bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the use of contraceptives associated with periodontal diseases? A systematic review and meta-analyses
Authors: Castro Micaele Maria Lopes , Ferreira Maria Karolina Martins , Prazeres Iasmin Encaua Essashika , de Oliveira Nunes Paula Beatriz , Magno Marcela Baraúna , Rösing Cassiano Kuchenbecker , Maia Lucianne Cople , Lima Rafael Rodrigues
Published: February 2021

Background

Previous studies indicated an impact of hormonal contraceptive use on oral health. This systematic review aimed to investigate the evidence supporting the impact of the use of hormonal contraceptives and periodontal diseases.

Methods

This study is based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and based on the PECO acrostic. Inclusion criteria comprised observational studies including women (P), which evaluated hormonal contraceptive users (E) and hormonal contraceptive non-users (C), to verify the association between this hormonal therapy and the periodontal diseases (O). Searches were performed on 5 databases: PubMed, Scopus, Web of Science, Cochrane Library, LILACS and grey literature (OpenGrey and Google Scholar). After the selection process, the included studies were evaluated qualitatively. Moreover, quantitative data were analyzed in two meta-analyses for clinical attachment loss (CAL) and probing depth (PD). Finally, the level of certainty was measured with the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) tool between periodontal clinical parameters.

Results

18 articles were eligible for the qualitative synthesis and 7 of them were selected for quantitative analysis. Hence, 15 of the eligible articles reported an association between the use of hormonal contraceptives and severity of periodontal disease. However, 6 articles demonstrated high risk of bias and were excluded from quantitative synthesis. The meta-analysis showed a statistically significant difference for CAL (MD 0.24 [0.09, 0.40];p = 0.002), but in PD (MD 0.05 [− 0.05, 0.15];p = 0.33) such difference was not identified. A very low level of evidence was found between the clinical parameters.

Conclusions

The use of hormonal contraceptives may be associated to severity of periodontal diseases. However, the quantitative analysis points to an inconclusive outcome due to the high level of heterogeneity. The association is biologically plausible, however additional studies are warranted to better elucidate the clinical significance of this possible association.
Addressing the physician burnout epidemic with resilience curricula in medical education: a systematic review
Authors: Seo Chanhee , Corrado Mario , Fournier Karine , Bailey Tayler , Haykal Kay-Anne
Published: February 2021

Background

A variety of stressors throughout medical education have contributed to a burnout epidemic at both the undergraduate medical education (UGME) and postgraduate medical education (PGME) levels. In response, UGME and PGME programs have recently begun to explore resilience-based interventions. As these interventions are in their infancy, little is known about their efficacy in promoting trainee resilience. This systematic review aims to synthesize the available research evidence on the efficacy of resilience curricula in UGME and PGME.

Methods

We performed a comprehensive search of the literature using MEDLINE, EMBASE, PsycINFO, Educational Resources Information Centre (ERIC), and Education Source from their inception to June 2020. Studies reporting the effect of resilience curricula in UGME and PGME settings were included. A qualitative analysis of the available studies was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of bias was assessed using the ROBINS-I Tool.

Results

Twenty-one studies met the inclusion criteria. Thirteen were single-arm studies, 6 quasi-experiments, and 2 RCTs. Thirty-eight percent (8/21; n = 598) were implemented in UGME, while 62 % (13/21, n = 778) were in PGME. There was significant heterogeneity in the duration, delivery, and curricular topics and only two studies implemented the same training model. Similarly, there was considerable variation in curricula outcome measures, with the majority reporting modest improvement in resilience, while three studies reported worsening of resilience upon completion of training. Overall assessment of risk of bias was moderate and only few curricula were previously validated by other research groups.

Conclusions

Findings suggest that resilience curricula may be of benefit to medical trainees. Resilience training is an emerging area of medical education that merits further investigation. Additional research is needed to construct optimal methods to foster resilience in medical education.
Automated detection of colorectal tumors based on artificial intelligence
Authors: Lee Kwang-Sig , Son Sang-Hyuk , Park Sang-Hyun , Kim Eun Sun
Published: February 2021

Background

This study developed a diagnostic tool to automatically detect normal, unclear and tumor images from colonoscopy videos using artificial intelligence.

Methods

For the creation of training and validation sets, 47,555 images in the jpg format were extracted from colonoscopy videos for 24 patients in Korea University Anam Hospital. A gastroenterologist with the clinical experience of 15 years divided the 47,555 images into three classes of Normal (25,895), Unclear (2038) and Tumor (19,622). A single shot detector, a deep learning framework designed for object detection, was trained using the 47,255 images and validated with two sets of 300 images—each validation set included 150 images (50 normal, 50 unclear and 50 tumor cases). Half of the 47,255 images were used for building the model and the other half were used for testing the model. The learning rate of the model was 0.0001 during 250 epochs (training cycles).

Results

The average accuracy, precision, recall, and F1 score over the category were 0.9067, 0.9744, 0.9067 and 0.9393, respectively. These performance measures had no change with respect to the intersection-over-union threshold (0.45, 0.50, and 0.55). This finding suggests the stability of the model.

Conclusion

Automated detection of normal, unclear and tumor images from colonoscopy videos is possible by using a deep learning framework. This is expected to provide an invaluable decision supporting system for clinical experts.
Physical accessibility of primary care facilities for people with disabilities: a cross-sectional survey in 31 countries
Authors: Groenewegen Peter P. , Kroneman Madelon , Spreeuwenberg Peter
Published: February 2021

Background

Primary care is the first point of care, also for people with disabilities. The accessibility of primary care facilities is therefore very important. In this study we analysed comparative data on physical accessibility of general practices (GP practices) in 31 (mainly) European countries.

Methods

We used data from the QUALICOPC study, conducted in 2011 among GPs in 34 (mainly European) countries and constructed a physical accessibility scale. We applied multilevel analysis to assess the differences between and within countries and to test hypotheses, related to characteristics of the practices and of the countries.

Results

We found large differences between countries and a strong clustering of physical accessibility within countries. Physical accessibility was negatively related to the age of the GPs, and was less in single-handed and in inner city practices. Of the country variables only the length of the period of social democratic government participation during the previous decades was positively related to physical accessibility.

Conclusion

A large share of the variation in physical accessibility of GP practices was on the level of countries. This means that national policies can be used to increase physical accessibility of GP practices.
Tunable expression rate control of a growth-decoupled T7 expression system by l-arabinose only
Authors: Stargardt Patrick , Striedner Gerald , Mairhofer Juergen
Published: February 2021

Background

Precise regulation of gene expression is of utmost importance for the production of complex membrane proteins (MP), enzymes or other proteins toxic to the host cell. In this article we show that genes under control of a normally Isopropyl β-d-1-thiogalactopyranoside (IPTG)-inducible PT7-lacO promoter can be induced solely with l-arabinose in a newly constructed Escherichia coli expression host BL21-AI, a strain based on the recently published approach of bacteriophage inspired growth-decoupled recombinant protein production.

Results

Here, we show that BL21-AI is able to precisely regulate protein production rates on a cellular level in an l-arabinose concentration-dependent manner and simultaneously allows for reallocation of metabolic resources due to l-arabinose induced growth decoupling by the phage derived inhibitor peptide Gp2. We have successfully characterized the system under relevant fed-batch like conditions in microscale cultivation (800 µL) and generated data proofing a relevant increase in specific yields for 6 different Escherichia coli derived MP-GFP fusion proteins by using online-GFP signals, FACS analysis, SDS-PAGE and western blotting.

Conclusions

In all cases tested, BL21-AI outperformed the parental strain BL21-AI, operated in growth-associated production mode. Specific MP-GFP fusion proteins yields have been improved up to 2.7-fold. Therefore, this approach allows for fine tuning of MP production or expression of multi-enzyme pathways where e.g. particular stoichiometries have to be met to optimize product flux.
Monoclonal antibodies and chimeric antigen receptor (CAR) T cells in the treatment of colorectal cancer
Authors: Jin Ke-Tao , Chen Bo , Liu Yu-Yao , Lan H uan-Rong , Yan Jie-Ping
Published: February 2021

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer deaths worldwide. Besides common therapeutic approaches, such as surgery, chemotherapy, and radiotherapy, novel therapeutic approaches, including immunotherapy, have been an advent in CRC treatment. The immunotherapy approaches try to elicit patients` immune responses against tumor cells to eradicate the tumor. Monoclonal antibodies (mAbs) and chimeric antigen receptor (CAR) T cells are two branches of cancer immunotherapy. MAbs demonstrate the great ability to completely recognize cancer cell-surface receptors and blockade proliferative or inhibitory pathways. On the other hand, T cell activation by genetically engineered CAR receptor via the TCR/CD3 and costimulatory domains can induce potent immune responses against specific tumor-associated antigens (TAAs). Both of these approaches have beneficial anti-tumor effects on CRC. Herein, we review the different mAbs against various pathways and their applications in clinical trials, the different types of CAR-T cells, various specific CAR-T cells against TAAs, and their clinical use in CRC treatment.
Smartphone-based dispatch of community first responders to out-of-hospital cardiac arrest - statements from an international consensus conference
Authors: Metelmann Camilla , Metelmann Bibiana , Kohnen Dorothea , Brinkrolf Peter , Andelius Linn , Böttiger Bernd W. , Burkart Roman , Hahnenkamp Klaus , Krammel Mario , Marks Tore , Müller Michael P. , Prasse Stefan , Stieglis Remy , Strickmann Bernd , Thies Karl Christian
Published: February 2021

Background

Over the past decade Smartphone-based activation (SBA) of Community First Responders (CFR) to out-of-hospital cardiac arrests (OHCA) has gained much attention and popularity throughout Europe. Various programmes have been established, and interestingly there are considerable differences in technology, responder spectrum and the degree of integration into the prehospital emergency services. It is unclear whether these dissimilarities affect outcome. This paper reviews the current state in five European countries, reveals similarities and controversies, and presents consensus statements generated in an international conference with the intention to support public decision making on future strategies for SBA of CFR.

Methods

In a consensus conference a three-step approach was used: (i) presentation of current research from five European countries; (ii) workshops discussing evidence amongst the audience to generate consensus statements; (iii) anonymous real-time voting applying the modified RAND-UCLA Appropriateness method to adopt or reject the statements. The consensus panel aimed to represent all stakeholders involved in this topic.

Results

While 21 of 25 generated statements gained approval, consensus was only found for 5 of them. One statement was rejected but without consensus. Members of the consensus conference confirmed that CFR save lives. They further acknowledged the crucial role of emergency medical control centres and called for nationwide strategies.

Conclusions

Members of the consensus conference acknowledged that smartphone-based activation of CFR to OHCA saves lives. The statements generated by the consensus conference may assist the public, healthcare services and governments to utilise these systems to their full potential, and direct the research community towards fields that still need to be addressed.
Changes in the proportion of clinical clusters contribute to the phenotypic evolution of Behçet’s disease in Japan
Authors: Soejima Yutaro , Kirino Yohei , Takeno Mitsuhiro , Kurosawa Michiko , Takeuchi Masaki , Yoshimi Ryusuke , Sugiyama Yumiko , Ohno Shigeru , Asami Yukiko , Sekiguchi Akiko , Igarashi Toshihisa , Nagaoka Shohei , Ishigatsubo Yoshiaki , Nakajima Hideaki , Mizuki Nobuhisa
Published: February 2021

Background

We hypothesized that Behçet’s disease (BD) consists of several clinical subtypes with different severity, resulting in heterogeneity of the disease. Here, we conducted a study to identify clinical clusters of BD.

Methods

A total of 657 patients registered in the Yokohama City University (YCU) regional BD registry between 1990 and 2018, as well as 6754 patients who were initially registered in the Japanese Ministry of Health, Labour and Welfare (MHLW) database between 2003 and 2014, were investigated. The YCU registry data regarding the clinical manifestations of BD, human leukocyte antigen (HLA) status, treatments, and hospitalizations were analyzed first, followed by similar analyses of the MHLW for validation. A hierarchical cluster analysis was independently performed in both patient groups.

Results

A hierarchical cluster analysis determined five independent clinical clusters in the YCU cohort. Individual counterparts of the YCU clusters were confirmed in the MHLW registry. Recent phenotypical evolutions of BD in Japan, such as increased gastrointestinal (GI) involvement, reduced complete type according to the Japan Criteria, and reduced HLA-B51 positivity were associated with chronologically changing proportions of the clinical clusters.

Conclusions

In this study, we identified independent clinical clusters among BD patients in Japan and found that the proportion of each cluster varied over time. We propose five independent clusters namely “mucocutaneous”, “mucocutaneous with arthritis”, “neuro”, “GI”, and “eye.”
Molecule Set Comparator (MSC): a CDK-based open rich‐client tool for molecule set similarity evaluations
Authors: Rajan Kohulan , Hein Jan-Mathis , Steinbeck Christoph , Zielesny Achim
Published: February 2021

The open rich-client Molecule Set Comparator (MSC) application enables a versatile and fast comparison of large molecule sets with a unique inter-set molecule-to-molecule mapping obtained e.g. by molecular-recognition-oriented machine learning approaches. The molecule-to-molecule comparison is based on chemical descriptors obtained with the Chemistry Development Kit (CDK), such as Tanimoto similarities, atom/bond/ring counts or physicochemical properties like logP. The results are summarized and presented graphically by interactive histogram charts that can be examined in detail and exported in publication quality.
Random attractor for second-order stochastic delay lattice sine-Gordon equation
Authors: Li Xintao , She Lianbing , Shan Zhenpei
Published: February 2021

In this paper, we prove the existence of random $\mathcal{D}$
D
-attractor for the second-order stochastic delay sine-Gordon equation on infinite lattice with certain dissipative conditions, and then establish the upper bound of Kolmogorov ε-entropy for the random $\mathcal{D}$
D
-attractor.
On an SE(Is)(Ih)AR epidemic model with combined vaccination and antiviral controls for COVID-19 pandemic
Authors: De la Sen M. , Ibeas A.
Published: February 2021

In this paper, we study the nonnegativity and stability properties of the solutions of a newly proposed extended SEIR epidemic model, the so-called SE(Is)(Ih)AR epidemic model which might be of potential interest in the characterization and control of the COVID-19 pandemic evolution. The proposed model incorporates both asymptomatic infectious and hospitalized infectious subpopulations to the standard infectious subpopulation of the classical SEIR model. In parallel, it also incorporates feedback vaccination and antiviral treatment controls. The exposed subpopulation has three different transitions to the three kinds of infectious subpopulations under eventually different proportionality parameters. The existence of a unique disease-free equilibrium point and a unique endemic one is proved together with the calculation of their explicit components. Their local asymptotic stability properties and the attainability of the endemic equilibrium point are investigated based on the next generation matrix properties, the value of the basic reproduction number, and nonnegativity properties of the solution and its equilibrium states. The reproduction numbers in the presence of one or both controls is linked to the control-free reproduction number to emphasize that such a number decreases with the control gains. We also prove that, depending on the value of the basic reproduction number, only one of them is a global asymptotic attractor and that the solution has no limit cycles.
COVID-19-associated coagulopathy: thromboembolism prophylaxis and poor prognosis in ICU
Authors: Zheng Runhui , Zhou Jing , Song Bin , Zheng Xia , Zhong Ming , Jiang Li , Pan Chun , Zhang Wei , Xia Jiaan , Chen Nanshan , Wu Wenjuan , Zhang Dingyu , Xi Yin , Lin Zhimin , Pan Ying , Liu Xiaoqing , Li Shiyue , Xu Yuanda , Li Yimin , Tan Huo , Zhong Nanshan , Luo Xiaodan , Sang Ling
Published: February 2021

Background

Coronavirus disease 2019 (COVID-19) is associated with coagulation abnormalities which are indicators of higher mortality especially in severe cases.

Methods

We studied patients with proven COVID-19 disease in the intensive care unit of Jinyintan Hospital, Wuhan, China from 30 to 2019 to 31 March 2020.

Results

Of 180 patients, 89 (49.44 %) had died, 85 (47.22 %) had been discharged alive, and 6 (3.33 %) were still hospitalised by the end of data collection. A D-dimer concentration of > 0.5 mg/L on admission was significantly associated with 30 day mortality, and a D-dimer concentration of > 5 mg/L was found in a much higher proportion of non-survivors than survivors. Sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulation (DIC) scoring systems were dichotomised as < 4 or ≥ 4 and < 5 or ≥ 5, respectively, and the mortality rate was significantly different between the two stratifications in both scoring systems. Enoxaparin was administered to 68 (37.78 %) patients for thromboembolic prophylaxis, and stratification by the D-dimer concentration and DIC score confirmed lower mortality in patients who received enoxaparin when the D-dimer concentration was > 2 than < 2 mg/L or DIC score was ≥ 5 than < 5. A low platelet count and low serum calcium concentration were also related to mortality.

Conclusions

A D-dimer concentration of > 0.5 mg/L on admission is a risk factor for severe disease. A SIC score of > 4 and DIC score of > 5 may be used to predict mortality. Thromboembolic prophylaxis can reduce mortality only in patients with a D-dimer concentration of > 2 mg/L or DIC score of ≥ 5.
Validation study of the Italian version of Temporal Focus Scale: psychometric properties and convergent validity
Authors: Diotaiuti Pierluigi , Valente Giuseppe , Mancone Stefania
Published: February 2021

Background

Over the last decade, international research has produced a large number of studies that have stressed the importance of temporal focus in various aspects of the lives of individuals, groups and organizations. This first Italian validation study of the Temporal Focus Scale (TFS) has shown a reliable measurement to assess the tendency of individuals to characteristically think about different periods of their lives.

Methods

TFS/I was administered to a sample of 1458 participants, while three other convenience samples (N1 = 453; N2 = 544; N3 = 168) were used for convergent validity testing.

Results

Confirmatory factor analysis confirmed a three-factor solution (including 10 items) with good indices of fit to data, e.g., χ2 = 49.533, CFI = 0.992, TLI = 0.986, RMSEA = 0.034, RMSEA 90% CI .018–.048. Convergent validity assessment confirmed predictive indications with variables such as life satisfaction, optimistic/pessimistic orientation, perceived general self-efficacy, self-regulatory modes, anxiety, depression.

Conclusion

The temporal focus has proven to be a significant feature associated with various aspects of both well-being and personal discomfort. By virtue of its good psychometric properties, the TFS can be an integrative tool along with others for a better evaluation of the person’s profile in different contexts such as education, coaching, psychotherapy, counseling and career guidance.
Altered identity: fleeting colors and obscured surfaces in Van Gogh’s Landscapes in Paris, Arles, and Saint-Rémy
Authors: Pozzi Federica , Basso Elena , Centeno Silvia A. , Smieska Louisa M. , Shibayama Nobuko , Berns Roy , Fontanella Megan , Stringari Lena
Published: February 2021

The Thannhauser Collection of the Solomon R. Guggenheim Museum, New York, represents an important survey of European avant-garde art production during the late 19th and early 20th centuries. Among the works included in this collection are three paintings by Vincent van Gogh, namely Roadway with Underpass (1887), Landscape with Snow (1888), and Mountains at Saint-Rémy (1889). These examples each exhibit some degree of surface alteration, including fading of specific pigments and, in one case, a non-original, discolored varnish, resulting in obscured color and spatial relationships, as well as being the subject of questions regarding authenticity in the case of the two earlier pictures. Initial examination involved documentation of the brushwork, paint quality, and distribution of colors under magnification. Infrared (IR) and ultraviolet (UV) photography, as well as X-radiography, provided additional information on the surface coatings, the structure of the works, and their supports. Subsequently, an in-depth scientific investigation of the ground and paint layers, with a special focus on fading colors and altered surfaces, was carried out non-invasively with point and macro-X-ray fluorescence (XRF) spectroscopy, visible reflection spectroscopy, and multi-channel visible spectrum four-light imaging, followed by the analysis of cross sections and dispersed pigment samples by means of optical microscopy, transmission Fourier-transform infrared (FTIR) and Raman spectroscopies, and scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM/EDS), as well as high-performance liquid chromatography with photodiode array detection (HPLC-PDA) and pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). Results indicated that both the brushwork and artist's palette of all three paintings are consistent with data previously reported for other Van Gogh works and with pigments described in the artist’s letters to his friends and his brother Theo. Most notably, evidence of biodeterioration and paint alteration phenomena was found on Roadway with Underpass, while specific pigments such as eosin red—historically sold as geranium lake—were detected in areas of Landscape with Snow and Mountains at Saint-Rémy that display severe fading. In addition to assisting the development of a suitable plan for the conservation of the 1887 painting, this study traces the progression of Van Gogh’s practice over three years critical to his artistic development, discusses the historical context in which each masterpiece was created, identifies the range of materials and techniques used, and addresses authenticity questions by providing a comparison with results of scientific analysis from other similar works.
Opioid therapy duration before naldemedine treatment is a significant independent risk of diarrhea: a retrospective cohort study
Authors: Okamoto Akiharu , Ikemura Kenji , Mizutani Eri , Iwamoto Takuya , Okuda Masahiro
Published: February 2021

Background

The most common adverse event (AE) associated with opioid analgesics is opioid-induced constipation (OIC). Naldemedine (NAL) is widely used for the treatment of OIC. However, diarrhea has been reported as the most common treatment-emergent AE of NAL, and little is known about the risk factors associated with the development of diarrhea during NAL administration. This study examined the risk factors for NAL-induced diarrhea via a retrospective chart review of hospitalized patients.

Methods

The data of 101 hospitalized adult patients who received NAL for the first time for the treatment of OIC at Mie University Hospital between June 2017 and December 2018 were extracted from electronic medical records. According to the inclusion and exclusion criteria, 70 of the 101 patients were enrolled in this study. Diarrhea was defined as “diarrhea” on the medical record within 2 weeks of NAL administration. Univariate and multivariate analyses were performed to identify risk factors for the development of diarrhea in patients receiving NAL.

Results

Twenty-two of the 70 patients enrolled (31%) developed diarrhea within 2 weeks of NAL administration. The median duration (range) of NAL treatment before diarrhea onset was 3 (1–12) days. Patients with diarrhea had a significantly longer duration of opioid therapy before NAL administration than patients without diarrhea (P=0.002). Multivariate logistic regression analysis indicated that the independent risk factors for the development of NAL-induced diarrhea were NAL administration after more than 17 days of opioid therapy (odds ratio [OR]=7.539; P=0.016) and pancreatic cancer (OR=6.217; P=0.025). In fact, the incidence of diarrhea in patients who were administered NAL within a day of opioid therapy was significantly lower than that in patients who were administered NAL after more than 17 days of opioid therapy (13% vs. 54%, P=0.030).

Conclusions

These results suggested that a prolonged duration of opioid therapy prior to NAL initiation is associated with increased incidence of diarrhea.
Pharmacist-physician collaborative care for outpatients with left ventricular assist devices using a cloud-based home medical management information-sharing system: a case report
Authors: Katada Yoshiki , Yonezawa Atsushi , Utsumi Momoe , Kitada Noriaki , Sato Yu-ki , Matsumura Katsuyuki , Sukeishi Asami , Nakagawa Shunsaku , Imai Satoshi , Nakagawa Takayuki , Minakata Kenji , Kanemitsu Hideo , Minatoya Kenji , Nomoto Shinichi , Matsubara Kazuo
Published: February 2021

Background

The standard anticoagulation therapy for patients implanted with left ventricular assist devices (LVADs) includes warfarin therapy. We developed a cloud-based home medical management information-sharing system named as LVAD@home. The LVAD@home system is an application designed to be used on iPad tablet computers. This system enables the sharing of daily information between a patient and care providers in real time. In this study, we reported cases of outpatients with LVADs using this system to manage anticoagulation therapy.

Case presentation

The patient, a man in his 40s with end-stage heart failure owing to non-ischemic dilated cardiomyopathy, underwent LVAD implantation and warfarin was started on postoperative day 1. He started to use LVAD@home to manage warfarin therapy after discharge (postoperative day 47). He sent his data to care providers daily. By using this system, the pharmacist observed his signs of reduced dietary intake 179 days after discharge, and after consulting the physician, told the patient to change the timing of the next measurement earlier than usual. On the next day, the prothrombin time-international normalized ratio increased from 2.0 to 3.0, and thus the dose was decreased by 0.5 mg. Four patients used this system to monitor warfarin therapy from October 2015 to March 2018. In these patients, the time in therapeutic range was 90.1 ± 1.3, which was higher than that observed in previous studies. Additionally, there were no thromboembolic events or bleeding events.

Conclusions

The cloud-based home management system can be applied to share real-time patient information of factors, including dietary intake that interact with warfarin. It can help to improve long-term anticoagulation outcomes in patients implanted with LVAD.
Study protocol: a pilot quasi-experimental trial of tele-rehabilitation and tele-drain care post-mastectomy
Authors: Asano Miho , Koh Gerald Choon-Huat , Madhukumar Preetha , Teng Gladys Yu Hui , Liew Petrina Li Ling , Nagalingam Saraswathi , Tan May Leng Mabel , Ng Yee Sien , Tan Benita Kiat Tee
Published: February 2021

Background

Breast cancer is the leading cancer affecting women in Singapore. Its survivors commonly experience decline in physical function and quality of life post-mastectomy, due to their upper limb morbidity and wound issues. Rehabilitation can address the aforementioned issues. When rehabilitation is accessible and easy to adhere, it can optimize recovery.

Home-based tele-rehabilitation guided by healthcare professionals and self-managed by patients can potentially optimize the patients’ adherence to rehabilitation and recovery. With that in mind, a team of breast cancer specialists (oncologists, nurses, and therapists) in Singapore has developed one of the first tele-rehabilitation systems for local women undergoing a unilateral mastectomy. To our knowledge, no such systems have been evaluated or proven effective as a treatment option among local breast cancer patients with acute disabilities.

Methods

This is a pilot quasi-experimental trial that aims to evaluate the feasibility of tele-rehabilitation and tele-drain care compared to usual care. Up to 40 patients (20 per group) will be recruited for this trial. They will be assigned to an intervention group that receives rehabilitation via a tele-rehabilitation system or a control group that receives rehabilitation in person at their clinic. The primary outcome of this trial is rehabilitation participation (i.e., the time spent on rehabilitation). The secondary outcomes are upper extremity functioning, perceived health, and quality of life.

Discussion

As part of this pilot trial, patients who opt in for the tele-rehabilitation will be asked to share their experience with and thoughts on the tele-rehabilitation system. With the evidence obtained from the tele-rehabilitation patients of this trial, we will be able to improve the current system for our future trial. Further, our additional data on rehabilitation participation, physical function, and quality of life will help us design a sufficiently powered future main trial.

Trial registration

The trial was approved by the National Healthcare Group’s Domain Specific Review Board (#2019/00283) and registered withwww.ClinicalTrials.gov(#NCT04269967) in February 2020.
Application of a simplified Grey Wolf optimization technique for adaptive fuzzy PID controller design for frequency regulation of a distributed power generation system
Authors: Padhy Sasmita , Panda Sidhartha
Published: February 2021

A Simplified Grey Wolf Optimizer (SGWO) is suggested for resolving optimization tasks. The simplification in the original Grey Wolf Optimizer (GWO) method is introduced by ignoring the worst category wolves while giving priority to the better wolves during the search process. The advantage of the presented SGWO over GWO is a better solution taking less execution time and is demonstrated by taking unimodal, multimodal, and fixed dimension test functions. The results are also contrasted to the Gravitational Search Algorithm, the Particle Swarm Optimization, and the Sine Cosine Algorithm and this shows the superiority of the proposed SGWO technique. Practical application in a Distributed Power Generation System (DPGS) with energy storage is then considered by designing an Adaptive Fuzzy PID (AFPID) controller using the suggested SGWO method for frequency control. The DPGS contains renewable generation such as photovoltaic, wind, and storage elements such as battery and flywheel, in addition to plug-in electric vehicles. It is demonstrated that the SGWO method is superior to the GWO method in the optimal controller design task. It is also seen that SGWO based AFPID controller is highly efficacious in regulating the frequency compared to the standard PID controller. A sensitivity study is also performed to examine the impact of the unpredictability in the parameters of the investigated system on system performance. Finally, the novelty of the paper is demonstrated by comparing with the existing publications in an extensively used two-area test system.
A dynamic and mosaic basement membrane controls cell intercalation in Drosophila ovaries
Authors: Van De Bor Véronique , Loreau Vincent , Malbouyres Marilyne , Cerezo Delphine , Placenti Audrey , Ruggiero Florence , Noselli Stéphane
Published: February 2021

Basement membranes (BM) are extracellular matrices assembled into complex and highly organized networks essential for organ morphogenesis and function. However, little is known about the tissue origin of BM components and their dynamics in vivo. Here, we unravel the assembly and role of the BM main component, Collagen type IV (ColIV), in Drosophila ovarian stalk morphogenesis. Stalks are short strings of cells assembled through cell intercalation that link adjacent follicles and maintain ovarian integrity. We show that stalk ColIV has multiple origins and is assembled following a regulated pattern leading to a unique BM organisation. Absence of ColIV leads to follicle fusion, as observed upon ablation of stalk cells. ColIV and integrins are both required to trigger cell intercalation and maintain mechanically strong cell-cell attachment within the stalk. These results show how the dynamic assembly of a mosaic BM controls complex tissue morphogenesis and integrity.
Characterization of human bone marrow niches with metabolome and transcriptome profiling
Authors: Ayhan Selda , Nemutlu Emirhan , Uçkan Çetinkaya Duygu , Kır Sedef , Özgül Rıza Köksal
Published: February 2021

Bone marrow (BM) niches are special microenvironments that work in harmony with each other for the regulation and maintenance of hematopoiesis. Niche investigations have thus far been limited to various model organisms and animal studies; therefore, little is known about different niches in healthy humans. In this study, a special harvesting method for the collection of BM from two different anatomical regions in the iliac crest of humans was used to investigate the presence of different niches in BM. Additionally, metabolomic and transcriptomic profiles were compiled using comparative ‘omics’ technologies, and the main cellular pathways and corresponding transcripts and metabolites were identified. As a result, we found that the energy metabolism between the regions was different. This study provides basic broad data for regenerative medicine in terms of the design of the appropriate microenvironment for in vitro hematopoietic niche modeling, and identifies the normal reference values that can be compared in hematological disease.
Circulating prostate cancer cells have differential resistance to fluid shear stress-induced cell death
Authors: Hope Jacob M. , Bersi Matthew R. , Dombroski Jenna A. , Clinch Andrea B. , Pereles Rebecca S. , Merryman W. David , King Michael R.
Published: February 2021

Circulating tumor cells (CTCs) are exposed to fluid shear stress (FSS) of greater than 1000 dyn/cm2 (100 Pa) in circulation. Normally, CTCs that are exposed to FSS of this magnitude die. However, some CTCs develop resistance to this FSS, allowing them to colonize distant organs. We explored how prostate CTCs can resist cell death in response to forces of this magnitude. The DU145, PC3 and LNCaP human prostate cancer cell lines were used to represent cells of different metastatic origins. The cell lines were briefly treated with an average FSS of 3950 dyn/cm2 (395 Pa) using a 30 G needle and a syringe pump. DU145 cells had no change in cell viability, PC3 cells had some cell death and LNCaP cells exhibited significant cell death. These cell death responses correlated with increased cell membrane damage, less efficient membrane repair and increased stiffness. Additionally, FSS treatment prevented the LNCaP FSS-sensitive cell line from forming a growing tumor in vivo. This suggests that these properties play a role in FSS resistance and could represent potential targets for disrupting blood-borne metastasis.
Nuclear localization of p65 reverses therapy-induced senescence
Authors: Salunkhe Sameer , Mishra Saket V. , Nair Jyothi , Shah Sanket , Gardi Nilesh , Thorat Rahul , Sarkar Debashmita , Rajendra Jacinth , Kaur Ekjot , Dutt Shilpee
Published: February 2021

Senescence is the arrest of cell proliferation and is a tumor suppressor phenomenon. In a previous study, we have shown that therapy-induced senescence of glioblastoma multiforme (GBM) cells can prevent relapse of GBM tumors. Here, we demonstrate that ciprofloxacin-induced senescence in glioma-derived cell lines and primary glioma cultures is defined by SA-β-gal positivity, a senescence-associated secretory phenotype (SASP), a giant cell (GC) phenotype, increased levels of reactive oxygen species (ROS), γ-H2AX and a senescence-associated gene expression signature, and has three stages of senescence –initiation, pseudo-senescence and permanent senescence. Ciprofloxacin withdrawal during initiation and pseudo-senescence reinitiated proliferation in vitro and tumor formation in vivo. Importantly, prolonged treatment with ciprofloxacin induced permanent senescence that failed to reverse following ciprofloxacin withdrawal. RNA-seq revealed downregulation of the p65 (RELA) transcription network, as well as incremental expression of SMAD pathway genes from initiation to permanent senescence. Ciprofloxacin withdrawal during initiation and pseudo-senescence, but not permanent senescence, increased the nuclear localization of p65 and escape from ciprofloxacin-induced senescence. By contrast, permanently senescent cells showed loss of nuclear p65 and increased apoptosis. Pharmacological inhibition or genetic knockdown of p65 upheld senescence in vitro and inhibited tumor formation in vivo. Our study demonstrates that levels of nuclear p65 define the window of reversibility of therapy-induced senescence and that permanent senescence can be induced in GBM cells when the use of senotherapeutics is coupled with p65 inhibitors.
Importin α phosphorylation promotes TPX2 activation by GM130 to control astral microtubules and spindle orientation
Authors: Guo Haijing , Wei Jen-Hsuan , Zhang Yijun , Seemann Joachim
Published: February 2021

Spindle orientation is important in multiple developmental processes as it determines cell fate and function. The orientation of the spindle depends on the assembly of a proper astral microtubule network. Here, we report that the spindle assembly factor TPX2 regulates astral microtubules. TPX2 in the spindle pole area is activated by GM130 (GOLGA2) on Golgi membranes to promote astral microtubule growth. GM130 relieves TPX2 inhibition by competing for importin α1 (KPNA2) binding. Mitotic phosphorylation of importin α at serine 62 (S62) by CDK1 switches its substrate preference from TPX2 to GM130, thereby enabling competition-based activation. Importin α S62A mutation impedes local TPX2 activation and compromises astral microtubule formation, ultimately resulting in misoriented spindles. Blocking the GM130–importin α–TPX2 pathway impairs astral microtubule growth. Our results reveal a novel role for TPX2 in the organization of astral microtubules. Furthermore, we show that the substrate preference of the important mitotic modulator importin α is regulated by CDK1-mediated phosphorylation.
Cutaneous tactile sensitivity before and after tail loss and regeneration in the leopard gecko (Eublepharis macularius)
Authors: Bradley Stefanie S. , Howe Erika , Bent Leah R. , Vickaryous Matthew K.
Published: February 2021

Amongst tetrapods, mechanoreceptors on the feet establish a sense of body placement and help to facilitate posture and biomechanics. Mechanoreceptors are necessary for stabilizing the body while navigating through changing terrains or responding to a sudden change in body mass and orientation. Lizards such as the leopard gecko (Eublepharis macularius) employ autotomy – a voluntary detachment of a portion of the tail – to escape predation. Tail autotomy represents a natural form of significant (and localized) mass loss. Semmes–Weinstein monofilaments were used to investigate the effect of tail autotomy (and subsequent tail regeneration) on tactile sensitivity of each appendage of the leopard gecko. Prior to autotomy, we identified site-specific differences in tactile sensitivity across the ventral surfaces of the hindlimbs, forelimbs and tail. Repeated monofilament testing of both control (tail-intact) and tail-loss geckos had a significant sensitization effect (i.e. decrease in tactile threshold, maintained over time) in all regions of interest except the palmar surfaces of the forelimbs in post-autotomy geckos, compared with baseline testing. Although the regenerated tail is not an exact replica of the original, tactile sensitivity is shown to be effectively restored at this site. Re-establishment of tactile sensitivity on the ventral surface of the regenerate tail points towards a (continued) role in predator detection.
A study on the use of henna plant (Lawsonia inermis Linn) for the treatment of fungal disease (Trichophypton verrucosum) in calves
Authors: HIZLI H.
Published: February 2021

The aim of this study was to investigate the usability of henna plant (Lawsonia inermis Linn) in the treatment of dermatophytosis lesions (Trichophypton verrucosum) in cattle. The animal material of the trial consisted of 50 holstein calves between the ages of 4 and 6 months, who were found to have a dermatophytosis lesion on their face and neck in their clinical examination. The experiment was organized on a three-group repeated measurement trial plan. I. Group: Trichlorfon (Neguvon 75%, Bayer) ointment, II. Group: Henna applied, and III. Group: Control Group, no treatment, and 20 (10 females, 10 males), 20 (10 females, 10 males), and 10 (5 females, 5 males) totally 50 calves used, respectively. The research was continued for 14 days until the lesions were completely healed. I. and II. Groups were observed the best healing in the calves, respectively. In the III. Group without any treatment, there was no improvement and the lesions were enlarged. In addition, the effect of gender in the treatment process of dermatophytosis lesions was insignificant. As a result of this study, it is thought that henna plant can be used in the treatment of dermatophytosis.
Effect of Cefazolin on endometrial cytology and reagent test strips parameters in bovine endometritis
Authors: BARAKAT Τ.Μ. , SHAWKY G. , ABSY G. , ABD EL-RAHMAN RAGAB M.
Published: February 2021

Endometritis is one of uterine disorders in dairy cows causing low fertility. This study explored effects of intrauterine (IU) infusion of Cefazolin on endometrial cytology and reagent test strips parameters (leukocyte esterase [LE] and pH) in bovine subclinical endometritis. A total of 90 cows at 49-56 days in milk (DIM) diagnosed for subclinical endometritis were divided randomlyinto three groups, group I (n = 35), treated with IU infusion of 2 grams Cefazolin (Zinol ®, Pharco) diluted with 50 ml saline; group II (n = 28), treated with IU infusion of 2 gramsCephalexin (Ceporex®, GlaxoSmithKline) diluted with 50 ml saline; group III (n = 27), cows kept as untreated control. Cytological examination and reagent test strips were performed in uterine material derived with the cotton swab technique before treatment program and repeated two times later, in 10 days interval. The cows were artificially inseminated at first oestrous after the end of treatment program and conception rates were evaluated. After the end of treatment program, polymorphonuclear cells (PMN) decreased significantly (P <0.05) in Cefazolin and Cephalexin groups (3.23% and 4.39% respectively) compared tocontrol (24.89%) group, also means of LE in these groups became significantly (P<0.05) lower. The Ph value decreased after treatment, this reduction was significant after the first dose of Cefazolin, while in Cephalexin reduction of pH became significant after second dose. Cefazolin had conception rate (77.14%) significantly (P<0.05) higher than cephalexin and control groups (57.14% and 25.93% respectively). Cefazolin and Cephalexin decrease uterine PMN, LE concentration. The pH value after treatment by Cefazolin was lower than in Cephalexin. Moreover, treatment with Cefazolin resulted in a significantly higher conception rate. Thus, Cefazolin is recommended for the treatment of subclinical endometritis in dairy cows.
The effects of water deprivation-induced dehydration on serum acute phase protein concentrations in sheep
Authors: DINLER AY C. , ULUTAS B.
Published: February 2021

The effects of dehydration on serum acute phase proteins (APPs) concentrations are unknown in sheep. In this study, it was aimed to reveal the effect of dehydration on the blood concentrations of serum amyloid a (SAA), haptoglobin (Hp), ceruloplasmin (Cp) and fibrinogen (Fb) in Kivircik cross-breeds sheep. The animal materials of the study consisted of 20 healthy sheep. They were divided into 4 equal groups: systemic inflammation group (SIG), a single dose of 5 ml Freund’s complete adjuvant (FCA) was administered intramuscularly, drinking water were provided as ad libitum; dehydration group (DEH), a single dose of 5 ml placebo 0.9% NaCl was administered intramuscularly and water was deprived for consecutive 5 days; systemic inflammation+dehydrationgroup (SIG+DEH), a single dose of 5 ml FCA was administered intramuscularly and water was deprived for consecutive 5 days; and the control group (CON), a single dose of 5 ml placebo 0.9% NaCl was administered intramuscularly and drinking water was provided as ad libitum. Also, feed was offered ad libitum throughout the experimental period in all study groups. Blood samples were collected on days 0 (baseline values), 1, 3, 5, and 7 while clinical examinations were performed daily during the study. Significant increases were found in serum Hp, SAA, Cp and plasma Fb concentrations in SIG and SIG+DEH groups. There was a significant increase only in serum Hp concentration over time in the DEH group. In conclusion, this study exhibited that Hp concentration increased as part of an acute phase reaction in water deprivation-induced dehydration in Kivircik cross-breeds sheep.