bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Botulinum Toxin-A Injection on Lateral Pterygoid Muscle in Patients with Painful Temporomandibular Joint Click: A Randomized Clinical Trial Study
Authors: Rezazadeh Fahimeh , Esnaashari Negin , Azad Azita , Emad Sara
Published: July 2021

Background: The aim of this study was to investigate the effect of Botulinum toxin-A (BTX-A) injection in lateral pterygoid (LP) muscle and analyze the efficacy of this treatment modality in reducing Temporomandibular disorder (TMD) symptoms. TMD is the main cause of nondental pain in the orofacial area. The most common symptoms of temporomandibular disorder are joints pain and sound and limitation of jaw function. Botulinum toxin (BTX) injection in LP temporarily paralysesis the muscle. BTX injection is considered as a potential treatment for TMD, due to its pain relieving characteristic and its ability to reduce muscle activity. However, these evidences are mostly case series and more studies are required to prove its efficacy. Methods: Thirty-eight patients (19 women and 19 men, mean age: 26.53 years) with painful unilateral temporomandibular joint click and LP muscle tenderness entered the study. They were divided into two groups; one received extraoral Botax injection in LP muscle, and the other was injected by placebo. Pain severity, jaw’s range of movement, click severity and Helkimo-Index, were taken recorded at first and also in follow upin first visit and in one week, one month and three months after intervention. Data were analyzed using Repeated measures ANOVA and t-test.Results: The result showed that click severity was not significantly different between BTX and placebo groups (p=0.07). Pain and Helkimo index were decreased significantly in BTX group (p=0.00 and P=0.006 respectively); however, there was no significant difference when compared between the two groups (P=0.22 and p=1 respectively). There was a significant difference in lateral movements between the groups (p=0.00) but not in protrusion movement (p=0.095).Conclusions: It can be concluded that although some studies state that BTX injection can make the click sound disappear, in this study we did not find a significant difference between two groups. Furthermore, our results showed that click and pain severity were decreased, but the difference was not statistically significant. Therefore, further studies with more dosage of BTX and higher participants seem to be necessary.Trial registration: The local Ethics Committee of Shiraz University of Medical Science approved this research under Ethics code: IR.SUMS.REC. 2018/10/01 and IRCT number: IRCT20130521013406N3.
Clinical Significance of Pancreatic Calcifications: A 15-Year Single Center Observational Study
Authors: Wang Wei , Chai Li , Zhu Naiyi , Wang Qingrou , Chai Weimin , Shen Baiyong
Published: July 2021

Objective

Pancreatic calcifications (PC) are considered specific for chronic pancreatitis (CP), but PC may also be present in non-CP diseases. The aims are to understand the pattern of calcifications in different diseases and to determine they were related to malignant diseases.
Methods

A retrospective study was performed including patients with PC or CP undergoing surgery in the Department of General Surgery of Ruijin Hospital from January 2003 to June 2018.
Results

PC were observed in 168 (4.5%) of the 3755 patients with pancreatic diseases. The majority of patients with PC had three kinds of CP (73.2%) while 26.8% had other five kinds of non-CP diseases. The incidences of PC in the pancreatic diseases were lower than these in previous studies. In patients with non-CP diseases, the incidence of PC in malignant intraductal papillary mucinous neoplasm (IPMN) was significantly higher than benign IPMN (8.3% vs. 0.7%, p = 0.004). In 204 patients with CP, pancreatic calcification (OR = 3.7), advanced age (> 55 years), high BMI (> 24 kg/m2), parenchymal atrophy and pancreatic mass were independent predictors for malignancy. In patients of CP wih pancreatic mass (n = 81), the ability of PC (OR = 28.6) to predict malignancy increased nearly sevenfold.
Conclusion

The disease spectrum with PC was very diverse but the incidences of PC in the pancreatic diseases were low. PC may be related to malignant IPMN in non-CP diseases and is related to malignancy in the patients with CP, including the cases without pancreatic mass.
Brush swab as a noninvasive surrogate for tissue biopsies in oral cancer patients to develop clinically translatable epigenetic biomarkers
Authors: Viet Chi Tonglien , Zhang Xinyu , Xu Ke , Yu Gary , Asam Kesava , Thomas Carissa M. , Callahan Nicholas F. , Doan Coleen , Walker Paul C. , Nguyen Khanh , Kidd Stephanie C. , Lee Steve C. , Grandhi Anupama , Allen Clint T. , Young Simon , Melville James C. , Shum Jonathan W. , Viet Dan T. , Herford Alan S. , Roden Dylan F. , Gonzalez Manuel Lora , Aouizerat Bradley E.
Published: July 2021

Background

Oral squamous cell carcinoma (OSCC) has poor survival rates. There is a pressing need to develop more precise risk assessment methods to tailor clinical treatment. Epigenome-wide association studies in OSCC have not produced a viable biomarker. These studies have relied on methylation array platforms, which are limited in their ability to profile the methylome. In this study, we use MethylCap-Seq (MC-Seq), a comprehensive methylation quantification technique, and brush swab samples, to develop a noninvasive, readily translatable approach to profile the methylome in OSCC patients.
Methods

Three OSCC patients underwent collection of cancer and contralateral normal tissue and brush swab biopsies, totaling 4 samples for each patient. Epigenome-wide DNA methylation quantification was performed using the SureSelectXT Methyl-Seq platform. DNA quality and methylation site resolution were compared between brush swab and tissue samples. Correlation and methylation value difference were determined for brush swabs vs. tissues for each respective patient and site (i.e., cancer or normal). Correlations were calculated between cancer and normal tissues and brush swab samples for each patient to determine the robustness of DNA methylation marks using brush swabs in clinical biomarker studies.
Results

There were no significant differences in DNA yield between tissue and brush swab samples. Mapping efficiency exceeded 90% across all samples, with no differences between tissue and brush swabs. The average number of CpG sites with at least 10x depth of coverage was 2,716,674 for brush swabs and 2,903,261 for tissues. Matched tissue and brush swabs had excellent correlation (r = 0.913 for cancer samples and r = 0.951 for normal samples). The methylation profile of the top 1,000 CpGs was significantly different between cancer and normal samples (mean p-value = 0.00021) but not different between tissues and brush swabs (mean p-value = 0.11).
Conclusions

Our results demonstrate that MC-Seq is an efficient platform for epigenome profiling in cancer biomarker studies, with broader methylome coverage than array-based platforms. Brush swab biopsy provides adequate DNA yield for MC-Seq, and taken together, our findings set the stage for development of a non-invasive methylome quantification technique for oral cancer with high translational potential.
Osteoblasts-derived Exosomes as Novel Communicators in Particle Induced Periprosthetic Osteolysis
Authors: de Souza Wanderson , Piperni Sara G. , Ruivo Carolina F. , Bastos Nuno , Cardoso Patrícia , Oliveira Maria J. , Rocha Luís A. , Granjeiro José M. , Fernandes Maria H. , Melo Sonia A. , Ribeiro Ana R.
Published: July 2021

BackgroundThe inflammatory response to titanium implant-derived wear particles is considered as the hallmark of periprosthetic osteolysis, an event that cause pain, reduce patient motility, ultimately leading to the need of a revision surgery. Although macrophages are major cell players, other cell types such as bone cells can indirectly contribute to periprosthetic osteolysis, however the mechanisms are not fully understood. Exosomes (Exos) has been related with several bone pathologies, with growing body of literature recognizing them as actively shuttle molecules through the body, with their cargo being completely dependent of external stimuli (e.g. chemicals and metals ions and particles). Till the moment, the role of wear debris on osteoblasts exosomes biogenesis is absent and the possible contribution of Exos to osteoimmune communication and periprosthetic osteolysis is still in its infancy. Taking that in consideration, in this work we investigate the effect of wear debris on Exo biogenesis, where two bone cell models were exposed to titanium dioxide nanoparticles (TiO2 NPs) similar in size and composition to wear debris associated with prosthetic implants. The contribution of Exos to periprosthetic osteolysis was evaluated performing functional tests stimulating primary human macrophages with bone-derived Exos.ResultsFor the first time, we report that TiO2 NPs enter in multivesicular bodies, the nascent of Exos and altered osteoblasts derived exosomes secretion and cargo. No significant differences were observed in Exos morphology and size, however mass spectrometry analysis identified urokinase-type plasminogen activator (uPA), specifically enriched in Exos derived from bone cells pre-incubated with TiO2 NPs. Functional tests confirmed the activation of human macrophages towards a mixed phenotype with consequent secretion of pro and anti-inflammatory cytokines. ConclusionsThe external stimuli of osteoblasts to TiO2 NPs induced a dose dependent secretion of Exos, suggesting alterations in their biogenesis as well as in their cargo. Functional tests reveal that enriched uPA exosomal cargo is stimulating macrophages towards a mixed M1 and M2 phenotype inducing the release of pro-and anti-inflammatory signals that are characteristic of periprosthetic osteolysis. Interestingly, uPA may be proposed, in the future, as a possible candidate biomarker to early diagnose particle induced periprosthetic osteolysis, since uPA was also detected in the pseudocapsular interface around implants of patients with loosening of total hip prosthesis and joint replacement surgery, suggesting their active role in disease progression.
Impacts of Storm Surges on a Changing Climate: a Global Bibliometric Analysis of the Coastal Zone
Authors: Leal Karine Bastos , Robaina Luís Eduardo de Souza , De Lima André de Souza
Published: July 2021

An increase in the global mean sea is predicted during the 21st century as a consequence of global average temperature projections. In addition, changes in the strength of atmospheric cyclonic storms may alter the development of storm surges, exacerbating the risks to coastal communities. Based on the fact that the interest and range of papers are growing on this topic, this study aims to present the global scientific production status of studies that have correlated climate change and the impact of storm surges on the coastal zone leading to erosion and flooding (inundation) via a bibliometric analysis. We analyzed 429 papers published in journals between 1991 and February 2021 from the Scopus database. Through the VOSviewer and Bibliometrix R package, we describe the most relevant countries, affiliations, journals, authors, and keywords. Our results demonstrate that there has been an exponential growth in the research topic, and that authors from the United States and the United Kingdom are the most prolific. Among the 1454 authors found, 10 researchers published at least 5 papers on the topic and obtained at least 453 citations in the period. The most represented journals were the Journal of Coastal Research, Climatic Change, and Natural Hazards. We also found, and discuss, the lack of standardization in the choice of keywords, of which climate change, storm surge, and sea level rise are the most frequent. Finally, we have written a guide to facilitate the authors' bibliographic review.
Impact of natural selection on global patterns of genetic variation, and association with clinical phenotypes, at genes involved in SARS-CoV-2 infection.
Authors: Zhang Chao , Verma Anurag , Feng Yuanqing , Melo Marcelo Cardoso dos Reis , McQuillan Michael , Hansen Matthew , Lucas Anastasia , Park Joseph , Ranciaro Alessia , Thompson Simon , Rubel Meghan , Campbell Michael , Beggs William , Hirbo Jibril , Mpoloka Sununguko Wata , Mokone Gaonyadiwe George , Jones Marcus , Nyambo Thomas , Meskel Dawit Wolde , Belay Gurja , Fokunang Charles , Njamnshi Alfred , Omar Sabah , Williams Scott , Rader Daniel , Ritchie Marylyn , Fuente Cesar de la , Sirugo Giorgio , Tishkoff Sarah
Published: July 2021

We investigated global patterns of genetic variation and signatures of natural selection at host genes relevant to SARS-CoV-2 infection (ACE2, TMPRSS2, DPP4, and LY6E). We analyzed novel data from 2,012 ethnically diverse Africans and 15,997 individuals of European and African ancestry with electronic health records, and integrated with global data from the 1000GP. At ACE2, we identified 41 non-synonymous variants that were rare in most populations, several of which impact protein function. However, three non-synonymous variants were common among Central African hunter-gatherers from Cameroon and are on haplotypes that exhibit signatures of positive selection. We identify strong signatures of selection impacting variation at regulatory regions influencing ACE2 expression in multiple African populations. At TMPRSS2, we identified 13 amino acid changes that are adaptive and specific to the human lineage. Genetic variants that are targets of natural selection are associated with clinical phenotypes common in patients with COVID-19.
The Clinical Performance and Effectiveness of the Multiple-Attending-Physicians System Compared with the Single-Attending-Physician System in Inpatient Setting: A Mixed-Method Study
Authors: Park Daeho , Hamada Toshihiro , Imaoka Shintaro , Taniguchi Shohei , Ohtsuka Yuma , Wakunami Yu , Lee Young , Kamimoto Minako , Inoue Kazuoki , Son Daisuke , Matsumoto Hiromi , Shimosaka Takuya , Sasaki Shuichi , Lee Youngee , Koda Masahiko , Taniguchi Shin-ichi
Published: July 2021

BackgroundConsidering work styles especially of solo attending physicians, medical facilities have been required to effectively utilize sufficient human resources in many countries. Therefore, we compared cross-sectionally clinical performance of the single- and the multiple-attending physicians groups in inpatient care. Furthermore, we also qualitatively analyzed physicians’ working burden and quantitively assessed advantages / disadvantages of those attending physicians systems.MethodIn this cross-sectional study, we extract electronic health record of patients from a hospital in Japan from April 2017 to October 2018 to compare anonymous statistical data including average lengths of hospital stay and patient outcome between the single-attending and multiple-attending-physicians system. Then, we conducted a questionnaire survey for all physicians of single and multiple-attending physician systems, asking their physical and psychiatric working burden, and their reasons and comments on their working styles.ResultThe average length of hospital stay was significantly shorter in the multiple-attending physicians system than in the single-attending physicians system, while patients’ age, gender and diagnoses were similar. From the questionnaire survey, although physical burden in multiple-attending physicians system tended to be lower than that in single-attending physician system, no significant difference was found in all categories. Advantages of multiple-attending physicians system extracted from qualitative analysis are 1) Improvement of physicians ’ quality of life (QOL), 2) Lifelong-learning effect, and 3) Improving the quality of medical care, while disadvantages were 1) Risk of miscommunication, 2) Conflicting treatment policies among physicians, and 3) unfamiliar culture with multiple-attending physicians system.ConclusionMultiple-attending-physicians system in inpatient care may reduce physical burden on physicians, and not only improve QOL of physicians but lead to lifelong learning and improving the quality of medical care.
Cancer Patients’ Preferences for Psychological Counselling: A Cross-Sectional Study Using Full-Profile Conjoint Analysis in Japan
Authors: Kanako Ichikura , Sayuri Shimizu , Noriko Oshima , Yosuke Ariizumi , Toshihide Fujie , Shin-ichi Yamauchi , Toshiaki Ishikawa , Yasuaki Nakajima , Yuko Fukase , Norio Murayama , Hanako Murase , Hirokuni Tagaya , Takashi Takeuchi , Satoshi Miyake , Eisuke Matsushima
Published: July 2021

Background: Psychological counselling is an effective non-pharmacological intervention for cancer patients facing psychological distress. However, there are barriers to applying counselling in clinical settings because some cancer patients feel that it is a burden and subsequently drop out. This study assessed cancer patients’ preferences for psychological counselling using a conjoint analysis approach.Methods: We conducted a single-center, cross-sectional study using a self-reported questionnaire. The data were collected from outpatients and inpatients at the departments of Respiratory Medicine, Gastrointestinal Surgery, Female Pelvic Surgery, and Head and Neck Surgery from a university hospital between March 2018 and March 2020. The questionnaire, developed from an interview with a clinical psychologist, asked for patients’ preferences for counselling with 48 scenarios according to a combination of type, length, price, and frequency. We conducted a conjoint analysis, calculating the relative importance and part-worth value of each factor.Results: According to the conjoint analysis modeling, cancer patients consider the type as the most important factor when deciding whether to undergo counselling (relative importance: 37.5%), followed by frequency (23.4%), price (19.6%), and length (19.5%). Cancer patients value life reviews highly among the four counselling types. However, women and younger patients valued counselling for emotional control the highest, with advanced cancer patients valuing counselling for problem solving the most.Conclusions: The results reveal that cancer patients consider the type and content of counselling to be the most important factors in the selection process, although preferences depend on individual characteristics. This is the first study to clarify cancer patients’ preferences for psychological counselling using conjoint analysis and proposes a new economical method in the psycho-oncology field.
New Primary Vs True Recurrence In Relapsed Retroperitoneal Liposarcoma: An Analysis of Clinicopatholgical Characteristic Differences And Relapse-Free Survival
Authors: Deng Huan , Cao Bo , Cui Hao , Liu Guibin , Li Hanghang , Song Liqiang , Zhao Ruiyang , Chen Runkai , Wei Bo
Published: July 2021

Background This study aimed to classify relapsed retroperitoneal liposarcoma (RLS) as new primary (NP) or true recurrence (TR) and to assess the implications for therapeutic management of these classifications. Methods Patients with recurrent RLS were classified as NP if the relapse was different from the former tumor’s pathology subtype and anatomical location. Kaplan-Meier curves were adapted to estimate relapse-free survival (RFS), and logistic regression analysis was used to explore the factors related to NP.Results Total 177 patients with relapsed RLS were included in this study. The median tumor sizes were 16 cm (IQR, 13-22 cm, NP) and 18 cm (IQR, 12-25 cm, TR) (P=0.003). Multifocal tumors (89.2% vs 73.8%, P=0.011) and multiple pathology subtypes (52.7% vs 31.1%, P=0.004) were more common in the NP group and tended to invade wider anatomical areas (85.1% vs 71.8%, P=0.037). The median RFS was 17 months (IQR, 7-35 months) in the NP group and 12 months (IQR, 5-23 months) in the TR group, and NP patients showed a longer RFS than TR patients (P=0.004). When the log-rank test was conducted, low-grade pathology, tumor growth rate ≤ 1.25 cm/month and tumor size ≤ 16.5 cm had a significant influence on the NP phenomenon (P=0.015, 0.019, and 0.028, respectively). Logistic regression analysis illustrated that current surgeries, pathology subtype varieties and pathology grade were independent risk factors for NP (P=0.017, 0.019, and 0.025, respectively).Conclusion NP patients have longer RFS than TR patients, and their tumors tend to have multiple pathology subtypes and tumors and are more likely to invade wider anatomical areas. This classification contributes to a better understanding of RLS and provides new evidence for different therapeutic management of relapsed tumors.
From Networked Robotics to Cloud and Big Data Supercharged Robotics: A Survey and Analysis
Authors: Chowdhury Muhammed Tawfiq , Yan Feng
Published: July 2021

In recent years, with the prosperity of big data and cloud computing, robotics is evolving from conventional networked robotics to internet-scale connected, big data driven, and cloud resources supercharged multi-robot systems. In this survey paper, we present a survey of an advancing, pioneering, and multi-disciplinary ﬁeld of research at the intersection of wireless sensor networks (WSN), robotics and big data. We discuss the concepts of networked robots. Networked robots refer to multiple robots working together in coordination with diﬀerent types of embedded computers, sensors, and human users. Networked robotics allows multiple robots and supporting entities to execute tasks that are well beyond the capabilities of a single robot. The recent initiation of cloud technologies is opening new prospects for the provisioning of advanced robotic services based on the cooperation of some connected robots, smart environments and devices powered by the huge computational and storage capability of the cloud servers. We have recently witnessed the emergence of cloud computing on one hand and robotics platforms on the other hand. These two areas have been merging and resulting in the cloud robotics model to oﬀer more distant services. Since networked robots require high computational and processing power, big data is becoming a dominant factor in networked and cloud robotics. This survey paper elaborates the primary concepts of networked and cloud robotics, their applications, challenges as well as the importance of big data in robotics, particularly, networked and cloud robotics and the noteworthy works in these areas.
Genetic Mechanisms Determining Grain Number Distribution Along the Spike and Their Effect on Yield Components in Wheat
Authors: Mizuno Nobuyuki , Ishikawa Goro , Kojima Hisayo , Tougou Makoto , Kiribuchi-Otobe Chikako , Fujita Masaya , Nakamura Kazuhiro
Published: July 2021

The number of wheat grains is one of the major determinant of yield. Many quantitative trait loci (QTLs) and some causal genes such as GNI-A1 and WAPO-A1 that are associated with grain number per spike (GNS) have been identified, but the underlying mechanisms remain largely unknown. We analyzed QTLs for grain number and other related traits using 188 doubled haploid lines derived from the Japanese high-yield variety, Kitahonami, as a parent to elucidate the genetic mechanism determining grain number. The major QTLs for grain number at the apical, central and basal parts of the spike were identified in different chromosomal regions. We considered GNI-A1 and WAPO-A1 as candidate genes controlling grain number at the central and basal parts of the spike, respectively. Kitahonami had the favorable 105Y allele of GNI-A1 and WAPO-A1b allele, and unfavorable alleles of QTLs for grain number at the apical part of spikes. Pyramiding the favorable alleles of these QTLs significantly increased GNS without significantly reducing thousand-grain weight (TGW). In contrast, the accumulation of favorable alleles of QTLs for TGW significantly decreased GNS, whereas days to heading positively correlated with GNS. Late heading increased the spikelet number per spike, resulting in a higher GNS. Pyramiding of the QTLs for TGW and days to heading also altered the GNS. In conclusion, GNS is a complex trait controlled by many QTLs, and it is essential for breeding to design.
The continuity of prime numbers can lead to even continuity(The ultimate)
Authors: Ling Xie
Published: July 2021

n continuous prime numbers can combine a group of continuous even numbers. If an adjacent prime number is followed, the even number will continue.For example, if we take prime number 3, we can get even number 6. If we follow an adjacent prime number 5, we can get even numbers by using 3 and 5: 6, 8 and 10.If a group of continuous prime numbers 3,5,7,11,... P, we can get a group of continuous even numbers 6,8,10,12,..., 2n. Then if an adjacent prime number q is followed, the original group of even numbers 6,8,10,12,..., 2n will be finitely extended to 2 (n + 1) or more adjacent even numbers. My purpose is to prove that the continuity of prime numbers will lead to even continuity as long as 2 (n + 1) can be extended.If the continuity of even numbers is discontinuous, it violates the Bertrand Chebyshev theorem of prime numbers.Because there are infinitely many prime numbers: 3, 5, 7, 11,...We can get infinitely many continuous even numbers: 6,8,10,12,...
Transmission of Multidrug/Rifampicin-Resistant Mycobacterium Tuberculosis in Chongqing, China: A Retrospective Observational Study Using Whole-Genome Sequencing
Authors: Zhao Bing , Liu Chunfa , Fan Jiale , Ma Aijing , He Wencong , He Guangxue , Hu Yan , zhao yanlin
Published: July 2021

Background: Multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) is a global barrel for ‘Stop TB plan’. China has the second highest MDR/RR-TB burden in whole world wide. Understanding the transmission dynamic is facilitated for disease control. Methods: Whole genome sequencing (WGS) data from patients of Chongqing tuberculosis control institute were used for phylogenetic classifications, resistance predictions, and cluster analysis as indicator for recent transmission (RT). Factors associated with MDR/RR-TB were defined by a logistic regression model. Results: A total of 223 cases of MDR/RR-TB were recorded between Jan 1, 2018 and Dec 31, 2020, and 200 cases obtained relevant treatment information. The patients who are older than 55 year old were more likely to suffering from death. 178 MDR/RR strains were obtained WGS data, 152 were classified as lineage 2 strains. 80 (44.9%, 80 of 178) strains were in 20 genomic clusters that differed by 12 or fewer single nucleotide polymorphisms (SNPs), indicating RT. Patients who were infected with lineage 2 strains is a significant factor driving the epidemic towards MDR/RR-TB. Resistance mutations of first-line tuberculosis drugs analysis found that 79 (98.8%) of all 80 strains defined as RT have same mutations among each clusters totally. 55% (44 of 80) of the MDR/RR-TB strains accumulated additional drug resistance mutations along the transmission chain, especially fluoroquinolones (FQs) (63.6%, 28 of 44). Conclusions: The age is the most significant factor that causes death of MDR/RR-TB patients. RT of MDR/RR strains is not only drove the MDR/RR-TB epidemic, but also accumulated more serious resistance along the transmission chains.
The Effects of Verapamil, Hydralazine and Doxazosin on Renin, Aldosterone and The Ratio Thereof
Authors: Veldhuizen Gregory P , Alnazer Rawan M , de Leeuw Peter W. , Kroon Abraham A
Published: July 2021

PURPOSE

Hydralazine, doxazosin and verapamil are currently recommended by the Endocrine Society as acceptable bridging treatment in those in whom full cessation of antihypertensive medication is infeasible during screening for primary aldosteronism (PA). This is under the assumption that they cause minimal to no effect on the aldosterone-to-renin ratio, the most widely used screening test for PA. However, limited evidence is available regarding the effects of these particular drugs on said ratio.
METHODS

In the present study, we retrospectively assessed the changes in aldosterone, renin and aldosterone-to-renin values in essential hypertensive participants before and after treatment with either hydralazine (n = 26), or doxazosin (n = 20) or verapamil (n = 15). All samples were taken under highly standardised conditions.
RESULTS

Hydralazine resulted in a borderline significant rise in active plasma renin concentration (19 vs 25 mIU/L, p = 0.067) and a significant fall in the aldosterone-to-renin ratio (38 vs 24, p = 0.017). Doxazosin caused declines in both plasma aldosterone concentration (470 vs 330 pmol/L, p = 0.028) and the aldosterone-to-renin ratio (30 vs 20, p = 0.020). With respect to verapamil, we found no statistically significant effect on any of these outcome variables.
CONCLUSION

We conclude that the assumption that these drugs can be used with little consequence to the aldosterone-to-renin cannot be substantiated. While it is possible that they are indeed the best option when full antihypertensive drug cessation is infeasible, the potential effects of these drugs must still be taken into account when interpreting the aldosterone-to-renin ratio.
Synthetic Phytosiderophore, Proline-2′-Deoxymugineic Acid, is Efficiently Utilized by Dicots
Authors: Ueno Daisei , Ito Yuta , Ohnishi Miho , Miyake Chikahiro , Sohtome Takayuki , Suzuki Motofumi
Published: July 2021

Purpose: Phytosiderophores (PS) from grasses solubilize sparingly soluble iron (Fe), and the resultant PS-Fe is an Fe source, even for dicots. Recently, the synthetic PS proline-2′-deoxymugineic acid (PDMA) has been developed as a moderately biodegradable Fe fertilizer for grasses. We aimed to investigate whether PDMA-Fe is also a good Fe source for dicots.Methods: The availability of PDMA-Fe to cucumber was evaluated in calcareous soil and hydroponic cultures under pH 7.0–9.0 by determining chlorophyll concentration, PSII activity, and Fe uptake. EDDHA-Fe, EDTA-Fe, and citrate-Fe were used as controls. The reducibility of Fe chelates by roots was measured to determine the mechanism underlying differences in availability. Expressions of Fe deficiency-inducible genes (CsFRO1 and CsIRT1) were analyzed to estimate the Fe status in plants. Results: Application of PDMA-Fe and EDDHA-Fe to calcareous soil reduced Fe-deficient chlorosis to a similar extent; however, shoot Fe concentration was higher in the PDMA-Fe treatment. In the hydroponic culture, PDMA-Fe had higher availability than the other chelates at every pH, which was confirmed by higher PSII activity and lower expression of Fe deficiency-inducible genes. The reducibility assay revealed that the reduction level of PDMA-Fe was greater than that of EDTA-Fe and citrate-Fe under alkaline pH.Conclusion: PDMA-Fe is utilized by cucumber roots more efficiently than traditional synthetic chelates in both calcareous soil and hydroponic cultures. The higher availability of PDMA-Fe may be attributed to its higher reducibility. Our findings suggest that PDMA-Fe could be a good Fe fertilizer for dicots.
Overexpression of MdIPT8 Encodes an Isopentenyl Transferase Enzyme Enhances Resistance to Colletotrichum Gloeosporioides in apple (Malus Domestica)
Authors: Shi Jiajun , Zhang Feng , Jiang Qiu , Yuan Yuhong , Nie Xiaolin , Zhou Ying , Wang Zhigang , Ma Yue , Wang Feng
Published: July 2021

Apple (Malus domestica) is a delicious fruit and have high economic value. However, numerous destructive fungi affect apple tree and limit the development of apple production. Many researches showed that salicylic acid and jasmonic acid improved plant resistance to fungal disease, but the potential mechanisms between cytokinin and fungal disease were hardly reported. The IPT gene family encodes the proteins of synthetizing cytokinin and plays an indispensable role in plant biological stress. In our previous study, we found the disease resistance in autotetraploid apple was much better than ‘Hanfu’ and we analyze the gene expression in ‘Hanfu’ and autotetraploid apple. We found the MdIPT8 gene was significantly different expressed. Therefore, we focused on MdIPT genes. We uncovered ten IPT genes in the ‘Hanfu’ whole genome, that are unevenly distributed across five chromosomes. Phylogenetic analysis indicated this family falling into two groups. Moreover, the transcriptional analysis of ten IPT genes indicated MdIPT8 can be induced under Colletotrichum gloeosporioides stress stimulating in apple leaves. The MdIPT8 protein coalesced to green fluorescent protein pinpointed to the chloroplast. Finally, we confirmed that the overexpression of MdIPT8 increased resistance to C. gloeosporioides. Additionally, the endogenous cytokinin content of ‘Hanfu’ leaves increased under the stress of C. gloeosporioides and exogenous cytokinin improved the disease resistance of leaves. Our findings supply an overview of the identification of apple IPT gene family and increases the understanding of cytokinin in apple anthracnose resistance study.
Neutrophil Extracellular Traps Participate in the Development of Gastric Cancer Associated Thrombosis
Authors: Li Jiacheng , Zou Xiaoming , Yang Shifeng , Jin Jiaqi , Zhu Lei , Li Changjian , Yang Hao , Zhang Ange , Chen Chongyan
Published: July 2021

Background: Development of venous thromboembolism (VTE) is associated with high mortalities among gastric cancer (GC) patients. Neutrophil extracellular traps (NETs) have been reported to correlated with prothrombotic state in some diseases. We hypothesize that NETs participate in the development of GC-associated thrombosis.Methods: The level of NETs in blood and tissue samples of patients were analyzed by ELISA, flow cytometry and immunofluorescence (IF). NETs generation and hypercoagulation of platelets and endothelial cells (ECs) in vitro were observed by IF. NETs procoagulant activity (PCA) was performed by fibrin formation and thrombin-antithrombin complex (TAT) assays. Thrombosis in vivo was measured in murine model induced by flow stenosis in the inferior vena cave (IVC).Results: NETs were likely to form in blood and tissue samples of GC patients compared with healthy individuals. In vitro studies that GC cells and their conditioned medium (CM), but not gastric mucosal epithelial cell can stimulate NETs releasing from neutrophils. In addition, NETs induced hypercoagulable state of platelets by up-regulating the expression of phosphatidylserine (PS) and P-selectin on the cells. Furhter, NETs stimulated adhesion of normal platelets on glass surfaces. Similarly, NETs triggered the conversion of ECs to hypercoagulable phenotypes by down-regulating the expression of their intercellular tight junctions but up-regulating that of tissue factor (TF). Treatment of normal platelets or ECs with NETs augmented the level of plasma fibrin formation and TAT complex. Meanwhile, in the models of IVC stenosis, tumor-bearing mice showed stronger ability to form thrombi and NETs were abundantly accumulated in the thrombi compared with control mice. Notably, combination of DNase-1, activated protein C (APC) and Sivelestat markedly abolished the PCA of NETs.Conclusions: Our findings demonstrate that GC-induced NETs strongly increase the risks of VTE development both in vitro and in vivo. NETs are potential therapeutic targets in the prevention and treatment of VTE in GC patients.
The Functional Outcome of Patients Following Spinal Injury in Asia Metropolitans: Does the Prehospital Spine Immobilization Matter?
Authors: Chen Hsuan An , Hsu Shuo Ting , Shin Sang Do , Jamaluddin Sabariah Faizah , Son Do Ngoc , Hong Ki Jeong , Tanaka Hideharu , Sun Jen Tang , Chiang Wen-Chu
Published: July 2021

Prehospital spinal immobilization is a widely used procedure in the emergency medical service (EMS) system worldwide, while the incidence of patients with spinal injury (SI) is relatively low, and unnecessary prehospital spinal immobilization is associated with patient complications. This study aimed to determine the association between prehospital spine immobilization and favorable functional outcomes at hospital discharge among trauma patients with SI. We conducted a retrospective cohort study using the Pan-Asia Trauma Outcomes Study (PATOS) registry data from January 1, 2016, to November 30, 2018. A total of 759 patients with SI were enrolled from 43,752 trauma patients in the PATOS registry during the study period. The subjects had a median age of 58 years ( Q1−Q3,41−72), and 438 (57.7%) patients had prehospital spine immobilization. Overall, prehospital spinal immobilization was not associated with favorable functional outcomes at discharge in multivariable logistic regression (aOR, 1.06; 95%CI 0.62−1.81, p = 0.826). However, in the subgroup of cervical SI, prehospital spinal immobilization was associated with favorable functional outcomes at discharge (aOR, 3.14; 95%CI 1.04−9.50; p = 0.043). Therefore, we suggest that paramedics should be more careful when determining cervical SI and using prehospital immobilization.
Discovering Spatial-temporal Patterns of COVID-19 Pandemic in South Korea: A Data-driven Approach using Dynamic Mode Decomposition
Authors: Kim Sungchan , Kim Minseok , Lee Sunmi , Lee Young Ju
Published: July 2021

A novel severe acute respiratory syndrome coronavirus 2 emerged in December 2019, and it took only a few months for WHO to declare COVID-19 as a pandemic in March 2020. It is very challenging to discover complex spatial-temporal transmission mechanisms. However, it is crucial to capture essential features of regional-temporal patterns of COVID-19 to implement prompt and effective prevention or mitigation interventions. In this work, we develop a novel framework of compatible window-wise dynamic mode decomposition (CwDMD) for nonlinear infectious disease dynamics. The compatible window is a selected representative subdomain of time series data, in which compatibility between spatial and temporal resolutions is established so that DMD can provide meaningful data analysis. A total of four compatible windows have been selected from COVID-19 time-series data from January 20, 2020, to May 10, 2021, in South Korea. The spatiotemporal patterns of these four windows are then analyzed. Several hot and cold spots were identified, their spatial-temporal relationships, and some hidden regional patterns were discovered. Our analysis reveals that the first wave was contained in Daegu and Gyeongbuk area but it spread rapidly to the whole of South Korea after the second wave. Later on, the spatial distribution is seen to become more homogeneous after the third wave. Our analysis also identifies that some patterns are not related to regional relevance. These findings have then been analyzed and associated with the inter-regional and local characteristics of South Korea. Thus, the present study is expected to provide public health officials helpful insights for future regional-temporal specific mitigation plans.
A Novel Approach to Safe Special Fitness Testing in Judo Players
Authors: Błach Wiesław , Ambroży Tadeusz , Obmiński Zbigniew , Malliaronopoulos Nikos , Migasiewicz Juliusz , Ozimek Mariusz , Grymanowski Jaromir , Rydzik Łukasz
Published: July 2021

Background: Measurements of physical fitness indices obtained in laboratory tests using an ergometer or a treadmill are very accurate, but they involve selected groups of muscles and do not reproduce the structure of the sport-specific exercise in judo. For this reason, researchers seek for the tests that use movements similar to the characteristic offensive techniques used during competitions (i.e. throwing). The most commonly recommended is the seoi-nage throwing test, known as SJFT (special judo fitness test).The aim of the study was to develop a new test in which uke is replaced by a dummy, in order to reduce the injury rate and ensure the safety of the participants.Methods: During the 3-week period, competitors from different weight classes performed at the beginning and then after the 2-week period one 1-minute series of continual dummy throws using the o-goshi technique and the seoi-nage technique. Post-exercise physiological responses (heart rate [HR] and blood lactate levels [La]) were evaluated.﻿Results: Significant improvements were reported in o-goshi performance level after the training period. Physiological responses to exercise did not change significantly after training sessions. On both measurement days, post-exercise La levels were similar for o-goshi and seoi-nage throws, whereas post-exercise HR was significantly greater after seoi-nage throws.Conclusions: The dummy throwing test can be a recommended alternative to uke throwing due to the elimination of the risk of injuries to practising athletes.
Evaluation of Standard Dosing for Selected Broad Spectrum Hydrophilic Antibiotics in Critically Ill Patients with Augmented Renal Clearance: An Observational Study
Authors: Almutairi Majed , Sulaiman Khalid Al , Alenazi Sultan , Vishwakarma Ramesh , Aljuhani Ohoud
Published: July 2021

Background: Inappropriate antibiotics dosing in critically ill patients with augmented renal clearance (ARC) may be associated with pathogens resistance and worse outcomes. Unfortunately, studies regarding the relationship between ARC and clinical outcomes in patients treated with antibiotics medication are rare. The study aims to evaluate the efficacy and clinical outcomes of selected broad spectrum hydrophilic antibiotics (Meropenem, Imipinem, Piperacillin/Tazobactam) in augmented renal function critically ill patients with confirmed infections.Methods: A retrospective cohort study in critically ill patients who were admitted to intensive care units (ICUs) at King Abdulaziz Medical City (KAMC)-Riyadh and received broad-spectrum Hydrophilic antibiotics (Meropenem, Imipenem, or Piperacillin/Tazobactam) with confirmed infection. All the patients who met our inclusion criteria during the study period (01/01/2018 – 31/12/2019) were included. Eligible patients have been divided into two groups (augmented renal clearance (ARC) Vs. Non-ARC) according to the estimated creatinine clearance (CrCl) to assess pathogen eradication at 10-14 days. Results: A total of 2682 patients were screened; 133 patients were included in the study. The eradication of pathogen at 10-14 days in ARC group was non-inferior to non-ARC group (OR 1.08; 95% CI, 0.41–2.78 p = 0.88). The Resistance (OR 0.78; 95% CI, 0.25–2.40 p = 0.66), and Persistence after 3 days (OR 0.88; 95% CI, 0.35–2.18 p = 0.78) were not significantly different between the groups. In other words, patients with ARC have the same rate of resistance and persistence of pathogen after three days. There was no difference in the 30-day mortality between the two groups (OR 0.22; 95% CI, 0.04–1.40 p = 0.11). Also, there was no difference in the ICU length of stay (LOS) nor in hospital LOS between the two groups (22.0 days vs. 17.5 days, p = 0.37), and (51.0 days vs. 30.0 days, p = 0.07) respectively. Conclusion: Using standard dosing of hydrophilic broad-spectrum antibiotics in ARC patients was not inferior to non-ARC patients in terms of the pathogen eradication, resistance, and persistence. Further randomized clinical and interventional studies are required to confirm our findings.
SOD1 mutation spectrum and natural history of ALS patients in a 15-year Cohort in Southeastern China
Authors: Chen Lu-xi , Xu Hai-feng , Wang Pei-Shan , Yang Xin-Xia , Wu Zhi-Ying , li hongfu
Published: July 2021

Background

Mutations in superoxide dismutase 1 gene (SOD1) are the most frequent high penetrant genetic cause for amyotrophic lateral sclerosis (ALS) in the Chinese population. A detailed natural history of SOD1-mutated ALS patients will provide key information for ongoing genetic clinical trials.
Methods

We screened for SOD1 mutations using whole exome sequencing (WES) in Chinese ALS cases from 2017 to 2021. Functional studies were then performed to confirm the pathogenicity of novel variants. In addition, we enrolled previously reported SOD1 mutations in our centers from 2007 to 2017. The SOD1 mutation spectrum, age at onset (AAO), diagnostic delay, and survival duration were analyzed.
Results

We found two novel SOD1 variants (p.G17H and p.E134*) that exerted both gain-of-function and loss-of-function effects in vitro. Combined with our previous SOD1-mutated patients, thirty-two probands with 21 SOD1 mutations were included with the four most frequently occurring mutations of p.V48A, p.H47R, p.C112Y, and p.G148D. SOD1 mutations account for 58.9% of familial ALS (FALS) cases. The mean (SD) AAO was 46 ± 11.4 years with a significant difference between patients carrying mutations in exon 1 [n = 5, 34.6 (12.4) years] and exon 2 [n = 8, 51.4 (8.2) years] (p = 0.038). The mean of the diagnostic delay of FALS patients is significantly earlier than the sporadic ALS (SALS) patients [9.5 (4.8) years vs 20.3 (9.3) years, p = 0.0026]. In addition, male patients survived longer than female patients (40 months vs 16 months, p = 0.05).
Conclusion

Our results expanded the spectrum of SOD1 mutations, highlighted the mutation distribution, and summarized the natural history of SOD1-mutated patients in Southeastern China. Male patients were found to have better survival, and FALS patients received an earlier diagnosis. Our findings assist in providing a detailed clinical picture, which is important for ongoing genetic clinical trials.
Molecular Analysis of STin2 (Intron 2) Variant of The SLC6A4 Gene in Children and Adolescents With Attention Deficit Hyperactivity Disorder
Authors: Amiri Shahrokh , Asadian Mahan , Khaniani Mahmoud Shekari , Derakhshan Sima Mansouri , Rahmani Negar Pourhossein , Shafiee-Kandjani Ali Reza , Fanid Leila Mehdizadeh
Published: July 2021

Background

Attention deficit hyperactivity disorder (ADHD) is recognized as one of the most familiar childhood psychiatric disorders. Many molecular genetic reviews suggest that genes play a crucial role in susceptibility to ADHD. The serotonin transporter gene (SLC6A4) has polymorphisms that seem to correlate with ADHD development. The association between ADHD and the SLC6A4 gene variants in the Iranian population has not been investigated yet. This study analyzes the STin2 (intron 2) variant of the SLC6A4 gene in Iranian children and adolescents with ADHD .
Materials and Methods

In this retrospective case-control study, 86 ADHD patients and 99 healthy volunteers aged 5 to 14 years old were enrolled as the case group and the control group, respectively. The STin2 (intron2) fragment of the SLC6A4 gene was amplified using specific primers by conventional PCR, and three STin2 alleles of the SLC6A4 gene (STin2.9, STin2.10, and STin2.12) were examined using the acrylamide gel method.
Results

We found no significant difference between the ADHD and the control groups in STin2.9(34.9% vs 39.4%, p-value = 0.824), STin2.10(29.1% vs 23.2%, p-value = 1.354), and STin2.12(36% vs 36.4%, p-value = 0.986) variants.
Conclusion

It is concluded that there was no association between the frequency of STin2 variant alleles of the SLC6A4 gene andADHD, but in the study of risk estimation, it was found that allele 10 of this variant is a risk allele in ADHD patients.