bluuebunny/crossref_metadata_2025 huggingface dataset:
A modified proximally based nail bed flap approach for benign subungual bone tumors in the distal phalanx
Authors: Hong Seok Woo , Kim Jihyeung , Jang Seonpyo , Lee Min Ho , Gong Hyun Sik , Baek Goo Hyun
Published: November 2019

Background:

Complete tumor removal and damaged nail bed repair are critical factors that determine the success of subungual tumor excision. We examined a modified proximally based nail bed flap approach for excision of subungual bone tumors of the distal phalanx and present cases where this approach was used, along with postoperative functional and cosmetic outcomes.

Methods:

Twenty-four benign subungual bone tumors, identified from 23 patients (9 males and 14 females), were included in this study. All patients underwent tumor excision by the modified proximally based nail bed flap approach. Pain was assessed using a numeric rating scale, and cosmesis was self-assessed using a visual analog scale preoperatively and 1 year postoperatively. We measured sensation of the involved digit tip, relative to opposite-side sensation, using static and moving two-point discrimination and Semmes–Weinstein monofilament tests 1 year postoperatively. Lastly, we assessed postoperative nail deformities and tumor recurrence as potential surgical complications.

Results:

Mean pain severity and cosmesis were significantly improved 1 year postoperatively. There were no significant differences in the digit tip sensation between the involved and the opposite-side digits 1 year postoperatively. We observed one case of tumor recurrence and four cases of postoperative nail deformities.

Conclusions:

The modified proximally based nail bed flap approach showed satisfactory functional and cosmetic outcomes. This approach enables a low rate of recurrence after removal of benign subungual bone tumors in the short term and cosmetically superior nail bed repair. Level of evidence: Therapeutic, IV
The rise and fall of biodiversity offsetting in the Lodge Hill large-scale housing development, South East England
Authors: Bormpoudakis Dimitrios , Tzanopoulos Joseph , Apostolopoulou Evangelia
Published: November 2019

In this paper, we aim to shed light on the geographies that led both to the selection of Lodge Hill for the construction of a large-scale housing development and to the subsequent attempt to use biodiversity offsetting to compensate for its environmental impacts. We draw on extensive fieldwork from 2012 to 2016, and diverge from previous studies on offsetting by focusing less on issues related to metrics and governance and shifting our analytic attention to the economic and urban geographies surrounding the Lodge Hill case. We argue that this approach can offer not only an empirically grounded account of why offsetting is being selected to address the impacts of specific urban development projects, but also an in-depth understanding of the factors that determine offsetting’s actual implementation on the ground. Viewing the Lodge Hill case through the frame of urbanization allows us to better grasp the how, why and when particular alliances of actors contest and/or support the implementation of biodiversity offsetting. Our analytical lens also helps exposing the fragility of neoliberal natures and the roles inter-capitalist competition and species biology and ecology can play on the success or failure of neoliberal policies.
MoMI-G: modular multi-scale integrated genome graph browser
Authors: Yokoyama Toshiyuki T. , Sakamoto Yoshitaka , Seki Masahide , Suzuki Yutaka , Kasahara Masahiro
Published: November 2019

Background

Genome graph is an emerging approach for representing structural variants on genomes with branches. For example, representing structural variants of cancer genomes as a genome graph is more natural than representing such genomes as differences from the linear reference genome. While more and more structural variants are being identified by long-read sequencing, many of them are difficult to visualize using existing structural variants visualization tools. To this end, visualization method for large genome graphs such as human cancer genome graphs is demanded.

Results

We developed MOdular Multi-scale Integrated Genome graph browser, MoMI-G, a web-based genome graph browser that can visualize genome graphs with structural variants and supporting evidences such as read alignments, read depth, and annotations. This browser allows more intuitive recognition of large, nested, and potentially more complex structural variations. MoMI-G has view modules for different scales, which allow users to view the whole genome down to nucleotide-level alignments of long reads. Alignments spanning reference alleles and those spanning alternative alleles are shown in the same view. Users can customize the view, if they are not satisfied with the preset views. In addition, MoMI-G has Interval Card Deck, a feature for rapid manual inspection of hundreds of structural variants. Herein, we describe the utility of MoMI-G by using representative examples of large and nested structural variations found in two cell lines, LC-2/ad and CHM1.

Conclusions

Users can inspect complex and large structural variations found by long-read analysis in large genomes such as human genomes more smoothly and more intuitively. In addition, users can easily filter out false positives by manually inspecting hundreds of identified structural variants with supporting long-read alignments and annotations in a short time.

Software availability

MoMI-G is freely available athttps://github.com/MoMI-G/MoMI-Gunder the MIT license.
The midline approach for endotracheal intubation using GlideScope video laryngoscopy could provide better glottis exposure in adults: a randomized controlled trial
Authors: Jiang Lianxiang , Qiu Shulin , Zhang Peng , Yao Weidong , Chang Yan , Dai Zeping
Published: November 2019

Background

Previous studies have demonstrated that the common laryngoscopic approach (right-sided) and midline approach are both used for endotracheal intubation by direct laryngoscopy. Although the midline approach is commonly recommended for video laryngoscopy (VL) in the clinic, there is a lack of published evidences to support this practice. This study aimed to evaluate the effects of different video laryngoscopic approaches on intubation.

Methods

Two hundred sixty-two patients aged 18 years who underwent elective surgery under general anaesthesia and required endotracheal intubation were included in the present prospective, randomized, controlled study. The participants were randomly and equally allocated to the right approach (Group R) or midline approach (Group M). All the intubations were conducted by experienced anaesthetists using GlideScope video laryngoscopy. The primary outcomes were Cormack-Lehane laryngoscopic views (CLVs) and first-pass success (FPS) rates. The secondary outcomes were the time to glottis exposure, time to tracheal intubation, haemodynamic responses and other adverse events. Comparative analysis was performed between the groups.

Results

Finally, 262 patients completed the study, and all the tracheas were successfully intubated. No significant differences were observed in the patient characteristics and airway assessments (P > 0.05). Compared with Group R, Group M had a better CLV (χ2 = 14.706, P = 0.001) and shorter times to glottis exposure (8.82 ± 2.04 vs 12.38 ± 1.81; t = 14.94; P < 0.001) and tracheal intubation (37.19 ± 5.01 vs 45.23 ± 4.81; t = 13.25; P < 0.001), but no difference was found in the FPS rate (70.2% vs 71.8%; χ2 = 0.074; P = 0.446) and intubation procedure time (29.86 ± 2.56 vs 30.46 ± 2.97, t = 1.75, P = 0.081). Between the groups, the rates of hoarseness or sore throat, minor injury, hypoxemia and changes in SBP and HR showed no significant difference (P > 0.05).

Conclusion

Although the FPS rate did not differ based on the laryngoscopic approach, the midline approach could provide better glottis exposure and shorter times to glottis exposure and intubation. The midline approach should be recommended for teaching in VL-assisted endotracheal intubation.

Trial registration

The study was registered on May 18, 2019 in the Chinese Clinical Trial Registry (ChiCTR1900023252).
European Medicines Agency Policy 0070: an exploratory review of data utility in clinical study reports for academic research
Authors: Ferran Jean-Marc , Nevitt Sarah J.
Published: November 2019

Background

Clinical study reports (CSRs) have been increasingly utilised within academic research in recent years. European Medicines Agency (EMA) Policy 0070 ‘Phase 1,’ which came into effect in January 2015, requires the publication of regulatory documents such as CSRs from central applications in an anonymised format. EMA Policy 0070 requires sponsors to demonstrate careful consideration of data utility within anonymised CSRs published within the scope of the policy, yet the concept of data utility is not clearly defined in the associated anonymisation guidance.

Objective

To review the use of data from CSRs in published academic research and to hypothesise the potential data utility of CSRs anonymised under the objectives of EMA Policy 0070 for future academic research.

Methods

Review of the objectives, research methodologies and findings of academic research reports using unpublished data from CSRs (prior to EMA Policy 0070). Semi-structured interviews with authors of academic research reports, including questions related to data utility of anonymised CSRs published under EMA Policy 0070.

Results

Thirteen academic research reports were identified and reviewed. The research purposes ranged from assessment of reporting bias, comparison of methods and results with published data sources, detailed evaluation of harms and adverse events, re-analysis and novel analyses including systematic reviews and meta-analysis. All of the examples identified required access to the methods and results sections of CSRs (including aggregated summary tables) and research purposes relating to evaluation of adverse events also required access to participant narratives. Retaining anonymised participant narratives relating to interventions, findings and events, while maintaining an acceptably low risk of participant re-identification, may provide an important gain in data utility and further understanding of drug safety profiles.

Conclusions

This work provides an initial insight into the previous use of CSR data and current practices for including regulatory data in academic research. This work also provides early guidance to qualitatively assess and document data utility within anonymised CSRs published under EMA Policy 0070.
Primary diffuse meningeal melanomatosis – a rare form of meningeal melanoma: case report
Authors: Garbacz Tomasz , Osuchowski Michał , Bartosik-Psujek Halina
Published: November 2019

Background

Meningeal melanomatosis is a rare type of central nervous system neoplasm (with incidence ranging between 3 and 5%) that develops in the course of malignant melanoma. In a small percentage of cases, meningeal melanomatosis may develop without a primary focus. It affects the leptomeninx. The clinical activity of the disease is uncharacteristic, with a number of neurological symptoms developing over weeks or months.

Case presentation

A 45-year-old male patient presented with consciousness disturbance, cognitive dysfunctions, seizures and progressive paresis. None of the examinations performed, including cerebrospinal fluid examination, neuroimaging and biopsy of the leptomeninges, permitted us to establish a diagnosis during the patient’s hospital stay. The diagnosis of meningeal melanomatosis was established after an autopsy had been carried out.

Conclusions

In the absence of unequivocal test results, it is also worth taking into account the primary changes in the leptomeninx, including those caused by melanoma.
Multimodal lifestyle intervention using a web-based tool to improve cardiometabolic health in patients with serious mental illness: results of a cluster randomized controlled trial (LION)
Authors: Looijmans Anne , Jörg Frederike , Bruggeman Richard , Schoevers Robert A. , Corpeleijn Eva
Published: November 2019

Background

Unhealthy lifestyle behaviours contribute to alarming cardiometabolic risk in patients with serious mental illness (SMI). Evidence-based practical lifestyle tools supporting patients and staff in improving patient lifestyle are lacking.

Methods

This multi-site randomized controlled pragmatic trial determined the effectiveness of a twelve-month multimodal lifestyle approach, including a web-based tool to improve patients’ cardiometabolic health, versus care-as-usual. Using the web tool, nurses (trained in motivational interviewing) assisted patients in assessing their lifestyle behaviours, creating a risk profile and constructing lifestyle goals, which were discussed during fortnightly regular care visits. Twenty-seven community-care and sheltered-living teams were randomized into intervention (N = 17) or control (N = 10) groups, including 244 patients (140 intervention/104 control, 49.2% male, 46.1 ± 10.8 years) with increased waist circumference (WC), BMI or fasting glucose. The primary outcomes concerned differences in WC after six and twelve months intervention, while BMI and metabolic syndrome Z-score were secondary outcome measures.

Results

General multilevel linear mixed models adjusted for antipsychotic medication showed that differences in WC change between intervention and control were − 0.15 cm (95%CI: − 2.49; 2.19) after six and − 1.03 cm (95%CI: − 3.42; 1.35) after twelve months intervention; however, the differences were not statistically significant. No intervention effects were found for secondary outcome measures. The intervention increased patients’ readiness to change dietary behaviour.

Conclusion

A multimodal web-based intervention facilitating nurses to address lifestyle changes in SMI patients did not improve patient cardiometabolic health. Web-tool use was lower than expected and nurses need more lifestyle coaching knowledge and skills. The type of intervention and delivery mode need optimization to realize effective lifestyle care for SMI patients.

Trial registration

Dutch Trial Registry,www.trialregister.nl, NTR3765, 21 December 2012.
Rural vs urban residence and experience of discrimination among people with severe mental illnesses in Ethiopia
Authors: Forthal Sarah , Fekadu Abebaw , Medhin Girmay , Selamu Medhin , Thornicroft Graham , Hanlon Charlotte
Published: November 2019

Background

Few studies have addressed mental illness-related discrimination in low-income countries, where the mental health treatment gap is highest. We aimed to evaluate the experience of discrimination among persons with severe mental illnesses (SMI) in Ethiopia, a low-income, rapidly urbanizing African country, and hypothesised that experienced discrimination would be higher among those living in a rural compared to an urban setting.

Methods

The study was a cross-sectional survey of a community-ascertained sample of people with SMI who underwent confirmatory diagnostic interview. Experienced discrimination was measured using the Discrimination and Stigma Scale (DISC-12). Zero-inflated negative binomial regression was used to estimate the effect of place of residence (rural vs. urban) on discrimination, adjusted for potential confounders.

Results

Of the 300 study participants, 63.3% had experienced discrimination in the previous year, most commonly being avoided or shunned because of mental illness (38.5%). Urban residents were significantly more likely to have experienced unfair treatment from friends (χ2(1) = 4.80; p = 0.028), the police (χ2(1) =11.97; p = 0.001), in keeping a job (χ2(1) = 5.43; p = 0.020), and in safety (χ2(1) = 5.00; p = 0.025), and had a significantly higher DISC-12 score than those living in rural areas (adjusted risk ratio: 1.66; 95% CI: 1.18, 2.33).

Conclusions

Persons with SMI living in urban settings report more experience of discrimination than their rural counterparts, which may reflect a downside of wider social opportunities in urban settings. Initiatives to expand access to mental health care should consider how social exclusion can be overcome in different settings.
Addressing context to understand physical activity among Muslim university students: the role of gender, family, and culture
Authors: Aljayyousi Ghadir Fakhri , Abu Munshar Maher , Al-Salim Farid , Osman El Rayah
Published: November 2019

Background

Physical inactivity is a crucial risk factor for the development of chronic health issues, which have a high incidence among Arabs living in the Gulf Cooperation Council (GCC) countries. The Qatar Stepwise Survey 2012 reported that approximately 44% of young adults 18–44 years of age had insufficient levels of physical activity. Family is a powerful source of information and socialization for adolescents and has a strong influence on their attitudes, decision-making, and behaviors.

Methods

The purpose of this study is to understand how university students’ physical activity can be influenced by sociocultural factors, particularly family health values and Muslim Arab culture. Using the criterion sampling strategy, 20 undergraduate Muslim students (Female students =10, Male students = 10) aged from 18 to 23 years who were Qatari or born and also raised in Qatar were recruited and interviewed. Participants were asked if they consider themselves active or not, about their perception of family health values regarding physical activity and the factors shaping these values, and the influence of family values on their physical activity behavior. The interviews were transcribed verbatim, coded, and analyzed following inductive analysis.

Results

The majority of the participants were influenced by their family health values, which were shaped by Qatari culture and the culture of origin for non-Qatari and were implicitly shaped by Islam. Participants reported that their role models of physical activity were males (fathers and male siblings), a health condition will motivate their families to be physically active,and families give priority to work and academic achievement over physical activity. A few participants showed that there was explicit influence of Islam on their physical activity, because culture’s influence was veiling religion’s. Culture was seen as a facilitator for physical activity from the males’ perspectives, which was not the case for female participants who reported the negative influence of culture on their physical activity because of the limited choices available for them. Non-Qatari students revealed that their culture of origin (such as Syria, Palestine, Egypt, Somalia, Bangladesh, Sudan, Pakistan and India) was the dominant factor in shaping their family health values.

Conclusions

The findings address gaps in the literature about families’ health values regarding physical activity in Qatar, the influence of the different ecologies surrounding these values, and the physical activity behaviors of university students. Knowledge about these factors can aid in the development of family-based interventions designed to motivate adolescents to be physically active, which should be religion- and culture-tailored.
Health-related quality of life and its socio-economic and cultural predictors among advanced cancer patients: evidence from the APPROACH cross-sectional survey in Hyderabad-India
Authors: Jacob Jean , Palat Gayatri , Verghese Naina , Chandran Priya , Rapelli Vineela , Kumari Sanjeeva , Malhotra Chetna , Teo Irene , Finkelstein Eric , Ozdemir Semra
Published: November 2019

Background

Patients with advanced cancer often experience poor health-related quality-of-life (HRQoL) due to cancer and treatment-related side-effects. With India’s palliative care landscape in its infancy, there is a concern that advanced cancer patients, especially individuals who are from disadvantaged populations experience poor HRQoL outcomes. We aim to assess HRQoL of advanced cancer patients in terms of general well-being (physical, functional, emotional, and social/family well-being), pain experiences, psychological state, and spiritual well-being, and determine the relationship between belonging to a disadvantaged group and HRQoL outcomes. We hypothesize that patients from disadvantaged or minority backgrounds, identified in this paper as financially distressed, female, lower years of education, lower social/family support, minority religions, and Non-General Castes, would be associated with worse HRQoL outcomes compared to those who are not from a disadvantaged group.

Methods

We administered a cross-sectional survey to 210 advanced cancer patients in a regional cancer center in India. The questionnaire included standardized instruments for general well-being (FACT-G), pain experiences (BPI), psychological state (HADS), spiritual well-being (FACT-SP); socio-economic and demographic characteristics.

Results

Participants reported significantly lower general well-being (mean ± SD) (FACT-G = 62.4 ± 10.0) and spiritual well-being (FACT-SP = 32.7 ± 5.5) compared to a reference population of cancer patients in the U.S. Patients reported mild to moderate pain severity (3.2 ± 1.8) and interference (4.0 ± 1.6), normal anxiety (5.6 ± 3.1) and borderline depressive symptoms (9.7 ± 3.3). Higher financial difficulty scores predicted most of the HRQoL domains (p ≤ 0.01), and being from a minority religion predicted lower physical well-being (p ≤ 0.05) and higher pain severity (p ≤ 0.05). Married women reported lower social/family well-being (p ≤ 0.05). Pain severity and interference were significant predictors of most HRQoL domains.

Conclusions

Advanced cancer patients, especially those with lower financial well-being and belonging to minority religions, reported low physical, functional, emotional, social/family, and spiritual well-being, and borderline depressive symptoms. Future studies should be directed at developing effective interventions supporting vulnerable groups such as those with financial distress, and those belonging to minority religions.
A childhood immunization education program for parents delivered during late pregnancy and one-month postpartum: a randomized controlled trial
Authors: Otsuka-Ono Hiroko , Hori Narumi , Ohta Hiroshi , Uemura Yukari , Kamibeppu Kiyoko
Published: November 2019

Background

Improved immunization rates have reduced the incidence of vaccine-preventable diseases (VPDs) in advanced nations. Japan’s unique vaccination system classifies vaccines into routine vaccines ostensibly required under the Preventive Vaccination Law and recommended but optional vaccines, although all vaccines are in fact voluntary. In Japan, low immunization rates, particularly for optional vaccines, have resulted in high rates of sequelae and death. The decision as to whether a child will receive a vaccine depends on the parents, who must obtain information, make inquiries, and make the required payment, the last of which is a major barrier. This randomized, controlled trial was conducted to evaluate the effectiveness of an immunization education program designed to meet mothers’ needs.

Methods

This randomized controlled trial assigned pregnant women to intervention or control groups. The intervention was individual education sessions involving the children’s fathers in shared decision-making on whether or not to immunize their child. A survey was conducted before and after the intervention. Data were analyzed using the intention-to-treat principle.

Results

Of 225 pregnant women, 175 (78%) participated and 171 replied to the post-survey. At age 3 months, intervention infants had higher self-reported immunization rates for hepatitis B virus vaccine (76% vs. 49%; P < 0.001) and rotavirus vaccine (84% vs. 68%; P = 0.019) than control group infants. The percentage of parents intending to vaccinate their infants was higher in the intervention group (77% vs. 52%; P < 0.01). Improvements in scores for basic knowledge (mean [SD]: 5.5 [3.6] vs. 3.0 [3.8], range: 10–30; P < 0.001), advanced knowledge (mean [SD]: 5.1 [2.4] vs. 2.8 [2.5], range: 5–15; P < 0.001), and health literacy regarding immunization (mean [SD]: 0.5 [0.8] vs. 0.2 [0.6], range: 1–5; P < 0.01) were higher in the intervention group. The rate of decision making by both parents (68% vs. 52%; P < 0.05) was higher in the intervention group.

Conclusions

Our findings confirmed the program’s effectiveness. The intervention improved immunization rates, the percentage of parents intending to vaccinate their infants and knowledge scores. Interventions which directly and indirectly involved fathers in shared decision-making on whether to immunize their child were effective, as were individualized interventions that provided parents with access to up-to-date information.

Trial registration

UMIN000012575. Registered 14 December 2013 (The study was prospectively registered).
Older multimorbid patients’ experiences on integration of services: a systematic review
Authors: Boye Lilian Keene , Mogensen Christian Backer , Mechlenborg Tine , Waldorff Frans Boch , Andersen Pernille Tanggaard
Published: November 2019

Background

Half of the older persons in high-income counties are affected with multimorbidity and the prevalence increases with older age. To cope with both the complexity of multimorbidity and the ageing population health care systems needs to adapt to the aging population and improve the coordination of long-term services. The objectives of this review were to synthezise how older people with multimorbidity experiences integrations of health care services and to identify barriers towards continuity of care when multimorbid.

Methods

A systematic literature search was conducted in February 2018 by in Scopus, Embase, Cinahl, and Medline using the PRISMA guidelines. Inclusion criteria: studies exploring patients’ point of view, ≥65 and multi-morbid. Quality assessment was conducted using COREQ. Thematic synthesis was done.

Results

Two thousand thirty studies were identified, with 75 studies eligible for full text, resulting in 9 included articles, of generally accepted quality.

Integration of health care services was successful when the patients felt listened to on all the aspects of being individuals with multimorbidity and when they obtained help from a care coordinator to prioritize their appointments. However, they felt frustrated when they did not have easy access to their health providers, when they were not listened to, and when they felt they were discharged too early. These frustrations were also identified as barriers to continuity of care.

Conclusions

Health care systems needs to adapt to people with multimorbidity and find solutions on ways to create flexible systems that are able to help older patients with multimorbidity, meet their individual needs and their desire to be involved in decisions regarding their care. A Care coordinator may be a solution.
Health professionals’ acceptance and willingness to pay for hepatitis B virus vaccination in Gondar City Administration governmental health institutions, Northwest Ethiopia
Authors: Abiye Siwule , Yitayal Mezgebu , Abere Giziew , Adimasu Asefa
Published: November 2019

Background

Hepatitis B virus (HBV) infection is a global public health problem. The burden of the disease is high in low and middle income countries like Ethiopia. However, for highly vulnerable groups such as health professionals, vaccination coverage is a major issue in the developing countries where health professionals are expected to pay for vaccination. Therefore, the objective of this study was to assess health professionals’ acceptance and willingness to pay (WTP) and associated factors for vaccination against HBV.

Methods

Cross-sectional study was conducted from March to April, 2017 in Gondar city administration governmental health institutions among 423 health professionals. Simple random sampling method was employed to select the study participants. Data were collected using self- administered questionnaire. Tobit model was used to analyze the determinants of WTP and the maximum amount of money the individuals might pay for HBV vaccination. P-value < 0.05 was considered statistically significant.

Result

A total of 423 health professionals (physicians, nurses, midwives, laboratory technicians/technologists, and others) participated in the study with a response rate of 100, and 62.4% of them were willing to pay for HBV vaccination. The mean amount of money the participants might pay for HBV vaccination was 325.83 ± 283.46 ETB (US$ 14.39 ± 12.52). The study indicated that the WTP for HBV vaccination of health professionals from health centers was 179.41 ETB less compared to health professionals from hospital. The WTP for HBV vaccination of the participants who had no experience of seeing previous patients with HBV was 157.87 ETB less compared to participants who had experience of seeing previous patients with HBV. As monthly income of the study participants increased by one ETB, the WTP was increased by 0.027 ETB.

Conclusion

The study revealed that the mean amount of money the participants might pay for HBV vaccination was much less than the market price for HBV vaccination. Type of workplace and experience of seeing/observing patients with HBV, and income were the predictors of WTP for HBV vaccination. Availing the vaccine with affordable cost in governmental health institutions may increase WTP of health professionals for HBV vaccination.
Redirecting photosynthetic electron flux in the cyanobacterium Synechocystis sp. PCC 6803 by the deletion of flavodiiron protein Flv3
Authors: Thiel Kati , Patrikainen Pekka , Nagy Csaba , Fitzpatrick Duncan , Pope Nicolas , Aro Eva-Mari , Kallio Pauli
Published: November 2019

Background

Oxygen-evolving photoautotrophic organisms, like cyanobacteria, protect their photosynthetic machinery by a number of regulatory mechanisms, including alternative electron transfer pathways. Despite the importance in modulating the electron flux distribution between the photosystems, alternative electron transfer routes may compete with the solar-driven production of CO2-derived target chemicals in biotechnological systems under development. This work focused on engineered cyanobacterial Synechocystis sp. PCC 6803 strains, to explore possibilities to rescue excited electrons that would normally be lost to molecular oxygen by an alternative acceptor flavodiiron protein Flv1/3—an enzyme that is natively associated with transfer of electrons from PSI to O2, as part of an acclimation strategy towards varying environmental conditions.

Results

The effects of Flv1/3 inactivation by flv3 deletion were studied in respect to three alternative end-products, sucrose, polyhydroxybutyrate and glycogen, while the photosynthetic gas fluxes were monitored by Membrane Inlet Mass Spectrometry (MIMS) to acquire information on cellular carbon uptake, and the production and consumption of O2. The results demonstrated that a significant proportion of the excited electrons derived from photosynthetic water cleavage was lost to molecular oxygen via Flv1/3 in cells grown under high CO2, especially under high light intensities. In flv3 deletion strains these electrons could be re-routed to increase the relative metabolic flux towards the monitored target products, but the carbon distribution and the overall efficiency were determined by the light conditions and the genetic composition of the respective pathways. At the same time, the total photosynthetic capacity of the Δflv3 strains was systematically reduced, and accompanied by upregulation of oxidative glycolytic metabolism in respect to controls with the native Flv1/3 background.

Conclusions

The observed metabolic changes and respective production profiles were proposedly linked with the lack of Flv1/3-mediated electron transfer, and the associated decrease in the intracellular ATP/NADPH ratio, which is bound to affect the metabolic carbon partitioning in the flv3-deficient cells. While the deletion of flv3 could offer a strategy for enhancing the photosynthetic production of desired chemicals in cyanobacteria under specified conditions, the engineered target pathways have to be carefully selected to align with the intracellular redox balance of the cells.
Senescent synovial fibroblasts accumulate prematurely in rheumatoid arthritis tissues and display an enhanced inflammatory phenotype
Authors: Del Rey Manuel J. , Valín Álvaro , Usategui Alicia , Ergueta Sandra , Martín Eduardo , Municio Cristina , Cañete Juan D. , Blanco Francisco J. , Criado Gabriel , Pablos José L.
Published: November 2019

Background

Accumulation of senescent cells has been associated with pro-inflammatory effects with deleterious consequences in different human diseases. The purpose of this study was to analyze cell senescence in human synovial tissues (ST), and its impact on the pro-inflammatory function of synovial fibroblasts (SF).

Results

The expression of the senescence marker p16INK4a (p16) was analyzed by immunohistochemistry in rheumatoid arthritis (RA), osteoarthritis (OA), and normal ST from variably aged donors. The proportion of p16(+) senescent cells in normal ST from older donors was higher than from younger ones. Although older RA and OA ST showed proportions of senescent cells similar to older normal ST, senescence was increased in younger RA ST compared to age-matched normal ST. The percentage of senescent SA-β-gal(+) SF after 14 days in culture positively correlated with donor’s age. Initial exposure to H2O2or TNFα enhanced SF senescence and increased mRNA expression ofIL6,CXCL8,CCL2andMMP3and proteins secretion. Senescent SF show a heightenedIL6,CXCL8andMMP3mRNA and IL-6 and IL-8 protein expression response upon further challenge with TNFα. Treatment of senescent SF with the senolytic drug fenofibrate normalizedIL6,CXCL8andCCL2mRNA expression.

Conclusions

Accumulation of senescent cells in ST increases in normal aging and prematurely in RA patients. Senescence of cultured SF is accelerated upon exposure to TNFα or oxidative stress and may contribute to the pathogenesis of synovitis by increasing the production of pro-inflammatory mediators.
An evaluation of HHV-6 as an etiologic agent in Hodgkin lymphoma and brain cancer using IARC criteria for oncogenicity
Authors: Wells Michael J. , Jacobson Steven , Levine Paul H.
Published: November 2019

Background

Human herpesvirus-6 (HHV-6) is a ubiquitous double-stranded DNA virus that can cause roseola infantum, encephalitis, and seizure disorders. Several studies have shown an association between HHV-6 and cancer but confirmation of an etiologic role is lacking. We reviewed the criteria for viral causation of cancer used by The International Agency for Research on Cancer (IARC) for six oncogenic viruses and applied criteria to published reports of HHV-6 and its association with Hodgkin lymphoma and brain tumors.

Methods

Our major criteria for oncogenicity were finding evidence of the virus in every tumor cell and prevention of the tumor by an antiviral vaccine. Our six minor criteria included: 1) suggestive serologic correlation, such as higher virus antibody levels in cases compared to controls; 2) evidence of the virus in some but not all tumor cells, and 3) time space clustering. We focused on Epstein-Barr virus (EBV) as the primary virus for comparison as HHV-6 and EBV are both Herpesviridae, ubiquitous infections, and EBV is well-accepted as a human oncovirus. Particular attention was given to Hodgkin lymphoma (HL) and brain cancer as these malignancies have been the most studied.

Results

No studies reported HHV-6 satisfying either of the major criteria for oncogenicity. Of the minor criteria used by IARC, serologic studies have been paramount in supporting EBV as an oncogenic agent in all EBV-associated tumors, but not for HHV-6 in HL or brain cancer. Clustering of cases was suggestive for both HL and brain cancer and medical intervention suggested by longer survival in patients treated with antiviral agents was reported for brain cancer.

Conclusion

There is insufficient evidence to indicate HHV-6 is an etiologic agent with respect to HL and brain cancers. We suggest that methods demonstrating EBV oncogenicity be applied to HHV-6. It is important that one study has found HHV-6 in all cancer cells in oral cancer in a region with elevated HHV-6 antibodies and therefore HHV-6 can still be considered a possible human oncogenic virus.
Mash Screen: high-throughput sequence containment estimation for genome discovery
Authors: Ondov Brian D. , Starrett Gabriel J. , Sappington Anna , Kostic Aleksandra , Koren Sergey , Buck Christopher B. , Phillippy Adam M.
Published: November 2019

The MinHash algorithm has proven effective for rapidly estimating the resemblance of two genomes or metagenomes. However, this method cannot reliably estimate the containment of a genome within a metagenome. Here, we describe an online algorithm capable of measuring the containment of genomes and proteomes within either assembled or unassembled sequencing read sets. We describe several use cases, including contamination screening and retrospective analysis of metagenomes for novel genome discovery. Using this tool, we provide containment estimates for every NCBI RefSeq genome within every SRA metagenome and demonstrate the identification of a novel polyomavirus species from a public metagenome.
Non-Interventional Factors Influencing Velopharyngeal Function For Speech In Initial Cleft Palate Repair: A Systematic Review Protocol
Authors:   Cleft Multidisciplinary Collaborative, Sainsbury David , Williams Caroline , de Blacam Catherine , Mullen Joanne , Chadha Ambika , Wren Yvonne , Hodgkinson Peter
Published: November 2019

Background

This systematic review aims to inform the development of a screening tool which pre-operatively predicts which children are likely to develop velopharyngeal insufficiency, one of the causes of poor speech outcomes, following cleft palate repair. This would be highly beneficial as it would inform pre-operative counselling of parents, allow targeted speech and language therapy, and enable meaningful comparison of outcomes between surgeons, techniques, and institutions. Currently, it is unclear which factors influence speech outcomes. A systematic review investigating the non-interventional factors which potentially influence speech outcomes following cleft palate repair is warranted. This may be illuminating in itself or provide foundations for future studies.

Methods

A systematic review will be carried out according to Cochrane methodology and reported according to PRISMA guidelines (PLoS Med 6: e1000097, 2009). Systematic review software will be used to facilitate three-stage screening by two independent reviewers experienced in cleft lip and palate. Thereafter, data extraction and GRADE assessment will be performed in duplicate by five independent reviewers experienced in cleft lip and palate. Studies reporting the proportion of patients who were recommended or underwent secondary speech surgery for velopharyngeal insufficiency following primary surgery for cleft palate will be included.

The study findings will be tabulated and summarised. The primary outcome measure will be further speech surgery (either recommended or performed). The secondary outcome measure will be perceptual speech assessment for the presence of velopharyngeal insufficiency. A meta-analysis is planned. However, if this is not possible, due to the anticipated marked heterogeneity of study characteristics, pre-operative assessment, and the recorded outcome measures, a narrative synthesis will be undertaken.

Discussion

This systematic review may provide sufficient data to inform the development of a screening tool to predict the risk of velopharyngeal insufficiency prior to cleft palate repair. However, it is anticipated that these findings will provide the foundation for future studies in this area.

Systematic review registration

Registered on 19 December 2016 with PROSPERO CRD42017051624
Analysis of technical efficiency of potato (Solanum tuberosum L.) production in Chilga District, Amhara National Regional State, Ethiopia
Authors: Wassihun Agerie Nega , Koye Tigabu Dagnew , Koye Abebe Dagnew
Published: November 2019

Background

Potato is one of the major staple crops in the Eastern and Central Africa sub-region. Its importance continues to rise due to increased urbanization and demand for potato is projected. This increase will definitely come with its share of challenges that need to be addressed. This study was aimed to measure the level of technical efficiency, yield loss due to inefficiency and identify the factors that influence the efficiency levels of potato producers’ in Chilga District. Primary data were collected from 150 farmers selected using multistage sampling procedure and analyzed using descriptive statistics, a parametric stochastic frontier production function models.

Results

The results of the study indicated that the minimum, maximum and average yields of potato production in the sample households were 1000, 36,000 and 13,108 kg/ha, respectively. The stochastic frontier and Cobb–Douglas functional form with a one-step approach was employed to analyze efficiency and factors affecting efficiency in potato production. The mean technical efficiency (TE) was found to be 46%, and about 17,782.43 kg of potato output per hectare was lost due to inefficiency factors implying there is a room for improvement in technical efficiency by 54% with the present technology. The Stochastic Production Frontier (SPF) result revealed that DAP at 5% and Oxen, MDE and seed at 1% probability level significantly influencing potato production. The socio-economic variables that exercised important role for variations in technical efficiency positively were age and improved seed and nevertheless distance to market was found to increase inefficiency significantly among farm household.

Conclusions

There is considerable difference in the efficiency level among plots. Hence if inputs are used to their maximum potential, there will be considerable gain from improvement in technical efficiency. The estimated SPF model together with the inefficiency parameters shows that age and improved seed variety were influenced by inefficiency negatively whereas distance to market increased the level of technical inefficiency.
Offenders with mental disorders in prison and the courts: links to rates of civil detentions and the number of psychiatric beds in England – longitudinal data from 1984 to 2016
Authors: Keown Patrick , McKenna Dannielle , Murphy Hannah , McKinnon Iain
Published: November 2019

Background

The Mental Health Act in England and Wales allows for two types of detention in hospital: civil and forensic detentions. An association between the closure of mental illness beds and a rise in civil detentions has been reported.

Aims

To examine changes in the rate of court orders and transfer from prison to hospital for treatment, and explore associations with civil involuntary detentions, psychiatric bed numbers and the prison population.

Method

Secondary analysis of routinely collected data with lagged time series analysis. We focused on two main types of forensic detentions in National Health Service (NHS) hospitals and private units: prison transfers and court treatment orders in England from 1984 to 2016. NHS bed numbers only were available.

Results

There was an association between the number of psychiatric beds and the number of prison transfers. This was strongest at a time lag of 2 years with the change in psychiatric beds occurring first. There was an association between the rate of civil detentions and the rate of court orders. This was strongest at a time lag of 3 years. Linear regression indicated that 135 fewer psychiatric beds were associated with one additional transfer from prison to hospital; and as the rate of civil detentions increased by 72, the rate of court treatment orders fell by one.

Conclusions

The closure of psychiatric beds was associated with an increase in transfers from prison to hospital for treatment. The increase in civil detentions was associated with a reduction in the rate of courts detaining to hospital individuals who had offended.

Declaration of interest

None.
“Exceptional and Unimportant”?
Authors: Medema Steven G.
Published: November 2019

The notion of a Pigovian tradition in externality theory, against which Ronald Coase and others reacted beginning in the 1960s, has a long history. This article, though, suggests that the literature of economics evidences no such tradition, and that the discussion of externalities largely disappeared from the literature following Pigou’s 1920 treatment, only to reemerge, in very different form, in the 1950s. Such concern as there was with externalities was largely technical—as an impediment to the attainment of an efficient equilibrium—rather than with externalities as important real-world phenomena that required addressing via “Pigovian” policy instruments. It was only in the late 1950s and 1960s, with the growing social and political concern about large-scale pollution, that externality analysis came to capture the attention of economists, but even this early work on environmental topics was less straightforwardly Pigovian than one might expect.
Adam Smith’s Labor Theory of (Real) Value
Authors: Peach Terry
Published: November 2019

This article provides a rebuttal of Roy H. Grieve’s critique of Peach 2009, “Adam Smith and the Labor Theory of (Real) Value: A Reconsideration.” It is shown that Grieve cannot represent accurately the position he purports to criticize, that his criticisms are directed at phantom targets of his own creation, that his grasp of central concepts (including the labor theory of value) is flawed, and that he simply ignores material that does not suit his mordacious ends. Although Grieve’s stated purpose is to defend the scholarly status quo, it is argued that his misplaced efforts do nothing to salvage an interpretation that stands in need of fundamental revision, the authoritative voices invoked by Grieve in his support notwithstanding.
External Validation of Pretreatment Pathological Tumor Extent in Patients with Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer
Authors: Brinkmann Sebastian , Noordman Bo J. , Hölscher Arnulf H. , Biermann Katharina , van Klaveren David , Bollschweiler Elfriede , Pütz Katharina , van Lanschot J. Jan B. , Drebber Uta
Published: November 2019

Background

This study was conducted to validate a pretreatment (i.e. prior to neoadjuvant chemoradiotherapy) pathological staging system in the resection specimen after neoadjuvant chemoradiotherapy for esophageal cancer. The study investigated the prognostic value of pretreatment pathological T and N categories (prepT and prepN categories) in both an independent and a combined patient cohort.

Methods

Patients with esophageal cancer treated with neoadjuvant chemotherapy and esophagectomy between 2012 and 2015 were included. PrepT and prepN categories were estimated based on the extent of tumor regression and regressional changes of lymph nodes in the resection specimen. The difference in Akaike’s information criterion (ΔAIC) was used to assess prognostic performance. PrepN and ypN categories were combined to determine the effect of nodal sterilization on prognosis. A multivariable Cox regression model was used to identify combined prepN and ypN categories as independent prognostic factors.

Results

The prognostic strength of the prepT category was better than the cT and ypT categories (ΔAIC 7.7 vs. 3.0 and 2.9, respectively), and the prognostic strength of the prepN category was better than the cN category and similar to the ypN category (ΔAIC 29.2 vs. − 1.0 and 27.9, respectively). PrepN + patients who became ypN0 had significantly worse survival than prepN0 patients (2-year overall survival 69% vs. 86% in 137 patients; p = 0.044). Similar results were found in a combined cohort of 317 patients (2-year overall survival 62% vs. 85%; p = 0.002). Combined prepN/ypN stage was independently associated with overall survival.

Conclusions

These results independently confirm the prognostic value of prepTNM staging. PrepTNM staging is of additional prognostic value to cTNM and ypTNM. PrepN0/ypN0 patients have a better survival than prepN +/ypN0 patients.