bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Serum Creatinine Levels and Risk of Type 2 Diabetes Mellitus in Korea
Authors: Song Do Kyeong , Lee Hyejin , Hong Young Sun , Sung Yeon-Ah
Published: December 2020

Reduced skeletal muscle has been suggested as a risk factor for type 2 diabetes mellitus (T2DM). Serum creatinine is used as a surrogate for muscle mass. Therefore, low serum creatinine levels may be associated with an increased risk of T2DM. We aimed to evaluate the association between serum creatinine levels and the risk of T2DM. We analyzed a total of 264,832 nondiabetic adults in Korea. In men, serum creatinine levels and the risk for T2DM showed an inverse J-shaped association even after adjustment for age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and fasting plasma glucose. In women, there was a trend that serum creatinine levels were inversely associated with the risk of T2DM among those with serum creatinine below 1.1 mg/dl. However, serum creatinine levels were not significantly associated with the risk of T2DM after adjustment for age, BMI, SBP, DBP, and fasting plasma glucose. Reduced levels of serum creatinine were significantly associated with an increased risk of T2DM in men with creatinine below 1.20 mg/dl. There was a trend that decreased levels of serum creatinine were associated with an increased risk of T2DM among women, although this result was not statistically significant.
Optimality in COVID-19 vaccination strategies determined by heterogeneity in human-human interaction networks
Authors: Goldenbogen Björn , Adler Stephan , Bodeit Oliver , Wodke Judith , Escalera-Fanjul Ximena , Korman Aviv , Krantz Maria , Bonn Lasse , Torres Rafael Moran , Haffner Johanna , Karnetzki Maxim , Maintz Ivo , Mallis Lisa , Prawitz Hannah , Segelitz Patrick , Seeger Martin , Linding Rune , Klipp Edda
Published: December 2020

Interactions between humans cause transmission of SARS-CoV-2. We demonstrate that heterogeneity in human-human interactions give rise to non-linear infection networks that gain complexity with time. Consequently, targeted vaccination strategies are challenged as such effects are not accurately captured by epidemiological models assuming homogeneous mixing. With vaccines being prepared for global deployment determining optimality for swiftly reaching population level immunity in heterogeneous local communities world-wide is critical. We introduce a model that predicts the effect of vaccination into an ongoing COVID-19 outbreak using precision simulation of human-human interaction and infection networks. We show that simulations incorporating non-linear network complexity and local heterogeneity can enable governance with performance-quantified vaccination strategies. Vaccinating highly interactive people diminishes the risk for an infection wave, while vaccinating the elderly reduces fatalities at low population level immunity. Interestingly, a combined strategy is not better due to non-linear effects. While risk groups should be vaccinated first to minimize fatalities, significant optimality branching is observed with increasing population level immunity. Importantly, we demonstrate that regardless of immunization strategy non-pharmaceutical interventions are required to prevent ICU overload and breakdown of healthcare systems. The approach, adaptable in real-time and applicable to other viruses, provides a highly valuable platform for the current and future pandemics.
What a Stranded Whale With Scoliosis Can Teach us About Human Idiopathic Scoliosis
Authors: de Reuver Steven , IJsseldijk Lonneke , Homans Jelle , Willems Dorien , Veraa Stefanie , Stralen Marijn van , Kik Marja , Kruyt Moyo , Gröne Andrea , Castelein René
Published: December 2020

Scoliosis is a deformation of the spine that may have several known causes, but humans are the only mammal known to develop scoliosis without any obvious underlying cause. This is called ‘idiopathic’ and is the most common type. Recent observations showed that human scoliosis, regardless of its cause, has a relatively uniform three-dimensional anatomy. We hypothesize that scoliosis is a universal compensatory mechanism of the spine, independent of cause and/or species. We had the opportunity to study the rare occurrence of scoliosis in a whale (Balaenoptera acutorostrata) that stranded in July 2019 in the Netherlands. A multidisciplinary team of biologists, pathologists, veterinarians, taxidermists, radiologists and orthopaedic surgeons conducted necropsy and imaging analysis. (Dorso-)lateral blunt traumatic injury to two vertebrae caused an acute lateral deviation of the spine, which had initiated the development of compensatory curves in regions of the spine without anatomical abnormalities. Three-dimensional analysis of these compensatory curves showed strong resemblance with different types of human scoliosis, amongst which idiopathic. This suggests that any decompensation of spinal equilibrium can lead to a uniform response, regardless of underlying cause or species. The unique biomechanics of the upright human spine, with significantly decreased rotational stability, explains why only in humans this universal mechanism of scoliosis can occur without an obvious cause, and is thus still called ‘idiopathic’.
Student Perspectives of Extended Clinical Placements in Optometry: A Qualitative Study
Authors: Kirkman Jacqueline , Bentley Sharon , Armitage James , Woods Craig
Published: December 2020

BackgroundThe number of students enrolled in health courses at Australian universities is rising, increasing demand for clinical placements. Optometry students have historically undertaken clinical training in short-block rotations at University-led teaching clinics in metropolitan locations. This is changing, with some optometry programs adopting extended placements similar to the longitudinal clerkships seen in the medical field. These placements are conducted in private community-based practices across Australia and New Zealand with many incorporating a rural component to the training. This study sought to explore optometry students’ experience of extended placements. MethodsNine focus groups were undertaken with 42 final year optometry students upon completion of a 26 week placement (of which at least half was undertaken in a non-metropolitan area, or area where a shortage of optometrists has been identified). Focus groups were audio recorded and transcribed verbatim. Thematic analysis was conducted according to Braun and Clarke’s 6 step method. Key themes were determined following an inductive qualitative descriptive approach to analysis. ResultsFour key themes emerged from the analysis. ‘Changing identity’, was about how the students grew both personally and professionally, with the extended placement being considered the vital component that allowed students to begin thinking of themselves as clinicians. ‘Practicing resilience’ related to circumstances where students experienced personality clashes, miscommunications, bullying, and boundary crossing. ‘Optometrist under instruction’, related to students feeling that the placement was an ideal opportunity to trial the everyday reality of work without the obligation of an ongoing commitment or employment contract. Finally, ‘Rural practice is more rewarding’, was about practicing rurally being a ‘rite of passage’, a chance to seek different experiences, meet new people and for students to challenge themselves professionally. ConclusionsStudents felt that the placement prepared them for real-world practice. The majority of students enjoyed their placements. However, there were instances where the student-supervisor relationship was strained. This resulted in high levels of anxiety that was made worse by a perceived lack of university support. Students believed rural placements offered them a richer experience when compared with metropolitan placements.
Isolation and Characterization of a Halophilic Modicisalibacter Sp. Strain Wilcox from Produced Water
Authors: Marsh William , Heise Brenden , Krzmarzick Mark , Murdoch Robert , Fathepure Babu
Published: December 2020

We report the isolation a halophilic bacterium that degrades both aromatic and aliphatic hydrocarbons as the sole sources of carbon at high salinity from produced water. Phylogenetic analysis of 16S rRNA-gene sequences shows the isolate is a close relative of Modicisalibacter tunisiensis isolated from an oil-field water in Tunisia. We designate our isolate as Modicisalibacter sp. strain Wilcox. Genome analysis of strain Wilcox revealed the presence of a repertoire of genes involved in the metabolism of both aliphatic and aromatic hydrocarbons. Laboratory studies corroborated the predicted hydrocarbon degradation potential. The strain degraded benzene, toluene, ethylbenzene, and xylenes at salinities ranging from 0.016 to 4.0 M NaCl, with optimal degradation at 1 M NaCl. Also, the strain degraded phenol, benzoate, biphenyl and phenylacetate as the sole sources of carbon at 2.5 M NaCl. Among aliphatic compounds, the strain degraded n-decane and n-hexadecane as the sole sources of carbon at 2.5 M NaCl. Genome analysis also predicted the presence of many heavy metal resistance genes including genes for metal efflux pumps, transport proteins, and enzymatic detoxification. Overall, due to its ability to degrade many hydrocarbons and withstand high salt and heavy metals, strain Wilcox may prove useful for remediation of produced waters.
Comparison of Two Novel Swept-Source Optical Coherence Tomography Devices to A Partial Coherence Interferometry-Based Biometer
Authors: Chan Tommy , Yu Marco , Chiu Vivian , Lai Gilda , Leung Christopher , Chan Poemen
Published: December 2020

Purpose To evaluate the repeatability and agreement of cornea and biometry measurements obtained with two swept-source optical coherence tomography (SSOCT) and a partial coherence interferometry-based device.METHODS This is a cross-sectional study. Forty-eight eyes of 48 patients had three consecutive measurements for ANTERION (Heidelberg Engineering, Germany), CASIAII (Tomey, Japan) and IOLMaster500 (Carl Zeiss Meditec, USA) on the same visit. Mean keratometry (Km), central cornea thickness (CCT), anterior chamber depth (ACD) and axial length (AL) were recorded. Corneal astigmatic measurements were converted into vector components – J0 and J45. Intra-device repeatability and agreements of measurements amongst the devices were evaluated using repeatability coefficients (RCs) and Bland-Altman plots, respectively. RESULTS All devices demonstrated comparable repeatability for Km (p≥0.138). ANTERION had the lowest RC for J0 amongst the devices (p≤0.039). Systematic difference was found for the Km and J0 obtained with IOLMaster500 compared to either SSOCTs (p≤0.010). The ACD and AL measured by IOLMaster500 showed a higher RC compared with either SSOCTs (p<0.002). Systematic difference was found in CCT and ACD between the two SSOCTs (p<0.001), and in AL between ANTERION and IOLMaster500 (p<0.001), with a mean difference of 1.6 µm, 0.022mm and 0.021 mm, respectively. CONCLUSIONS Both SSOCTs demonstrated smaller test-retest variability for measuring ACD and AL compared with IOLMaster500. There were significant disagreement in keratometry and AL measurements between the SSOCTs and PCI-based device; their measurements should not be considered as interchangeable but the disagreement could be refined by readjustment of intraocular lens constant in clinical practice.
Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease
Authors: Lewis-Israeli Yonatan , Wasserman Aaron , Gabalski Mitchell , Ball Kristen , Volmert Brett , Yang Weiyang , Li Bo , Zou Jinyun , Ni Guangming , Pajares Natalia , Chatzistavrou Xanthippi , Zhou Chao , Qiu Zhen , Li Wen , Aguirre Aitor
Published: December 2020

Congenital heart defects (CHD) constitute the most common birth defect in humans, affecting approximately 1% of all live births. Our ability to understand how these disorders originate is hindered by our limited ability to model the complexity of the human heart in vitro. There is a pressing need to develop more faithful organ-like platforms recapitulating complex in vivo phenotypes to study human development and disease in vitro. Here we report a novel method to generate human heart organoids by self-assembly using pluripotent stem cells. Our method is fully defined, highly efficient, scalable, shows high reproducibility and is compatible with screening and high-throughput approaches. Human heart organoids (hHOs) are generated using a two-step canonical Wnt signaling modulation strategy using a combination of chemical inhibitors and growth factors in completely defined culture conditions. hHOs faithfully recapitulate human cardiac development and are similar to age-matched fetal cardiac tissues at the transcriptomic, structural and cellular level. hHOs develop sophisticated internal chambers with well-organized multi-lineage cell-type regional identities reminiscent of the heart fields and the atrial and ventricular chambers, as well as the epicardium, endocardium, and coronary vasculature, and exhibit functional activity. We also show that hHOs can recreate complex metabolic disorders associated with CHD by establishing the first in vitro human model of diabetes during pregnancy (DDP) to study embryonic CHD. morphological and metabolically effects of increased glucose and insulin, showing the capability of modeling the effects of diabetes during pregnancy (DDP). Our heart organoid model constitutes a powerful novel tool for translational studies in human cardiac development and disease.
Pregnancy Complications in Venezuelan Women With Malaria
Authors: Romero Mariestefany , Leiba Elizabeth , Carrión-Nessi Fhabián Stevens , Freitas-DeNobrega Diana Carolina , Gamardo Ángel , Chavero Melynar , Figuera Luisamy , Camejo-Ávila Natasha Andreína , Marcano María Victoria , Lopez-Perez Mary , Forero-Peña David Alberto
Published: December 2020

BackgroundPregnant women are particularly vulnerable to malaria infections, increasing the risk of maternal-foetal complications, mainly in areas of high endemicity. However, few studies of malaria in pregnancy (MiP) have been carried out in Latin America, a region with low endemicity and transmission of both, Plasmodium falciparum and P. vivax. Despite the high malaria burden in Venezuela in the last years, no recent studies of MiP have been conducted. Hence, epidemiological and clinical characteristics of pregnant women with malaria in Venezuela are described herein.MethodsA retrospective study in pregnant women attending to the “Ruíz y Páez” University Hospital Complex, Bolívar state, Venezuela between February and October, 2019 was carried out. Epidemiological, clinical, and laboratory information was analysed.ResultsThirty-seven out of 52 pregnant women analysed, were infected with P. vivax. Age ranged between 15 and 39 years, and adolescent pregnancies were common. Malaria infection was diagnosed mainly during the third trimester of pregnancy (63.4%). The distribution of symptoms and signs as well as clinical laboratory values was similar among Plasmodium spp. Although uncomplicated malaria was most frequent, 30% (13/52) had severe anaemia. A high proportion of studied women (44%) presented at least one complication during the pregnancy or delivery. Spontaneous abortion was recorded in four women, and three foetal deaths were observed. Six women had preterm delivery without any further complication.ConclusionsA high prevalence of maternal and foetal complications was found in the studied population, highlighting the requirement for a careful medical follow up during the prenatal check-ups, aimed to reduce the negative impact of malaria in the new-born and mother.
The Model and Strategic Design of Taoist Chinese Temples Built in the 19th Century in Klang Valley, Malaysia
Authors: Yeong YM , Utaberta Nangkula , ismail Nor Atiah Ismail , Rahman Khairul aidil Abd
Published: December 2020

Chinese Taoist temples feature distinctive architecture styles which signify Chinese descendants. Majority of these authentic designs are inherited and imitated from ancient China c. 1600–221 BC ( the Shang dynasty (商朝) c.1600-1046 BCE and Zhou dynasty (周朝) 1046-256 BC), particularly with regard to Geomancy or feng shui (风水). This paper aimed to investigate the design typology, model, and strategic design of Chinese Taoist temples constructed in the 19th century in Malaysia. Ten temples were selected for analysis, and these samples were assessed qualitatively under consolidation of building model for analyzation. Results revealed that none of the buildings formed a quadrangle; instead, these building models were merely strategized in either a rectangular or a square shape. This could be due to the topological features and scales of the buildings. The results also showed that all the sample buildings attempted to compromise the theory of quadrangle, which is a good mechanism for air ventilation. Only half of the sample buildings achieved the scientific theory of ‘efficient pollutant clearance’ for maintaining air quality within the interior of the buildings as the remaining 50% of the building samples did not have a water outlet built within the parameter of their courtyards. The findings suggest that the owners of these buildings may not have an in-depth understanding of the principle of ‘quadrangle’. Therefore, the author suggests that a model of design typology must be clearly formulated in order to conceptualize a better interior environment for Chinese Taoist temples.
DFT Study of the Structural, Electronic, Bonding Nature, NBO Analysis, and Thermodynamic Properties of Halogenated (F, Cl, Br) and Heteroatom (O, N, S) doped Cyclopropane
Authors: Ubana Emmanuel , Louis Hitler , Enudi Obieze C. , Edim Moses M. , David Prince , Ita Benedict I.
Published: December 2020

Background: The chemistry of cyclopropanes has been widely studied over the years as a result of its high reactivity which is due to its highly strained ring. The cyclopropane ring is highly significant in drug research as the 10th most frequently found ring in small molecules and as such, there is a need for research to improve further the reactivity of cyclopropanes in natural products and pharmaceuticals. In this work, we present an extremely comprehensive and detailed investigation on a variety of properties of cyclopropane including Geometrical properties, bonding nature, bond polarity index (BPI), natural bond orbitals (NBO), orbital charge analysis, Density of states (DOS), molecular electrostatic potential (MEP), UV-spectral analysis, electron ionization, affinity and accompanied process, local reactivity parameters and the effects of substitution of heteroatoms Nitrogen (N-doped C3H8), Oxygen (S-doped C3H8) and Sulphur (S-doped C3H8) each in the place of carbon atom (otherwise known as doping) and also the substitution effects of Fluorine, Chlorine and Bromine each on one hydrogen atom in cyclopropane molecule (halogenation) and investigate how it chemically affects the properties outlined above. Results: It is observed from conceptual (CDFT) results that S-doped C3S has the highest reactivity of all the molecules studied. The UV-spectral analysis also predicts doped C3S as the molecule that gives the highest Bathochromic shift of all the molecules. Some other properties studied also give us the most potential sites for electrophilic and nucleophilic attack by electrophiles and nucleophiles. The NBO investigation revealed the strongest stabilization to the cyclopropane molecule for the heteroatoms follow the trend C3S<C3N<C3O. It is also observed that for the halogens the strongest stabilization for the cyclopropane molecule follows the trend C3Br<C3Cl<C3F<C3. The strong intra-molecular hyperconjugation interaction of the 2-centered bond (BD) and CR electrons of C-C anti C-C bond in the ring leads to stabilization of the cyclopropane ring as evident from the order perturbation energy analysis. Conclusion: The results obtained from the research will help scientists further improve on the reactivity of cyclopropanes as a motif in drug discovery through substitution (halogenation) and doping with heteroatoms (O, S, N)
A Novel Heterozygous Missense Variant in YWHAG Gene Cause Early-Onset Epilepsy in a Chinese Family
Authors: Yi Zhi , Song Zhenfeng , Xue Jiao , Yang Chengqing , Li Fei , Pan Hua , Feng Xuan , Zhang Ying , Pan Hong
Published: December 2020

The authors have requested that this preprint be removed from Research Square.
Microbiomes Attached to Fresh Perennial Ryegrass- are Temporally Resilient and Adapt to Changing Ecological Niches
Authors: Huws Sharon , Edwards Joan. E. , Lin Wanchang , Rubino Francesco , Alston Mark , Swarbreck David , Caim Shabhonam , Stevens Pauline Rees , Pachebat Justin , Won Mi-Young , Oyama Linda B. , Creevey Christopher J. , Kingston-Smith Alison H.
Published: December 2020

BackgroundGut microbiomes, such as the rumen, greatly influence host nutrition due to their feed energy-harvesting capacity. We investigated temporal ecological interactions facilitating energy-harvesting at the fresh perennial ryegrass (PRG)-biofilm interface in the rumen using an in sacco approach and prokaryotic metatranscriptomic profiling. ResultsNetwork analysis identified two distinct sub-microbiomes primarily representing primary (<4h) and secondary (>4h) colonisation phases and the most transcriptionally active bacterial families (i.e Fibrobacteriaceae, Selemondaceae and Methanobacteriaceae) did not interact with either sub-microbiome, indicating non-cooperative behaviour. Conversely, Prevotellaceae had most transcriptional activity within the primary sub-microbiome (focussed on protein metabolism) and Lachnospiraceae within the secondary sub-microbiome (focussed on carbohydrate degradation). Putative keystone taxa, with low transcriptional activity, were identified within both sub-microbiomes, highlighting the important synergistic role of minor bacterial families, however, we hypothesise that they may be ‘cheating’ in order to capitalise on the energy-harvesting capacity of other microbes. In terms of chemical cues underlying transition from primary to secondary colonisation phases, we suggest that AI-2 based quorum sensing plays a role, based on LuxS gene expression data, coupled with changes in PRG chemistry. ConclusionsIn summary, we show that fresh PRG-attached prokaryotes are resilient and adapt quickly to changing niches. This study provides the first major insight into the complex temporal ecological interactions occurring at the plant-biofilm interface within the rumen. The study also provides valuable insights into potential plant breeding strategies for development of the utopian plant, allowing optimal sustainable production of ruminants.
Estimating Landscape Vulnerability to Soil Erosion by RUSLE Model Using GIS and Remote Sensing: A Case of Zariema watershed, Northern Ethiopia
Authors: Hagos Yonas
Published: December 2020

Background:Zariema watershed located in the Tekeze basin Northern highlands of Ethiopia has been a subject to serious problem of soil erosion. Soil degradation due to soil erosion is one of the key environmental and socioeconomic case which threats soil nutrient depletion and food security in northern Ethiopian highlands. This study was conducted to estimate the soil loss rate and identify hotspot areas using RUSLE model in the Zariema watershed, Tekeze basin, Ethiopia.Methods:The rainfall – runoff erosivity(R) factor was determined from mean annual rainfall, soil erodibility(K) factor from soil map, Topographic factor (Ls) were generated from DEM, Crop management factor (C) and Conservation support practice factor(P) obtained from land use/land cover map. Finally, the factors were integrated with Arc GIS 10.3 tools to estimate soil loss rates and landscape vulnerability to soil erosion of the study watershed. Results:Annual Soil losses rates were estimated to be between 0 ton ha-1 year-1 in plain areas and 989 ton ha-1 year-1 in steep slope areas of the study watershed. The total annual soil loss from the entire watershed area of 2239.33Sq. Km was about 3,603,895.23 tons. About 31.41% of the study areas were affected through the soil loss hazard which is above acceptable soil loss rate 11 ton ha-1 year-1. The spatial hazard classification rate was 68.59% of the watershed area categorized as slight (0 – 11 ton ha-1 year-1), 8.03% moderate (12 – 18 ton ha-1 year-1), 7.64% high (19 – 30 ton ha-1 year-1), 6.65% very high (31 – 50 ton ha-1 year-1) and 9.09% severe (>51 ton ha-1 year-1). Conclusion:As a result, In the cultivation land around steep slope the soil loss rate was in sever condition. To mitigate the severity of the soil erosion in the identified prone area which accounts for about 31.41% of the total watershed area immediate action of soil and water conservation required.
Bioinformatics Analysis of the Expression and Role of microRNA-221-3p in the Head and Neck Squamous Cell Carcinoma
Authors: Zhou Ziyan , Wu Wenling , Li Jixi , Liu Chang , Xiao Zixi , Lai Qinqiao , Qin Rongxing , Shen Mingjun , Shi Shuo , kang min
Published: December 2020

BackgroundHead and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer subtype globally, associated with a high rate of morbidity and mortality. However, the target genes of miR-221-3p and the underlying mechanism involved in HNSCC were not known. Therefore, in the current study, we studied the role of miR-221-3p in the HNSCC. MethodsTissues collected from 48 control and 21 HNSCC patients were processed to check the differential expression of miR-221-3p by RT-qPCR. Overexpression of microRNA-221-3p (miR-221-3p) is significantly correlated to the onset and progression of HNSCC. We also conducted the meta-analysis of the cancer literature from the cancer genome atlas (TCGA) and the Gene Expression Omnibus (GEO) database to estimate the expression of miR-221-3p in HNSCC. The miR-221-3p target genes in the HNSCC were predicted with the miRWalk and TCGA databases, and functionally annotated via the Gene Ontology Finally, Spearman’s analysis was used to determine the role of the related target genes in important pathways involved in the development of HNSCC. ResultsWe observed a significantly higher expression of miR-221-3p in HNSCC compared to the normal with a summary receiver operating characteristic (sROC) of 0.86(95% Cl: 0.83,0.89). The KEGG and GO comprehensive analysis predicted that miR-221-3p might be involved in the development of HNSCC through the following metabolic pathways, viz Drug metabolism - cytochrome P450 UGT1A7 and MAOB may be important genes for the role of mir-221-3p.ConclusionsOur results indicate that miR-221-3p may be used as a non-invasive and hypersensitive biomarker in the diagnosis. Thus, it can be concluded that miR-221-3p is an extremely important gene locus involved in the process of the deterioration and eventual tumorigenesis of HNSCC.
Identification and Clinical Validation of Genes Signatures with Grade and Survival in Head and Neck Carcinomas
Authors: Ma Wei , Cao Qing , She Wandong
Published: December 2020

Background: The mechanism of transition from low-grade to high-grade head and neck carcinomas (HNC) still remains unclear. This study aimed to explore the genes expression profiles that drive malignancy from low to high-grade HNC, as well as analyze their correlations with survival.Methods: Gene expressions and clinical data of HNC were downloaded from the Gene Expression Omnibus (GEO) repository. The significantly different genes (SDGs) between low and high-grade HNC were screened by GEO2R tool and R software. Bioinformatics functions of SDGs were investigated by the enrichment analyses. Univariate and multivariate cox regressions were performed to identify prognostic SDGs of progression-free survival (PFS) and disease-specific survival (DSS). Receiver operating curve (ROC) was established to evaluate the ability to predict the prognosis. Then, the correlations between SDGs and clinical features were evaluated. The genes were experimentally validated by RT-PCR in clinical specimens.Results: 35 SDGs were identified in 47 low-grade and 30 high-grade HNC samples. Enrichment analysis showed these SDGs were enriched in the DNA repair pathway and the regulation of I−kappaB kinase/NF−kappaB signaling pathway. Cox regression analyses showed that CXCL14, SLC44A1 and UBD were significantly associated with DSS, and PPP2R2C and SLC44A1 were associated with PFS. Patients at a high-risk or low-risk for prognosis were established based on genes signatures. High-risk patients had significantly shorter DSS and PFS than low-risk patients (P=0.033, 0.010 respectively). Multivariate cox regression showed human papillomavirus (HPV) (P=0.033), lymph node status (P=0.032) and residual status (P＜0.044) were independent risk factors for PFS. ROC curves showed the risk score had better efficacy to predict survival both for DSS and PFS (AUC=0.858, 0.901 respectively). In addition, we found UBD, PPP2R2C and risk score were significantly associated with HPV status (all P＜0.05). The experiment results showed CXCL14 and SLC44A1 were significantly overexpressed in the HNC grade I/II tissues and the UBD was overexpressed in the HNC grade III/IV tissues.Conclusions: Our results suggested that SDGs had different expression profiles between the low-grade and high-grade HNC, and these genes may serve as prognostic biomarker to predict the survival.
Bridging the Research to Practice Gap: A Systematic Scoping Review of Implementation of Interventions for Cancer-Related Fatigue Management
Authors: Agbejule Oluwaseyifunmi Andi , Hart Nicolas H. , Ekberg Stuart , Koczwara Bogda , Ladwa Rahul , Simonsen Camilla , Pinkham Elizabeth P , Chan Raymond Javan
Published: December 2020

Background. Cancer-related fatigue (CRF) is one of the most common and distressing symptoms in people with cancer. Whilst efficacy of interventions for CRF have been extensively investigated, less has been done to ensure successful translation into routine clinical practice. The aim of this systematic scoping review was to synthesise knowledge surrounding the implementation of CRF interventions, summarise the processes and outcomes of implementation strategies used, and identify opportunities for further research.Methods. PubMed, Cochrane CENTRAL, EMBASE and CINAHL databases were searched through to December 2020. The Cochrane Effective Practice and Organisation of Care (EPOC) Group taxonomy and the RE-AIM Framework were used to guide the evaluation of implementation strategies and outcomes, respectively. Results. Six studies were included. Three used implementation frameworks (PARIHS, KTA, Cullens & Adams’ Implementation Guide) to guide implementation. Overall, the implementation strategies used across all studies were reported to have directly resulted in immediate changes at the clinician level (e.g., increased clinician behaviours, self-efficacy, attitudes, knowledge of CRF management). No clear relationship was found between the use of implementation models and the number or type of implementation strategies used. For outcomes, Effectiveness and Implementation were the most highly reported RE-AIM measures followed by Reach then Maintenance. Adoption was the least reported.Conclusions. Despite the high prevalence of CRF and evidence-based interventions for managing CRF, there is limited evidence informing the sustainable implementation of these interventions. There was an absence of external indicator reporting (e.g., start-up and ongoing intervention costs) in included studies, limiting the transability of study findings. Further, factors such as lack of clinician time, insufficient program funding, and unsustainable maintenance costs, were highlighted as key implementation barriers of CRF programs. This scoping systematic review emphasises the lack of quality CRF implementation studies presently available in the literature leading to a disconnect between effective CRF interventions, routine clinical care, and cancer survivors at present. Further, this review also highlights the need for robust study designs guided by established frameworks to methodically design and evaluate the implementation of CRF management interventions in the future.
The value of complete remission according to positron emission tomography prior to autologous stem cell transplantation in lymphoma: a population-based study showing improved outcome
Authors: Noring Kristina , Carlsten Mattias , Sonnevi Kristina , Wahlin Björn
Published: December 2020

Background

Chimeric antigen-receptor T-cell and bispecific antibody therapies will likely necessitate a reconsideration of the role of autologous stem-cell transplantation (ASCT) in lymphoma. Patients who are likely to profit from ASCT need to be better identified.
Methods

Here, we investigated the value of positron emission tomography/computerized tomography (PET/CT) before ASCT. All 521 patients transplanted for lymphoma 1994–2019 at Karolinska (497 conditioned with BEAM) were included.
Results

Outcome improved over three calendar periods 1994–2004, 2005–2014, 2015–2019 (2-year overall survival [OS]: 66%, 73%, 83%; P = 0.018). Non-relapse mortality (NRM) at 100 days over the three periods were 9.8%, 3.9%, 2.9%, respectively. The OS improvement between 1994–2004 and 2005–2014 was due to lower NRM (P = 0.027), but the large OS advance from 2015 was not accompanied by a significant reduction in NRM (P = 0.6). The fraction of PET/CT as pre-ASCT assessment also increased over time: 1994–2004, 2%; 2005–2014, 24%; 2015–2019, 60% (P < 0.00005). Complete responses (PET/CT-CR) were observed in 77% and metabolically active partial responses (PET/CT-PR) in 23%. PET/CT-CR was a predictor for survival in the entire population (P = 0.0003), also in the subpopulations of aggressive B-cell (P = 0.004) and peripheral T-cell (P = 0.024) lymphomas. Two-year OS and progression-free survival (OS/PFS) for patients in PET/CT-CR were in relapsed/refractory aggressive B-cell lymphoma 87%/75% and peripheral T-cell lymphoma 91%/78%. The corresponding figures in PET/CT-PR were 43%/44% and 33%/33%. Patients with solitary PET/CT-positive lesions showed acceptable outcome with ASCT followed by local irradiation (2-year OS/PFS 80%/60%). CT was less discriminative: 2-year OS/PFS: CT-CR, 76%/66%; CT-PR, 62%/51%. Outcome was inferior after BEAC compared with BEAM conditioning.
Conclusions

We conclude that the improved outcome reflects better, PET/CT-informed, identification of patients who should proceed to ASCT. The excellent survival of patients in PET/CT-CR indicates that ASCT should remain part of standard therapy for lymphoma.
WITHDRAWN: Effects of dietary Clostridium butyricum supplementation on growth performance, intestinal barrier function, immune response, and intestinal permeability in broiler chickens with necrotic enteritis
Authors: xu xiao , Yang Shunli , Olajide Joshua Seun , Qu Zigang , Gong Zhenxing , Wang Jing , Zhang Yanbing , Wang Heng , Xiong Ling , Zhang Kun , Zhou Enmin , Cai Jianping
Published: December 2020

Background
Necrotic enteritis (NE), which is caused by Clostridium perfringens (C. perfringens), is an economically important disease in broiler. Among normal flora in the broiler intestinal, Clostridium butyricum (C. butyricum) has been identified as a probiotic agent that reduces the susceptibility of broilers to C. perfringens. It also promotes the repair of broiler intestinal damage from harmful intestinal pathogens. However, the effects of C. butyricum infection on broiler intestinal integrity during NE are largely unknown. In this study, we investigated the effects of C. butyricum on the growth performance, intestinal morphology and barrier function, and the functions of immune-related cytokines under NE in broilers.
Results
Infected group (PC) showed significant decrease in the average daily gain (ADG, p < 0.01) and increase in feed conversion ratio (FCR, p < 0.01) compared with C. butyricum (NECB1 and NECB2) through dietary supplement. Supplementation of C. butyricum (NECB1 and NECB2) restored the intestinal villus height, increased the crypt depth, and reduced the intestinal damage under NE. Furthermore, broilers infected with NE (PC) had higher serum IgA and endotoxin content, and after addition with C. butyricum (NECB1 and NECB2) returned to normal level. In addition, compared with PC, supplementation of C. butyricum (NECB1 and NECB2) restored intestinal barrier function-related genes (such as CLDN-1, CLDN-3, OCLN, MUC2, ZO-1, and CLDN5), cytokines (such as TNF-α, IL-10, IL-6, and TGFB1) and C. perfringens plc gene expression. Moreover, C. butyricum (NECB1 and NECB2) could restore the decrease in Gt (p < 0.01) and Isc caused by NE (PC). In addition, NECB2 reduced the upregulation of FD4 flux caused by NE infection (p < 0.01).
Conclusion
Dietary supplementation of C. butyricum into broilers with NE improved chicken growth performance, intestinal morphology, intestinal barrier function, and immune function. Notably, no statistical difference was observed with the addition of C. butyricum at different time points.
Clinical Outcomes After Endovascular and Microsurgical Treatment of Very Small Intracranial Aneurysms: Report of a Consecutive Series and Meta-analysis
Authors: Zheng Jianfeng , Sun Xiaochuan , Zhang Xiaodong
Published: December 2020

Objective: We conducted a systematic review and meta-analysis of studies evaluating endovascular coiling or microsurgical clipping of very small intracranial aneurysms (IAs), including 126 patients treated in our center.Data Sources: The electronic database of PubMed, Embase, and Web of Science were systematically searched for studies on endovascular or microsurgical treatment of very small IAs. The search was performed by using the keywords and medical subject heading (MeSH) terms: “intracranial aneurysm,” “cerebral aneurysm,” “outcome,” “endovascular,” “coil,” “embolization,” “coiling,” “surgical,” “neurosurgical,” “microsurgical,” “clip,” “clipping,” “small,” and “tiny” in both AND and OR combinations.Study Selection: Only studies of very small (Size ≤ 3 mm) ruptured or unruptured IAs patients undergoing endovascular coiling or microsurgical clipping were included.Data Extraction: Data collection and quality assessment were conducted independently by two authors.Data Synthesis: A total of 6 studies provided data on 362 very small UIAs and 9 studies provided data on 703 very small RIAs. Of 362 patients with very small UIAs, 6 (1.7%) cases had operation-related neurological deficits, and no patient died. Of 731 patients with very small RIAs, the morbidity and mortality were 13.0% and 4.7%, respectively. Morbidity due procedure-related complications was 8.3% (95% CI, 3.5% to 13.1%) in coiled very small RIAs patients compared with 20.6% (95% CI, 10.5% to 30.8%) in clipped very small RIAs patients. Mortality due to procedure-related complications was 5.3% (95% CI, 2.9% to 7.7%) in coiled very small RIAs patients compared with 4.7% (95% CI, 2.0% to 7.3%) in clipped very small RIAs patients. No significant differences were found in the incidence of poor outcomes observed between microsurgical and endovascular treatment for very small RIA patients (RR, 1.38; 95% CI, 0.99 - 1.93; P = 0.06).Conclusions Very small UIAs can be treated effectively and safely with good long-term outcomes. However, very small RIAs patients are at high risk of poor outcome and the incidence of neurological complication should not be ignored.
Intravenous Immunoglobulin Rich in Neutralising Antibodies to SARS-CoV-2 as a Passive Immunity Modality in Healthy Individuals at Risk of Infection With COVID-19: Study Protocol for an Open Label, Active Control Phase 1/2 Study.
Authors: Gavagna Guy , Clifton-Bligh Roderick , Lemech Charlotte , Williams Suzanne , Elefantis Elena , Nair Hari , Farrugia Albert
Published: December 2020

Background The COVID-19 pandemic has demonstrated the fragility of our healthcare systems and the need for rapid development of effective care strategies. Global efforts to develop novel therapeutics have intensified, but in late November 2020, few are approved. There is an urgent need for novel therapeutics to limit further spread of COVID-19. Passive immunity by infusing neutralising anti-SARS-CoV-2 antibodies provides a method to prevent infection in individuals at heightened risk such as frontline health care workers. Convalescent plasma (CP) collected from donors who have recovered from an infectious disease can be pooled and fractionated into hyperimmune intravenous immunoglobulin (HIVIG), a concentrated formulation with enriched levels of pathogen-specific antibodies. HIVIG are established for therapeutic and prophylactic administration across many infectious diseases and possess many advantages over CP including consistent high titres of antiviral antibodies without ABO matching or risk of transfusion related acute lung injury (TRALI) or transfusion associated circulatory overload (TACO), lower infusion volume, simpler storage, longer shelf life, and easier administration. Method A parallel group, open-label, active control, phase 1/2 trial which allocates healthy adult healthcare workers never infected with SARS-CoV-2 to receive a single intravenous infusion of either CP or HIVIG. This clinical trial is the first to establish whether a HIVIG preparation concentrated with antibodies to SARS-CoV-2 is safe when administered to healthcare workers in the prevention of COVID-19, and to assess whether the anti-SARS-CoV-2 antibodies in the HIVIG are pharmacokinetically equivalent to those in unmodified CP.Discussion Trials to date suggest that allocation of limited CP may be optimised if used for prevention rather than treatment of COVID-19. This HIVIG (CovimmuneTM, Aegros Ltd.) is manufactured by a novel plasma fractionation technology (HaemaFracTM, Aegros Ltd.) which offers high purity and a greater protein yield from smaller batches of starting plasma than is possible with conventional fractionation techniques. If successful, this approach can be rapidly scaled up for implementation into clinical practice and contribute to the sustainability of healthcare systems during the current and future pandemics. The more prevention and treatment options available to address the COVID-19 pandemic, the stronger the position our society will hold. Trial registration Australia & New Zealand Clinical Trials Registry. Registration number: ACTRN12620001249943p. Date: 20/11/2020. https://www.anzctr.org.au/ACTRN12620001249943p.aspx
Unraveling the ecological processes modulating the population structure of Escherichia coli in a highly polluted urban stream network
Authors: Saraceno Martín , Lugo Sebastián Gómez , Ortiz Nicolás , Gómez Bárbara , García Carmen Sabio y , Frankel Nicolás , Graziano Martín
Published: December 2020

Escherichia coli dynamics in urban watersheds are affected by a complex balance among external inputs, niche modulation and genetic variability. To explore the ecological processes influencing E. coli spatial patterns, we analyzed its abundance and phylogenetic structure in water samples from a stream network with heterogeneous urban infrastructure and environmental conditions. Our results showed that environmental and infrastructure variables, such as macrophyte coverage, DIN and sewerage cover, mostly explained E. coli abundance, with a negative relationship between abundance and phylogroup richness. Moreover, main generalist phylogroups A and B1 were found in high proportion, which, together with an observed negative relationship between E. coli abundance and phylogroup richness suggests that their dominance is due to competitive exclusion. Low-frequency taxa were associated with sites of higher ecological disturbance, mainly involving simplified habitats, higher drainage infrastructure and septic tank density. In addition to the strong positive relationship between phylogroup richness and evenness, the occurrence of these phylogroups would be associated with increased facilitated dispersal. Nutrients also contributed to explaining phylogroup distribution. Our study highlights the differential contribution of distinct ecological processes to the patterns of E. coli in an urban watershed, which is useful for the monitoring and management of fecal pollution.
WITHDRAWN: Autoantibody to the Rab6A/Rab6B in Autoimmune Cerebellar Ataxia Associated with Sjogren’s Syndrome
Authors: Guo Liyuan , Ren Haitao , Fan Siyuan , Guan Hongzhi , Wang Jing
Published: December 2020

Background To report a novel autoantibody against Purkinje cell in a patient with autoimmune cerebellar ataxia (ACA) associated to Sjogren’s syndrome (SS).Methods The Patients on one centre with cerebellar ataxia of unknown cause, who were tested positive with tissue-based indirect immunofluorescence assay (TBA) on rat cerebellum sections and negative for comprehensive anti-neural autoantibodies panel, were investigated for novel autoantibody identification. Among them, one patient with comorbid ACA and SS was qualified for further exploration. His-immunoprecipitation (HIP) combined with mass spectrometric (MS) analysis was used to identify the target antigen, which was confirmed by recombinant cell based assay (CBA) and antibody neutralization experiments. Results TBA of the patient’s serum and cerebrospinal fluid (CSF) for autoantibody testing revealed binding of IgG antibody, mainly IgG1, to Purkinje cell and granular layer of rat cerebellum. Rab6A was identified as the autoantigen by MS and Western blot, subsequently verified by CBA with HEK293 cells expressing human Rab6A/Rab6B. Furthermore, recombinant human Rab6A/Rab6B protein to neutralize the autoantibodies’ tissue reaction was performed by a parallel confirmed approach.Conclusion Autoantibody against Rab6A/Rab6B may be a novel biomarker in diagnosis of ACA, especially in patients with comorbid ACA and SS. The role of the antibody in mechanism of ACA warrants further study.
Socio-cultural and economic barriers, and facilitators influencing men’s involvement in antenatal care including HIV testing: A qualitative study from urban Blantyre, Malawi
Authors: Sakala Doreen , Kumwenda Moses K. , Conserve Donaldson F. , Ebenso Bassey , Choko Augustine Talumba
Published: December 2020

Background Male partner involvement in antenatal care (ANC) is associated with positive maternal and neonatal outcomes. However, only a handful of men attend ANC with their partners. This study aimed to understand the underlying barriers and facilitators influencing men’s ANC attendance including HIV testing in Blantyre, Malawi.Methods Data were collected during a formative qualitative study of a cluster-randomised trial. Six focus group discussions (FGDs) with 42 men and women and 20 in-depth interviews (IDIs) were conducted at three primary health centres in urban Blantyre, Malawi. FGD participants were purposively sampled with IDI participants subsequently sampled after FGD participation. Thematic analysis was used to analyse the data.Results The economic requirement to provide for their families exerted pressure on men and often negatively affected their decision to attend ANC together with their pregnant partners despite obvious benefits. Peer pressure and the fear to be seen by peers queueing for services at ANC, an environment traditionally viewed as a space for women and children made men feel treated as trespassers and with some level of hostility rendering them feeling emasculated when they attend ANC. Health system problems associated with overall organization of the ANC services, which favours women created resistance among men to be involved. An association between ANC and HIV testing services discouraged men from attending ANC because of their fear of testing HIV-positive in the presence of their partners. The availability of a male friendly clinic offering a private, quick, supportive/sensitive and flexible service was considered to be an important incentive that would facilitate male men’s ANC attendance. Men described compensation to cover transport and opportunity cost for attending the clinic as a motivator to attending ANC services and accepting an HIV test. Conclusion Peer and economic influences were the most influential barriers of men attending ANC and testing for HIV with their pregnant partners. Addressing these socio-economic barriers and having a male friendly clinic are promising interventions to promote male ANC attendance in this setting.