bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of metatarsal domes on plantar pressures in older people with a history of forefoot pain
Authors: Landorf Karl B. , Ackland Claire A. , Bonanno Daniel R. , Menz Hylton B. , Forghany Saeed 
Published: May 2020

AbstractBackgroundForefoot pads such as metatarsal domes are commonly used in clinical practice for the treatment of pressure‐related forefoot pain, however evidence for their effects is inconsistent. This study aimed to evaluate the effects on plantar pressures of metatarsal domes in different positions relative to the metatarsal heads.MethodsParticipants in this study included 36 community‐dwelling adults aged 65 or older with a history of forefoot pain. Standardised footwear was used and plantar pressures were measured using the pedar®‐X in‐shoe plantar pressure measurement system. Peak pressure, maximum force and contact area were analysed using an anatomically‐based masking protocol that included three forefoot mask sub‐areas (proximal to, beneath, and distal to the metatarsal heads). Data were collected for two different types of prefabricated metatarsal domes of different densities (Emsold metatarsal dome and Langer PPT metatarsal pad) in three different positions relative to the metatarsal heads. Seven conditions were tested in this study: (i) control (no pad) condition, (ii) Emsold metatarsal dome positioned 5 mm proximal to the metatarsal heads, (iii) Emsold metatarsal dome positioned in‐line with the metatarsal heads, (iv), Emsold metatarsal dome positioned 5 mm distal to the metatarsal heads, (v) Langer PPT metatarsal pad positioned 5 mm proximal to the metatarsal heads, (vi) Langer PPT metatarsal pad positioned in‐line with the metatarsal heads, and (vii) Langer PPT metatarsal pad positioned 5 mm distal to the metatarsal heads.ResultsWhen analysed with the mask that was distal to the metatarsal heads, where the plantar pressure readings were at their highest, all metatarsal dome conditions led to significant reductions in plantar pressure at the forefoot compared to the control (no pad) condition (F3.9, 135.6 = 8.125, p < 0.001). The reductions in plantar pressure were in the order of 45–60 kPa. Both the Emsold metatarsal dome and the Langer PPT metatarsal pad, when positioned proximal to the metatarsal heads, managed to achieve this without adversely increasing plantar pressure proximally where the pad was positioned, however the Emsold metatarsal dome was most effective.ConclusionsMetatarsal domes reduce plantar pressure in the forefoot in older people with a history of forefoot pain. All metatarsal dome conditions significantly reduced peak pressure in the forefoot, however metatarsal domes that were positioned 5 mm proximal to the metatarsal heads provided the best balance of reducing plantar pressure distal to the metatarsal heads, where the pressure is at its greatest, but not adversely increasing plantar pressure proximally, where the bulk of the pad is positioned. In this proximal position, the Emsold metatarsal dome was more effective than the Langer PPT metatarsal pad and we cautiously recommend this forefoot pad for alleviating forefoot pressure in older people with forefoot pain.
Pretreatment thrombocytosis as an independent predictive factor for chemoresistance and poor survival in epithelial ovarian cancer
Authors: Nakao Sari , Minaguchi Takeo , Itagaki Hiroya , Hosokawa Yoshihiko , Shikama Ayumi , Tasaka Nobutaka , Akiyama Azusa , Ochi Hiroyuki , Matsumoto Koji , Satoh Toyomi 
Published: May 2020

Abstract
Background
Thrombocytosis is related to tumor stage and survival in ovarian cancer in addition to the common complications of malignant diseases, such as anemia and inflammation. The aim of our study was to clarify the precise prognostic impact of pretreatment thrombocytosis in epithelial ovarian cancer.

Methods
We retrospectively analyzed 280 consecutive patients who were treated for epithelial ovarian cancer at our institution between 2001 and 2011.

Results
Pretreatment thrombocytosis was observed in 18.9% of all patients and was associated with advanced FIGO stage, primary treatment, operation achievement, histologic subtype, microcytic hypochromic anemia (MHA), and nonmalignant inflammatory condition (P = 0.0018, 0.0028, 0.00050, 0.034, 0.00090 and 0.0022). In the patients who relapsed after primary adjuvant chemotherapy (n = 126), thrombocytosis was associated with a shorter treatment-free interval (TFI) (P = 0.0091). The univariate and multivariate analyses revealed that thrombocytosis was independently associated with TFI and MHA (P = 0.021 and 0.0091). Patients with thrombocytosis had worse progression-free survival (PFS) and overall survival (OS) than those without thrombocytosis (P <  0.0001 and <  0.0001). The multivariate analyses for prognostic factors demonstrated that thrombocytosis was significant for poor PFS and OS (P = 0.0050 and 0.022) independent of stage, histology, primary treatment, operation achievement, nonmalignant inflammatory condition and MHA.

Conclusions
The current findings indicate that the detrimental survival impact of pretreatment thrombocytosis in epithelial ovarian cancer may be independent of tumor extent but rather attributed to chemoresistance, further supporting the therapeutic potential of targeting thrombopoietic cytokines in the disease.
Heating, ventilation and air conditioning (HVAC) in intensive care unit
Authors: Saran Sai , Gurjar Mohan , Baronia Arvind , Sivapurapu Vijayalakshmi , Ghosh Pralay S. , Raju Gautham M. , Maurya Indubala 
Published: May 2020

AbstractThe aim of this review is to describe variation in standards and guidelines on ‘heating, ventilation and air-conditioning (HVAC)’ system maintenance in the intensive care units, across the world, which is required to maintain good ‘indoor air quality’ as an important non-pharmacological strategy in preventing hospital-acquired infections. An online search and review of standards and guidelines published by various societies including American Institute of Architects (AIA), American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE), Centers for Disease Control and Prevention (CDC), Department of Health Estates and Facilities Division, Health Technical Memorandum 2025 (HTM) and Healthcare Infection Control Practices Advisory Committee (HICPAC) along with various national expert committee consensus statements, regional and hospital-based protocols available in a public domain were retrieved. Selected publications and textbooks describing HVAC structural aspects were also reviewed, and we described the basic structural details of HVAC system as well as variations in the practised standards of HVAC system in the ICU, worldwide. In summary, there is a need of universal standards for HVAC system with a specific mention on the type of ICU, which should be incorporated into existing infection control practice guidelines.
Quantitative stain-free imaging and digital profiling of collagen structure reveal diverse survival of triple negative breast cancer patients
Authors: Gole Laurent , Yeong Joe , Lim Jeffrey Chun Tatt , Ong Kok Haur , Han Hao , Thike Aye Aye , Poh Yong Cheng , Yee Sidney , Iqbal Jabed , Hong Wanjin , Lee Bernett , Yu Weimiao , Tan Puay Hoon 
Published: May 2020

Abstract
Background
Stromal and collagen biology has a significant impact on tumorigenesis and metastasis. Collagen is a major structural extracellular matrix component in breast cancer, but its role in cancer progression is the subject of historical debate. Collagen may represent a protective layer that prevents cancer cell migration, while increased stromal collagen has been demonstrated to facilitate breast cancer metastasis.

Methods
Stromal remodeling is characterized by collagen fiber restructuring and realignment in stromal and tumoral areas. The patients in our study were diagnosed with triple-negative breast cancer in Singapore General Hospital from 2003 to 2015. We designed novel image processing and quantification pipelines to profile collagen structures using numerical imaging parameters. Our solution differentiated the collagen into two distinct modes: aggregated thick collagen (ATC) and dispersed thin collagen (DTC).

Results
Extracted parameters were significantly associated with bigger tumor size and DCIS association. Of numerical parameters, ATC collagen fiber density (CFD) and DTC collagen fiber length (CFL) were of significant prognostic value for disease-free survival and overall survival for the TNBC patient cohort. Using these two parameters, we built a predictive model to stratify the patients into four groups.

Conclusions
Our study provides a novel insight for the quantitation of collagen in the tumor microenvironment and will help predict clinical outcomes for TNBC patients. The identified collagen parameters, ATC CFD and DTC CFL, represent a new direction for clinical prognosis and precision medicine. We also compared our result with benign samples and DICS samples to get novel insight about the TNBC heterogeneity. The improved understanding of collagen compartment of TNBC may provide insights into novel targets for better patient stratification and treatment.
Where do we go from here? – Opportunities and barriers to the career development of trial managers: a survey of UK-based trial management professionals
Authors:   on behalf of the UK Trial Managers’ Network Executive Group, Mitchell Eleanor , Goodman Kirsteen , Hartley Suzanne , Hickey Helen , McDonald Alison M. , Meadows Helen M. , Rhodes Shelley , Taylor Jodi , Wakefield Natalie , Farrell Barbara 
Published: May 2020

Abstract
Background
Clinical trials commonly have a dedicated trial manager and effective trial management is essential to the successful delivery of high-quality trials. Trial managers have diverse experience and currently there is no standardised structured career pathway. The UK Trial Managers’ Network (UKTMN) surveyed its members to understand what is important to them with respect to career development since this would be important in the development of any initiative intended to develop a skilled workforce.

Methods
We conducted an online survey of UKTMN members, who are trial management professionals, working on academic-led trials in the UK. Members were asked what they perceive as opportunities and barriers to career development. Two reminders were sent to facilitate completion of the survey, and responders were offered the opportunity to enter a prize draw for waived fees at the UKTMN annual meeting. Data were analysed descriptively by using Stata (version 15.1), and free-text responses were reviewed for themes.

Results
The survey was sent to 819 UKTMN members; 433 responses were received, although 13 were from non-UKTMN members; thus 420 respondents' data were included in analyses. Respondents were representative of UKTMN membership; however, more responses were received by trial managers based in registered clinical trials units (CTUs). The top three opportunities for career development were (i) training, (ii) helping design trials and (iii) undertaking relevant qualifications. The top three barriers were (i) funding, (ii) few opportunities to get involved in development activities aside from managing a trial and (iii) unclear organisational career pathway. Almost all respondents (401/420, 95.4%) considered career development either very or quite important. Although all respondents had a day-to-day role in managing trials, there was huge disparity between job titles.

Conclusion
Career development is important to trial managers yet there is a lack of a structured pathway. The enablers and disablers to career development for trial managers should be clearly considered by the clinical trial community and, in particular, employers, sponsors and funders in order to develop a highly skilled workforce of trial managers, who are key to the delivery of trials.
Acyl-lipid desaturases and Vipp1 cooperate in cyanobacteria to produce novel omega-3 PUFA-containing glycolipids
Authors: Poole Leslie B. , Parsonage Derek , Sergeant Susan , Miller Leslie R. , Lee Jingyun , Furdui Cristina M. , Chilton Floyd H. 
Published: May 2020

Abstract
Background
Dietary omega-3 (n-3), long chain (LC-, ≥ 20 carbons), polyunsaturated fatty acids (PUFAs) derived largely from marine animal sources protect against inflammatory processes and enhance brain development and function. With the depletion of natural stocks of marine animal sources and an increasing demand for n-3 LC-PUFAs, alternative, sustainable supplies are urgently needed. As a result, n-3 18-carbon and LC-PUFAs are being generated from plant or algal sources, either by engineering new biosynthetic pathways or by augmenting existing systems.

Results
We utilized an engineered plasmid encoding two cyanobacterial acyl-lipid desaturases (DesB and DesD, encoding Δ15 and Δ6 desaturases, respectively) and “vesicle-inducing protein in plastids” (Vipp1) to induce production of stearidonic acid (SDA, 18:4 n-3) at high levels in three strains of cyanobacteria (10, 17 and 27% of total lipids in Anabaena sp. PCC7120, Synechococcus sp. PCC7002, and Leptolyngbya sp. strain BL0902, respectively). Lipidomic analysis revealed that in addition to SDA, the rare anti-inflammatory n-3 LC-PUFA eicosatetraenoic acid (ETA, 20:4 n-3) was synthesized in these engineered strains, and ~ 99% of SDA and ETA was complexed to bioavailable monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) species. Importantly, novel molecular species containing alpha-linolenic acid (ALA), SDA and/or ETA in both acyl positions of MGDG and DGDG were observed in the engineered Leptolyngbya and Synechococcus strains, suggesting that these could provide a rich source of anti-inflammatory molecules.

Conclusions
Overall, this technology utilizes solar energy, consumes carbon dioxide, and produces large amounts of nutritionally important n-3 PUFAs and LC-PUFAs. Importantly, it can generate previously undescribed, highly bioavailable, anti-inflammatory galactosyl lipids. This technology could therefore be transformative in protecting ocean fisheries and augmenting the nutritional quality of human and animal food products.
Microbial community dynamics in mesophilic and thermophilic batch reactors under methanogenic, phenyl acid-forming conditions
Authors: Prem Eva Maria , Stres Blaz , Illmer Paul , Wagner Andreas Otto 
Published: May 2020

Abstract
Background
Proteinaceous wastes exhibit high theoretical methane yields and their residues are considered valuable fertilisers. The routine anaerobic degradation of proteins often raises problems like high aromatic compound concentrations caused by the entry of aromatic amino acids into the system. A profound investigation of the consequences of aromatic compound exposure on various microorganisms, which cascade-like and interdependently degrade complex molecules to biogas, is still pending.

Results
In mesophilic samples, methane was predominantly produced via acetoclastic methanogenesis. The highest positive correlation was observed between phenylacetate (PAA) and Psychrobacter spp. and between phenylpropionate (PPA) and Haloimpatiens spp. Moreover, Syntrophus spp. negatively correlated with PAA (Spearman’s rank correlations coefficient (rs) = − 0.46, p < 0.05) and PPA concentrations (rs = − 0.44, p < 0.05) and was also associated with anaerobic benzene ring cleavage. In thermophilic samples, acetate was predominantly oxidised by Tepidanaerobacter spp. or Syntrophaceticus spp. in syntrophic association with a hydrogenotrophic methanogen. The genera Sedimentibacter and Syntrophaceticus correlated positively with both PAA and PPA concentrations. Moreover, Sedimentibacter spp., Tepidanaerobacter spp., Acetomicrobium spp., and Sporanaerobacter spp. were significant LEfSe (linear discriminant analysis effect size) biomarkers for high meso- as well as thermophilic phenyl acid concentrations. Direct negative effects of phenyl acids on methanogenic properties could not be proven.

Conclusions
Anaerobic phenyl acid formation is not restricted to specific microbial taxa, but rather done by various meso- and thermophilic bacteria. The cleavage of the highly inert benzene ring is possible in methanogenic batch reactors—at least in mesophilic fermentation processes. The results indicated that phenyl acids rather affect microorganisms engaged in preceding degradation steps than the ones involved in methanogenesis.
Impact of deltamethrin selection on kdr mutations and insecticide detoxifying enzymes in Aedes aegypti from Mexico
Authors: Contreras-Perera Yamili , Ponce-Garcia Gustavo , Villanueva-Segura Karina , Lopez-Monroy Beatriz , Rodríguez-Sanchez Iram P. , Lenhart Audrey , Manrique-Saide Pablo , Flores Adriana E. 
Published: May 2020

Abstract
Background
Insecticide resistance is a serious problem for vector control programmes worldwide. Resistance is commonly attributed to mutations at the insecticide’s target site or increased activity of detoxification enzymes.

Methods
We determined the knockdown concentration (KC50) and lethal concentration (LC50) of deltamethrin in six natural populations of adult Aedes aegypti from southeastern Mexico. These populations were then selected over five generations using the LC50 from the preceding generation that underwent selection, and the heritability of deltamethrin resistance was quantified. For each generation, we also determined the frequency of the kdr alleles L410, I1016 and C1534, and the levels of activity of three enzyme families (α- and β-esterases, mixed-function oxidases and glutathione S-transferases (GST)) associated with insecticide detoxification.

Results
There was an increase in KC50 and LC50 values in the subsequent generations of selection with deltamethrin (FS5vs FS0). According to the resistance ratios (RRs), we detected increases in LC50 ranging from 1.5 to 5.6 times the values of the parental generation and in KC50 ranging from 1.3–3.8 times the values of the parental generation. Triple homozygous mutant individuals (tri-locus, LL/II/CC) were present in the parental generations and increased in frequency after selection. The frequency of L410 increased from 1.18-fold to 2.63-fold after selection with deltamethrin (FS5vs FS0) in the populations analyzed; for I1016 an increase between 1.19-fold to 2.79-fold was observed, and C1534 was fixed in all populations after deltamethrin selection. Enzymatic activity varied significantly over the generations of selection. However, only α- esterase activity remained elevated in multiple populations after five generations of deltamethrin selection. We observed an increase in the mean activity levels of GSTs in two of the six populations analyzed.

Conclusions
The high levels of resistance and their association with high frequencies of kdr mutations (V410L, V1016I and F1534C) obtained through artificial selection, suggest an important role of these mutations in conferring resistance to deltamethrin. We highlight the need to implement strategies that involve the monitoring of kdr frequencies in insecticide resistance monitoring and management programmes.
Chagas vectors Panstrongylus chinai (Del Ponte, 1929) and Panstrongylus howardi (Neiva, 1911): chromatic forms or true species?
Authors: Villacís Anita G. , Dujardin Jean-Pierre , Panzera Francisco , Yumiseva César A. , Pita Sebastián , Santillán-Guayasamín Soledad , Orozco Marco I. , Mosquera Katherine D. , Grijalva Mario J. 
Published: May 2020

Abstract
Background
Chagas disease is a parasitic infection transmitted by “kissing bugs” (Hemiptera: Reduviidae: Triatominae) that has a huge economic impact in Latin American countries. The vector species with the upmost epidemiological importance in Ecuador are Rhodnius ecuadoriensis (Lent & Leon, 1958) and Triatoma dimidiata (Latreille, 1811). However, other species such as Panstrongylus howardi (Neiva, 1911) and Panstrongylus chinai (Del Ponte, 1929) act as secondary vectors due to their growing adaptation to domestic structures and their ability to transmit the parasite to humans. The latter two taxa are distributed in two different regions, they are allopatric and differ mainly by their general color. Their relative morphological similarity led some authors to suspect that P. chinai is a melanic form of P. howardi.

Methods
The present study explored this question using different approaches: antennal phenotype; geometric morphometrics of heads, wings and eggs; cytogenetics; molecular genetics; experimental crosses; and ecological niche modeling.

Results
The antennal morphology, geometric morphometrics of head and wing shape and cytogenetic analysis were unable to show distinct differences between the two taxa. However, geometric morphometrics of the eggs, molecular genetics, ecological niche modeling and experimental crosses including chromosomal analyses of the F1 hybrids, in addition to their coloration and current distribution support the hypothesis that P. chinai and P. howardi are separate species.

Conclusions
Based on the evidence provided here, P. howardi and P. chinai should not be synonymized. They represent two valid, closely related species.
Safety and efficacy of a new spot-on formulation of selamectin plus sarolaner in the treatment and control of naturally occurring flea infestations in cats presented as veterinary patients in Australia
Authors: Packianathan Raj , Pittorino Melissa , Hodge Andrew , Bruellke Natalie , Graham Kelly 
Published: May 2020

Abstract
Background
The safety and efficacy of a new spot-on formulation of selamectin plus sarolaner were evaluated for the treatment and control of natural flea infestations on cats in two non-randomised, multi-centre clinical trials conducted in 8 different locations in Queensland, Australia.

Methods
One hundred and four cats from 65 different households were enrolled across the two studies. Demographic characteristics of cats in the two studies were similar. The new spot-on formulation of selamectin and sarolaner was administered topically once a month for 3 consecutive months at a minimum dosage of 6 mg/kg selamectin (dose range 6–12 mg/kg) plus 1 mg/kg sarolaner (dose range 1–2 mg/kg). Cats were dosed on Days 0 (pre-treatment), 30 and 60 and physical examinations and flea counts were conducted on Days 0, 30, 60 and 90. Efficacy assessments were based on the percentage reduction in live flea counts post-treatment compared to Day 0.

Results
In Study A, at enrolment, primary cats had flea counts ranging from 6 to 107 (arithmetic mean 21.0). The selamectin and sarolaner spot-on formulation resulted in arithmetic mean efficacy of 98.0%, 100% and 100% on Days 30, 60 and 90, respectively. In Study B, at enrolment, primary cats had flea counts ranging from 6 to 22 (arithmetic mean 10.0). The selamectin and sarolaner spot-on formulation resulted in arithmetic mean efficacy of 99.7%, 100% and 100% on Days 30, 60 and 90, respectively.

Conclusions
The new spot-on formulation of selamectin plus sarolaner topically administered at monthly intervals at the minimum dosage of 6.0 mg/kg selamectin and 1.0 mg/kg sarolaner was safe and highly effective against natural infestations of fleas under a range of geographical conditions, representative of both tropical and subtropical regions of Australia.