bluuebunny/crossref_metadata_2025 huggingface dataset:
Omics-based tracking ofPseudomonas aeruginosapersistence in “eradicated” cystic fibrosis patients
Authors: Bartell Jennifer A. , Sommer Lea M. , Marvig Rasmus L. , Skov Marianne , Pressler Tacjana , Molin Søren , Johansen Helle Krogh
Published: October 2020

WheneverPseudomonas aeruginosais cultured from cystic fibrosis (CF) patient airways, the primary goal is eradication by antibiotic therapy. Success is defined by ≥6 months of negative bacterial airway cultures. However, we suspect thatP. aeruginosapersists in airways without clinical detection for long periods.

Out of 298P. aeruginosa-infected Copenhagen CF patients, we identified 80 with completeP. aeruginosamonitoring records and measured their maximumP. aeruginosa-free eradication periods (MEP). Isolates from 72 patients were whole-genome sequenced (n=567) and clone typed. Select isolate relatedness was examined through phylogenetic analysis and phenotypic multivariate modelling.

69 (86%) patients exhibited eradication in the monitoring period (2002–2018). Sequenced isolates bridged the MEP of 42 patients, and the same clone type persisted over the MEP in 18 (43%) patients. Patients with failed eradication were on average treated more intensively with antibiotics, but this may be linked to their more severe pre-MEP infection trajectories. Of the 42 patients, 26 also had sinus surgery; the majority (n=15) showed MEPs adjacent to surgery, and only five had persisting clone types. Importantly, combined phylogenetic–phenomic evaluation suggests that persisting clone types are a result of re-emergence of the same strain rather than re-infection from the environment, and similar relatedness is exhibited by paired lower and upper airway samples and in transmission cases.

In conclusion, nearly half of CF patients with supposed eradication may not truly be cleared of their original bacteria according to omics-based monitoring. This distinct cohort that is persistently infected would probably benefit from tailored antibiotic therapy.
Real world effects of COPD medications: a cohort study with validation against results from randomised controlled trials
Authors: Wing Kevin , Williamson Elizabeth , Carpenter James R. , Wise Lesley , Schneeweiss Sebastian , Smeeth Liam , Quint Jennifer K. , Douglas Ian
Published: October 2020

Real-world data provide the potential for generating evidence on drug treatment effects in groups excluded from trials, but rigorous, validated methodology for doing so is lacking. We investigated whether non-interventional methods applied to real-world data could reproduce results from the landmark TORCH COPD trial.

We performed a historical cohort study (2000–2017) of COPD drug treatment effects in the UK Clinical Practice Research Datalink (CPRD). Two control groups were selected from CPRD by applying TORCH inclusion/exclusion criteria and 1:1 matching to TORCH participants, as follows. Control group 1: people with COPD not prescribed fluticasone propionate (FP)-salmeterol (SAL); control group 2: people with COPD prescribed SAL only. FP-SAL exposed groups were then selected from CPRD by propensity score matching to each control group. Outcomes studied were COPD exacerbations, death from any cause and pneumonia.

2652 FP-SAL exposed people were propensity score matched to 2652 FP-SAL unexposed people while 991 FP-SAL exposed people were propensity score matched to 991 SAL exposed people. Exacerbation rate ratio was comparable to TORCH for FP-SALversusSAL (0.85, 95% CI 0.74–0.97versus0.88, 0.81–0.95) but not for FP-SALversusno FP-SAL (1.30, 1.19–1.42versus0.75, 0.69–0.81). In addition, active comparator results were consistent with TORCH for mortality (hazard ratio 0.93, 0.65–1.32versus0.93, 0.77–1.13) and pneumonia (risk ratio 1.39, 1.04–1.87versus1.47, 1.25–1.73).

We obtained very similar results to the TORCH trial for active comparator analyses, but were unable to reproduce placebo-controlled results. Application of these validated methods for active comparator analyses to groups excluded from randomised controlled trials provides a practical way for contributing to the evidence base and supporting COPD treatment decisions.
A genome-wide association study of severe asthma exacerbations in Latino children and adolescents
Authors: Yan Qi , Forno Erick , Herrera-Luis Esther , Pino-Yanes Maria , Qi Cancan , Rios Raimon , Han Yueh-Ying , Kim Soyeon , Oh Sam , Acosta-Pérez Edna , Zhang Rong , Hu Donglei , Eng Celeste , Huntsman Scott , Avila Lydiana , Boutaoui Nadia , Cloutier Michelle M. , Soto-Quiros Manuel E. , Xu Cheng-Jian , Weiss Scott T. , Lasky-Su Jessica , Kiedrowski Megan R. , Figueiredo Camila , Bomberger Jennifer , Barreto Mauricio L. , Canino Glorisa , Chen Wei , Koppelman Gerard H. , Burchard Esteban G. , Celedón Juan C.
Published: October 2020

Severe asthma exacerbations are a major cause of school absences and healthcare costs in children, particularly those in high-risk racial/ethnic groups.

To identify susceptibility genes for severe asthma exacerbations in Latino children and adolescents, we conducted a meta-analysis of genome-wide association studies (GWAS) in 4010 Latino youth with asthma in four independent cohorts, including 1693 Puerto Ricans, 1019 Costa Ricans, 640 Mexicans, 256 Brazilians and 402 members of other Latino subgroups. We then conducted methylation quantitative trait locus, expression quantitative trait locus and expression quantitative trait methylation analyses to assess whether the top single nucleotide polymorphism (SNP) in the meta-analysis is linked to DNA methylation and gene expression in nasal (airway) epithelium in separate cohorts of Puerto Rican and Dutch children and adolescents.

In the meta-analysis of GWAS, an SNP inFLJ22447(rs2253681) was significantly associated with 1.55 increased odds of severe asthma exacerbation (95% CI 1.34–1.79, p=6.3×10−9). This SNP was significantly associated with DNA methylation of a CpG site (cg25024579) at theFLJ22447locus, which was in turn associated with increased expression ofKCNJ2-AS1in nasal airway epithelium from Puerto Rican children and adolescents (β=0.10, p=2.18×10−7).

SNP rs2253681 was significantly associated with both DNA methylation of a cis-CpG inFLJ22447and severe asthma exacerbations in Latino youth. This may be partly explained by changes in airway epithelial expression of a gene recently implicated in atopic asthma in Puerto Rican children and adolescents (KCNJ2-AS1).
Donor-derived, cell-free DNA levels by next-generation targeted sequencing are elevated in allograft rejection after lung transplantation
Authors: Khush Kiran K. , De Vlaminck Iwijn , Luikart Helen , Ross David J. , Nicolls Mark R.
Published: October 2020

Surveillance after lung transplantation is critical to the detection of acute cellular rejection (ACR) and prevention of chronic lung allograft dysfunction (CLAD). Therefore, we measured donor-derived cell-free DNA (dd-cfDNA) implementing a clinical-grade, next-generation targeted sequencing assay in 107 plasma samples from 38 unique lung transplantation recipients with diagnostic cohorts classified as: (1) biopsy-confirmed or treated ACR, (2) antibody-mediated rejection (AMR), (3) obstructive CLAD, (4) allograft infection (INFXN) and (5) Stable healthy allografts (STABLE). Our principal findings are as follows: (1) dd-cfDNA level was elevated in ACR (median 0.91%; interquartile range (IQR): 0.39–2.07%), CLAD (2.06%; IQR: 0.57–3.67%) and an aggregated cohort of rejection encompassing allograft injury (1.06%; IQR: 0.38–2.51%), compared with the STABLE cohort (0.38%; IQR: 0.23–0.87%) (p=0.02); (2) dd-cfDNA level with AMR was elevated (1.34%; IQR: 0.34–2.40%) compared to STABLE, although it did not reach statistical significance (p=0.07) due to limitations in sample size; (3) there was no difference in dd-cfDNA for allograft INFXN (0.39%; IQR: 0.18–0.67%)versusSTABLE, which may relate to differences in “tissue injury” with the spectrum of bronchial colonisationversusinvasive infection; (4) there was no difference for dd-cfDNA in unilateralversusbilateral lung transplantation; (5) “optimal threshold” for dd-cfDNA for aggregated rejection events representing allograft injury was determined as 0.85%, with sensitivity=55.6%, specificity=75.8%, positive predictive value (PPV)=43.3% and negative predictive value (NPV)=83.6%. Measurement of plasma dd-cfDNA may be a clinically useful tool for the assessment of lung allograft health and surveillance for “tissue injury” with a spectrum of rejection.
NCMHap: a novel method for haplotype reconstruction based on Neutrosophic c-means clustering
Authors: Zamani Fatemeh , Olyaee Mohammad Hossein , Khanteymoori Alireza
Published: October 2020

Background

Single individual haplotype problem refers to reconstructing haplotypes of an individual based on several input fragments sequenced from a specified chromosome. Solving this problem is an important task in computational biology and has many applications in the pharmaceutical industry, clinical decision-making, and genetic diseases. It is known that solving the problem is NP-hard. Although several methods have been proposed to solve the problem, it is found that most of them have low performances in dealing with noisy input fragments. Therefore, proposing a method which is accurate and scalable, is a challenging task.

Results

In this paper, we introduced a method, named NCMHap, which utilizes the Neutrosophic c-means (NCM) clustering algorithm. The NCM algorithm can effectively detect the noise and outliers in the input data. In addition, it can reduce their effects in the clustering process. The proposed method has been evaluated by several benchmark datasets. Comparing with existing methods indicates when NCM is tuned by suitable parameters, the results are encouraging. In particular, when the amount of noise increases, it outperforms the comparing methods.

Conclusion

The proposed method is validated using simulated and real datasets. The achieved results recommend the application of NCMHap on the datasets which involve the fragments with a huge amount of gaps and noise.
Positive selection in admixed populations from Ethiopia
Authors: Walsh Sandra , Pagani Luca , Xue Yali , Laayouni Hafid , Tyler-Smith Chris , Bertranpetit Jaume
Published: October 2020

Background

In the process of adaptation of humans to their environment, positive or adaptive selection has played a main role. Positive selection has, however, been under-studied in African populations, despite their diversity and importance for understanding human history.

Results

Here, we have used 119 available whole-genome sequences from five Ethiopian populations (Amhara, Oromo, Somali, Wolayta and Gumuz) to investigate the modes and targets of positive selection in this part of the world. The site frequency spectrum-based test SFselect was applied to idfentify a wide range of events of selection (old and recent), and the haplotype-based statistic integrated haplotype score to detect more recent events, in each case with evaluation of the significance of candidate signals by extensive simulations. Additional insights were provided by considering admixture proportions and functional categories of genes. We identified both individual loci that are likely targets of classic sweeps and groups of genes that may have experienced polygenic adaptation. We found population-specific as well as shared signals of selection, with folate metabolism and the related ultraviolet response and skin pigmentation standing out as a shared pathway, perhaps as a response to the high levels of ultraviolet irradiation, and in addition strong signals in genes such as IFNA, MRC1, immunoglobulins and T-cell receptors which contribute to defend against pathogens.

Conclusions

Signals of positive selection were detected in Ethiopian populations revealing novel adaptations in East Africa, and abundant targets for functional follow-up.
Studying polymorphic variants of the NAT2 gene (NAT2*5 and NAT2*7) in Nenets populations of Northern Siberia
Authors: Tiis Roza Pavlovna , Osipova Ludmila Pavlovna , Lichman Daria Veniaminovna , Voronina Elena Nikolaevna , Filipenko Maxim Leonidovich
Published: October 2020

Background

N-acetyltransferase 2 plays a crucial role in the metabolism of a wide range of xenobiotics, including many drugs, carcinogens, and other chemicals in the human environment. The article presents for the first time data on the frequency of two important “slow” variants ofNAT2gene(NAT2*5, rs1801280 andNAT2*7, rs1799931),which significantly affect the rate of xenobiotics acetylation, among representatives of indigenous populations of Forest and Tundra Nenets in Northern Siberia. The aim of this study was to identify the frequencies of these variants and compare them with frequencies in other ethnic populations.

Results

NAT2*5(T341C) genotyping revealed frequencies of 28,0% and 38,6% for Tundra and Forest Nenets, respectively. The frequencies ofNAT2*7(G857A) variant were 9,8% and 8,2% for Tundra and Forest Nenets, respectively. Polymorphic variants frequencies for Nenets are intermediate between those in populations of Europeans and Asians. These results can probably be explained by the presence of both European and Asian components in Nenets gene pools.

Conclusions

The results of this study expand the knowledge ofNAT2polymorphism in world populations. These data may also help assess the genetic predisposition of Nenets to multifactorial diseases associated with polymorphism in theNAT2gene and, in general, contribute to the development of personalized medicine in reference to native people of Siberia.
Genome-wide identification and functional analysis of the TIFY gene family in the response to multiple stresses in Brassica napus L.
Authors: He Xin , Kang Yu , Li Wenqian , Liu Wei , Xie Pan , Liao Li , Huang Luyao , Yao Min , Qian Lunwen , Liu Zhongsong , Guan Chunyun , Guan Mei , Hua Wei
Published: October 2020

Background

TIFY is a plant-specific protein family with a diversity of functions in plant development and responses to stress and hormones, which contains JASMONATE ZIM-domain (JAZ), TIFY, PPD and ZML subfamilies. Despite extensive studies of TIFY family in many other species, TIFY has not yet been characterized in Brassica napus.

Results

In this study, we identified 77, 36 and 39 TIFY family genes in the genome of B. napus, B. rapa and B. oleracea, respectively. Results of the phylogenetic analysis indicated the 170 TIFY proteins from Arabidopsis, B. napus, B. rapa and B. oleracea could be divided into 11 groups: seven JAZ groups, one PPD group, one TIFY group, and two ZIM/ZML groups. The molecular evolutionary analysis showed that TIFY genes were conserved in Brassicaceae species. Gene expression profiling and qRT-PCR revealed that different groups of BnaTIFY members have distinct spatiotemporal expression patterns in normal conditions or following treatment with different abiotic/biotic stresses and hormones. The BnaJAZ subfamily genes were predominantly expressed in roots and up-regulated by NaCl, PEG, freezing, methyl jasmonate (MeJA), salicylic acid (SA) and Sclerotinia sclerotiorum in leaves, suggesting that they have a vital role in hormone signaling to regulate multiple stress tolerance in B. napus.

Conclusions

The extensive annotation and expression analysis of the BnaTIFY genes contributes to our understanding of the functions of these genes in multiple stress responses and phytohormone crosstalk in B. napus.
Genome-wide study of pineapple (Ananas comosus L.) bHLH transcription factors indicates that cryptochrome-interacting bHLH2 (AcCIB2) participates in flowering time regulation and abiotic stress response
Authors: Aslam Mohammad , Jakada Bello Hassan , Fakher Beenish , Greaves Joseph G. , Niu Xiaoping , Su Zhenxia , Cheng Yan , Cao Shijiang , Wang Xiaomei , Qin Yuan
Published: October 2020

Background

Transcription factors (TFs) are essential regulators of growth and development in eukaryotes. Basic-helix-loop-helix (bHLHs) is one of the most significant TFs families involved in several critical regulatory functions. Cryptochrome-interacting bHLH (CIB) and cryptochromes form an extensive regulatory network to mediate a plethora of pathways. Although bHLHs regulate critical biological processes in plants, the information about pineapple bHLHs remains unexplored.

Results

Here, we identified a total of 121 bHLH proteins in the pineapple genome. The identified genes were renamed based on the ascending order of their gene ID and classified into 18 subgroups by phylogenetic analysis. We found that bHLH genes are expressed in different organs and stages of pineapple development. Furthermore, by the ectopic expression of AcCIB2 in Arabidopsis and complementation of Atcib2 mutant, we verified the involvement of AcCIB2 in photomorphogenesis and abiotic stress response.

Conclusions

Our findings revealed that AcCIB2 plays an essential role in flowering time regulation and abiotic stress response. The present study provides additional insights into the current knowledge of bHLH genes and suggests their potential role in various biological processes during pineapple development.
Variation in the expression of a transmembrane protein influences cell growth in Arabidopsis thaliana petals by altering auxin responses
Authors: Miller Charlotte N. , Dumenil Jack , Lu Fu Hao , Smith Caroline , McKenzie Neil , Chapman Volodymyr , Ball Joshua , Box Mathew , Bevan Michael
Published: October 2020

Background

The same species of plant can exhibit very diverse sizes and shapes of organs that are genetically determined. Characterising genetic variation underlying this morphological diversity is an important objective in evolutionary studies and it also helps identify the functions of genes influencing plant growth and development. Extensive screens of mutagenised Arabidopsis populations have identified multiple genes and mechanisms affecting organ size and shape, but relatively few studies have exploited the rich diversity of natural populations to identify genes involved in growth control.

Results

We screened a relatively well characterised collection of Arabidopsis thaliana accessions for variation in petal size. Association analyses identified sequence and gene expression variation on chromosome 4 that made a substantial contribution to differences in petal area. Variation in the expression of a previously uncharacterised gene At4g16850 (named as KSK) had a substantial role on variation in organ size by influencing cell size. Over-expression of KSK led to larger petals with larger cells and promoted the formation of stamenoid features. The expression of auxin-responsive genes known to limit cell growth was reduced in response to KSK over-expression. ANT expression was also reduced in KSK over-expression lines, consistent with altered floral identities. Auxin responses were reduced in KSK over-expressing cells, consistent with changes in auxin-responsive gene expression. KSK may therefore influence auxin responses during petal development.

Conclusions

Understanding how genetic variation influences plant growth is important for both evolutionary and mechanistic studies. We used natural populations of Arabidopsis thaliana to identify sequence variation in a promoter region of Arabidopsis accessions that mediated differences in the expression of a previously uncharacterised membrane protein. This variation contributed to altered auxin responses and cell size during petal growth.
Molecular insights into the compatible and incompatible interactions between sugar beet and the beet cyst nematode
Authors: Ghaemi Razieh , Pourjam Ebrahim , Safaie Naser , Verstraeten Bruno , Mahmoudi Seyed Bagher , Mehrabi Rahim , De Meyer Tim , Kyndt Tina
Published: October 2020

Background

Sugar beet (Beta vulgaris subsp. vulgaris) is an economically important crop that provides nearly one third of the global sugar production. The beet cyst nematode (BCN), Heterodera schachtii, causes major yield losses in sugar beet and other crops worldwide. The most effective and economic approach to control this nematode is growing tolerant or resistant cultivars. To identify candidate genes involved in susceptibility and resistance, the transcriptome of sugar beet and BCN in compatible and incompatible interactions at two time points was studied using mRNA-seq.

Results

In the susceptible cultivar, most defense-related genes were induced at 4 dai while suppressed at 10 dai but in the resistant cultivar Nemakill, induction of genes involved in the plant defense response was observed at both time points. In the compatible interaction, alterations in phytohormone-related genes were detected. The effect of exogenous application of Methyl Jasmonate and ET-generator ethephon on susceptible plants was therefore investigated and the results revealed significant reduction in plant susceptibility. Genes putatively involved in the resistance of Nemakill were identified, such as genes involved in phenylpropanoid pathway and genes encoding CYSTM domain-containing proteins, F-box proteins, chitinase, galactono-1,4-lactone dehydrogenase and CASP-like protein. Also, the transcriptome of the BCN was analyzed in infected root samples and several novel potential nematode effector genes were found.

Conclusions

Our data provides detailed insights into the plant and nematode transcriptional changes occurring during compatible and incompatible interactions between sugar beet and BCN. Many important genes playing potential roles in susceptibility or resistance of sugar beet against BCN, as well as some BCN effectors with a potential role as avr proteins were identified. In addition, our findings indicate the effective role of jasmonate and ethylene in enhancing sugar beet defense response against BCN. This research provides new molecular insights into the plant-nematode interactions that can be used to design novel management strategies against BCN.
Estimation in meta-analyses of response ratios
Authors: Bakbergenuly Ilyas , Hoaglin David C. , Kulinskaya Elena
Published: October 2020

Background

For outcomes that studies report as the means in the treatment and control groups, some medical applications and nearly half of meta-analyses in ecology express the effect as the ratio of means (RoM), also called the response ratio (RR), analyzed in the logarithmic scale as the log-response-ratio, LRR.

Methods

In random-effects meta-analysis of LRR, with normal and lognormal data, we studied the performance of estimators of the between-study variance, τ2, (measured by bias and coverage) in assessing heterogeneity of study-level effects, and also the performance of related estimators of the overall effect in the log scale, λ. We obtained additional empirical evidence from two examples.

Results

The results of our extensive simulations showed several challenges in using LRR as an effect measure. Point estimators of τ2 had considerable bias or were unreliable, and interval estimators of τ2 seldom had the intended 95% coverage for small to moderate-sized samples (n<40). Results for estimating λ differed between lognormal and normal data.

Conclusions

For lognormal data, we can recommend only SSW, a weighted average in which a study’s weight is proportional to its effective sample size, (when n≥40) and its companion interval (when n≥10). Normal data posed greater challenges. When the means were far enough from 0 (more than one standard deviation, 4 in our simulations), SSW was practically unbiased, and its companion interval was the only option.
Comaneci device-assisted embolization of wide-necked carotid aneurysms with an unfavorable ratio
Authors: Molina-Nuevo Juan David , López-Martínez Lorena , Pedrosa-Jiménez María José , Juliá-Molla Enrique , Hernández-Fernández Francisco
Published: October 2020

Background

Endovascular treatment is the technique of choice for most intracranial aneurysms. However, the treatment of morphologically complex wide-necked aneurysms with an unfavorable anatomy is still a therapeutic challenge.

The purpose of the study is to describe the initial experience with the Comaneci embolization assist device for the treatment of wide-necked aneurysms with an unfavorable ratio for direct embolization.

Methods

We report a retrospective single-center analysis taken from a prospective database of consecutive aneurysms of the anterior circulation treated using the Comaneci device in the period from March 2017 to March 2019.

Results

Eighteen aneurysms were collected from 16 patients (9 women and 7 men) treated using the Comaneci device. The mean age was 48.4 years (range 36–81). Twelve patients had SAH, three were incidental aneurysms and one had compressive symptoms. A complete asymptomatic occlusion rate of 88.8% was obtained. The major complication rate was 5.55%.

Conclusion

The Comaneci embolization assist device is a safe, effective option for endovascular treatment of complex aneurysms with an unfavorable ratio.
A cross-sectional study on the correlation between cytokines in a pelvic environment and tubal factor infertility
Authors: Yan Jiacong , Liu Chengbo , Zhao Han , Wang Chunyan , Yao Huimei , Lu Qiong , Liu Jia , Feng Yun
Published: October 2020

Background

This cross-sectional study aimed to evaluate the levels of tumor necrosis factor-alpha (TNF-ɑ), interleukin-8 (IL-8), interleukin-6 (IL-6), and transforming growth factor-beta 1 (TGF-β1) in patients with primary and secondary tubal factor infertility (TFI) compared with fertile subjects, and to compare immune indexes in the serum and peritoneal fluid samples obtained from patients with TFI.

Methods

The pelvic fluid and peripheral blood of patients with TFI diagnosed by hysteroscopy and laparoscopy were taken as the study objects. The pelvic fluid and peripheral blood of patients who underwent hysteromyomectomy at the same time were taken as the control group. The contents of TNF-ɑ, IL-8, IL-6, and TGF-β1 in serum and peritoneal fluid were determined by enzyme-linked immunosorbent assay, and the levels of these cytokines in serum and pelvic fluid were compared between the two groups.

Results

Patients with secondary TFI showed significantly higher levels of TNF-ɑ, IL-8, IL-6 and TGF-β1 in the serum (26.15 ± 3.51 vs. 19.61 ± 0.157, 32.18 ± 15.13 vs. 5.73 ± 1.99, 38.84 ± 3.46 vs. 30.48 ± 0.61, and 38.37 ± 3.14 vs. 32.25 ± 1.69, respectively) and peritoneal fluid samples (129.73 ± 183.4 vs. 34.63 ± 0.56, 111.44 ± 207.42 vs. 15.34 ± 0.41, 80.01 ± 109.91 vs. 15.67 ± 0.52, and 82.54 ± 115.99 vs. 45.34 ± 0.41, respectively) compared with the control group. Patients with primary TFI exhibited significantly elevated concentration of TNF-α, IL-8, IL-6 and TGF-β1 in the peritoneal fluid samples (36.88 ± 2.67 vs. 34.63 ± 0.56, 19.47 ± 3.51 vs. 15.34 ± 0.41, 80.01 ± 109.91 vs. 15.67 ± 0.52, and 82.54 ± 115.99 vs. 45.34 ± 0.41, respectively) when compared to the controls. In patients with secondary infertility, the levels of TNF-α (26.15 ± 3.51 vs. 129.73 ± 183.4), IL-8 (32.18 ± 15.13 vs. 111.44 ± 207.42), IL-6 (38.84 ± 3.46 vs. 80.01 ± 109.91) and TGF-β1 (38.37 ± 3.14 vs. 82.54 ± 115.99) in the serum were significantly lower than those in the peritoneal fluid, whereas no significant difference was observed in the primary TFI group between the serum and peritoneal fluid cytokines levels.

Conclusion

The expression of cytokines in the pelvic environment of patients with TFI is upregulated compared to patients who do not have infertility issues. The detection of cytokines TNF-ɑ, IL-6, IL-8, and TGF-β1 in the pelvic fluid of tubal infertility patients can allow for further understanding of the etiology of TFI.
Maternal excessive gestational weight gain as a risk factor for autism spectrum disorder in offspring: a systematic review
Authors: Kheirouri Sorayya , Alizadeh Mohammad
Published: October 2020

Background

Abnormal gestational weight gain (GWG) is a prenatal complication that may contribute to long-term behavioral and neurodevelopmental differences in offspring. This systematic review summarizes research on the association between maternal GWG and risk of autism spectrum disorder (ASD) in offspring.

Methods

Google and electronic databases, including PubMed, SCOPUS, Embase, Cochrane Library and Google Scholar, were searched for original human studies published in English through June 2020. Articles that examined the association between GWG and risk of ASD in offspring were included. Duplicate and irrelevant studies were removed; and data were obtained through critical analysis.

Results

Of 96 articles searched, eight studies were included in the final review. All studies (n = 7) investigating the association of maternal excessive GWG with risk of ASD in offspring indicated that high GWG was independently associated with an increased risk of ASD. Of five studies investigating the association of inadequate GWG with the risk of ASD, four indicated that low GWG was not associated with an increased risk of ASD. Of seven studies examining the association of maternal pre-pregnancy BMI or weight with the risk of ASD, five reported that maternal pre-pregnancy BMI or weight did not appear to be independently associated with risk of ASD. The GWG-ASD association is independent of maternal BMI and child’s intellectual disability, but offspring’s genetic susceptibility connection to the GWG-ASD association remains a topic of debate.

Conclusions

The findings suggest that maternal excessive GWG may be associated with increased risk of ASD in offspring. However, insufficient GWG does not appear to have such association.
An exploratory study to evaluate visual function endpoints in non-advanced age-related macular degeneration
Authors: Narayanan Divya , Rodriguez John , Wallstrom Garrick , Welch Donna , Chapin Matthew , Arrigg Paul , Abelson Mark
Published: October 2020

Background

To prevent irreversible vision loss in age-related macular degeneration (AMD), it is critical to detect retinal dysfunction before permanent structural loss occurs. In the current study we evaluated a series of visual function tests to identify potential endpoints to detect visual dysfunction in non-advanced AMD.

Methods

A series of visual function tests were performed on 23 non-advanced AMD subjects (AREDS grade 1–4 on simplified scale) and 34 age-matched normals (AREDS grade 0). Tests included some commonly used endpoints such as ETDRS visual acuity (VA), low luminance (LL) 2.0ND ETDRS VA, MNREAD as well as newly developed tests such as the Ora-VCF™ test, Ora-tablet reading test, color sensitivity etc. Differences between the two groups were compared for each test. Test-retest repeatability and reproducibility was assessed on a subset of subjects and percent agreement was calculated.

Results

There was no difference in standard ETDRS VA between non-advanced AMD (0.06 ± 0.02 logMAR) and normal groups (0.04 ± 0.02 logMAR) (p = 0.57). LL 2.0 ETDRS VA and MNREAD showed no difference between the groups (p > 0.05). Ora-VCF™ test was significantly worse in the non-advanced AMD group compared to normals (0.67 ± 0.07 in AMD; 0.45 ± 0.04 in normals, p = 0.005). Non-advanced AMD subjects also had significantly worse reading performance using the Ora-tablet with LL 2.0ND (114.55 ± 11.22 wpm in AMD; 145.17 ± 9.55 wpm in normals p = 0.049). No significant difference between the groups was noted using other tests. Repeatability was 82% for Ora-VCF™ test and 92% for Ora-tablet LL 2.0ND reading. Reproducibility was 89% for both Ora-VCF™ test and Ora-tablet LL 2.0ND reading.

Conclusion

While there was no significant difference between non-advanced AMD and normal groups using some current common endpoints such as ETDRS VA, LL 2.0 ETDRS VA or MNREAD, Ora-VCF™ test and Ora-tablet LL 2.0ND reading tests were able to identify significant visual dysfunction in non-advanced AMD subjects. These tests show promise as endpoints for AMD studies.
Primary orbital extraskeletal osteosarcoma and review of literature
Authors: Hui Jingwen , Zhao Yun , Zhang Lei , Lin Jinyong , Zhao Hong
Published: October 2020

Background

Extraskeletal osteosarcoma is a malignant tumour composed of an osteoid and/or cartilaginous matrix; it arises in soft tissues without connection to the skeleton, and to our knowledge, this type of tumour is extremely rare.

Case presentation

The present study reports a 57-year-old man with primary orbital extraskeletal osteosarcoma who presented with a history of painful swelling in the left orbit that had occurred for 11 months. Imaging of the orbit showed an atypical, well-defined heterogeneous mass attached to the posterior globe of the left orbit. The patient underwent an anterior orbitotomy and complete excision of the tumour. The mass was originated from neither the globe nor the bony orbital wall but from the soft tissue. Histopathology demonstrated an extraskeletal osteosarcoma. After 13 months of follow-up, there was apparent recurrence of the tumour. The medical history showed no complaints of previous trauma or radiotherapy.

Conclusions

ESOS is a highly malignant tumour. Immunosuppression, trauma and adjuvant radiotherapy are possible predisposing factors in the development of this tumour. Prompt recognition and thorough treatment are essential for preventing orbital lesions and presence of metastasis from other organs.
Gender differential impact of bereavement on health outcomes: evidence from the China Health and Retirement Longitudinal Study, 2011–2015
Authors: Chen Zhuo , Ying Jiahui , Ingles Justin , Zhang Donglan , Rajbhandari-Thapa Janani , Wang Ruoxi , Emerson Kerstin Gerst , Feng Zhanchun
Published: October 2020

Background

Bereavement is the experience of an individual following the death of a person of significance to the individual, most often referring to the spouse. Increased morbidity, health care utilization, and mortality are known to be associated with bereavement. Given China’s growing population of older adults, there is a critical need to assess the health consequences of bereavement.

Method

We use data from the China Health and Retirement Longitudinal Study to examine the impact of bereavement on mental health and quality of life among a sample of mid- and older-aged adults. We use propensity score matching to construct a matching sample and difference-in-differences method to estimate the impact of bereavement on mental health and self-assessed health.

Results

We find bereavement is associated with increased depression symptoms among women (1.542 point or 0.229 standard deviations of Center for Epidemiologic Studies Depression (CES-D) 10 score) but not consistently for men over time. No statistically significant effect of bereavement on self-assessed health is found.

Conclusions

Our results show a harmful impact of bereavement on mental health among older women in China and point to the need for a comprehensive policy on survivor benefits in China, particularly for rural older women.
Effectiveness of upgraded maternity waiting homes and local leader training on improving institutional births: a cluster-randomized controlled trial in Jimma, Ethiopia
Authors: Kurji Jaameeta , Gebretsadik Lakew Abebe , Wordofa Muluemebet Abera , Morankar Sudhakar , Bedru Kunuz Haji , Bulcha Gebeyehu , Bergen Nicole , Kiros Getachew , Asefa Yisalemush , Asfaw Shifera , Mamo Abebe , Endale Erko , Thavorn Kednapa , Labonte Ronald , Taljaard Monica , Kulkarni Manisha A.
Published: October 2020

Background

Maternity waiting homes (MWHs), residential spaces for pregnant women close to obstetric care facilities, are being used to tackle physical barriers to access. However, their effectiveness has not been rigorously assessed. The objective of this cluster randomized trial was to evaluate the effectiveness of functional MWHs combined with community mobilization by trained local leaders in improving institutional births in Jimma Zone, Ethiopia.

Methods

A pragmatic, parallel arm cluster-randomized trial was conducted in three districts. Twenty-four primary health care units (PHCUs) were randomly assigned to either (i) upgraded MWHs combined with local leader training on safe motherhood strategies, (ii) local leader training only, or (iii) usual care. Data were collected using repeat cross-sectional surveys at baseline and 21 months after intervention to assess the effect of intervention on the primary outcome, defined as institutional births, at the individual level. Women who had a pregnancy outcome (livebirth, stillbirth or abortion) 12 months prior to being surveyed were eligible for interview. Random effects logistic regression was used to evaluate the effect of the interventions.

Results

Data from 24 PHCUs and 7593 women were analysed using intention-to-treat. The proportion of institutional births was comparable at baseline between the three arms. At endline, institutional births were slightly higher in the MWH + training (54% [n = 671/1239]) and training only arms (65% [n = 821/1263]) compared to usual care (51% [n = 646/1271]). MWH use at baseline was 6.7% (n = 256/3784) and 5.8% at endline (n = 219/3809). Both intervention groups exhibited a non-statistically significant higher odds of institutional births compared to usual care (MWH+ & leader training odds ratio [OR] = 1.09, 97.5% confidence interval [CI] 0.67 to 1.75; leader training OR = 1.37, 97.5% CI 0.85 to 2.22).

Conclusions

Both the combined MWH+ & leader training and the leader training alone intervention led to a small but non-significant increase in institutional births when compared to usual care. Implementation challenges and short intervention duration may have hindered intervention effectiveness. Nevertheless, the observed increases suggest the interventions have potential to improve women’s use of maternal healthcare services. Optimal distances at which MWHs are most beneficial to women need to be investigated.

Trial registration

The trial was retrospectively registered on the Clinical Trials website (https://clinicaltrials.gov) on 3rd October 2017. The trial identifier is NCT03299491.
Accurate implant fit and leg alignment after cruciate-retaining patient-specific total knee arthroplasty
Authors: Arnholdt Jörg , Kamawal Yama , Horas Konstantin , Holzapfel Boris M. , Gilbert Fabian , Ripp Axel , Rudert Maximilian , Steinert Andre F.
Published: October 2020

Background

For improved outcomes in total knee arthroplasty (TKA) correct implant fitting and positioning are crucial. In order to facilitate a best possible implant fitting and positioning patient-specific systems have been developed. However, whether or not these systems allow for better implant fitting and positioning has yet to be elucidated. For this reason, the aim was to analyse the novel patient-specific cruciate retaining knee replacement system iTotal™ CR G2 that utilizes custom-made implants and instruments for its ability to facilitate accurate implant fitting and positioning including correction of the hip-knee-ankle angle (HKA).

Methods

We assessed radiographic results of 106 patients who were treated with the second generation of a patient-specific cruciate retaining knee arthroplasty using iTotal™ CR G2 (ConforMIS Inc.) for tricompartmental knee osteoarthritis (OA) using custom-made implants and instruments. The implant fit and positioning as well as the correction of the mechanical axis (hip-knee-ankle angle, HKA) and restoration of the joint line were determined using pre- and postoperative radiographic analyses.

Results

On average, HKA was corrected from 174.4° ± 4.6° preoperatively to 178.8° ± 2.2° postoperatively and the coronal femoro-tibial angle was adjusted on average 4.4°. The measured preoperative tibial slope was 5.3° ± 2.2° (mean +/− SD) and the average postoperative tibial slope was 4.7° ± 1.1° on lateral views. The joint line was well preserved with an average modified Insall-Salvati index of 1.66 ± 0.16 pre- and 1.67 ± 0.16 postoperatively. The overall accuracy of fit of implant components was decent with a measured medial overhang of more than 1 mm (1.33 mm ± 0.32 mm) in 4 cases only. Further, a lateral overhang of more than 1 mm (1.8 mm ± 0.63) (measured in the anterior-posterior radiographs) was observed in 11 cases, with none of the 106 patients showing femoral notching.

Conclusion

The patient-specific iTotal™ CR G2 total knee replacement system facilitated a proper fitting and positioning of the implant components. Moreover, a good restoration of the leg axis towards neutral alignment was achieved as planned. Nonetheless, further clinical follow-up studies are necessary to validate our findings and to determine the long-term impact of using this patient- specific system.
Low rates of all-cause revision in displaced subcapital femoral neck fractures treated with hip hemiarthroplasty - a retrospective review of 4516 patients from a single institute
Authors: Yeung Chi-Yung , Tsai Shang-Wen , Wu Po-Kuei , Chen Cheng-Fong , Chang Ming-Chau , Chen Wei-Ming
Published: October 2020

Background

Femoral neck fracture (FNF) is among the commonest fractures affecting the geriatric population. Hemiarthroplasty (HA) is a standard treatment procedure and has been performed by hip surgeons for decades. Recently, primary total hip replacement has proved advantageous for the treatment of such fractures.

The aim of this study is to retrospectively review all causes of failure of all patients who underwent HA in our institute and reevaluated whether HA remains a favourable choice of treatment for patients with displaced FNFs.

Methods

A total of 4516 patients underwent HA at our centre from 1998 to 2017. The HA implants included unipolar and bipolar prostheses. Patients diagnosed with displaced FNF, underwent primary HA initially, required second revision procedures, and followed up for a minimum of 36 months were included in this study. Data were collected and comprehensively analysed.

Results

In 4516 cases, 99 patients underwent second surgeries. The revision rate was 2.19%. Reasons for failure were acetabular wear (n = 30, 30.3%), femoral stem subsidence (n = 24, 24.2%), periprosthetic fracture (n = 22, 22.2%), infection (n = 16, 16.2%), and recurrent dislocation (n = 7, 7.1%). The mean follow-up period was 78.1 months. The interval between failed HA and revision surgery was 22.8 months.

Conclusion

HA has a low revision rate and remains a favourable choice of treatment for patients with displaced FNFs.

Levels of evidence

Level III, Retrospective Cohort Study, Therapeutic Study.
The application of laparoscopy combined with indocyanine green fluorescence imaging technique for hepatic cystic echinococcosis
Authors: Li Yu-Peng , Ma Zhi-Gang , Tuxun Tuerhongjiang , Li Zhi-De , Meng Yuan , Chen Xiong
Published: October 2020

Background

With the mature application of laparoscopy in hepatobiliary surgery, laparoscopic treatment of hepatic cystic echinococcosis (CE) has made certain progress. But, due to the inherent limitations of laparoscopy and the growth characteristics of cystic echinococcosis, distinguishing the boundary between cystic lesion and normal hepatic parenchyma is pivotal importance for successful surgery. Indocyanine green (ICG) fluorescence imaging technology can view the boundary of lesion and normal tissue during the treatment of hepatic cystic echinococcosis. Applied laparoscopy combined with ICG fluorescence imaging technique for hepatic cystic echinococcosis may be an effective surgical strategy.

Methods

The clinical data contained nine patients with hepatic cystic echinococcosis who underwent laparoscopic surgery with indocyanine green fluorescence imaging technique in authors’ institution from December 2018 to December 2019 were retrospectively analyzed. Indocyanine green was administered intravenously three days prior to surgery. The fluorescence acquisition system for real-time imaging was used during the surgery and the patients were followed up after surgery.

Results

Of reported nine patients, six are male and the remaining three are female. The average age is (36.4 ± 7.6) years. For all subjects, surgical procedures were performed under laparoscopy with indocyanine green fluorescence system. This technique showed the clear boundary of the hepatic cyst with normal liver parenchyma. Total cystectomy in six patients, subtotal cystectomy in two patients and partial hepatectomy in one patient were performed respectively. The average operation time was 3.8 ± 0.9 h, blood loss 206.0 ± 120.7 ml. Neither blood transfusion nor post-operative complication was experienced. The average abdominal drainage time was 3.4 ± 0.9 days with hospital stay 5.7 ± 2.1 days. During the 6–12 months follow-up period, neither recurrence nor intraperitoneal implantation was found.

Conclusions

Applied laparoscopy combined with ICG fluorescence imaging technique for hepatic cystic echinococcosis is safe and feasible. Enhanced boundary image can assist surgeons to complete radical resection and reduce complications.
Mesoglycan for pain control after open excisional HAEMOrrhoidectomy (MeHAEMO): an observational multicentre study on behalf of the Italian Society of Colorectal Surgery (SICCR)
Authors: Gallo G. , Di Saverio S. , Clerico G. , Sturiale A . , Manigrasso M. , Luc A. Realis , Trompetto M. , Sammarco G. ,   the MeHAEMO Working Group, Ferrari Francesco , Carpino Antonio , Sena Giuseppe , Vescio Giuseppina , Stratta Emanuela , Luc Alberto Realis , Clerico Giuseppe , Trompetto Mario , Tonello Paolo , Cornaglia Silvia , Greco Vincenzo , Talarico Carlo , Tutino Roberta , Falco Nicola , Venturelli Paolina , Cocorullo Gianfranco , Pietroletti Renato , Rizza Vinicio , Milito Giovanni , Campanelli Michela , Lisi Giorgio , Brachitta Salvatore , Cavallaro Venera , Pecorella Giuseppe , Turri Bruno , Sasia Diego , Giuffrida Maria Carmela , Milone Marco , De Palma Giovanni , Bianco Vincenzo , Moggia Elisabetta , Talamo Giuseppina , Oggianu Angelo , Pili Michela , Palumbo Alessio , Fazio Marco , Aiello Domenico , Bianco Francesco , Bondurri Andrea , Gallo Gaetano , La Torre Marco , Mancini Stefano , Milito Giovanni , Perinotti Roberto , Pietroletti Renato , Serventi Alberto , Fiorino Marina
Published: October 2020

Background

Excisional haemorrhoidectomy is the gold standard technique in patients with III and IV degree haemorrhoidal disease (HD). However, it is associated with a significant rate of post-operative pain. The aim of our study was to evaluate the efficacy of mesoglycan in the post-operative period of patients who underwent open excisional diathermy haemorrhoidectomy (OEH).

Methods

This was a retrospective multicentre observational study. Three hundred ninety-eight patients from sixteen colorectal referral centres who underwent OEH for III and IV HD were enrolled. All patients were followed-up on the first post-operative day (T1) and after 1 week (T2), 3 weeks (T3) and 6 weeks (T4). BMI, habits, SF-12 questionnaire, VAS at rest (VASs), after defecation (VASd), and after anorectal digital examination (VASe), bleeding and thrombosis, time to surgical wound healing and autonomy were evaluated.

Results

In the mesoglycan group, post-operative thrombosis was significantly reduced at T2 (p < 0.05) and T3 (p < 0.005), and all patients experienced less post-operative pain at each time point (p < 0.001 except for VASe T4 p = 0.003). There were no significant differences between the two groups regarding the time to surgical wound healing or post-operative bleeding. There was an early recovery of autonomy in the mesoglycan group in all three follow-up periods (T2 p = 0.016; T3 p = 0.002; T4 p = 0.007).

Conclusions

The use of mesoglycan led to a significant reduction in post-operative thrombosis and pain with consequent early resumption of autonomy.

Trial registration NCT04481698—Mesoglycan for Pain Control After Open Excisional HAEMOrrhoidectomy (MeHAEMO) https://clinicaltrials.gov/ct2/show/NCT04481698?term=Mesoglycan+for+Pain+Control+After+Open+Excisional+HAEMOrrhoidectomy+%28MeHAEMO%29&draw=2&rank=1
Correction to: Skin rash following Administration of Apalutamide in Japanese patients with Advanced Prostate Cancer: an integrated analysis of the phase 3 SPARTAN and TITAN studies and a phase 1 open-label study
Authors: Uemura Hiroji , Koroki Yosuke , Iwaki Yuki , Imanaka Keiichiro , Kambara Takeshi , Lopez-Gitlitz Angela , Smith Andressa , Uemura Hirotsugu
Published: October 2020

An amendment to this paper has been published and can be accessed via the original article.