bluuebunny/crossref_metadata_2025 huggingface dataset:
Downregulation of miR-29c-3p is associated with a poor prognosis in patients with laryngeal squamous cell carcinoma
Authors: Fang Ruihua , Huang Yongjin , Xie Jinghua , Zhang Jianzhong , Ji Xiaobin
Published: October 2019

Background

Laryngeal squamous cell carcinoma (LSCC) is considered to be a common malignancy of the head and neck with poor prognosis for its late diagnosis, metastasis and recurrence. Growing evidence demonstrates that the dysregulation of miR-29c-3p (microRNA-29c-3p) plays an important role in various tumor processes. Our study investigates the expression of miR-29c-3p in LSCC and analyzes the correlation of its dysregulation with clinicopathologic parameters and prognosis.

Methods

The expression of hsa-miR-29c-3p in LSCC tissues and the adjacent normal laryngeal tissues was detected in 96 LSCC formalin-fixed paraffin-embedded tissues by quantitative real-time PCR (qRT-PCR). The SPSS statistical software package (17.0) was used to analyze the associations between miR-29c-3p expressions and various clinicopathological characteristics. The overall survival (OS) was analyzed by the Kaplan-Meier method and log-rank test, and we analyzed the independent factor of prognosis by Cox proportional hazard analysis.

Results

A downregulation of miR-29c-3p expression in LSCC was significantly correlated with smoking index, tumor size, tumor site, differentiation, T classification, TNM stage, and lymph node metastasis (P < 0.05), but there was no correlation with age and alcohol consumption (P > 0.05). In the multivariate survival analysis, low miR-29c-3p expression was associated with shorter overall survival (P < 0.05). Furthermore, miR-29c expression was an independent prognostic factor for laryngeal cancer patients.

Conclusions

MiR-29c-3p has different expression levels at different stages of tumor progression, suggesting that miR-29c-3p may be a promising biomarker for evaluating the progression of LSCC and the prognosis of patients with LSCC. MiR-29c-3p can also be a novel molecular target for anti-laryngeal cancer therapy.
Update on the management of colchicine resistant Familial Mediterranean Fever (FMF)
Authors: El Hasbani Georges , Jawad Ali , Uthman Imad
Published: October 2019

Background

Familial Mediterranean Fever (FMF), an autoinflammatory disease, is characterized by self-limited inflammatory attacks of fever and polyserositis along with high acute phase response. Although colchicine remains the mainstay in treatment, intolerance and resistance in a certain portion of patients have been posing a problem for physicians.

Main body

Like many autoimmune and autoinflammatory diseases, many colchicine-resistant or intolerant FMF cases have been successfully treated with biologics. In addition, many studies have tested the efficacy of biologics in treating FMF manifestations.

Conclusion

Since carriers of FMF show significantly elevated levels of serum TNF alpha, IL-1, and IL-6, FMF patients who failed colchicine were successfully treated with anti IL-1, anti IL-6, or TNF inhibitors drugs. It is best to use colchicine in combination with biologics.
A randomised controlled trial exploring the impact of a dedicated health and social care professionals team in the emergency department on the quality, safety, clinical and cost-effectiveness of care for older adults: a study protocol
Authors: Cassarino Marica , Robinson Katie , O’Shaughnessy Íde , Smalle Eimear , White Stephen , Devlin Collette , Quinn Rosie , Trépel Dominic , Boland Fiona , Ward Marie E. , McNamara Rosa , O’Connor Margaret , McCarthy Gerard , Ryan Damien , Galvin Rose
Published: October 2019

Background

Older people are frequent emergency department (ED) users who present with complex issues that are linked to poorer health outcomes following the index visit, often have increased ED length of stay, and tend to have raised healthcare costs. Encouraging evidence suggests that ED teams involving health and social care professionals (HSCPs) can contribute to enhanced patient flow and an improved patient experience by improving care decision-making and thus promoting timely and effective care. However, the evidence supporting the impact of HSCP teams assessing and intervening with older adults in the ED is limited and identifies important methodological limitations, highlighting the need for more robust and comprehensive investigations of this model of care. This study aims to evaluate the impact of a dedicated ED-based HSCP team on the quality, safety, and clinical- and cost-effectiveness of care of older adults when compared with usual care.

Methods

The study is a single-site randomised controlled trial whereby patients aged ≥65 years who present to the ED of a large Irish hospital will be randomised to the experimental group (ED-based HSCP assessment and intervention) or the control group (usual ED care). The recruitment target is 320 participants. The HSCP team will provide a comprehensive functional assessment as well as interventions to promote a safe discharge for the patient. The primary outcome is ED length of stay (from arrival to discharge). Secondary outcomes include: rates of hospital admissions from the ED, ED re-visits, unplanned hospital admissions and healthcare utilisation at 30 days, and 4 and 6 months of follow-up; patient functional status and quality of life (at baseline and follow-up); patient satisfaction; cost-effectiveness in terms of costs associated with ED-based HSCP compared with usual care; and perceptions on implementation by ED staff members.

Discussion

This is the first randomised controlled trial testing the impact of HSCPs working in teams in the ED on the quality, safety, and clinical- and cost-effectiveness of care for older patients. The findings of this study will provide important information on the effectiveness of this model of care for future implementation.

Trial registration

ClinicalTrials.gov, NCT03739515. Registered on 12 November 2018.
Single mutation at a highly conserved region of chloramphenicol acetyltransferase enables isobutyl acetate production directly from cellulose by Clostridium thermocellum at elevated temperatures
Authors: Seo Hyeongmin , Lee Jong-Won , Garcia Sergio , Trinh Cong T.
Published: October 2019

Background

Esters are versatile chemicals and potential drop-in biofuels. To develop a sustainable production platform, microbial ester biosynthesis using alcohol acetyltransferases (AATs) has been studied for decades. Volatility of esters endows high-temperature fermentation with advantageous downstream product separation. However, due to the limited thermostability of AATs known, the ester biosynthesis has largely relied on use of mesophilic microbes. Therefore, developing thermostable AATs is important for ester production directly from lignocellulosic biomass by the thermophilic consolidated bioprocessing (CBP) microbes, e.g., Clostridium thermocellum.

Results

In this study, we engineered a thermostable chloramphenicol acetyltransferase from Staphylococcus aureus (CATSa) for enhanced isobutyl acetate production at elevated temperatures. We first analyzed the broad alcohol substrate range of CATSa. Then, we targeted a highly conserved region in the binding pocket of CATSa for mutagenesis. The mutagenesis revealed that F97W significantly increased conversion of isobutanol to isobutyl acetate. Using CATSa F97W, we demonstrated direct conversion of cellulose into isobutyl acetate by an engineered C. thermocellum at elevated temperatures.

Conclusions

This study highlights that CAT is a potential thermostable AAT that can be harnessed to develop the thermophilic CBP microbial platform for biosynthesis of designer bioesters directly from lignocellulosic biomass.
Genetically encoded biosensors for lignocellulose valorization
Authors: Alvarez-Gonzalez Guadalupe , Dixon Neil
Published: October 2019

Modern society is hugely dependent on finite oil reserves for the supply of fuels and chemicals. Moving our dependence away from these unsustainable oil-based feedstocks to renewable ones is, therefore, a critical factor towards the development of a low carbon bioeconomy. Lignin derived from biomass feedstocks offers great potential as a renewable source of aromatic compounds if methods for its effective valorization can be developed. Synthetic biology and metabolic engineering offer the potential to synergistically enable the development of cell factories with novel biosynthetic routes to valuable chemicals from these sustainable sources. Pathway design and optimization is, however, a major bottleneck due to the lack of high-throughput methods capable of screening large libraries of genetic variants and the metabolic burden associated with bioproduction. Genetically encoded biosensors can provide a solution by transducing the target metabolite concentration into detectable signals to provide high-throughput phenotypic read-outs and allow dynamic pathway regulation. The development and application of biosensors in the discovery and engineering of efficient biocatalytic processes for the degradation, conversion, and valorization of lignin are paving the way towards a sustainable and economically viable biorefinery.
Transfection of Culicoides sonorensis biting midge cell lines with Wolbachia pipientis
Authors: Ghosh Arnab , Jasperson Dane , Cohnstaedt Lee W. , Brelsfoard Corey L.
Published: October 2019

Background

Biting midges of the genusCulicoidesvector multiple veterinary pathogens and are difficult to control. Endosymbionts particularlyWolbachia pipientismay offer an alternative to control populations ofCulicoidesand/or impact disease transmission in the form of population suppression or replacement strategies.

Methods

Culicoides sonorensiscell lines were transfected with aWolbachiainfection using a modified shell vial technique. Infections were confirmed using PCR and cell localization using fluorescentin situhybridization (FISH). The stability ofWolbachiainfections and density was determined by qPCR. qPCR was also used to examine immune genes in the IMD, Toll and JACK/STAT pathways to determine ifWolbachiawere associated with an immune response in infected cells.

Results

Here we have transfected twoCulicoides sonorensiscell lines (W3 and W8) with aWolbachiainfection (walbB) from donorAedes albopictusAa23 cells. PCR and FISH showed the presence ofWolbachiainfections in bothC. sonorensiscell lines. Infection densities were higher in the W8 cell lines when compared to W3. In stably infected cells, genes in the immune Toll, IMD and JAK/STAT pathways were upregulated, along with Attacin and an Attacin-like anti-microbial peptides.

Conclusions

The successful introduction ofWolbachiainfections inC. sonorensiscell lines and the upregulation of immune genes, suggest the utility of usingWolbachiafor a population replacement and/or population suppression approach to limit the transmission ofC. sonorensisvectored diseases. Results support the further investigation ofWolbachiainduced pathogen inhibitory effects inWolbachia-infectedC. sonorensiscell lines and the introduction ofWolbachiaintoC. sonorensisadultsviaembryonic microinjection to examine for reproductive phenotypes and host fitness effects of a novelWolbachiainfection.
A novel cooperative spectrum signal detection algorithm for underwater communication system
Authors: Xiaolin Jiang , Zhengyu Tang , Ronghui Wang
Published: October 2019

In order to further improve the spectrum resource detection probability and increase the spectrum utilization rate in underwater wireless communication systems, this paper designs a novel multi-layer cooperative spectrum sensing algorithm based on compressed sensing, which uses compressed sensing technology to estimate the spectrum to reduce the sampling rate and the overhead of sonar signals. This new algorithm seeks the optimal hyper-parameter through Bayesian model. The multi-layer Bayesian model is introduced into the Dirichlet process to realize the automatic grouping of compressed perceptual data with the information from the non-parametric grouping mechanism, and the optimal super-parameters are selected through the fusion center to determine the spectrum. Simulation results show that the proposed algorithm fully considers the temporal correlation of compressed perceptual data and effectively improves spectral sensing performance of underwater communication system.
Stationary distribution of a stochastic SIRD epidemic model of Ebola with double saturated incidence rates and vaccination
Authors: Wang Panpan , Jia Jianwen
Published: October 2019

In this paper, a stochastic SIRD model of Ebola with double saturated incidence rates and vaccination is considered. Firstly, the existence and uniqueness of a global positive solution are obtained. Secondly, by constructing suitable Lyapunov functions and using Khasminskii’s theory, we show that the stochastic model has a unique stationary distribution. Moreover, the extinction of the disease is also analyzed. Finally, numerical simulations are carried out to portray the analytical results.
Numerical treatment of stochastic heroin epidemic model
Authors: Rafiq M. , Raza Ali , Iqbal M. Usman , Butt Zubair , Naseem Hafiza Anum , Akram M. Ali , Butt M. Kamran , Khaliq Adil , Qurat-ul-Ain  , Azam Shamrash
Published: October 2019

We have presented the numerical analysis of a stochastic heroin epidemic model in this paper. The mean of stochastic heroin model is itself a deterministic solution. The effect of reproduction number has also been observed in the stochastic heroin epidemic model. We have developed some stochastic explicit and implicitly driven explicit methods for this model. But stochastic explicit methods have flopped for certain values of parameters. In support, some theorems and graphical illustrations are presented.
Detection of Pan drug resistance OXA-48 producing Providencia in an ICU patient for the first time in Nepal
Authors: Sah Ranjit , Khadka Shusila , Shrestha Gentle Sunder , Acharya Subhash , Aryal Diptesh , Shrestha Pramesh , Kattel Hari Prasad , Shah Niranjan Prasad , Pokhrel Bharat Mani , Singh Yogendra Prasad , Rijal Basista , Erdem Hakan
Published: October 2019

Abstracts

Background

Resistance to antimicrobial agents of pathogenic bacteria has become a major problem in routine medical practices. Carbapenem resistance has long been increasing. The production of carbapenem- hydrolysing β-lactamases (carbapenamases), which include NDM, KPC, OXA-48, IMP-1 and VIM is the most common mechanism.

Case presentation

A 56 years old male presented with fever and mental changes with progressively decreasing sensorium for the last 3 days. He was admitted to Intensive care unit (ICU) with a diagnosis of meningoencephalitis. On day seven, he developed ventilator associated pneumonia due Klebsiella pnemoniae and Acinetobacter baumannii. He was on meropenem, but the isolates were susceptible to colistin, tigecyclin and amikacin solely. Hence, amikacin was started with addition of intravenous and nebulized colistin. Subsequently, vital signs improved with resolution of fever. However, on day 18, he developed fever once again with a drop in blood pressure. Inotropic support was maintained, and echinocandins and tigecycline were added to the regimen.

Repeat blood and urine culture grew Providencia species, which were resistant to most of the drugs on phenotypic Kirby-Bauer disk diffusion method and are intrinsically resistant to colistin and tigecycline. Phenotypic detection of ESBL (combined disk method), MBL, KPCs, AmpC and co-producer were tested according to updated CLSI guideline and all were negative. But the Modified Hodges test was found to be positive. Consequenty, OXA-48 drug resistance pattern was brought into action by blank disc method according to A Tsakris et al., which revealed indentation of growth toward both EDTA and EDTA/PBA disk indicating production of OXA-48 carbapenamase. To confirm the resistance pattern we processed the isolated colonies for Xpert Carba-R (Cepheid) assay, which detected blaOXA-48 gene and confirmed the OXA-48 drug resistance pattern. Hence, the infecting organism was not susceptible to any of the antibiotics. The patient was kept under isolation and on 31th day of admission, he died of septic shock.

Conclusions

Carbapenamase production along with intrinsic colistin resistance in infecting bacterial pathogens can cause fatal outcomes in the resource limited countries like Nepal where new antibiotic combinations ceftazidime+ Avibactam, or aztreonam +avibactam are not available. Drug resistance patterns including OXA 48 producer should be characterized in all cases by standard phenotypic methods or by Xpert Carba-R assay and larger studies are required to know the exact burden of OXA 48 producer in Nepal.
Development of a telegenetics program in the Asia-Pacific/Middle East region.
Authors: Dawood Shaheenah S. , Dhar Aparna , Sharma Poonam , Kini Lata
Published: October 2019

15

Background: BRCA mutations is emerging as an agnostic marker for PARPi. Accessibility to genetic counselling is limited due to shortage of manpower and access to institutions that provide it. Our aim was to look at the incidence of pathogenic germline mutations in India/UAE and develop a virtual pathway, aimed at increasing accessibility to genetic counselling. Methods: 864 patients(pts) were tested in the UAE and India for germline mutations. Based on discussion between physicians and patients, an urgent need for genetic counseling was identified. A virtual platform (telegenetics) was constructed for those who sought genetic counseling due to a personal or family history of malignancies. Referral of pts was either self-based or through a treating physician. Primary goals included 1) ease of access for pts, 2) increase comprehension of the indications, implications and consequences of genetic testing, 3) decrease physician time in the clinic. 10 questions were developed determine pt and physician satisfaction. Results: 241(28.9%)pts had a pathogenic variant in BRCA1/BRCA. 115pts were enrolled in the pilot phase of the tele genetics program; all physician referred. Counselling was by a dedicated trained genetic counsellor through voice-call(43.5%), video-conferencing(47.8%) or in person when requested (8.7%). All pts completed a satisfaction survey. Majority of pts were comfortable sharing information on a virtual platform(80%), were happy with the quality of virtual connection(85%), and felt comfortable connecting with the genetic counselor(90%). Information is currently being collected from referring physicians. Conclusions: Our ongoing pilot phase reveals improved pt satisfaction and understanding of the information provided. A mobile application has been developed to enhance pt accessibility/convenience and physician connectivity with the testing phase of the app currently on going. To our knowledge this is the first tele genetics program to target the middle east/Asia pac region that is targeted to cope with increase in pt volumes, expand appropriate referrals, starting with pts who have a personal or family history of cancers, expanding to more complex high risk diseases over time.
What Filipinos, the world’s number one Internet users, want to know about cancer: A Google search analysis from 2015 to 2019.
Authors: Catedral Lance Isidore Garcenila , Leones Louis Mervyn Banua , Berba Carlo Miguel
Published: October 2019

23

Background: Filipinos were the world’s heaviest Internet users in 2018. It has been shown that they use the Internet to actively search for health-related information, but it has not yet been determined what kinds of information are sought. There is a gap in our present understanding of the information needs of the Filipino population in relation to cancer. The study assessed the cancer-related information needs of Filipinos using Internet search data from March 2015 to May 2019. Methods: A retrospective longitudinal study was done using Google AdWords Keyword Planner to identify search terms related to cancer from Internet users from the Philippines from June 2015 to May 2019. The identified search terms were assessed descriptively using Microsoft Excel version 16.26. The search terms were qualitatively categorized and described. Results: A total of 806 cancer-related search terms were identified, with 13,632,890 Google web searches, during the period under review. The top ten search terms with the highest monthly search volume in the Philippines (n=4,741,600, 34.78%) were “cancer,” “breast cancer,” “cervical cancer,” “prostate cancer,” “colon cancer,” “breast cancer symptoms,” “lung cancer,” “lung cancer symptoms,” “colon cancer symptoms,” and “lungs.” In this time period, Filipinos sought information on cancer-related signs and symptoms (n=3,307,640, 24.26%) and cancer treatment (n=604,070, 4.43%). Filipinos also searched for alternative, herbal, and natural cancer treatments, but the search volume accounted for a low percentage of the total searches (n=8,710, 0.06%). Searches for the search term, “cancer,” were highest on January to February, a trend observed from January 2016 to 2019. Conclusions: Our study provides insight into the cancer-related information needs of the Filipino population. This information may inform the development of targeted, cost-effective awareness campaigns through the Internet, which may be more effective if launched at the beginning of each year.
Simultaneous multi-cancer detection and tissue of origin (TOO) localization using targeted bisulfite sequencing of plasma cell-free DNA (cfDNA).
Authors: Oxnard Geoffrey R. , Klein Eric A. , Seiden Michael , Hubbell Earl , Venn Oliver , Jamshidi Arash , Zhang Nan , Beausang John F. , Gross Samuel , Kurtzman Kathryn N. , Fung Eric T. , Yecies Jessica , Shaknovich Rita , Fields Alexander P. , Sekeres Mikkael A. , Richards Donald A. , Yu Peter Paul , Aravanis Alex , Hartman Anne-Renee , Liu Minetta C.
Published: October 2019

44

Background: A noninvasive cfDNA blood test detecting multiple cancers at earlier stages could decrease cancer mortality. In earlier discovery work, whole-genome bisulfite sequencing outperformed whole-genome and targeted sequencing approaches for multi-cancer detection across stages at high specificity. Here, multi-cancer detection and TOO localization using bisulfite sequencing of plasma cfDNA to identify methylomic signatures was evaluated in preparation for clinical validation, utility, and implementation studies. Methods: 2301 analyzable participants (1422 cancer [ > 20 tumor types, all stages], 879 non-cancer) were included in this prespecified substudy from the Circulating Cell-free Genome Atlas (CCGA) (NCT02889978) study - a prospective, multi-center, observational, case-control study with longitudinal follow-up. Plasma cfDNA was subjected to a targeted methylation sequencing assay using high-efficiency methylation chemistry to enrich for methylation targets, and a machine learning classifier determined cancer status and tissue of origin (TOO). Observed methylation fragments characteristic of cancer and TOO were combined across targeted regions and assigned a relative probability of cancer and of a specific TOO. Results: Performance is reported at 99% specificity (ie, a combined false positive rate across all cancer types of 1%), a level required for population-level screening. Across cancer types, sensitivity ranged from 59 to 86%. Combined cancer detection (sensitivity [95% CI]) was 34% (27-43%) in stage I (n = 151), 77% (70-83%) in stage II (n = 171), 84% (79-89%) in stage III (n = 204), and 92% (88-95%) in stage IV (n = 281). TOO was provided for 94% of all cancers detected; of these, TOO was correct in > 90% of cases. Conclusions: Detection of multiple deadly cancers across stages using methylation signatures in plasma cfDNA was achieved with a single, fixed, low false positive rate, and simultaneously provided accurate TOO localization. This targeted methylation assay is undergoing validation in preparation for prospective clinical investigation as a cancer detection diagnostic. Clinical trial information: NCT02889978.
A phase I study of MR-HIFU hyperthermia (HT) with radiation (RT) and chemotherapy (CT) for recurrent rectal cancer.
Authors: Chu William , Huang Yuexi , Pichardo Samuel , Staruch Robert , Partanen Ari , McGuffin Merrylee , Chan Kelvin K. , Wong Shun , Czarnota Gregory J. , Hynynen Kullervo
Published: October 2019

78

Background: HT may improve cancer control and quality of life by sensitizing tumors to RT and CT. Inoperable recurrent rectal cancer has marginal outcomes with current retreatment regimens. We report the results from a first-in-human phase I study of MR-HIFU hyperthermia combined with RT and CT for recurrent rectal cancer. Methods: This ethics-approved study enrolled 6 patients fit for re-irradiation and chemotherapy; and with a MRI-visible and HIFU-accessible lesion. Patients received 30.6 Gy (17 fractions) and daily oral capecitabine, plus MR-HIFU HT immediately before RT on days 1, 8, and 15. Primary objectives were safety (acute toxicity) and treatment feasibility. Secondary objectives included late toxicity, pain palliation, quality of life, and radiologic response. HT was delivered with the Sonalleve MR-HIFU system on a 3T MRI. MR-based feedback control parameters were prescribed to achieve a mean temperature of 42.5°C in an 18 mm diameter target region for 30 minutes without exceeding 45°C. Results: One patient withdrew after completing 1/3 HT sessions due to scheduling and sedation difficulties. Five patients completed HT, RT and CT. There were no intraoperative complications, no adverse events or unintended tissue damage attributable to HT, RT, or CT. Table shows the best single continuous HT and mean temperatures (T90, T10), cumulative time in range (TIR), cumulative number of equivalent minutes at 43oC(CEM43) and day 90 imaging response. Sonication and MRI suite times were 36±13 and 226±78min. Conclusions: MR-HIFU HT was safely delivered in patients with recurrent rectal cancer. Treatment planning and patient set-up times decreased while beam-on time increased with experience. MR-HIFU HT combined with RT and CT appears feasible for primary tumours. Clinical trial information: NCT02528175. [Table: see text]
Novel CT-guided 188-rhenium brachytherapy device for local primary and secondary lung malignancies.
Authors: Belhadj-Tahar Hafid , Chen Jindde , Song Pieping , Zhao Jun , Quan Ming , Li Caixin , Gu Xingjian , Yang Guanghua , Gao Yong
Published: October 2019

96

Background: Stereotactic brachytherapy for extensive local tumors offers a very effective treatment option locally without significant complications in medically impaired patients. In this context, we have recently developed a new potential anticancer agent from Poly-L-Lysins dendrimer as a delivery nano system loaded with diffusible Imidazolic probes complexed with 188-Rhenium for targeting in particular hypoxic tumors resistant to conventional cancer treatments. The aim of the study is assessment the safety profile and therapeutic efficacy of anticancer agent derived from [188Re]rhenium-ligand as radioactive ligand loaded 5th generation poly-L-lysine dendrimer in patients with unresectable Lung Malignancies. Methods: The experiment agent “ 188Re-ImDendrim” is consisting of 5th generation poly-L-lysine dendrimer (20 nM) mixed with nitro-imidazole-methyl-1,2,3-triazol-methyl-di-(2-pycolyl) amine at GMP grade and labelled with [188Re]-rhenium. The study was approved by Shanghai East Hospital ethics committee. 5 patients received “188Re-ImDendrim” directly into lung tumors under CT-guidance, at an activity level of 162 MBq/cc of tumor (range 2 to 7 cm; mean diameter, 4 cm) . For voluminous tumors ( > 65 cc) the dose is given in divided injection spaced 2 weeks apart (Tumor of 115cc: 2 administrations, Tumor of 180 cc: 3 administrations). At H0.5, H 4, H24, H36 , H72 post-administration, the patient get a SPECT control. The response to treatment is evaluated thanks to PET/CT Standardized Uptake Values (SUVs). Results: Stereotactic administrations of “188-Rhenium-ImDendrim” were successfully carried out in all patients under local anesthesia. The radioactive product diffuses homogeneously in the tumor volume and remains 72 hours post-administration with no significant diffusion out site of injection. The One of the 5 patients reported discrete transitive hemoptysis as adverse events. All targeted tumors were responding at 12 weeks, with two complete responses. Conclusions: Percutaneous single and iterative administrations of this novel 188-Rhenium-Imdendrim brachytherapy device into lung cancers are safe and well tolerated. The initial data on therapeutic response are promising. Clinical trial information: EC.D (BG) 016.03.1.
Decision Making About Genetic Testing Among Women With a Personal and Family History of Breast Cancer
Authors: Scott Danika , Friedman Sue , Telli Melinda L. , Kurian Allison W.
Published: October 2019

PURPOSE:

To understand genetic testing use and decision making among patients with high genetic risk.

MATERIALS AND METHODS:

A survey of breast cancer survivors was administered online by a hereditary cancer nonprofit organization, Facing Our Risk of Cancer Empowered, from October 2017 to March 2018.

RESULTS:

Of 1,322 respondents, 46% had breast cancer at age < 45 years, 61% had a first-degree relative with cancer, and 84% underwent genetic testing, of whom 56% had a risk-associated pathogenic variant. Most (86%; 95% CI, 84% to 88%) tested respondents were very satisfied with their testing decision, versus 34% (95% CI, 27% to 41%) of untested respondents. Factors that encouraged testing included relatives’ cancer risk (75%; 95% CI, 73% to 78%), clinicians’ recommendations (68%; 95% CI, 66% to 71%), and potential treatment implications (67%; 95% CI, 64% to 69%). Factors that discouraged testing included insurance concerns (14%; 95% CI, 12% to 16%), cost (14%; 95% CI, 12% to 16%), and discrimination (9%; 95% CI, 7% to 11%). Thirty-nine percent (95% CI, 36% to 41%) recalled hearing from a clinician that genetic discrimination is illegal. Respondents often recalled clinicians informing them about inheritance patterns (65%; 95% CI, 62% to 67%), surgical implications (65%; 95% CI, 63% to 68%), and other cancer risks (66%; 95% CI, 63% to 68%) but less often that results could have potential implications for clinical trial eligibility (38%; 95% CI, 36% to 42%) or targeted therapies (14%; 95% CI, 12% to 16%). Patients who had genetic counseling were twice as likely to recall clinicians informing them about all queried topics. Results did not vary by diagnosis year.

CONCLUSION:

Among patients with high genetic risk, clinicians’ recommendations, potential treatment implications, and protections against discrimination were motivating factors to undergo genetic testing, but fewer than half recalled clinicians providing all this information, and this did not improve over time. Clinicians influence testing decisions and should inform patients about legal protections and treatment implications.
The Course of Obstructive Sleep Apnea Syndrome in Patients With Acromegaly During Treatment
Authors: Wolters Thalijn L C , Roerink Sean H P P , Drenthen Linda C A , van Haren-Willems Jolanda H G M , Wagenmakers Margaretha A E M , Smit Johannes W A , Hermus Adrianus R M M , Netea-Maier Romana T
Published: October 2019

Background

Obstructive sleep apnea syndrome (OSAS) is common in active acromegaly and negatively influences quality of life, morbidity, and mortality. This prospective study with 3 predetermined timepoints and a standardized treatment protocol investigates changes in sleep parameters during the first 2.5 years of acromegaly treatment.

Methods

Before initiation of acromegaly treatment (medical pretreatment followed by surgery), polysomnography (PSG) was performed in 27 consecutive patients with treatment-naive acromegaly. PSG was repeated after 1 year (N = 24) and 2.5 years (N = 23), and anthropometric and biochemical parameters were obtained.

Results

At baseline, 74.1% of the patients was diagnosed with OSAS. The respiratory disturbance index (RDI; P = 0.001), oxygen desaturation index (ODI; P = 0.001), lowest oxygen saturation (LSaO2; P = 0.007) and the Epworth Sleepiness Scale (ESS; P < 0.001) improved significantly during treatment, with the greatest improvement in the first year. After 2.5 years of treatment, all patients had controlled acromegaly. Of the 16 patients with repeated PSG and OSAS at baseline, 11 (68.8%) were cured of OSAS. Changes in RDI, ODI, LSaO2, and ESS correlated with insulin-like growth factor 1 levels.

Conclusion

OSAS has a high prevalence in active acromegaly. There is a substantial decrease in prevalence and severity of OSAS following acromegaly treatment, with the largest improvement during the first year. Most patients recover from OSAS following surgical or biochemical control of the acromegaly. Therefore, a PSG is advised after diagnosis of acromegaly. When OSAS is present, it should be treated and PSG should be repeated during acromegaly treatment.
Trabecular Bone Score Declines During the Menopause Transition: The Study of Women’s Health Across the Nation (SWAN)
Authors: Greendale Gail A , Huang MeiHua , Cauley Jane A , Liao Diana , Harlow Sioban , Finkelstein Joel S , Hans Didier , Karlamangla Arun S
Published: October 2019

Context

Rapid bone density loss starts during the menopause transition (MT). Whether other components of bone strength deteriorate before the final menstrual period (FMP) remains uncertain.

Objective

To discern whether trabecular bone score (TBS) declines during the MT.

Design

An 18-year longitudinal analysis from the Study of Women’s Health Across Nation.

Setting

Community-based cohort.

Participants

A total of 243 black, 164 Japanese, and 298 white, initially pre- or early perimenopausal women, who experienced their FMP.

Main Outcome Measures

TBS, an indicator of bone strength.

Results

Multivariable mixed effects regressions fitted piecewise linear models to repeated measures of TBS as a function of time before or after the FMP; covariates were age at FMP, race/ethnicity, and body mass index. Prior to 1.5 years before the FMP, in the referent individual (a white woman with age at FMP of 52.2 years and body mass index of 28.0 kg/m2), TBS evidenced no change (slope 0.12% per year, P = 0.2991). TBS loss began 1.5 years before the FMP, declining by 1.16% annually (P < 0.0001). Starting 2 years after the FMP, annual rate of TBS loss lessened to 0.89% (P < 0.0001). In the 5 years before through the 5 years after the FMP, in the referent individual, total TBS decline was 6.3% (P < 0.0001), but black participants’ total TBS loss was 4.90% (P = 0.0008, difference in black and white 10-year change). Results for Japanese did not differ from those of white women.

Conclusions

The occurrence of an MT-related decline in TBS supports the thesis that this period is particularly damaging to skeletal integrity.
Negative Effects of Age at Menarche on Risk of Cardiometabolic Diseases in Adulthood: A Mendelian Randomization Study
Authors: Cao Min , Cui Bin
Published: October 2019

Context

Observational studies have demonstrated that early menarche is associated with cardiometabolic diseases, but confounding factors make it difficult to infer causality.

Objective

We used Mendelian randomization (MR) to examine whether age at menarche (AAM) is causally associated with type 2 diabetes (T2D), coronary artery disease (CAD) and cardiometabolic traits.

Design and Methods

A 2-sample MR analysis was conducted using genome-wide association study (GWAS) summary statistics from the Diabetes Genetics Replication and Meta-analysis (DIAGRAM) consortium (n = 159 208) for T2D and the Coronary Artery Disease Genome-wide Replication and Meta-analysis plus the Coronary Artery Disease Genetics (CARDIoGRAMplusC4D) consortium (n = 184 305) for CAD. We used 122 instrumental variables (IVs) extracted from a published GWAS meta-analysis incorporating 182 416 women to determine the causal effect of AAM on cardiometabolic diseases, treating childhood and adult body mass index (BMI) as the confounders. Sensitivity analyses were also performed to detect the pleiotropy of the IVs.

Results

Employing the MR approach, we found that later AAM was associated with decreased risk of CAD (OR, 0.92 [95% CI, 0.88-0.96]; P = 2.06 × 10–4) in adults, as well as lower blood levels of log fasting insulin, log homeostatic model assessment of insulin resistance (HOMA-IR), log HOMA of β-cell function (HOMA-B), triglycerides, and diastolic blood pressure, but higher blood level of high-density lipoprotein. However, the associations were substantially attenuated after excluding BMI-related variants. MR analyses provide little evidence on the causal effect between AAM and T2D.

Conclusions

Our findings showed that AAM did not appear to have a causal effect on the risk of cardiometabolic diseases in adult life, as their associations observed in epidemiological studies might be largely mediated through excessive adiposity. We propose adiposity might be a primary target in future intervention strategy.
CLASP promotes microtubule bundling in metaphase spindle independently of Ase1/PRC1 in fission yeast
Authors: Ebina Hirohisa , Ji Liang , Sato Masamitsu
Published: October 2019

Microtubules in the mitotic spindle are organised by microtubule-associated proteins. In the late stage of mitosis, spindle microtubules are robustly organised through bundling by the antiparallel microtubule bundler Ase1/PRC1. In early mitosis, however, it is not well characterised whether spindle microtubules are actively bundled, as Ase1 does not particularly localise to the spindle at that stage.

Here we show that the conserved microtubule-associated protein CLASP (fission yeast Peg1/Cls1) facilitates bundling of spindle microtubules in early mitosis. The peg1 mutant displayed a fragile spindle with unbundled microtubules, which eventually resulted in collapse of the metaphase spindle and abnormal segregation of chromosomes. Peg1 is known to be recruited to the spindle by Ase1 to stabilise antiparallel microtubules in late mitosis. However, we demonstrate that the function of Peg1 in early mitosis does not rely on Ase1. The unbundled spindle phenotype of the peg1 mutant was not seen in the ase1 mutant, and Peg1 preferentially localised to the spindle even in early mitosis unlike Ase1. Moreover, artificial overexpression of Ase1 in the peg1 mutant partially suppressed unbundled microtubules. We thus conclude that Peg1 bundles microtubules in early mitosis, in a distinct manner from its conventional Ase1-dependent functions in other cell cycle stages.
Long noncoding RNA SNHG1 predicts poor prognosis and facilitates disease progression in acute myeloid leukemia
Authors: Tian Ming , Gong Wanjun , Guo Jingming
Published: October 2019

The role of long noncoding RNAs (lncRNAs) in acute myeloid leukemia (AML) is becoming increasingly concerned. Previous studies have reported that the lncRNA small nucleolar RNA host gene 1 (SNHG1) is involved in multiple human malignant tumors, while its expression and role in AML is still unexplored. Here, we show that SNHG1 is highly expressed in AML specimens from non-M3 patients, as well as AML cell lines. Meanwhile, upregulation of SNHG1 is correlated with poor prognosis. Notably, SNHG1 facilitates the proliferation and inhibits the apoptosis of AML cells in vitro. Consistent with these findings, knockdown of SNHG1 significantly inhibits AML progression in an immunodeficient mouse model. Mechanistically, we found that an anti-tumor microRNA-101 (miR-101) is upregulated and its target genes are downregulated in AML cells after SNHG1 knockdown. Further investigations display that SNHG1 can serve as a competing endogenous RNA (ceRNA) to inhibit miR-101. In conclusion, our data indicate that SNHG1 plays an important role in facilitating AML progression at least in part by negatively regulating miR-101, and meanwhile provide a new target for treating AML.
Spatial integration of mechanical forces by α-actinin establishes actin network symmetry
Authors: Senger Fabrice , Pitaval Amandine , Ennomani Hajer , Kurzawa Laetitia , Blanchoin Laurent , Théry Manuel
Published: October 2019

Cell and tissue morphogenesis depend on the production and spatial organization of tensional forces in the actin cytoskeleton. Actin network architecture is made of distinct modules characterized by specific filament organizations. The assembly of these modules are well described, but their integration in a cellular network is less understood. Here, we investigated the mechanism regulating the interplay between network architecture and the geometry of the extracellular environment of the cell. We found that α-actinin, a filament crosslinker, is essential for network symmetry to be consistent with extracellular microenvironment symmetry. It is required for the interconnection of transverse arcs with radial fibres to ensure an appropriate balance between forces at cell adhesions and across the actin network. Furthermore, this connectivity appeared necessary for the ability of the cell to integrate and to adapt to complex patterns of extracellular cues as they migrate. Our study has unveiled a role of actin filament crosslinking in the spatial integration of mechanical forces that ensures the adaptation of intracellular symmetry axes in accordance with the geometry of extracellular cues.

This article has an associated First Person interview with the first author of the paper.
MRI native T1 and T2 mapping of myocardial segments in hypertrophic cardiomyopathy: tissue remodeling manifested prior to structure changes
Authors: Huang Lu , Ran Lingping , Zhao Peijun , Tang Dazhong , Han Rui , Ai Tao , Xia Liming , Tao Qian
Published: October 2019

Objective:

The aim of this study was to examine the local myocardial segments in hypertrophic cardiomyopathy (HCM) by MRI T1 and T2 mapping, and to investigate how tissue remodeling correlates with structural and functional remodeling in HCM.

Methods:

47 patients with HCM and 19 healthy volunteers were enrolled in this study. All subjects underwent cardiac MRI at 3.0 T. Native T1 and T2 values, end-diastolic wall thickness (EDTH), and percentage of systolic wall thickening (PSWT) were assessed in the left ventricular segments according to the American Heart Association model. Myocardial segments were categorized as normal, non-hypertrophic, mild-hypertrophic, moderate-hypertrophic, and severe-hypertrophic based on EDTH. The difference among all five groups, and the correlation between native T1 and T2 values, EDTH, and PSWT were evaluated.

Results:

Native T1 and T2 values were significantly elevated in both non-hypertrophic and hypertrophic segments of HCM patients compared to controls (both p < 0.001). PSWT was preserved in non-hypertrophic segments (p = 0.838), while significantly impaired (p < 0.001) in hypertrophic segments. Native T1 value of severe hypertrophic segments in HCM was significantly higher than segments of mild and moderate hypertrophy (p < 0.05).

Conclusion:

In HCM patients, the non-hypertrophic myocardial segments already demonstrated significantly elevated T1 and T2 values, despite normal wall thickness and preserved contraction function. The finding suggests that tissue remodeling may precede morphological and functional remodeling in HCM. MRI native T1 and T2 mapping can provide additional value for HCM diagnosis at an early stage.

Advances in knowledge:

Myocardial tissue remodeling, as detected by MRI native T1 and T2 mapping, occurs earlier than morphological and functional changes in HCM patients.
Influence of delivery mode on maternal mental status one month after delivery at a perinatal center in Japan: A cross-sectional study
Authors: Suzuki Shunji
Published: October 2019

Background: Maternal mental status has been thought to be affected by the delivery modes. We examined the influence of delivery modes on the mental status of women who delivered at our institute in Japan.

Methods: Data were collected from the medical charts of 645 primiparous women without a history of mental disorders who delivered singleton babies and underwent a 1-month postpartum check-up at our institute from September 2018 to June 2019. The maternal mental status was examined based on the scores of the Edinburgh Postnatal Depression Scale (EPDS) and the Mother-Infant Bonding Scale (MIBS).

Results: The rate of high scores of the EPDS and the MIBS in women choosing elective cesarean section were higher than in women with vaginal delivery and emergency cesarean section.

Conclusion: A fulfilling birth-plan and birth-review may also be necessary for women choosing elective cesarean section.
The Analysis of Teachers’ Cyber Bullying, Cyber Victimization and Cyber Bullying Sensitivity Based On Various Variables
Authors: Yildirim Ahmet , Celikten Mustafa , Desiatov Tymofii , Lodatko Yevgeny
Published: October 2019

In recent years, cyberbullying, which can be considered as a new form of bullying, has emerged as a result of developments in the field of technology and communication. Cyberbullying has become a social problem which has affected individuals’ lives negatively. The key to success in the elimination of cyberbullying and its negative effects lies in cyberbullying sensitivity. The present study aims to analyze teachers’ cyberbullying and cyber victimization experiences and levels of cyberbullying sensitivity based on some variables which are supposed to develop awareness regarding cyberbullying. Using survey as a research model, the present study focused on 346 teachers working at schools affiliated with Ministry of National Education in Tasova District located in Amasya (Turkey). “Personal Information Form”, “The Revised Cyberbullying Inventory for University Students” and “Cyberbullying Sensitivity Scale” were used as data collection tools. SPSS package program was used for data analysis and frequency and percentage values of demographic variables. Independent T test was used for gender and marital status variables, and One-Way ANOVA test was used for age and level of education variables. The findings of the present study revealed that most of the participants used social media websites actively and spent at least 2 or 3 hours on these websites on a daily basis. Teachers usually have a Facebook and/or Instagram account, and benefit from social media for research purposes and playing games. It can be stated that teachers have a significantly high level of cyberbullying sensitivity. However, it was also indicated that even though participants worked as a teacher, they still did cyberbully and suffered from cyber victimization in the past. While a significant difference was observed only in the dimension of cyber sensitivity in terms of marital status, age and level of education, a significant difference wasn’t observed in the dimensions of cyberbullying, cyber victimization and cyber sensitivity in terms of gender.
Development of E-Modules Based on Local Wisdom in Central Learning Model at Kindergartens in Jambi City
Authors: Sofyan Hendra , Anggereini Evita , Saadiah Jamiatul
Published: October 2019

This study aims to produce e-modules based on valid and appropriate local wisdom in the Central Learning Model at kindergartens in Jambi. The product of this research is realized in the form of an electronic module using 3D Pageflip Professional software to determine the feasibility of e-modules as well as knowing the teacher's response to e-modules based on local wisdom in Central Learning Model at kindergartens in Jambi city. The type of this research is developing research that refers to the ADDIE model. After the e-learning module was created, the e-learning module was validated by the expert. Validation was carried out by two material experts and an e-learning module expert until the e-learning module is declared feasible. After the e-learning module has been validated and revised, a trial was then conducted by the respondent to see the perception results. The developed e-modules are stated in the valid category based on the results of the validation of the e-module material and the e-module design which obtains excellent criteria. The results of the questionnaire perception of 62 respondents (lecturers, teachers and students) on e-modules showed an average rate of 83% which is included in the excellent category. These results indicate that the e-module developed in this study is very feasible to use. E-Modules developed in this study are highly recommended for use by Lecturers, Students, and Teachers in the major of Early Childhood Education.