bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma HER2ECD a promising test for patient prognosis and prediction of response in HER2 positive breast cancer: results of a randomized study - SAKK 22/99
Authors: Eppenberger-Castori Serenella , Klingbiel Dirk , Ruhstaller Thomas , Dietrich Daniel , Rufle Daniel Alexander , Rothgiesser Karin , Pagani Olivia , Thürlimann Beat
Published: February 2020

Background

The HER2 extracellular domain shed in blood (HER2ECD) is reported to rise and fall in parallel with HER2+ breast cancer behavior. In this study, we evaluated the clinical relevance of plasma HER2ECD values in patients with metastatic breast cancer treated in the SAKK22/99 trial comparing trastuzumab monotherapy followed by trastuzumab-chemotherapy combination at progression versus upfront combination therapy.

Methods

Quantitative assessment of plasma HER2ECD was performed in 133 patients at baseline; after 2–24 h; at 3 weeks; at first response evaluation (8–9 weeks); and at tumor progression. Associations with tumor characteristics, disease course and trial treatment were evaluated.

Results

Baseline HER2ECD levels were stable within 24 h after the first trastuzumab injection. These plasma values correlated positively with the HER2 gene ratio (rs = 0.39, P < 0.001) and HER2 protein expression levels (rs = 0.36, P < 0.001) but not with ER/PR status of the primary tumor. HER2ECD baseline levels were positively associated with the presence of visceral disease (P = 0.05) and poor patients’ outcome (Cox-regression: P = 0.009). Patients with high baseline levels (> 35 ng/ml) had the worst overall survival (P = 0.03) if treated with upfront combination therapy. Conversely, patients with low HER2ECD baseline values (< 15 ng/ml) had longer time to progression on combined trastuzumab-chemotherapy when first treated with trastuzumab monotherapy (P = 0.02). Monitoring HER2ECD levels during the course of the trial revealed significant time (P = 0.001) and time-treatment arm interactions (P = 0.0007). Under upfront trastuzumab alone, the HER2ECD levels remained stable until just before disease progression. In patients responding to combination treatment HER2ECD levels decreased to > 20%.

Conclusions

Plasma HER2ECD levels in patients with metastatic breast cancer reflect HER2 disease status. This robust biomarker might help identifying patients without visceral disease profiting from a sequential treatment’s modality. Monitoring HER2ECD levels during trastuzumab monotherapy could help defining the optimal time to introduce chemotherapy.

Trial registration

Registration Number by ClinicalTrials.gov: NCT00004935, Trial number: SAKK22/99. Registered on 27 January 2003.
Knowledge and attitude towards cervical cancer among reproductive age group women in Gondar town, North West Ethiopia
Authors: Mengesha Ayelign , Messele Anteneh , Beletew Biruk
Published: February 2020

Background

Cervical cancer is the second most commonly diagnosed cancer and the third leading cause of cancer death in women worldwide. Nearly 83% of the world’s new cases and 85% of all cervical cancer-related deaths occur in developing countries. It is primarily caused by human papilloma virus (HPV); a sexually transmitted pathogen that could be prevented with safe sexual practice and using vaccines among others.

The aim of the study was to assess the knowledge and attitude of reproductive age group women towards cervical cancer and its prevention in Gondar town.

Methods

A descriptive community based cross-sectional study was carried out. An interviewer-administered questionnaire was employed for data collection. A multistage sampling technique was employed to select the study participants. Descriptive statistics like frequency, mean and percentage were computed using SPSS version 20 software program.

Results

Seven hundred and seventy women (n = 770) participated with a response rate of 100%. More than half, (65.1%) of the participants claim hearing of cervical cancer. However, majority (> 80%) of them lack knowledge that HPV is a causative agent of cervical cancer which is extremely worrying as the most important way to prevent cervical cancer is blocking HPV infection. Of those who had heard of it, only 107 (21.4%) said they have heard about Pap smear test. From them, less than half, 47 (43.9%) said that an apparently healthy woman should undergo the test at least three times in her life. This means in addition to the lack of information about the test, majority of those who had heard about it didn’t know how many times they should have the test in their life. Overall, only 153 (19.87%) of the participants were found having a good knowledge of cervical cancer and its prevention.

Conclusion

The overall knowledge of women towards cervical cancer was inadequate. On the other hand, those who had heard about it had a somewhat encouraging attitude. Mass media was the major source of information. But, any public health problem cannot be solved in isolation. Hence, initiating large-scale awareness campaigns is recommended.
In vitro Cariostatic effects of cinnamon water extract on nicotine-induced Streptococcus mutans biofilm
Authors: Alshahrani Abdulaziz M. , Gregory Richard L.
Published: February 2020

Background

Dental caries is one of the most prevalent chronic oral diseases worldwide. Dental caries is mainly associated withStreptococcus mutansand theLactobacillusspecies. A specific relationship was found between nicotine andS. mutansgrowth as the presence of nicotine increasedS. mutansbiofilm formation. Nicotine is able to increase the number ofS. mutansand extracellular polysaccharide (EPS) synthesis. Among the widely used herbs and spices is cinnamon which demonstrated a strong antibacterial activity against a wide variety of bacteria includingS. mutansand showed the ability to inhibitS. mutansbiofilm formation. Cinnamon essential oil, obtained from the leaves ofC. zeylanicum, has been demonstrated to be effective againstS. mutansandLactobacillus acidophilus, which are partially responsible for dental plaque formation and caries development. The aim of this study was to identify the effects of nicotine exposure on the inhibitory effects of cinnamon water extract onS. mutansbiofilm formation.

Materials and methods

A 24-h culture ofS. mutansUA159 in microtiter plates was treated with varying nicotine concentrations (0–32 mg/ml) in Tryptic Soy broth supplemented with 1% sucrose (TSBS) with or without a standardized concentration (2.5 mg/ml) of cinnamon water extract. A spectrophotometer was used to determine total growth absorbance and planktonic growth. The microtiter plate wells were washed, fixed and stained with crystal violet dye and the absorbance measured to determine biofilm formation.

Results

The presence of 2.5 mg/ml cinnamon water extract inhibits nicotine-inducedS. mutansbiofilm formation from 34 to 98% at different concentrations of nicotine (0–32 mg/ml).

Conclusion

The results demonstrated nicotine-inducedS. mutansbiofilm formation is decreased from 34 to 98% in the presence of 2.5 mg/ml cinnamon water extract. This provides further evidence about the biofilm inhibitory properties of cinnamon water extract and reconfirms the harmful effects of nicotine.
Effect of tuberculosis screening and retention interventions on early antiretroviral therapy mortality in Botswana: a stepped-wedge cluster randomized trial
Authors: Auld Andrew F. , Agizew Tefera , Mathoma Anikie , Boyd Rosanna , Date Anand , Pals Sherri L. , Serumola Christopher , Mathebula Unami , Alexander Heather , Ellerbrock Tedd V. , Rankgoane-Pono Goabaone , Pono Pontsho , Shepherd James C. , Fielding Katherine , Grant Alison D. , Finlay Alyssa
Published: February 2020

Background

Undiagnosed tuberculosis (TB) remains the most common cause of HIV-related mortality. Xpert MTB/RIF (Xpert) is being rolled out globally to improve TB diagnostic capacity. However, previous Xpert impact trials have reported that health system weaknesses blunted impact of this improved diagnostic tool. During phased Xpert rollout in Botswana, we evaluated the impact of a package of interventions comprising (1) additional support for intensified TB case finding (ICF), (2) active tracing for patients missing clinic appointments to support retention, and (3) Xpert replacing sputum-smear microscopy, on early (6-month) antiretroviral therapy (ART) mortality.

Methods

At 22 clinics, ART enrollees > 12 years old were eligible for inclusion in three phases: a retrospective standard of care (SOC), prospective enhanced care (EC), and prospective EC plus Xpert (EC+X) phase. EC and EC+X phases were implemented as a stepped-wedge trial. Participants in the EC phase received SOC plus components 1 (strengthened ICF) and 2 (active tracing) of the intervention package, and participants in the EC+X phase received SOC plus all three intervention package components. Primary and secondary objectives were to compare all-cause 6-month ART mortality between SOC and EC+X and between EC and EC+X phases, respectively. We used adjusted analyses, appropriate for study design, to control for baseline differences in individual-level factors and intra-facility correlation.

Results

We enrolled 14,963 eligible patients: 8980 in SOC, 1768 in EC, and 4215 in EC+X phases. Median age of ART enrollees was 35 and 64% were female. Median CD4 cell count was lower in SOC than subsequent phases (184/μL in SOC, 246/μL in EC, and 241/μL in EC+X). By 6 months of ART, 461 (5.3%) of SOC, 54 (3.2%) of EC, and 121 (3.0%) of EC+X enrollees had died. Compared with SOC, 6-month mortality was lower in the EC+X phase (adjusted hazard ratio, 0.77; 95% confidence interval, 0.61–0.97, p = 0.029). Compared with EC enrollees, 6-month mortality was similar among EC+X enrollees.

Conclusions

Interventions to strengthen ICF and retention were associated with lower early ART mortality. This new evidence highlights the need to strengthen ICF and retention in many similar settings. Similar to other trials, no additional mortality benefit of replacing sputum-smear microscopy with Xpert was observed.

Trial registration

Retrospectively registered: ClinicalTrials.gov (NCT02538952)
Real-state of autophagy signaling pathway in neurodegenerative disease; focus on multiple sclerosis
Authors: Hassanpour Mehdi , Hajihassani Fateme , Hiradfar Amirataollah , Aghamohammadzadeh Nasser , Rahbarghazi Reza , Safaie Nasser , Nouri Mohammad , Panahi Yunes
Published: February 2020

The occurrence of neurodegenerative disease is increasingly raised. From physiopathological aspect, the emergence of auto-reactive antibodies against the nervous system antigens contributes to de-myelination in Multiple sclerosis (MS). These features cause the nervous system dysfunction. The follow-up of molecular alterations could give us a real-state vision about intracellular status during pathological circumstances. In this review, we focus on the autophagic response during MS progression and further understand the relationship between autophagy and MS and its modulatory effect on the MS evolution. The authors reviewed studies published on the autophagy status in neurodegenerative disease and on the autophagy modulation in MS prognosis, diagnosis, and possible therapies. The inevitable role of autophagy was shown in the early-stage progression of MS. Due to critical role of autophagy in different stage of cell activity in nervous system, the distinct role of autophagy should not be neglected in the development, pathogenesis, and treatment of MS.
Correction to: Proposal for a definition for response to treatment, inactive disease and damage for JIA associated uveitis based on the validation of a uveitis related JIA outcome measures from the Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC)
Authors: Foeldvari Ivan , Klotsche Jens , Simonini Gabriele , Edelsten Clive , Angeles-Han Sheila T. , Bangsgaard Regitze , de Boer Joke , Brumm Gabriele , Torrent Rosa Bou , Constantin Tamas , DeLibero Cinzia , Diaz Jesus , Gerloni Valeria Maria , Guedes Margarida , Heiligenhaus Arnd , Kotaniemi Kaisu , Leinonen Sanna , Minden Kirsten , Miranda Vasco , Miserocchi Elisabetta , Nielsen Susan , Niewerth Martina , Pontikaki Irene , de Vicuna Carmen Garcia , Zilhao Carla , Yeh Steven , Anton Jordi
Published: February 2020

Following publication of the original article [1], we have been notified that the author Joan Calzada should not have been included to the team of authors. The authors’ team, thus, should be as follows:
Association between added sugar intake and micronutrient dilution: a cross-sectional study in two adult Swedish populations
Authors: González-Padilla Esther , A. Dias Joana , Ramne Stina , Olsson Kjell , Nälsén Cecilia , Sonestedt Emily
Published: February 2020

Background

The evidence on the impact of high sugar consumption on micronutrient dilution does not yet allow for the establishment of clear thresholds of consumption. To establish upper and lower limit intake thresholds for added sugar, more studies from different countries and multiple populations are needed. The aim of this study was to examine the association between the intakes of added sugar and various micronutrients among the adult Swedish population across almost two decades.

Methods

The data were obtained from the samples from two populations: 1) Riksmaten Adults, a national dietary survey (n = 1797, 44% male, aged 18–80 years, data collection from 2010 to 11) that assessed dietary intake using a 4-day web-based food diary; and 2) the Malmö Diet and Cancer Study, a population-based cohort study (n = 12,238, 45% male, aged 45–68 years, data collection from 1991 to 1994) that assessed dietary intake via a combination of a 7-day food diary, a food frequency questionnaire and an interview. The mean daily intake of nine micronutrients (calcium, folate, iron, magnesium, potassium, selenium, vitamin C, vitamin D, and zinc), adjusted for age, sex, BMI and energy intake, were examined across six added-sugar-intake groups (< 5%E, 5–7.5%E, 7.5–10%E, 10–15%E, 15–20%E, and >  20%E).

Results

We observed significant inverse associations between the intake of added sugar and the intake of all micronutrients in both populations. The associations were linear; however, we could not determine the threshold of added sugar intake beyond which the micronutrient intake was clearly compromised.

Conclusions

These findings suggest that in two Swedish populations the higher the intake of added sugar in the diet, the more likely it is that the intake of micronutrients will be compromised, in two Swedish populations. However, although the trends are significant and consistent with those obtained in other studies on the subject, future studies are needed in order to build the necessary scientific knowledge to establish a threshold of added sugar intake based on micronutrient dilution.
Ketamine decreases cell viability of bone explants and impairs bone healing in rats
Authors: Horváthy Dénes B. , Szántó Péter , Marschall Bence , Bagó Marcell , Csery Márton , Hornyák István , Doros Attila , Lacza Zsombor
Published: February 2020

Background

Ketamine is a widely used anesthetic in experimental medicine. We have also used ketamine for surgical interventions and imaging in rats and found significantly impaired ossification between identically performed experiments, which only differed in the number of anesthetic events. In order to investigate this phenomenon, we estimated the absorbed ionizing radiation and also studied whether ketamine administration has disadvantageous effect on bone cell viability.

Methods

Spongious bone chips and parietal bone disks were harvested from rats. Explants were incubated in stem cell media containing 0.02, 0.2 and 2 mM ketamine. After 3 days of incubation, tetrazolium-based spectrophotometric assay was performed to measure cell viability. Size-specific dose estimation was used to calculate ionizing radiation of computed tomography imaging.

Results

We found that ketamine supplementation with 0.2 mM slightly decreased cell viability, while 2 mM caused significant reduction both in the spongious and cortical explants. The cumulative ionizing radiation was found to be negligible compared to irradiation dosages used to impair ossification.

Conclusions

We conclude that multiple ketamine administration was responsible for the diminished regenerative potential of bone tissue in the present experimental setup. For this reason, we suggest that ketamine anesthesia should be avoided in studies investigating bone regeneration.
Immunohistochemical analysis of adipokine and adipokine receptor expression in the breast tumor microenvironment: associations of lower leptin receptor expression with estrogen receptor-negative status and triple-negative subtype
Authors: Llanos Adana A. M. , Lin Yong , Chen Wenjin , Yao Song , Norin Jorden , Chekmareva Marina A. , Omene Coral , Cong Lei , Omilian Angela R. , Khoury Thaer , Hong Chi-Chen , Ganesan Shridar , Foran David J. , Higgins Michael , Ambrosone Christine B. , Bandera Elisa V. , Demissie Kitaw
Published: February 2020

Background

The molecular mechanisms underlying the association between increased adiposity and aggressive breast cancer phenotypes remain unclear, but likely involve the adipokines, leptin (LEP) and adiponectin (ADIPOQ), and their receptors (LEPR, ADIPOR1, ADIPOR2).

Methods

We used immunohistochemistry (IHC) to assess LEP, LEPR, ADIPOQ, ADIPOR1, and ADIPOR2 expression in breast tumor tissue microarrays among a sample of 720 women recently diagnosed with breast cancer (540 of whom self-identified as Black). We scored IHC expression quantitatively, using digital pathology analysis. We abstracted data on tumor grade, tumor size, tumor stage, lymph node status, Ki67, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) from pathology records, and used ER, PR, and HER2 expression data to classify breast cancer subtype. We used multivariable mixed effects models to estimate associations of IHC expression with tumor clinicopathology, in the overall sample and separately among Blacks.

Results

Larger proportions of Black than White women were overweight or obese and had more aggressive tumor features. Older age, Black race, postmenopausal status, and higher body mass index were associated with higher LEPR IHC expression. In multivariable models, lower LEPR IHC expression was associated with ER-negative status and triple-negative subtype (P < 0.0001) in the overall sample and among Black women only. LEP, ADIPOQ, ADIPOR1, and ADIPOR2 IHC expression were not significantly associated with breast tumor clinicopathology.

Conclusions

Lower LEPR IHC expression within the breast tumor microenvironment might contribute mechanistically to inter-individual variation in aggressive breast cancer clinicopathology, particularly ER-negative status and triple-negative subtype.
Comments to “PRevention of INCisional hernia after liver transplantation (PRINC trial): study protocol for a randomized controlled trial.”
Authors: Strzelczyk Janusz Maciej
Published: February 2020

Prophylactic augmentation of the wound with mesh proposed by Kniepeiss et al is the world's first attempt to significantly reduce the risk of postoperative hernia in liver transplantation. Similar technique have been described 17 years ago in bariatric patients and confirmed by many studies in various clinical settings. The results of mesh hernia repair in patients on immunosuppressive therapy are not inferior from the data obtained from non- transplant surgery registers.

To reduce the risk of using the mesh in patients scheduled for liver transplantation authors chose absorbable mesh, that maintains the mechanical strength of the wound for up to 18 months. Half of the incisional hernias have been diagnoses more than 3 years from the original procedure.

For prevention of incisional hernias, there is no evidence to support the use of biologic/biosynthetic meshes.
Different electrode positioning for transcutaneous electrical nerve stimulation in the treatment of urgency in women: a study protocol for a randomized controlled clinical trial
Authors: Padilha Juliana Falcão , Avila Mariana Arias , Seidel Enio Júnior , Driusso Patricia
Published: February 2020

Background

Urgency is a complaint of sudden, compelling desire to pass urine, which is difficult to defer, caused by involuntary contraction of the detrusor muscle during the bladder-filling stage. To enable detrusor inhibition, electrotherapy resources such as transcutaneous tibial nerve stimulation (TTNS) and parasacral transcutaneous electrical stimulation (PTES) have been used. The objective this study is to publish the study protocol that aims to investigate whether urgency decreases after treatment with both of the techniques.

Methods

This randomized controlled clinical trial will include 99 women, aged more than 18 years old, with urgency (score ≥ 8 in the Overactive Bladder-Validated 8-Question Awareness Tool [OAB-V8]). Women will be randomly allocated into three groups: TTNS, PTES, and placebo. The following questionnaires will be applied: the Anamnesis Record, the Incontinence Questionnaire Overactive Bladder, the King’s Health Questionnaire, the 24-Hour Voiding Diary, and the OAB-V8, at four different time points: at baseline prior to the first session, at the 6th session, the 12th session and at follow-up. The current used for the transcutaneous electrical stimulation will be a symmetrical balanced biphasic pulsed current, for 12 sessions, twice a week, for 20 minutes. Qualitative variables will be displayed as frequency and percentage, quantitative variables as mean and standard deviation. Comparison of urgency severity among groups will be performed with a repeated measures ANOVA, considering the effect of the three groups and the four evaluations, and interactions among them.

Discussion

The present study aims to contribute evidence for a more in-depth discussion on electrode positioning for electrostimulation used in urgency treatment. It should be emphasized that, based on the possibility of confirming the hypothesis that urgency will decrease in a similar way after both treatments (TTNS and PTES), the PTES will be used as an option for positioning the electrodes alternatively to the tibial nerve region in special populations, such as amputees or people with severe lower limb sensory impairment.

Trial registration

Brazilian Registry of Clinical Trials (ReBEC) ID:RBR-9rf33n, date of registration: 17 May 2018.
Adding nutrients to the biocontrol strain JK-SH007 promotes biofilm formation and improves resistance to stress
Authors: Fu Huanhuan , Chen Feifei , Liu Wanhui , Kong Weiliang , Wang Chaoen , Fang Xueqi , Ye Jianren
Published: February 2020

Burkholderia pyrrocinia JK-SH007 is an important biocontrol strain for the prevention and treatment of poplar canker disease. Its powerful biocontrol function is inseparable from its successful colonization of poplar trees. Bacterial biofilms can ensure the long-term colonization of a host. To explore the mechanism of action of biofilms in the biocontrol process, we manipulated various exogenous factors to explore the morphology of the JK-SH007 biofilm in vitro. The addition of glycerol and MgSO4 to TSB medium stimulated biofilm production, increased the resistance of JK-SH007 to disease, enhanced the survival of JK-SH007 in nutrient-poor environments and maintained the antagonistic ability of JK-SH007 against the poplar canker pathogen. Therefore, we constructed and optimized a biofilm-forming system to produce a large number of stable JK-SH007 biofilms. The optimized system showed that the optimal incubation time for JK-SH007 biofilm formation was 14 h, the optimal temperature of the static culture was 25 °C, and the optimal pH was 5. The optimal medium for biofilm formation was TSB medium, 1% glycerol and 50 mM MgSO4. RT-qPCR experiments showed that an increase in the expression of the suhB gene promoted JK-SH007 biofilm formation, while an increase in the expression level of the ropN gene inhibited JK-SH007 biofilm formation. The possible mechanism by which JK-SH007 was inhibited by biofilm formation under natural culture was revealed. These results indicate the importance of adding nutrients to JK-SH007 biocides produced on a commercial scale. This is the first report of JK-SH007 producing a long-lasting biofilm that guarantees antagonism.
Robust energy disaggregation using appliance-specific temporal contextual information
Authors: Schirmer Pascal Alexander , Mporas Iosif , Sheikh-Akbari Akbar
Published: February 2020

An extension of the baseline non-intrusive load monitoring approach for energy disaggregation using temporal contextual information is presented in this paper. In detail, the proposed approach uses a two-stage disaggregation methodology with appliance-specific temporal contextual information in order to capture time-varying power consumption patterns in low-frequency datasets. The proposed methodology was evaluated using datasets of different sampling frequency, number and type of appliances. When employing appliance-specific temporal contextual information, an improvement of 1.5% up to 7.3% was observed. With the two-stage disaggregation architecture and using appliance-specific temporal contextual information, the overall energy disaggregation accuracy was further improved across all evaluated datasets with the maximum observed improvement, in terms of absolute increase of accuracy, being equal to 6.8%, thus resulting in a maximum total energy disaggregation accuracy improvement equal to 10.0%.
Multipliers for Jacobi expansions in the Hardy spaces
Authors: Xue Zhong , Shi Yehao , Li Zhongkai
Published: February 2020

The purpose of the paper is to study the coefficient multipliers of the Hardy spaces $H^{p}$Hp associated with Jacobi expansions of exponential type. The main results are about the boundedness from $H^{p}$Hp to $\ell ^{q}$ℓq of the multiplier operators in terms of Jacobi expansions of exponential type for (i) $p=1$p=1, $2\le q<\infty $2≤q<∞; (ii) $\gamma ( \alpha ,\beta )^{-1}< p<1\le q<\infty $γ(α,β)−1<p<1≤q<∞, under appropriate conditions, where $\gamma (\alpha ,\beta )\in (1,\infty ]$γ(α,β)∈(1,∞] is a number depending on the parameters of the Jacobi system.
Separating the signal from the noise in metagenomic cell-free DNA sequencing
Authors: Burnham Philip , Gomez-Lopez Nardhy , Heyang Michael , Cheng Alexandre Pellan , Lenz Joan Sesing , Dadhania Darshana M. , Lee John Richard , Suthanthiran Manikkam , Romero Roberto , De Vlaminck Iwijn
Published: February 2020

Background

Cell-free DNA (cfDNA) in blood, urine, and other biofluids provides a unique window into human health. A proportion of cfDNA is derived from bacteria and viruses, creating opportunities for the diagnosis of infection via metagenomic sequencing. The total biomass of microbial-derived cfDNA in clinical isolates is low, which makes metagenomic cfDNA sequencing susceptible to contamination and alignment noise.

Results

Here, we report low biomass background correction (LBBC), a bioinformatics noise filtering tool informed by the uniformity of the coverage of microbial genomes and the batch variation in the absolute abundance of microbial cfDNA. We demonstrate that LBBC leads to a dramatic reduction in false positive rate while minimally affecting the true positive rate for a cfDNA test to screen for urinary tract infection. We next performed high-throughput sequencing of cfDNA in amniotic fluid collected from term uncomplicated pregnancies or those complicated with clinical chorioamnionitis with and without intra-amniotic infection.

Conclusions

The data provide unique insight into the properties of fetal and maternal cfDNA in amniotic fluid, demonstrate the utility of cfDNA to screen for intra-amniotic infection, support the view that the amniotic fluid is sterile during normal pregnancy, and reveal cases of intra-amniotic inflammation without infection at term.
Uncovering a hidden diversity: optimized protocols for the extraction of dsDNA bacteriophages from soil
Authors: Göller Pauline C. , Haro-Moreno Jose M. , Rodriguez-Valera Francisco , Loessner Martin J. , Gómez-Sanz Elena
Published: February 2020

Background

Bacteriophages (phages) are the most numerous biological entities on Earth and play a crucial role in shaping microbial communities. Investigating the bacteriophage community from soil will shed light not only on the yet largely unknown phage diversity, but may also result in novel insights towards their functioning in the global biogeochemical nutrient cycle and their significance in earthbound ecosystems. Unfortunately, information about soil viromes is rather scarce compared to aquatic environments, due to the heterogeneous soil matrix, which rises major technical difficulties in the extraction process. Resolving these technical challenges and establishing a standardized extraction protocol is, therefore, a fundamental prerequisite for replicable results and comparative virome studies.

Results

We here report the optimization of protocols for the extraction of phage DNA from agricultural soil preceding metagenomic analysis such that the protocol can equally be harnessed for phage isolation. As an optimization strategy, soil samples were spiked with Listeria phage A511 (Myovirus), Staphylococcus phage 2638AΔLCR (Siphovirus) and Escherichia phage T7 (Podovirus) (each 106 PFU/g soil). The efficacy of phage (i) elution, (ii) filtration, (iii) concentration and (iv) DNA extraction methods was tested. Successful extraction routes were selected based on spiked phage recovery and low bacterial 16S rRNA gene contaminants. Natural agricultural soil viromes were then extracted with the optimized methods and shotgun sequenced. Our approach yielded sufficient amounts of inhibitor-free viral DNA for shotgun sequencing devoid of amplification prior library preparation, and low 16S rRNA gene contamination levels (≤ 0.2‰). Compared to previously published protocols, the number of bacterial read contamination was decreased by 65%. In addition, 379 novel putative complete soil phage genomes (≤ 235 kb) were obtained from over 13,000 manually identified viral contigs, promising the discovery of a large, previously inaccessible viral diversity.

Conclusion

We have shown a considerably enhanced extraction of the soil phage community by protocol optimization that has proven robust in both culture-dependent as well as through viromic analyses. Our huge data set of manually curated soil viral contigs substantially increases the amount of currently available soil virome data, and provides insights into the yet largely undescribed soil viral sequence space.
The experience of sudden loss of a colleague or neighbor following the MH17 plane crash in the Ukraine: a qualitative interview study
Authors: Yzermans C. Joris , Baliatsas Christos , Van der Velden Peter G. , Dückers Michel L. A.
Published: February 2020

Background

The literature on loss and traumatic grief after disasters provides findings on the impact of losing a partner, child or close friend on partners, parents and friends. However, little attention has been given to the broader everyday social environment of deceased persons. The present study constitutes a qualitative exploration of the impact on colleagues and neighbors following the MH17 airplane disaster in the Ukraine, July 2014.

Methods

Eighteen structured interviews were conducted with eleven colleagues and seven neighbors. The interviews focused on the relation(−ship) with the victim, on the disaster, the first days and weeks hereafter, and the status one and a half years after the crash.

Results

Especially for colleagues and neighbors with an intensive, long-lasting relation and ties based on friendship and trust, the impact of the sudden death was large. The MH17 disaster was considered a special event, different from, for instance, an “ordinary” accident. It was actively covered by the media and a recurrent conversation topic in meetings with other people. In the workplace, employers and less involved colleagues show empathy for a limited period of time, but grief has an expiration date – a moment where it gets more difficult to others or influences productivity. The appreciation for rituals in the workplace or in the neighborhood varies.

Conclusions

The interviews indicate a “hierarchy of bereavement”. People are not part of the typical inner circle, but feel “affected” and experience little social recognition and acknowledgment, particularly in the longer term. As such, colleagues and neighbors may experience loneliness and/or isolation. Generally, there is no need to consult a practitioner, despite the experience of health complaints such as intrusive dreaming and lack of sleep.
Variability in lutetium-177 SPECT quantification between different state-of-the-art SPECT/CT systems
Authors: Peters Steffie M. B. , Meyer Viol Sebastiaan L. , van der Werf Niels R. , de Jong Nick , van Velden Floris H. P. , Meeuwis Antoi , Konijnenberg Mark W. , Gotthardt Martin , de Jong Hugo W. A. M. , Segbers Marcel
Published: February 2020

Background

Quantitative SPECT imaging in targeted radionuclide therapy with lutetium-177 holds great potential for individualized treatment based on dose assessment. The establishment of dose-effect relations requires a standardized method for SPECT quantification. The purpose of this multi-center study is to evaluate quantitative accuracy and inter-system variations of different SPECT/CT systems with corresponding commercially available quantitative reconstruction algorithms. This is an important step towards a vendor-independent standard for quantitative lutetium-177 SPECT.

Methods

Four state-of-the-art SPECT/CT systems were included: Discovery™ NM/CT 670Pro (GE Healthcare), Symbia Intevo™, and two Symbia™ T16 (Siemens Healthineers). Quantitative accuracy and inter-system variations were evaluated by repeatedly scanning a cylindrical phantom with 6 spherical inserts (0.5 – 113 ml). A sphere-to-background activity concentration ratio of 10:1 was used. Acquisition settings were standardized: medium energy collimator, body contour trajectory, photon energy window of 208 keV (± 10%), adjacent 20% lower scatter window, 2 × 64 projections, 128 × 128 matrix size, and 40 s projection time. Reconstructions were performed using GE Evolution with Q.Metrix™, Siemens xSPECT Quant™, Siemens Broad Quantification™ or Siemens Flash3D™ algorithms using vendor recommended settings. In addition, projection data were reconstructed using Hermes SUV SPECT™ with standardized reconstruction settings to obtain a vendor-neutral quantitative reconstruction for all systems. Volumes of interest (VOI) for the spheres were obtained by applying a 50% threshold of the sphere maximum voxel value corrected for background activity. For each sphere, the mean and maximum recovery coefficient (RCmean and RCmax) of three repeated measurements was calculated, defined as the imaged activity concentration divided by the actual activity concentration. Inter-system variations were defined as the range of RC over all systems.

Results

RC decreased with decreasing sphere volume. Inter-system variations with vendor-specific reconstructions were between 0.06 and 0.41 for RCmean depending on sphere size (maximum 118% quantification difference), and improved to 0.02–0.19 with vendor-neutral reconstructions (maximum 38% quantification difference).

Conclusion

This study shows that eliminating sources of possible variation drastically reduces inter-system variation in quantification. This means that absolute SPECT quantification for 177Lu is feasible in a multi-center and multi-vendor setting; however, close agreement between vendors and sites is key for multi-center dosimetry and quantitative biomarker studies.
Iliac Crest Bone Grafting for the Management of Anterior Shoulder Instability in Patients with Glenoid Bone Loss: a Systematic Review of Contemporary Literature
Authors: Malahias Michael-Alexander , Chytas Dimitrios , Raoulis Vasileios , Chronopoulos Efstathios , Brilakis Emmanouil , Antonogiannakis Emmanouil
Published: February 2020

Background

A number of clinical trials have been published assessing the role of iliac crest bone grafting for the management of recurrent anterior instability with glenoid bone loss in contemporary practice. We therefore performed a systematic review of contemporary literature to examine the effect of iliac crest bone grafting on postoperative outcomes of these patients. Our hypothesis is that contemporary iliac crest bone block techniques are associated with low reoperation and complication rates combined with satisfactory functional results.

Methods

The US National Library of Medicine (PubMed/MEDLINE), the Cochrane Database of Systematic Reviews, and EMBASE were searched between January 2008 and December 2019 for relevant publications.

Results

Following the application of the inclusion-exclusion criteria, nine articles were found eligible for our analysis. In total, 261 patients (mean age range, 25.5–37.5 years; mean follow-up range, 20.6–42 months) were included in the studies of the current review. The mean modified Coleman score was 48.6 (range 37–65), indicating an overall low-to-moderate methodological quality. In the short term, the overall all-cause reoperation rate was 6.1%, while the rate of recurrent instability was 4.8%. The graft non-union rate was 2.2%, while the rate of osteolysis, graft fracture, and infection was 0.4%, 0.9%, and 1.7%, respectively. Finally, hardware-related complications, such as screw breakage or symptomatic mechanical irritation around the screw insertion, occurred in 3.9% of the patients.

Conclusions

Iliac crest bone block techniques in contemporary practice are safe and effective in the short-term (< 4 years) follow-up for the management of anterior shoulder instability with substantial glenoid bone deficiency. However, further studies of higher quality and longer follow-up are required to establish the therapeutic value of these techniques as well as to clarify whether there are differences in the outcomes of arthroscopic and open iliac crest bone block procedures.
Impact of bottle size on in-home consumption of wine: feasibility and acceptability randomised cross-over study
Authors: Mantzari Eleni , Galloway Catherine , Hollands Gareth , Pechey Rachel , Zupan Zorana , Pilling Mark , Marteau Theresa
Published: February 2020

Background

Reducing alcohol consumption across populations would prevent many non-communicable diseases. Large packages increase food and non-alcoholic drink consumption and large glasses increase wine consumption. Smaller bottles may reduce alcohol consumption but their impact is uncertain. This study aims to (i) explore the feasibility and acceptability of conducting a large-scale randomised study to assess the impact of bottle size on in-home wine consumption and (ii) estimate the effect size and variance of the intervention on consumption to inform the design of future studies.

Methods

Cross-over randomised study in which 16 households in Cambridge, England, consuming at least two 750-ml bottles of wine each week, received a pre-set volume of wine biweekly for 4 weeks, in 750-ml and 375-ml bottles, in random order. Consumption was assessed by recording the number of empty and partially full bottles at the end of each biweekly period. At the end of the study, household representatives were interviewed about their experiences of participating in the study.

Results

The study procedures proved feasible. Comparable to similar trials, 14% of identified eligible households (18/125) consented to participate in the study. Attrition between consent and study completion was 11% (2/18) and 0% between study periods and 13% of households (2/16) correctly identified the study aim. The study procedures were considered acceptable. After adjusting for guest and out-of-home consumption, the difference in consumption between the 750-ml (3385.2 ml; SD = 1698.5) and 375-ml bottles (3376.7 ml; SD = 1719.0) was 8.4 ml (SD = 1235.4; 95%CI − 596.9, 613.8). Results suggest a possible order effect, with households receiving the 375-ml bottles first consuming more wine out of the 750-ml bottles and vice versa. This might also reflect an increase in consumption with study duration. Households receiving the 375-ml bottles first (6315.9 ml; SD = 3293.5) also drank less wine overall than those receiving the 750-ml bottles first (7335.4 ml; SD = 3735.4).

Discussion

The findings support the feasibility and acceptability of running a large-scale randomised study to assess the impact of bottle size on in-home wine consumption. Due to the heterogeneous patterning of results, a future study will be powered using the variance observed in the current study to detect a meaningful reduction of 250 ml of wine when consumed from smaller compared with larger bottles.

Trial registration

Open Science Framework (OSF):rmk43; May 23, 2017.
A Phytopharmacological review of a Mediterranean plant: Lavandula stoechas L
Authors: Ez zoubi Yassine , Bousta Dalila , Farah Abdellah
Published: February 2020

The Mediterranean region is characterized by a diverse vegetation cover, and theLavandulagenus is one of the most important medicinal and aromatic plants in this region. It has been used in traditional medicine as a treatment for anxiety and insomnia and to improve sleep quality for a long history. Lavender is commonly used in perfumes, soaps, bath powders, and scented sachets. It can flavor teas or food even at low concentrations. Several ethnopharmacological studies have demonstrated its use in treating several diseases; it has anti-inflammatory, antioxidant, antispasmodic, sedative, insecticidal, antimicrobial and antifungal activities. This paper reviews the geographical distribution, traditional uses, chemical composition, and pharmacological activities of theLavandula stoechas.
The development of PROmunication: a training-tool for clinicians using patient-reported outcomes to promote patient-centred communication in clinical cancer settings
Authors: Skovlund Pernille C. , Ravn Sissel , Seibaek Lene , Thaysen Henriette Vind , Lomborg Kirsten , Nielsen Berit Kjærside
Published: February 2020

Background

The value of using real-time patient-reported outcome (PRO) measures in cancer communication has gained attention both in the clinic and in research. Despite this, no internationally accepted guidelines or training programs for clinicians on how to engage in patient-centred communication based on PROs exist. Lack of training may complicate implementation and systematic use of PROs in the clinic. We aimed to develop a short and feasible manual and training session in PRO-based dialogue rooted in patient-centred communication, coined PROmunication.

Methods

PROmunication was implemented in two studies using PROs in different clinical cancer settings. We interviewed clinicians twice during the development phase. First, adopting a clinical perspective, they provided ideas for content, length and structure of the training session and the manual. Second, they approved the draft of the manual with minor adjustments on how to document clinician-patient communication. The final version of the PROmunication tool was built on clinicians’ input, theory on patient-centred communication, a literature review, and didactic considerations.

Results

The one-page manual gave clinicians a brief and clear overview of how to prepare for, undergo and document a PRO-based consultation. Illustrations and verbal phrases were offered to operationalize and facilitate patient-centred communication. The training session included elements like evidence-based knowledge about the rationale, benefits and challenges of using PROs and comprised theory, experimental training and instructions for the use of the manual in clinical practice. Ad hoc training and feedback in the clinic followed the training session.

Conclusions

This paper presents the development of a short, theory-driven manual and training session intended to support and engage clinicians in PRO-based dialogue leading to patient-centred communication. Further testing of the tool is necessary and adjustments may be required if the PROmunication tool should be applied in other clinical settings were patients are seen regularly. An evaluation of the tool is planned to be performed in future studies. Training in PROmunication may further systematic and consistent use of PRO data in the consultation, leading to patient-centred consultations and increased patient involvement.
The GhREV transcription factor regulate the development of shoot apical meristem in cotton (Gossypium hirsutum)
Authors: YANG Doudou , Jing AN , Fangjun LI , Egrinya ENEJI A. , Xiaoli TIAN , Zhaohu LI
Published: February 2020

Background

Manual topping is a routine agronomic practice for balancing the vegetative and reproductive growth of cotton (Gossypium hirsutum) in China, but its cost-effectiveness has decreased over time. Therefore, there is an urgent need to replace manual topping with new approaches, such as biological topping. In this study, we examined the function of GhREV transcription factors (a class III homeodomain-leucine zipper family, HD-ZIP III) in regulating the development of shoot apical meristem (SAM) in cotton with the purpose of providing candidate genes for biological topping of cotton in the future.

Results

We cloned four orthologous genes ofAtREVin cotton, namelyGhREV1,GhREV2,GhREV3, andGhREV4. All theGhREVsexpressed in roots, stem, leaves, and SAM. Compared withGhREV1andGhREV3, the expression level ofGhREV2andGhREV4was higher in the SAM. However, only GhREV2 had transcriptional activity. GhREV2 is localized in the nucleus; and silencing it via virus-induced gene silencing (VIGS) produced an abnormal SAM. Two key genes, GhWUSA10 and GhSTM, which involved in regulating the development of plant SAM, showed about 50% reduction in their transcripts in VIGS-GhREV2plants.

Conclusion

GhREV2 positively regulates the development of cotton SAM by regulatingGhWUSA10andGhSTM potentially.
Formulation and development of floating multiple-unit minitablets of Nimodipine without using a gas-generating agent: in vitro and in vivo characterization
Authors: Panda M. , Rao M. E. B. , Patra C. N. , Panda J. , Panigrahi K. C. , Patro G.
Published: February 2020

Background

Floating drug delivery systems have been reported for different active pharmaceutical ingredients as single-unit tablets with gas-generating agents. In this present research, the formulation of floating multiple-unit minitablets of Nimodipine without using gas-generating agent was attempted with an objective of increased residence time, sustain-release and improved oral bioavailability. Solid dispersion with different ratios (1:0.5, 1:1, 1:1.5, 1:2, 1:2.5) of drug with the lipophilic carrier such as Compritol ATO 888, Gelucire 43/01, G39/01 and Precirol ATO 05 was formulated using melt granulation technique. The adsorbent Sylysia 350 to lipophilic carrier is maintained at 1:1. The granules were compressed into minitablets weighing 15 mg and were filled into a ‘0’ size capsule.

Results

Differential scanning calorimetry study justified no interaction of the drug with excipients. The formulations which exhibited desirable flow property, floating lag time less than 1 min and floating time of 12 h were further characterized for various post-compression parameters. The optimized single-dose (capsule) of floating multiple-unit minitablets of Nimodipine consisting of 60 mg of drug, 120 mg of G43/01 and 120 mg of Sylysia 350 showed an average of floating lag time within 24.48 s, floating time of 14.32 h and sustained-release up to 12 h. Pharmacokinetic study of the optimized formulation (F9) showed nearly 2.5 times increase in area under the curve with increased residence time in comparison to aqueous suspension of Nimodipine. The stability study revealed no significant change in various parameters before and after storage.

Conclusion

Hence, gelucire 43/01-based multiple-unit minitablets of Nimodipine can be considered a promising approach for sustaining the drug release with gastric retention for 12 h without using gas-generating agent.