bluuebunny/crossref_metadata_2025 huggingface dataset:
The Spanish spatial city size distribution
Authors: González-Val Rafael
Published: July 2020

This paper analyses the Spanish city size distribution from a new perspective, focusing on the role played by distance. Using un-truncated data from all cities in 1900 and 2011, we study the spatial distribution of cities and how the city size distribution varies with distance. First, K-densities are estimated to identify different spatial patterns depending on city size, with significant patterns of dispersion found for medium-sized and large cities. Second, using a distance-based approach that considers all possible combinations of cities within a 200-kilometre radius, we analyse the influence of distance on the city size distribution parameters, considering both the Pareto and lognormal distributions. The results validate the Pareto distribution in most of the cases regardless of city size, and the lognormal distribution at short distances.
An archive of data from resonant column and cyclic torsional shear tests performed on Italian clays
Authors: Facciorusso Johann
Published: July 2020

Measurement of soil properties under cyclic and dynamic loading conditions is a critical task in the solution of most geotechnical earthquake engineering problems. The main dynamic properties of soils are usually expressed in terms of shear modulus, G, and damping ratio, D, and they are generally obtained from laboratory tests at different strain levels. Dynamic geotechnical problems often require a site-level or territorial approach involving a considerable number of dynamic laboratory tests that might be too expensive and time-consuming. Thus, it is a common practice to use empirical relationships between dynamic parameters and measurements from routine geotechnical tests. Therefore, the availability of a large and reliable archive of multiple testing results constitutes a fundamental step for geotechnical earthquake engineers and researchers. To this aim, a large data-set of the index and dynamic parameters measured from 170 undisturbed clay samples obtained from 90 sites in Central and Northern Italy is made available, and its use and application are further described and discussed.
Lenalidomide/rituximab induces high molecular response in untreated follicular lymphoma: LYSA ancillary RELEVANCE study
Authors: Delfau-Larue Marie-Helene , Boulland Marie-Laure , Beldi-Ferchiou Asma , Feugier Pierre , Maisonneuve Hervé , Casasnovas Rene-Olivier , Lemonnier François , Pica Gian Matteo , Houot Roch , Ysebaert Loic , Tilly Hervé , Eisenmann Jean-Claude , Le Gouill Steven , Ribrag Vincent , Godmer Pascal , Glaisner Sylvie , Cartron Guillaume , Xerri Luc , Salles Gilles André , Fest Thierry , Morschhauser Franck
Published: July 2020

Complete molecular response (CMR) after first-line immunochemotherapy reflects treatment efficacy and may predict prognosis in patients with follicular lymphoma (FL). RELEVANCE is the first phase 3 trial comparing the chemotherapy-free regimen lenalidomide/rituximab (R2) vs rituximab/chemotherapy (R-Chemo) in previously untreated FL patients (ClinicalTrials.gov identifier: NCT01650701). The objective of the minimal residual disease (MRD) analysis was to determine the ability of a chemotherapy-free regimen to induce CMR. Of 440 French patients participating in the Lymphoma Study Association (LYSA) RELEVANCE MRD study, all 222 patients with a BIOMED-2–detectable BCL2-JH translocation at diagnosis were analyzed. MRD was quantified by droplet digital polymerase chain reaction with a sensitivity ≤10−4. At week 24 (end of induction treatment), 98% and 78% of patients achieved CMR in peripheral blood (PB) and bone marrow (BM), respectively. Achievement of CMR (in PB and/or BM) had a significant impact on progression-free survival (PFS), with 3-year PFS of 84% and 55% for patients with CMR and detectable MRD, respectively (P = .015). CMR at week 24 was reached more frequently in the R2 arm (105/117; 90%) than in the R-Chemo arm (70/90; 77%) (P = .022). The poor prognostic value in terms of PFS for the persistence of molecular disease was observed irrespective of treatment arm (interaction test, P = .31). In agreement with the clinical results of the RELEVANCE trial, our results show that R2 immunomodulatory treatment in first-line FL can achieve high rates of CMR.
Cognitive and sensorimotor function in participants being treated for trigeminal neuralgia pain
Authors: Coats Rachel O. , Crossley Kirsty L. , Conlin Naomi , Wu Jianhua , Zakrzewska Joanna M. , Pavitt Sue H. , Phillips Nicholas , Mon-Williams Mark
Published: July 2020

Background

Trigeminal neuralgia (TN) is an orofacial condition defined by reoccurring, spontaneous, short-lived but excruciating stabbing pain. Pharmacological interventions constitute the first-line treatment for TN, with antiepileptic drugs commonly prescribed. People treated for TN pain with antiepileptic drugs describe cognitive and motor difficulties affecting activities of daily living, and report poorer quality of life. We undertook the first comprehensive objective evaluation of sensorimotor and cognitive performance in participants being treated for TN pain with antiepileptic drugs relative to age-matched controls.

Methods

Participants (43 TN, 41 control) completed a battery of sensorimotor (steering, aiming and tracking) and cognitive (working memory, processing speed, inhibition) tasks.

Results

The TN group performed significantly worse than controls on the sensorimotor tracking and aiming tasks and across all cognitive measures.

Conclusions

The data explain why patients treated with antiepileptic drugs report impairment when conducting activities of daily living (given the need for cognitive and motor capability within most of these). The study is an important first step in: (i) ensuring there is adequate information on the impact of pharmacological treatment; (ii) identifying measures to determine optimal medication dosage and track change over time; (iii) creating an evidence base that could allow scientific justification of alternative pain treatment options for TN (e.g. the costs/benefits of surgery).
Evaluation of fecal DNA extraction protocols for human gut microbiome studies
Authors: Lim Mi Young , Park Yong-Soo , Kim Jung-Ha , Nam Young-Do
Published: July 2020

Background

DNA extraction is an important factor influencing the microbiome profile in fecal samples. Considering that the QIAamp DNA Stool Mini Kit, one of the most commonly used DNA extraction kits, is no longer manufactured, this study aimed to investigate whether a new commercially available kit, the QIAamp PowerFecal Pro DNA Kit, yields comparable microbiome profiles with those previously obtained using the QIAamp DNA Stool Mini Kit.

Results

We extracted DNA from fecal samples of 10 individuals using three protocols (protocol P of the QIAamp PowerFecal Pro DNA Kit, and protocols SB and S of the QIAamp DNA Stool Mini Kit with and without an additional bead-beating step, respectively) in triplicate. Ninety extracted DNA samples were subjected to 16S rRNA gene sequencing. DNA quality measured by 260/280 absorbance ratios was found to be optimal in protocol P. Additionally, the DNA quantity and microbiome diversity obtained using protocol P were significantly higher than those of protocol S, however, did not differ significantly from those of protocol SB. Based on the overall microbiome profiles, variations between protocol P and protocol SB or S were significantly less than between-individual variations. Furthermore, most genera were not differentially abundant in protocol P compared to the other protocols, and the number of differentially abundant genera, as well as the degree of fold-changes were smaller between protocols P and SB than between protocols P and S.

Conclusions

The QIAamp PowerFecal Pro DNA Kit exhibited microbiome analysis results that were comparable with those of the QIAamp DNA Stool Mini Kit with a bead-beating step. These results will prove useful for researchers investigating the gut microbiome in selecting an alternative protocol to the widely used but discontinued kit.
Comparative transcriptomics analysis revealing flower trichome development during flower development in two Lonicera japonica Thunb. cultivars using RNA-seq
Authors: Li Jianjun , Ye Chenglin , Chang Cuifang
Published: July 2020

Background

Lonicera japonicaThunb. (L. japonica) has the functions of clearing away heat and detoxifying, broad-spectrum antibacterial and anti-virus, etc. More than 70% of anti-inflammatory and cold Chinese patent medicines containL. japonica. Trichomes comprise specialized multicellular structures that have the capacity to synthesize and secrete secondary metabolites and protect plants from biotic and abiotic stresses. The extraction of trichome secretions has great commercial value. However, little is known about the trichome formation mechanism inL. japonica. Therefore, the study of trichome development between different varieties provides a basis for selecting suitable planting resources.

Results

Here, we present a genome-wide comparative transcriptome analysis between twoL. japonicacultivars, toward the identification of biological processes and functional gene activities that occur during flowering stage trichome development. In this study, the density and average lengths of flower trichomes were at their highest during three-green periods (S2). Using the Illumina RNA-Seq method, we obtained 134,304 unigenes, 33,733 of which were differentially expressed. In an analysis of 40 differentially expressed unigenes (DEGs) involved in trichome development, 29 of these were transcription factors. The DEGs analysis of plant hormone signal transduction indicated that plant growth and development may be independent of gibberellin (GA) and cytokinine (CTK) signaling pathways, and plant stress may be independent of jasmonic acid (JA) and ethylene (ET) signaling pathways. We screened several genes involved in the floral biosynthesis of odors, tastes, colors, and plant hormones, and proposed biosynthetic pathways for sesquiterpenoid, triterpenoid, monoterpenoid, flavonoid, and plant hormones. Furthermore, 82 DEGs were assigned to cell cycles and 2616 were predicted as plant resistance genes (PRGs).

Conclusions

This study provides a comprehensive characterization of the expression profiles of flower development during the seven developmental stages ofL. japonica, thereby offering valuable insights into the molecular networks that underly flower development inL. japonica.
Genetic variation implicates plasma angiopoietin-2 in the development of acute kidney injury sub-phenotypes
Authors: Bhatraju Pavan K. , Cohen Max , Nagao Ryan J. , Morrell Eric D. , Kosamo Susanna , Chai Xin-Ya , Nance Robin , Dmyterko Victoria , Delaney Joseph , Christie Jason D. , Liu Kathleen D. , Mikacenic Carmen , Gharib Sina A. , Liles W. Conrad , Zheng Ying , Christiani David C. , Himmelfarb Jonathan , Wurfel Mark M.
Published: July 2020

Background

We previously identified two acute kidney injury (AKI) sub-phenotypes (AKI-SP1 and AKI-SP2) with different risk of poor clinical outcomes and response to vasopressor therapy. Plasma biomarkers of endothelial dysfunction (tumor necrosis factor receptor-1, angiopoietin-1 and 2) differentiated the AKI sub-phenotypes. However, it is unknown whether these biomarkers are simply markers or causal mediators in the development of AKI sub-phenotypes.

Methods

We tested for associations between single-nucleotide polymorphisms within the Angiopoietin-1, Angiopoietin-2, and Tumor Necrosis Factor Receptor 1A genes and AKI- SP2 in 421 critically ill subjects of European ancestry. Top performing single-nucleotide polymorphisms (FDR < 0.05) were tested for cis-biomarker expression and whether genetic risk for AKI-SP2 is mediated through circulating biomarkers. We also completed in vitro studies using human kidney microvascular endothelial cells. Finally, we calculated the renal clearance of plasma biomarkers using 20 different timed urine collections.

Results

A genetic variant, rs2920656C > T, near ANGPT2 was associated with reduced risk of AKI-SP2 (odds ratio, 0.45; 95% CI, 0.31–0.66; adjusted FDR = 0.003) and decreased plasma angiopoietin-2 (p = 0.002). Causal inference analysis showed that for each minor allele (T) the risk of developing AKI-SP2 decreases by 16%. Plasma angiopoietin-2 mediated 41.5% of the rs2920656 related risk for AKI-SP2. Human kidney microvascular endothelial cells carrying the T allele of rs2920656 produced numerically lower levels of angiopoietin-2 although this was not statistically significant (p = 0.07). Finally, analyses demonstrated that angiopoietin-2 is minimally renally cleared in critically ill subjects.

Conclusion

Genetic mediation analysis provides supportive evidence that angiopoietin-2 plays a causal role in risk for AKI-SP2.
Nephrotic syndrome due to minimal-change disease superimposed on anti-glomerular basement membrane antibody positive glomerulonephritis; a case report
Authors: Shibata Yuko , Fukuoka Kazuhito , Yokota Riyo , Lee Heryon , Sayo Hikaru , Ikegaya Noriko , Mori Kiyotaka , Yamamoto Jin , Isomura Aya , Nagahama Kiyotaka , Shimoyamada Hiroaki , Kawakami Takahisa , Komagata Yoshinori , Kaname Shinya
Published: July 2020

Background

The prognosis for renal function in anti-GBM glomerulonephritis (anti-GBM GN) is extremely poor, and when renal impairment progresses severely, it is difficult to expect improvement. In addition, it is also known that once the disease activity can be controlled by aggressive treatment, its recurrence is rare. We experienced an anti-GBM GN that improved from severe renal dysfunction and relapsed. A possible cause was the superimpose of nephrotic syndrome due to minimal change disease (MCD).

Case presentation

A 30-year-old man was admitted to our hospital because of general malaise, fever, oliguria and renal dysfunction. The patient’s laboratory data showed serum creatinine as high as 6.6 mg/dl, and severe inflammation (C-reactive protein 20.6 mg/dl). Anti-glomerular basement membrane antibody (anti-GBM Ab) was detected in his serum, which led to the diagnosis of anti-GBM GN. Treatment was initiated with high-dose glucocorticoid (GC) and plasma exchange therapy (PE), and the patient’s renal function and oliguria improved rapidly and he was discharged 40 days after admission. Renal biopsy findings showed cellular crescents associated with linear IgG depositions along the glomerular tufts compatible with anti-GBM GN, but only about one-third of the glomeruli was involved, suggesting that it still remains an early stage of the disease. However, 2 months after discharge, he had a relapse and was readmitted due to severe proteinuria with positive anti-GBM Ab. On the second admission, after high-dose GC and PE combined with intravenous cyclophosphamide, and remission was achieved. Despite the relatively minor renal biopsy findings, the patient showed rapid renal dysfunction and relatively rapid improvement with our treatment. Electron microscopy of the renal biopsy tissue showed significant foot process effacement on podocytes in the apparently normal glomeruli, without electron dense deposits.

Conclusion

On the basis of clinical course and renal pathology, it is suggested that the present case was a rare complication of an early stage of anti-GBM GN and minimal change nephrotic syndrome. Although the simultaneous development of anti-GBM GN and MCD with anti-GBM antibody is unclear, it might have been precipitated by influenza infection or some unknown factor.
The prognosis of hepatoid adenocarcinoma of the stomach: a propensity score-based analysis
Authors: Zhou Kai , Wang Anqiang , Ao Sheng , Chen Jiahui , Ji Ke , He Qifei , Ji Xin , Wu Xiaojiang , Zhang Ji , Li Zhongwu , Bu Zhaode , Ji Jiafu
Published: July 2020

Background

To investigate whether there is a distinct difference in prognosis between hepatoid adenocarcinoma of the stomach (HAS) and non-hepatoid adenocarcinoma of the stomach (non-HAS) and whether HAS can benefit from radical surgery.

Methods

We retrospectively reviewed 722 patients with non-HAS and 75 patients with HAS who underwent radical gastrectomy between 3 November 2009 and 17 December 2018. Propensity score matching (PSM) analysis was used to eliminate the bias among the patients in our study. The relationships between gastric cancer type and overall survival (OS) were evaluated by the Kaplan-Meier method and Cox regression.

Results

Our data demonstrate that there was no statistically significant difference in the OS between HAS and non-HAS {K-M, P = log rank (Mantel-Cox), (before PSM P = 0.397); (1:1 PSM P = 0.345); (1:2 PSM P = 0.195)}. Moreover, there were no significant differences in the 1-, 2-, or 3-year survival rates between patients with non-HAS and patients with HAS (before propensity matching, after 1:1 propensity matching, and after 1:2 propensity matching).

Conclusion

HAS was generally considered to be an aggressive gastric neoplasm, but its prognosis may not be as unsatisfactory as previously believed.
Treatment patterns and health outcomes in metastatic renal cell carcinoma patients treated with targeted systemic therapies in the UK
Authors: Hawkins Robert , Fife Kate , Hurst Michael , Wang Meng , Naicker Niroshini , Nolasco Sarah , Eisen Tim , Matakidou Athena , Gordon Jason
Published: July 2020

Background

Patients with metastatic renal cell carcinoma (mRCC) treated with targeted systemic therapies have demonstrated favourable outcomes in randomised controlled trials, however real-world evidence is limited. Thus, this study aimed to determine the effectiveness of targeted systemic therapies for patients with mRCC in routine clinical practice in the UK.

Methods

A retrospective, observational, longitudinal study based on chart review of newly diagnosed adult mRCC patients treated at two UK hospitals from 2008 to 2015 was conducted. Targeted systemic therapies recommended for use in mRCC patients were evaluated across first to third lines of therapy (1LOT-3LOT). Important exclusions were treatment with cytokine therapy and within non-standard of care clinical trials. Primary outcome measure was overall survival (OS); data were analysed descriptively and using Kaplan-Meyer analysis.

Results

652 patients (65.3% male, 35.0% ≥70 years) were included. In 1LOT, 98.5% of patients received sunitinib or pazopanib. In 2LOT and 3LOT, 99.0 and 94.4% received axitinib or everolimus. Median OS was 12.9, 6.5 and 5.9 months at 1LOT, 2LOT and 3LOT respectively. Estimated OS at 1-year was 52.4% (95% CI: 48.6–56.4%) in 1LOT, 31.5% (25.2–39.5%) in 2LOT and 23.8% (10.1–55.9%) in 3LOT. Median OS from 1LOT in favourable, intermediate and poor MSKCC were 39.7, 15.8 and 6.1 months respectively.

Conclusions

In this study, treatment was consistent with current National Institute for Health and Care Excellence (NICE) guidelines for mRCC patients. Although the study population favoured poorer prognosis patients, outcomes were more favourable than those for England at the same time. However, overall survival in this ‘real-world’ population remains poor and indicates significant unmet need for effective and safe treatment options to improve survival among mRCC patients.
Short-term outcomes of robotic- versus laparoscopic-assisted Total Gastrectomy for advanced gastric Cancer: a propensity score matching study
Authors: Yang Changdong , Shi Yan , Xie Shaohui , Chen Jun , Zhao Yongliang , Qian Feng , Hao Yingxue , Tang Bo , Yu Peiwu
Published: July 2020

Background

Few studies have been designed to evaluate the short-term outcomes between robotic-assisted total gastrectomy (RATG) and laparoscopy-assisted total gastrectomy (LATG) for advanced gastric cancer (AGC). The purpose of this study was to assess the short-term outcomes of RATG compared with LATG for AGC.

Methods

We retrospectively evaluated 126 and 257 patients who underwent RATG or LATG, respectively. In addition, we performed propensity score matching (PSM) analysis between RATG and LATG for clinicopathological characteristics to reduce bias and compared short-term surgical outcomes.

Results

After PSM, the RATG group had a longer mean operation time (291.14 ± 59.18 vs. 270.34 ± 52.22 min, p = 0.003), less intraoperative bleeding (154.37 ± 89.68 vs. 183.77 ± 95.39 ml, p = 0.004) and more N2 tier RLNs (9.07 ± 5.34 vs. 7.56 ± 4.50, p = 0.016) than the LATG group. Additionally, the total RLNs of the RATG group were almost significantly different compared to that of the LATG group (34.90 ± 13.05 vs. 31.91 ± 12.46, p = 0.065). Moreover, no significant differences were found between the two groups in terms of the length of incision, proximal resection margin, distal resection margin, residual disease and postoperative hospital stay. There was no significant difference in the overall complication rate between the RATG and LATG groups after PSM (23.8% vs. 28.6%, p = 0.390). Grade II complications accounted for most of the complications in the two cohorts after PSM. The conversion rates were 4.55 and 8.54% in the RATG and LATG groups, respectively, with no significant difference (p = 0.145), and the ratio of splenectomy were 1.59 and 0.39% (p = 0.253). The mortality rates were 0.8 and 0.4% for the RATG and LATG groups, respectively (p = 1.000).

Conclusion

This study demonstrates that RATG is comparable to LATG in terms of short-term surgical outcomes.
Anti-vascular endothelial growth factor in neovascular age-related macular degeneration – a systematic review of the impact of anti-VEGF on patient outcomes and healthcare systems
Authors: Finger Robert P. , Daien Vincent , Eldem Bora M. , Talks James S. , Korobelnik Jean-Francois , Mitchell Paul , Sakamoto Taiji , Wong Tien Yin , Pantiri Krystallia , Carrasco Joao
Published: July 2020

Background

Systematically review the evidence describing the impact of anti–vascular endothelial growth factor (anti-VEGF) therapy on neovascular age-related macular degeneration (nAMD) patient outcomes and healthcare resource utilization.

Methods

A systematic literature review was completed using Medline and EMBASE for publications prior to July 2018, and proceedings from major ophthalmology conferences (January 2016 to July 2018). The search strategy combined terms for nAMD with terms for anti-VEGF and study design. The review focused on publications describing the impact of anti-VEGF on blindness, visual impairment, vision-related quality of life (VRQoL), mortality, and costs. The search targeted data collected in epidemiological or observational studies to reflect real-world outcomes but also considered modeling-based approaches.

Results

The use of anti-VEGF in clinical practice was associated with significant reduction in the incidence of blindness by nAMD. Population-based analyses reported reduction in incidence among the general population of 47% (9.1 cases/100,000 in 2006 to 4.8 cases/100,000 in 2011). Among patients aged ≥50 years, a reduction of 50% was observed (52.2 cases/100,000 in 2000 to 25.7 cases/100,000 in 2010). In some cases, the odds of decreased vision (defined as decline from normal to moderate, moderate to severe, or severe to blindness) fell by 41% following introduction of anti-VEGF. Patients’ VRQoL improved with treatment, with patients reporting a positive impact shortly after treatment was initiated. Change on National Eye Institute 25-Item Visual Function Questionnaire score from baseline to month 12 ranged from 0.7 to 4.4. Although nAMD patients report signs of depression and anxiety, the evidence suggests that there is no association between the use of anti-VEGF and the prevalence or diagnosis of depression. The introduction of anti-VEGF led to increased overall treatment costs due to replacement of existing less frequently administered treatments (e.g. photodynamic therapy) and increased number of patients treated (prior to anti-VEGF, only ~ 20% of patients were eligible for treatment).

Conclusions

The introduction of anti-VEGF agents has been associated with a positive impact on patient-relevant outcomes, including a significant reduction in incidence of blindness and visual impairment by nAMD. Anti-VEGF agents replaced less-effective treatments, improving patient outcomes and broadening the patient population eligible for treatment.
Barriers to access to outpatient mental health care for refugees and asylum seekers in Switzerland: the therapist’s view
Authors: Kiselev Nikolai , Morina Naser , Schick Matthis , Watzke Birgit , Schnyder Ulrich , Pfaltz Monique C.
Published: July 2020

Background

More than 120,000 refugees and asylum seekers are currently living in Switzerland. The prevalence of mental disorders among this population is significantly higher than that in the general population. While effective treatment options and cross-cultural, specialized treatment centers exist, they tend to be overloaded by their target populations. General outpatient primary health care providers might be able to compensate for the lack of specialized treatment slots. To date, however, it is unknown how often and under what conditions (e.g., length of waiting lists) refugees and asylum seekers are treated outside of specialized centers and whether there are barriers that prevent providers in outpatient settings from treating more patients in this subgroup. The present study aimed to assess the challenges and barriers faced by psychiatrists and psychotherapists working in outpatient settings in Switzerland in treating refugees and asylum seekers to determine the potential capacity of this group to provide mental health care.

Methods

An online survey was conducted during the winter of 2017/2018. The survey was constructed in three official languages and took 10–15 min to complete. Spearman’s correlations, Mann-Whitney U-Tests, and Chi-squared tests were conducted to analyze the data.

Results

Eight hundred and sixty-seven (N = 867) psychotherapists and psychiatrists working in outpatient settings completed the survey: 43% of them reported having treated between 1 and 9 refugees or asylum seekers in the past 12 months, and a further 13% reported treating 10 or more. Interpreters were used for almost every other patient with a refugee or asylum-seeker background. At the same time, the funding of interpreters, as well as the funding of treatment in general, were reported to be the biggest hurdles to treating more refugees and asylum seekers.

Conclusions

Given the low number of patients rejected for capacity reasons (between 2 and 5%) and the median waiting times for the admission of new patients ranging between 2 and 3 weeks, outpatient primary mental health care providers might treat more refugees and asylum seekers and relieve specialized treatment centers. However, barriers such as lack of funding of interpreters seem to hinder them. Appropriate steps by the authorities are needed to improve the current situation.
Patient and health system delay among TB patients in Ethiopia: Nationwide mixed method cross-sectional study
Authors: Datiko Daniel G. , Jerene Degu , Suarez Pedro
Published: July 2020

Background

Effective tuberculosis (TB) control is the end result of improved health seeking by the community and timely provision of quality TB services by the health system. Rapid expansion of health services to the peripheries has improved access to the community. However, high cost of seeking care, stigma related TB, low index of suspicion by health care workers and lack of patient centered care in health facilities contribute to delays in access to timely care that result in delay in seeking care and hence increase TB transmission, morbidity and mortality. We aimed to measure patient and health system delay among TB patients in Ethiopia.

Methods

This is mixed method cross-sectional study conducted in seven regions and two city administrations. We used multistage cluster sampling to randomly select 40 health centers and interviewed 21 TB patients per health center. We also conducted qualitative interviews to understand the reasons for delay.

Results

Of the total 844 TB patients enrolled, 57.8% were men. The mean (SD) age was 34 (SD + 13.8) years. 46.9% of the TB patients were the heads of household, 51.4% were married, 24.1% were farmers and 34.7% were illiterate. The median (IQR) patient, diagnostic and treatment initiation delays were 21 (10–45), 4 (2–10) and 2 (1–3) days respectively. The median (IQR) of total delay was 33 (19–67) days; 72.3% (595) of the patients started treatment after 21 days of the onset of the first symptom. Poverty, cost of seeking care, protracted diagnostic and treatment initiation, inadequate community based TB care and lack of awareness were associated with delay. Community health workers reported that lack of awareness and the expectation that symptoms would resolve by themselves were the main reasons for delay.

Conclusion

TB patients’ delay in seeking care remains a challenge due to limited community interventions, cost of seeking care, prolonged diagnostics and treatment initiation. Therefore, targeted community awareness creation, cost reduction strategies and improving diagnostic capacity are vital to reduce delay in seeking TB care in Ethiopia.
The quality of drinking and domestic water from the surface water sources (lakes, rivers, irrigation canals and ponds) and springs in cholera prone communities of Uganda: an analysis of vital physicochemical parameters
Authors: Bwire Godfrey , Sack David A. , Kagirita Atek , Obala Tonny , Debes Amanda K. , Ram Malathi , Komakech Henry , George Christine Marie , Orach Christopher Garimoi
Published: July 2020

Background

Water is the most abundant resource on earth, however water scarcity affects more than 40% of people worldwide. Access to safe drinking water is a basic human right and is a United Nations Sustainable Development Goal (SDG) 6. Globally, waterborne diseases such as cholera are responsible for over two million deaths annually. Cholera is a major cause of ill-health in Africa and Uganda. This study aimed to determine the physicochemical characteristics of the surface and spring water in cholera endemic communities of Uganda in order to promote access to safe drinking water.

Methods

A longitudinal study was carried out between February 2015 and January 2016 in cholera prone communities of Uganda. Surface and spring water used for domestic purposes including drinking from 27 sites (lakes, rivers, irrigation canal, springs and ponds) were tested monthly to determine the vital physicochemical parameters, namely pH, temperature, dissolved oxygen, conductivity and turbidity.

Results

Overall, 318 water samples were tested. Twenty-six percent (36/135) of the tested samples had mean test results that were outside the World Health Organization (WHO) recommended drinking water range. All sites (100%, 27/27) had mean water turbidity values greater than the WHO drinking water recommended standards and the temperature of above 17 °C. In addition, 27% (3/11) of the lake sites and 2/5 of the ponds had pH and dissolved oxygen respectively outside the WHO recommended range of 6.5–8.5 for pH and less than 5 mg/L for dissolved oxygen. These physicochemical conditions were ideal for survival of Vibrio. cholerae.

Conclusions

This study showed that surface water and springs in the study area were unsafe for drinking and had favourable physicochemical parameters for propagation of waterborne diseases including cholera. Therefore, for Uganda to attain the SDG 6 targets and to eliminate cholera by 2030, more efforts are needed to promote access to safe drinking water. Also, since this study only established the vital water physicochemical parameters, further studies are recommended to determine the other water physicochemical parameters such as the nitrates and copper. Studies are also needed to establish the causal-effect relationship between V. cholerae and the physicochemical parameters.
Combined signaling of NF-kappaB and IL-17 contributes to Mesenchymal stem cells-mediated protection for Paraquat-induced acute lung injury
Authors: Zhang Lichun , Wang Yu , Shen Haitao , Zhao Min
Published: July 2020

Background

Paraquat (PQ) is an herbicide widely used in the world. PQ can cause pulmonary toxicity and even acute lung injury. Treatment for PQ poisoning in a timely manner is still a challenge for clinicians. Mesenchymal stem cell (MSC) transplantation has hold potentials for the treatment of several lung diseases including PQ poisoning. The aim of this study is to examine the mechanisms mediated by MSC transplantation to protect PQ-induced lung injury.

Methods

Here we performed the whole genome sequencing and compared the genes and pathways in the lung that were altered by PQ or PQ together with MSC treatment.

Results

The comparison in transcriptome identified a combined mitigation in NF-kappaB signaling and IL-17 signaling in MSC transplanted samples.

Conclusion

This study not only reiterates the important role of NF-kappaB signaling and IL-17 signaling in the pathogenesis of PQ-induced toxicity, but also provides insight into a molecular basis of MSC administration for the treatment of PQ-induced toxicity.
Patients’ and clinicians’ perspectives on a ‘fast-track’ pathway for patients with sciatica in primary care: qualitative findings from the SCOPiC stratified care trial
Authors: Saunders Benjamin , Konstantinou Kika , Artus Majid , Foster Nadine E , Bartlam Bernadette
Published: July 2020

Background

Sciatica is common and associated with significant impacts for the individual and society. The SCOPiC randomised controlled trial (RCT) (trial registration: ISRCTN75449581) tested stratified primary care for sciatica by subgrouping patients into one of three groups based on prognostic and clinical indicators. Patients in one group were ‘fast-tracked’ for a magnetic resonance imaging (MRI) scan and spinal specialist opinion. This paper reports qualitative research exploring patients’ and clinicians’ perspectives on the acceptability of this ‘fast-track’ pathway.

Methods

Semi-structured interviews were conducted with 20 patients and 20 clinicians (general practitioners, spinal specialist physiotherapists, spinal surgeons). Data were analysed thematically and findings explored using Normalisation Process Theory (NPT) and ‘boundary objects’ concept.

Results

Whilst the ‘fast-track’ pathway achieved a degree of ‘coherence’ (i.e. made sense) to both patients and clinicians, particularly in relation to providing early reassurance based on MRI scan findings, it was less ‘meaningful’ to some clinicians for managing patients with acute symptoms, reflecting a reluctance to move away from the usual ‘stepped care’ approach. Both groups felt a key limitation of the pathway was that it did not shorten patient waiting times between their spinal specialist consultation and further treatments.

Conclusion

Findings contribute new knowledge about patients’ and clinicians’ perspectives on the role of imaging and spinal specialist opinion in the management of sciatica, and provide important insights for understanding the ‘fast-track’ pathway, as part of the stratified care model tested in the RCT.

Future research into the early referral of patients with sciatica for investigation and specialist opinion should include strategies to support clinician behaviour change; as well as take into account the role of imaging in providing reassurance to patients with severe symptoms in cases where imaging reveals a clear explanation for the patient’s pain, and where this is accompanied by a thorough explanation from a trusted clinical expert.
Indocyanine green fluorescence-guided intraoperative detection of peritoneal carcinomatosis: systematic review
Authors: Baiocchi Gian Luca , Gheza Federico , Molfino Sarah , Arru Luca , Vaira Marco , Giacopuzzi Simone
Published: July 2020

Background

To review the available clinical data about the value of Indocyanine Green (ICG) fluorescence imaging for intraoperative detection of peritoneal carcinomatosis.

Methods

We conducted a systematic review, according to the PRISMA guidelines, for clinical series investigating the possible role of ICG fluorescence imaging in detecting peritoneal carcinomatosis during surgical treatment of abdominal malignancies. With the aim to analyze actual application in the daily clinical practice, papers including trials with fluorophores other than ICG, in vitro and animals series were excluded. Data on patients and cancer features, timing, dose and modality of ICG administration, sensitivity, specificity and accuracy of fluorescence diagnosis of peritoneal nodules were extracted and analyzed.

Results

Out of 192 screened papers, we finally retrieved 7 series reporting ICG-guided detection of peritoneal carcinomatosis. Two papers reported the same cases, thus only 6 series were analyzed, for a total of 71 patients and 353 peritoneal nodules. The investigated tumors were colorectal carcinomas in 28 cases, hepatocellular carcinoma in 16 cases, ovarian cancer in 26 cases and endometrial cancer in 1 case. In all but 4 cases, the clinical setting was an elective intervention in patients known as having peritoneal carcinomatosis. No series reported a laparoscopic procedure. Technical data of ICG management were consistent across the studies. Overall, 353 lesions were harvested and singularly evaluated. Sensitivity varied from 72.4 to 100%, specificity from 54.2 to 100%. Two series reported that planned intervention changed in 25 and 29% of patients, respectively.

Conclusion

Indocyanine Green based fluorescence of peritoneal carcinomatosis is a promising intraoperative tool for detection and characterization of peritoneal nodules in patients with colorectal, hepatocellular, ovarian carcinomas. Further prospective studies are needed to fix its actual diagnostic value on these and other abdominal malignancies with frequent spread to peritoneum.
Histopathological distinction of non-invasive and invasive bladder cancers using machine learning approaches
Authors: Yin Peng-Nien , KC Kishan , Wei Shishi , Yu Qi , Li Rui , Haake Anne R. , Miyamoto Hiroshi , Cui Feng
Published: July 2020

Background

One of the most challenging tasks for bladder cancer diagnosis is to histologically differentiate two early stages, non-invasive Ta and superficially invasive T1, the latter of which is associated with a significantly higher risk of disease progression. Indeed, in a considerable number of cases, Ta and T1 tumors look very similar under microscope, making the distinction very difficult even for experienced pathologists. Thus, there is an urgent need for a favoring system based on machine learning (ML) to distinguish between the two stages of bladder cancer.

Methods

A total of 1177 images of bladder tumor tissues stained by hematoxylin and eosin were collected by pathologists at University of Rochester Medical Center, which included 460 non-invasive (stage Ta) and 717 invasive (stage T1) tumors. Automatic pipelines were developed to extract features for three invasive patterns characteristic to the T1 stage bladder cancer (i.e., desmoplastic reaction, retraction artifact, and abundant pinker cytoplasm), using imaging processing software ImageJ and CellProfiler. Features extracted from the images were analyzed by a suite of machine learning approaches.

Results

We extracted nearly 700 features from the Ta and T1 tumor images. Unsupervised clustering analysis failed to distinguish hematoxylin and eosin images of Ta vs. T1 tumors. With a reduced set of features, we successfully distinguished 1177 Ta or T1 images with an accuracy of 91–96% by six supervised learning methods. By contrast, convolutional neural network (CNN) models that automatically extract features from images produced an accuracy of 84%, indicating that feature extraction driven by domain knowledge outperforms CNN-based automatic feature extraction. Further analysis revealed that desmoplastic reaction was more important than the other two patterns, and the number and size of nuclei of tumor cells were the most predictive features.

Conclusions

We provide a ML-empowered, feature-centered, and interpretable diagnostic system to facilitate the accurate staging of Ta and T1 diseases, which has a potential to apply to other types of cancer.
Invasive non-typhoidal Salmonella infections in sub-Saharan Africa: a systematic review on antimicrobial resistance and treatment
Authors: Tack Bieke , Vanaenrode Jolien , Verbakel Jan Y. , Toelen Jaan , Jacobs Jan
Published: July 2020

Background

Non-typhoidalSalmonella(NTS) are a frequent cause of invasive infections in sub-Saharan Africa. They are frequently multidrug resistant (co-resistant to ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol), and resistance to third-generation cephalosporin and fluoroquinolone non-susceptibility have been reported. Third-generation cephalosporins and fluoroquinolones are often used to treat invasive NTS infections, but azithromycin might be an alternative. However, data on antibiotic treatment efficacy in invasive NTS infections are lacking. In this study, we aimed to assess the spatiotemporal distribution of antimicrobial resistance in invasive NTS infections in sub-Saharan Africa and to describe the available evidence and recommendations on antimicrobial treatment.

Methods

We conducted a systematic review of all available literature on antimicrobial resistance and treatment in invasive NTS infections. We performed a random effects meta-analysis to assess the temporal distribution of multidrug resistance, third-generation cephalosporin resistance, and fluoroquinolone non-susceptibility. We mapped these data to assess the spatial distribution. We provided a narrative synthesis of the available evidence and recommendations on antimicrobial treatment.

Results

Since 2001, multidrug resistance was observed in 75% of NTS isolates from all sub-Saharan African regions (95% confidence interval, 70–80% and 65–84%). Third-generation cephalosporin resistance emerged in all sub-Saharan African regions and was present in 5% (95% confidence interval, 1–10%) after 2010. Fluoroquinolone non-susceptibility emerged in all sub-Saharan African regions but did not increase over time. Azithromycin resistance was reported in DR Congo. There were no reports on carbapenem resistance. We did not find high-quality evidence on the efficacy of antimicrobial treatment. There were no supranational guidelines. The “Access group” antibiotics ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol and “Watch group” antibiotics ceftriaxone, cefotaxime, and ciprofloxacin were recommended as the first-choice antibiotics in national guidelines or reviews. These also recommended (a switch to) oral fluoroquinolones or azithromycin.

Conclusions

In addition to the widespread multidrug resistance in invasive NTS infections in sub-Saharan Africa, resistance to third-generation cephalosporins and fluoroquinolone non-susceptibility was present in all regions. There was a lack of data on the efficacy of antimicrobial treatment in these infections, and supranational evidence-based guidelines were absent.
Bidirectional knotless barbed versus conventional smooth suture for closure of surgical wounds in inguinal castration in horses
Authors: Adler Ditte Marie Top , Østergaard Stine , Jørgensen Elin , Jacobsen Stine
Published: July 2020

Background

Castration of the stallion is one of the most frequently performed surgical procedures in the horse. Recently barbed suture materials for surgical wound closure were introduced to the market with manufacturers claiming that these sutures enhance speed and security as they eliminate the need to tie knots. Recently, it has been suggested that this type of suture may increase postoperative complications. This study aimed at investigating and comparing a bidirectional absorbable knotless barbed suture (KBS) to a conventional smooth suture (SS) for wound closure of inguinal castrations in the horse. This was done by evaluating short-term and post-discharge complications and by comparing the time spent on suturing the surgical wounds after bilateral inguinal castration, which was performed on 45 horses undergoing castration at The Large Animal Teaching Hospital at University of Copenhagen from September 2017 to May 2019.

Results

Short-term complications were few; at 24 h minor swelling occurred in 29 and 33% of horses sutured with KBS and SS respectively and cutaneous dehiscence during recovery occurred in two horses of each group. Post-discharge follow-up revealed that three horses needed veterinary attention for treatment of complications (scrotal swelling (n = 1, KBS); wound exudation (n = 1, SS) and wound dehiscence after return to pasture (n = 1, SS)). Wound closure was achieved 6 min faster with KBS than with SS (P < 0.0001).

Conclusions

Use of the KBS suture did not result in increased occurrence of postoperative complications. Wound closure was faster with KBS than with SS in equine bilateral inguinal castration. Our results show that KBS can safely be used in the horse following bilateral inguinal castrations without adverse effects and with a reduction in suturing time.
Occurrence of various pathogenic and opportunistic fungi in skin diseases of domestic animals: a retrospective study
Authors: Dworecka-Kaszak Bożena , Biegańska Małgorzata J. , Dąbrowska Iwona
Published: July 2020

Background

Fungal infection of animals or humans are common all over the world. Some of microorganisms like fungi, exist on the skin and can be transmitted onto other individuals, other animal species or even humans and cause skin infections. Moreover, they can be the causative agents of severe generalized infections especially in immunocompromised individuals. The study aimed to evaluate the most frequent etiological agents of skin diseases and to compare the prevalence of animal fungal infections in Poland, and to discuss the possibility of transmission to humans in Poland.

Results

The obtained results are culture based. The fungi most frequently isolated from group of animals with skin lesions were Malassezia pachydermatis (29.14%), and Candida yeasts (27.07%), and dermatophytes (23.5%), including Microsporum canis as majority of them (59.25%), and Trichophyton genus (40.7%), most of them T. mentagrophytes, while Malassezia pachydermatis represented (80%) of isolates in animals with otitis externa. In over 19% of positive fungal cultures obtained from external ear canals Candida yeasts, mainly C. albicans, were identified.

Conclusions

Dermatomycoses in companion animals are caused by both, mycelial fungi and yeasts. Most frequently isolated were Malassezia pachydermatis and Candida spp. Dermatophytes (Trichophyton, Microsporum), were also cultured, but the total number of these isolates seems to decrease. We have not found Cryptococcus neoformans in tested clinical samples.
LINC00667/miR-449b-5p/YY1 axis promotes cell proliferation and migration in colorectal cancer
Authors: Yu Juan , Wang Furang , Zhang Jun , Li Jing , Chen Xiaoguang , Han Guangsen
Published: July 2020

Background

Long non-coding RNAs (lncRNAs) have been defined as vital regulators in the progression of human cancers, including colorectal cancer (CRC). Long intergenic non-protein coding RNA 667 (LINC00667) is a tumor promoter in several cancer types, while its role in CRC remains to be unmasked. This study focused on exploring the potential function and regulatory mechanism of LINC00667 in CRC.

Methods

qRT-PCR analysis was applied to detect the expression of LINC00667 in CRC cells. Loss-of function assays revealed the role of LINC00667 silencing in regulating CRC cell proliferation, apoptosis and migration. In vivo study demonstrated the effect of LINC00667 silencing on CRC cell growth. Mechanism experiments were conducted to determine the upstream or the downstream molecular mechanism of LINC00667 in CRC cells.

Results

LINC00667 was expressed at high level in CRC cells. LINC00667 knockdown significantly inhibited CRC cell growth and migration. YY1 transcription factor induced the upregulation of LINC00667 in CRC cells by transcriptionally activating LINC00667. In addition, miR-449b-5p could interact with LINC00667 in CRC cells. Intriguingly, miR-449b-5p directly targeted to YY1, thus inhibiting YY1 expression. YY1 recovered the CRC cell functions impaired by LINC00667 silencing.

Conclusions

LINC00667 is transcriptionally activated by YY1 and promotes cell proliferation and migration in CRC by sponging miR-449b-5p to upregulate YY1.