Such knowledge could contribute to early diagnosis of cervical cancer.

Results

From the sequence analysis of p53 gene fragment isolated by polymerase chain reactions (PCR), nineteen (19) polymorphic variants were identified. Missense mutations occurred in 47% of the samples, 32% were silent mutations, 16% were frameshift mutations and 5% nonsense mutations. Socio-biological characteristics of the study participants revealed that 60% have husbands with multiple sexual partners and that only 23.3% of the participants have ever had the Papanicolaou (Pap) smear test prior to diagnosis, whilst 20% were unaware of the screening test.

Conclusions

Increased severity of cervical carcinoma staging as revealed from the histopathological analysis was found to be associated with accumulation of higher levels of mutations in the p53 gene. Molecular analysis of p53 gene mutations may prove useful as a screening biomarker for cervical cancer.
SOX10Mutation Screening for 117 Patients with Kallmann Syndrome
Authors: Shima Hirohito , Tokuhiro Etsuro , Okamoto Shingo , Nagamori Mariko , Ogata Tsutomu , Narumi Satoshi , Nakamura Akie , Izumi Yoko , Jinno Tomoko , Suzuki Erina , Fukami Maki
Published: March 2021

Introduction

Kallmann syndrome (KS) is a genetically heterogeneous condition characterized by hypogonadotropic hypogonadism (HH) and olfactory dysfunction. Although SOX10, a causative gene for Waardenburg syndrome (WS) and peripheral demyelinating neuropathy, central demyelination, WS, and Hirschsprung disease (PCWH) has previously been implicated in KS, the clinical significance of SOX10 variants as the cause of KS remains uncertain.

Patients and Methods

A total of 117 patients with KS underwent mutation screening of SOX10 and 14 other causative genes for KS/HH. Rare SOX10 variants were subjected to in silico and in vitro analyses. We also examined clinical data of the patients and their parents with SOX10 variants.

Results

Sequence analysis identified 2 heterozygous variants of SOX10 (c.1225G > T, p.Gly409* and c.475C > T, p.Arg159Trp) in patients 1–3, as well as in the parents of patients 1 and 3. The variants were assessed as pathogenic/likely pathogenic, according to the American College of Medical Genomics guidelines. Both variants lacked in vitro transactivating activity for the MITF promoter and exerted no dominant-negative effects. Patients 1–3 carried no pathogenic variants in other genes examined. The patients presented with typical KS, while such features were absent in the parents of patients 1 and 3. None of the 5 variant-positive individuals exhibited hypopigmentation, while 1 and 2 individuals exhibited complete and partial hearing loss, respectively.

Conclusion

These results provide evidence that SOX10 haploinsufficiency accounts for a small percentage of KS cases. SOX10 haploinsufficiency is likely to be associated with a broad phenotypic spectrum, which includes KS without other clinical features of WS/PCWH.
Prepubertal gonad investment modulates thymus function: evidence in a teleost fish
Authors: Paiola Matthieu , Moreira Catarina , Hétru Julie , Duflot Aurélie , Pinto Patricia I. S. , Scapigliati Giuseppe , Knigge Thomas , Monsinjon Tiphaine
Published: March 2021

Thymus plasticity following gonadectomy or sex hormone replacement has long since exemplified sex hormone effects on the immune system in mammals and, to a lesser extent, in ‘lower vertebrates’, including amphibians and fish. Nevertheless, the underlying physiological significances as well as the ontogenetic establishment of this crosstalk remain largely unknown. Here, we used a teleost fish, the European sea bass, Dicentrarchus labrax, to investigate: (1) whether the regulation of thymus plasticity relies on resource trade-off with somatic growth and reproductive investment and (2) if the gonad–thymus interaction takes place during gonadal differentiation and development. Because gonadal development and, supposedly, thymus function in sea bass depend on environmental changes associated with the winter season, we evaluated thymus changes (foxn1 expression, and thymocyte and T cell content) in juvenile D. labrax raised for 1 year under either constant or fluctuating photoperiod and temperature. Importantly, in both conditions, intensive gonadal development following sex differentiation coincided with a halt of thymus growth, while somatic growth continued. To the best of our knowledge, this is the first study showing that gonadal development during prepuberty regulates thymus plasticity. This finding may provide an explanation for the initiation of the thymus involution related to ageing in mammals. Comparing fixed and variable environmental conditions, our work also demonstrates that the extent of the effects on the thymus, which are related to reproduction, depend on ecophysiological conditions, rather than being directly related to sexual maturity and sex hormone levels.
The Impact of Lower Limb Immobilization and Rehabilitation on Angiogenic Proteins and Capillarization in Skeletal Muscle
Authors: GLIEMANN LASSE , RYTTER NICOLAI , JØRGENSEN TUE SMITH , PIIL PETER , CARTER HOWARD , NYBERG MICHAEL , GRASSI MARCELLO , DAUMER MARTIN , HELLSTEN YLVA
Published: March 2021

Purpose

Skeletal muscle vascularization is important for tissue regeneration after injury and immobilization. We examined whether complete immobilization influences capillarization and oxygen delivery to the muscle and assessed the efficacy of rehabilitation by aerobic exercise training.

Methods

Young healthy males had one leg immobilized for 14 d and subsequently completed 4 wk of intense aerobic exercise training. Biopsies were obtained from musculus vastus lateralis, and arteriovenous blood sampling for assessment of oxygen extraction and leg blood flow during exercise was done before and after immobilization and training. Muscle capillarization, muscle and platelet content of vascular endothelial growth factor (VEGF), and muscle thrombospondin-1 were determined.

Results

Immobilization did not have a significant impact on capillary per fiber ratio or capillary density. The content of VEGF protein in muscle samples was reduced by 36% (P = 0.024), and VEGF to thrombospondin-1 ratio was 94% lower (P = 0.046). The subsequent 4-wk training period increased the muscle VEGF content and normalized the muscle VEGF to thrombospondin-1 ratio but did not influence capillarization. Platelet VEGF content followed the trend of muscle VEGF. At the functional level, oxygen extraction, blood flow, and oxygen delivery at rest and during submaximal exercise were not affected by immobilization or training.

Conclusions

The results demonstrate that just 2 wk of leg immobilization leads to a strongly reduced angiogenic potential as evidenced by reduced muscle and platelet VEGF content and a reduced muscle VEGF to thrombospondin-1 ratio. Moreover, a subsequent period of intensive aerobic exercise training fails to increase capillarization in the previously immobilized leg, possibly because of the angiostatic condition caused by immobilization.
Microstructural Plasticity in the Hippocampus of Healthy Older Adults after Acute Exercise
Authors: CALLOW DANIEL D. , WON JUNYEON , ALFINI ALFONSO J. , PURCELL JEREMY J. , WEISS LAUREN R. , ZHAN WANG , SMITH J. CARSON
Published: March 2021

Introduction

The hippocampus experiences structural and functional decline with age and is a critical region for memory and many cognitive processes. Exercise is beneficial for the aging brain and shows preferential benefits for hippocampal volume, activation, and memory-related cognitive processes. However, research thus far has primarily focused on the effects of exercise on long-term volumetric changes in the hippocampus using structural magnetic resonance imaging. Critically, microstructural alterations within the hippocampus over short time intervals are associated with neuroplasticity and cognitive changes that do not alter its volume but are still functionally relevant. However, it is not yet known if microstructural neuroplasticity occurs in the hippocampus in response to a single session of exercise.

Methods

We used a within-subject design to determine if a 30-min bout of moderate-intensity aerobic exercise altered bilateral hippocampal diffusion tensor imaging measures in healthy older adults (n = 30) compared with a seated rest control condition.

Results

Significantly lower fractional anisotropy and higher mean diffusivity were found after exercise relative to seated rest within the bilateral hippocampus, and this effect was driven by higher radial diffusivity. No significant differences in axial diffusivity were observed.

Conclusions

These findings suggest that a single exercise session can lead to microstructural alterations in the hippocampus of healthy older adults. These differences may be associated with changes in the extracellular space and glial, synaptic, and dendritic processes within the hippocampus. Repeated microstructural alterations resulting from acute bouts of exercise may accumulate and precede larger volumetric and functional improvements in the hippocampus.
Altered Triceps Surae Muscle–Tendon Unit Properties after 6 Months of Static Stretching
Authors: MOLTUBAKK MARIE M. , VILLARS FABIENNE O. , MAGULAS MELINA M. , MAGNUSSON STIG P. , SEYNNES OLIVIER R. , BOJSEN-MØLLER JENS
Published: March 2021

Introduction

This study examined the effects of 24 wk of daily static stretching of the plantarflexors (unilateral 4 × 60-s stretching, whereas the contralateral leg served as a control; n = 26) on joint range of motion (ROM), muscle–tendon unit morphological and mechanical properties, neural activation, and contractile function.

Methods

Torque–angle/velocity was obtained in passive and active conditions using isokinetic dynamometry, whereas muscle–tendon morphology and mechanical properties were examined using ultrasonography.

Results

After the intervention, ROM increased (stretching, +11° ± 7°; control, 4° ± 8°), and passive torque (stretching, −10 ± 11 N·m; control, −7 ± 10 N·m) and normalized EMG amplitude (stretching, −3% ± 6%; control, −3% ± 4%) at a standardized dorsiflexion angle decreased. Increases were seen in passive tendon elongation at a standardized force (stretching, +1.3 ± 1.6 mm; control, +1.4 ± 2.1 mm) and in maximal passive muscle and tendon elongation. Angle of peak torque shifted toward dorsiflexion. No changes were seen in tendon stiffness, resting tendon length, or gastrocnemius medialis fascicle length. Conformable changes in ROM, passive dorsiflexion variables, tendon elongation, and angle of peak torque were observed in the nonstretched leg.

Conclusions

The present findings indicate that habitual stretching increases ROM and decreases passive torque, altering muscle–tendon behavior with the potential to modify contractile function.
Interpretable Machine Learning Model for Early Prediction of Mortality in ICU Patients with Rhabdomyolysis
Authors: LIU CHAO , LIU XIAOLI , MAO ZHI , HU PAN , LI XIAOMING , HU JIE , HONG QUAN , GENG XIAODONG , CHI KUN , ZHOU FEIHU , CAI GUANGYAN , CHEN XIANGMEI , SUN XUEFENG
Published: March 2021

Purpose

Rhabdomyolysis (RM) is a complex set of clinical syndromes that involves the rapid dissolution of skeletal muscles. Mortality from RM is approximately 10%. This study aimed to develop an interpretable and generalizable model for early mortality prediction in RM patients.

Method

Retrospective analyses were performed on two electronic medical record databases: the eICU Collaborative Research Database and the Medical Information Mart for Intensive Care III database. We extracted data from the first 24 h after patient ICU admission. Data from the two data sets were merged for further analysis. The merged data sets were randomly divided, with 70% used for training and 30% for validation. We used the machine learning model extreme gradient boosting (XGBoost) with the Shapley additive explanation method to conduct early and interpretable predictions of patient mortality. Five typical evaluation indexes were adopted to develop a generalizable model.

Results

In total, 938 patients with RM were eligible for this analysis. The area under the receiver operating characteristic curve (AUC) of the XGBoost model in predicting hospital mortality was 0.871, the sensitivity was 0.885, the specificity was 0.816, the accuracy was 0.915, and the F1 score was 0.624. The XGBoost model performance was superior to that of other models (logistic regression, AUC = 0.862; support vector machine, AUC = 0.843; random forest, AUC = 0.825; and naive Bayesian, AUC = 0.805) and clinical scores (Sequential Organ Failure Assessment, AUC = 0.747; Acute Physiology Score III, AUC = 0.721).

Conclusions

Although the XGBoost model is still not great from an absolute performance perspective, it provides better predictive performance than other models for estimating the mortality of patients with RM based on patient characteristics in the first 24 h of admission to the ICU.