bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational identification of biomarker genes for lung cancer considering treatment and non-treatment studies
Authors: Maharjan Mona , Tanvir Raihanul Bari , Chowdhury Kamal , Duan Wenrui , Mondal Ananda Mohan
Published: December 2020

Background

Lung cancer is the number one cancer killer in the world with more than 142,670 deaths estimated in the United States alone in the year 2019. Consequently, there is an overreaching need to identify the key biomarkers for lung cancer. The aim of this study is to computationally identify biomarker genes for lung cancer that can aid in its diagnosis and treatment. The gene expression profiles of two different types of studies, namely non-treatment and treatment, are considered for discovering biomarker genes. In non-treatment studies healthy samples are control and cancer samples are cases. Whereas, in treatment studies, controls are cancer cell lines without treatment and cases are cancer cell lines with treatment.

Results

The Differentially Expressed Genes (DEGs) for lung cancer were isolated from Gene Expression Omnibus (GEO) database using R software tool GEO2R. A total of 407 DEGs (254 upregulated and 153 downregulated) from non-treatment studies and 547 DEGs (133 upregulated and 414 downregulated) from treatment studies were isolated. Two Cytoscape apps, namely, CytoHubba and MCODE, were used for identifying biomarker genes from functional networks developed using DEG genes. This study discovered two distinct sets of biomarker genes – one from non-treatment studies and the other from treatment studies, each set containing 16 genes. Survival analysis results show that most non-treatment biomarker genes have prognostic capability by indicating low-expression groups have higher chance of survival compare to high-expression groups. Whereas, most treatment biomarkers have prognostic capability by indicating high-expression groups have higher chance of survival compare to low-expression groups.

Conclusion

A computational framework is developed to identify biomarker genes for lung cancer using gene expression profiles. Two different types of studies – non-treatment and treatment – are considered for experiment. Most of the biomarker genes from non-treatment studies are part of mitosis and play vital role in DNA repair and cell-cycle regulation. Whereas, most of the biomarker genes from treatment studies are associated to ubiquitination and cellular response to stress. This study discovered a list of biomarkers, which would help experimental scientists to design a lab experiment for further exploration of detail dynamics of lung cancer development.
A comparative study on production of extracellular hydrolytic enzymes of Candida species isolated from patients with surgical site infection and from healthy individuals and their co-relation with antifungal drug resistance
Authors: Erum Rakhshanda , Samad Farkhunda , Khan Adnan , Kazmi Shahana Urooj
Published: December 2020

Background

Surgical site infection (SSI) is a crucial dilemma of surgery. Patients with SSIs not only face difficulty in treatment but also bear extra cost with high mortality rate. Resistant strains of Candida have emerged as an important nosocomial pathogen. Proteinase and phospholipase are exo- enzymes ofCandidaspecies, have importance with respect to their contribution in diseases. This study focused on prevalence ofCandidaspecies in surgical wound, their resistance to antifungal drugs, co-relation of these resistance with virulence potential ofCandidaspecies and comparison of production level of exo-enzymes ofCandidaspecies isolated from patients with SSIs and healthy individuals to highlights their role in SSIs.

Results

A total of (n = 555) swab samples were investigated. (n = 450) samples were collected from patients with SSIs and (n = 105) were collected from healthy individuals. Samples were subjected for the identification ofCandidaspecies which were subsequently investigated for antifungal susceptibility, MICs and enzymatic activity ofCandidaspecies. Out of 128 strains ofCandidaspp. isolated from SSIs, 54(42.18%) were identified asC. albicansfollowed byC. glabrata32(25%),C. parapsilosis17(13.28%),C. krusei13(10.16%) andC. tropicalis12(9.38%).C. albicansisolates showed 100% susceptibility to voriconazole and amphotericin B followed by itraconazole 98% and fluconazole 89%. Out of 6 fluconazole resistantC. albicans5(83.33%) were able to produce phospholipase while out of 48 fluconazole-susceptible strains 17(35.42%) were found to be phospholipase producer. Out of 54C. albicansisolated from surgical wound 46(85.18%) and 49(90.74%) were found to be phospholipase and proteinase producer respectively, whereas out of 20C. albicansisolates from healthy subjects 14(70%) produce proteinase and 12(60%) produce phospholipase. There were significant statistical differences found between the level of enzyme production byC. albicans, in relation to both sites (P = 0.014).

Conclusion

Study revealed that prevalence ofCandidaspecies is high in SSIs. Phospholipase and proteinase activity were more pronounced inCandidaSpecies from surgical wound in contrast to species from healthy individuals suggests these enzymes may have been responsible for the severity of infection in surgical wound patients.
Role of aspartate ammonia-lyase in Pasteurella multocida
Authors: Wang Zui , Li Li , Liu Peng , Wang Chen , Lu Qin , Liu Lina , Wang Xiaozhong , Luo Qingping , Shao Huabin
Published: December 2020

Background

Pasteurella multocida is responsible for a highly infectious and contagious disease in birds, leading to heavy economic losses in the chicken industry. However, the pathogenesis of this disease is poorly understood. We recently identified an aspartate ammonia-lyase (aspA) in P. multocida that was significantly upregulated under iron-restricted conditions, the protein of which could effectively protect chicken flocks against P. multocida. However, the functions of this gene remain unclear. In the present study, we constructed aspA mutant strain △aspA::kan and complementary strain C△aspA::kan to investigate the function of aspA in detail.

Result

Deletion of the aspA gene in P. multocida resulted in a significant reduction in bacterial growth in LB (Luria-Bertani) and MH (Mueller-Hinton) media, which was rescued by supplementation with 20 mM fumarate. The mutant strain △aspA::kan showed significantly growth defects in anaerobic conditions and acid medium, compared with the wild-type strain. Moreover, growth of △aspA::kan was more seriously impaired than that of the wild-type strain under iron-restricted conditions, and this growth recovered after supplementation with iron ions. AspA transcription was negatively regulated by iron conditions, as demonstrated by quantitative reverse transcription-polymerase chain reaction. Although competitive index assay showed the wild-type strain outcompetes the aspA mutant strain and △aspA::kan was significantly more efficient at producing biofilms than the wild-type strain, there was no significant difference in virulence between the mutant and the wild-type strains.

Conclusion

These results demonstrate that aspA is required for bacterial growth in complex medium, and under anaerobic, acid, and iron-limited conditions.
A preoperative mortality risk assessment model for Stanford type A acute aortic dissection
Authors: Kuang Juntao , Yang Jue , Wang Qiuji , Yu Changjiang , Li Ying , Fan Ruixin
Published: December 2020

Background

Acute aortic dissection type A is a life-threatening disease required emergency surgery during acute phase. Different clinical manifestations, laboratory tests, and imaging features of patients with acute aortic dissection type A are the risk factors of preoperative mortality. This study aims to establish a simple and effective preoperative mortality risk assessment model for patients with acute aortic dissection type A.

Methods

A total of 673 Chinese patients with acute aortic dissection type A who were admitted to our hospital were retrospectively included. All patients were unable to receive surgically treatment within 3 days from the onset of disease. The patients included were divided into the survivor and deceased groups, and the endpoint event was preoperative death. Multivariable analysis was used to investigate predictors of preoperative mortality and to develop a prediction model.

Results

Among the 673 patients, 527 patients survived (78.31%) and 146 patients died (21.69%). The developmental dataset had 505 patients, calibration by Hosmer Lemeshow was significant (χ2 = 3.260, df = 8, P = 0.917) and discrimination by area under ROC curve was 0.8448 (95% CI 0.8007–0.8888). The validation dataset had 168 patients, calibration was significant (χ2 = 5.500, df = 8, P = 0.703) and the area under the ROC curve was 0.8086 (95% CI 0.7291–0.8881). The following independent variables increased preoperative mortality: age (OR = 1.008, P = 0.510), abrupt chest pain (OR = 3.534, P < 0.001), lactic in arterial blood gas ≥ 3 mmol/L (OR = 3.636, P < 0.001), inotropic support (OR = 8.615, P < 0.001), electrocardiographic myocardial ischemia (OR = 3.300, P = 0.001), innominate artery involvement (OR = 1.625, P = 0.104), right common carotid artery involvement (OR = 3.487, P = 0.001), superior mesenteric artery involvement (OR = 2.651, P = 0.001), false lumen / true lumen of ascending aorta ≥ 0.75 (OR = 2.221, P = 0.007). Our data suggest that a simple and effective preoperative death risk assessment model has been established.

Conclusions

Using a simple and effective risk assessment model can help clinicians quickly identify high-risk patients and make appropriate medical decisions.
COSMIN Risk of Bias tool to assess the quality of studies on reliability or measurement error of outcome measurement instruments: a Delphi study
Authors: Mokkink L. B. , Boers M. , van der Vleuten C. P. M. , Bouter L. M. , Alonso J. , Patrick D. L. , de Vet H. C. W. , Terwee C. B.
Published: December 2020

Background

Scores on an outcome measurement instrument depend on the type and settings of the instrument used, how instructions are given to patients, how professionals administer and score the instrument, etc. The impact of all these sources of variation on scores can be assessed in studies on reliability and measurement error, if properly designed and analyzed. The aim of this study was to develop standards to assess the quality of studies on reliability and measurement error of clinician-reported outcome measurement instruments, performance-based outcome measurement instrument, and laboratory values.

Methods

We conducted a 3-round Delphi study involving 52 panelists.

Results

Consensus was reached on how a comprehensive research question can be deduced from the design of a reliability study to determine how the results of a study inform us about the quality of the outcome measurement instrument at issue. Consensus was reached on components of outcome measurement instruments, i.e. the potential sources of variation. Next, we reached consensus on standards on design requirements (n = 5), standards on preferred statistical methods for reliability (n = 3) and measurement error (n = 2), and their ratings on a four-point scale. There was one term for a component and one rating of one standard on which no consensus was reached, and therefore required a decision by the steering committee.

Conclusion

We developed a tool that enables researchers with and without thorough knowledge on measurement properties to assess the quality of a study on reliability and measurement error of outcome measurement instruments.
A qualitative exploration of two risk calculators using video-recorded NHS health check consultations
Authors: Riley Victoria , Ellis Naomi J. , Cowap Lisa , Grogan Sarah , Cottrell Elizabeth , Crone Diane , Chambers Ruth , Clark-Carter David , Fedorowicz Sophia , Gidlow Christopher
Published: December 2020

Background

The aim of the study was to explore practitioner-patient interactions and patient responses when using QRISK®2 or JBS3 cardiovascular disease (CVD) risk calculators. Data were from video-recorded NHS Health Check (NHSHC) consultations captured as part of the UK RIsk COmmunication (RICO) study; a qualitative study of video-recorded NHSHC consultations from 12 general practices in the West Midlands, UK. Participants were those eligible for NHSHC based on national criteria (40–74 years old, no existing diagnoses for cardiovascular-related conditions, not on statins), and practitioners, who delivered the NHSHC.

Method

NHSHCs were video-recorded. One hundred twenty-eight consultations were transcribed and analysed using deductive thematic analysis and coded using a template based around Protection Motivation Theory.

Results

Key themes used to frame the analysis were Cognitive Appraisal (Threat Appraisal, and Coping Appraisal), and Coping Modes (Adaptive, and Maladaptive). Analysis showed little evidence of CVD risk communication, particularly in consultations using QRISK®2. Practitioners often missed opportunities to check patient understanding and encourage risk- reducing behaviour, regardless of the risk calculator used resulting in practitioner verbal dominance. JBS3 appeared to better promote opportunities to initiate risk-factor discussion, and Heart Age and visual representation of risk were more easily understood and impactful than 10-year percentage risk. However, a lack of effective CVD risk discussion in both risk calculator groups increased the likelihood of a maladaptive coping response.

Conclusions

The analysis demonstrates the importance of effective, shared practitioner-patient discussion to enable adaptive coping responses to CVD risk information, and highlights a need for effective and evidence-based practitioner training.

Trial registration

ISRCTN ISRCTN10443908. Registered 7th February 2017.
Severe weight loss after minimally invasive oesophagectomy is associated with poor survival in patients with oesophageal cancer at 5 years
Authors: Koterazawa Yasufumi , Oshikiri Taro , Takiguchi Gosuke , Urakawa Naoki , Hasegawa Hiroshi , Yamamoto Masashi , Kanaji Shingo , Yamashita Kimihiro , Matsuda Takeru , Nakamura Tetsu , Suzuki Satoshi , Kakeji Yoshihiro
Published: December 2020

Background

Patients often experience severe weight loss after oesophagectomy. Enteral nutrition via a feeding jejunostomy tube (FT) is commonly practised. This study aimed to assess the effect of severe weight loss postoperatively and enteral nutrition via an FT on long-term prognosis after oesophagectomy.

Methods

This study analysed 317 patients who underwent minimally invasive oesophagectomy at Kobe University Hospital and Hyogo Cancer Center from 2010 to 2015. The patients’ body weight was evaluated at 3 months postoperatively. They were organised into the severe weight loss (n = 65) and moderate weight loss (n = 252) groups. Furthermore, they were categorised into the FT group (184 patients who had an FT placed during oesophagectomy) and no-FT group (133 patients without FT). Patients (119 per group) matched for the FT and no-FT groups were identified via propensity score matching.

Results

The 5-year overall survival (OS) rate in the severe weight loss group was significantly lower (p = 0.024). In the multivariate analysis, tumour invasion depth (pT3-4), preoperative therapy and severe weight loss had a worse OS (hazard ratio = 1.89; 95% confidence interval = 1.12–3.17, hazard ratio = 2.11; 95% confidence interval = 1.25–3.54, hazard ratio = 1.82; 95% confidence interval = 1.02–3.524, respectively). No significant differences in the number of severe weight loss patients and OS were found between the FT and no-FT groups.

Conclusion

Severe weight loss is significantly associated with poor OS. In addition, enteral nutrition via an FT did not improve the severe weight loss and OS.
Liquid biopsy for patients with IBD-associated neoplasia
Authors: Kinugasa Hideaki , Hiraoka Sakiko , Nouso Kazuhiro , Yamamoto Shumpei , Hirai Mami , Terasawa Hiroyuki , Yasutomi Eriko , Oka Shohei , Ohmori Masayasu , Yamasaki Yasushi , Inokuchi Toshihiro , Takahara Masahiro , Harada Keita , Tanaka Takehiro , Okada Hiroyuki
Published: December 2020

Background

It is often difficult to diagnose inflammatory bowel disease (IBD)-associated neoplasia endoscopically due to background inflammation. In addition, due to the absence of sensitive tumor biomarkers, countermeasures against IBD-associated neoplasia are crucial. The purpose of this study is to develop a new diagnostic method through the application of liquid biopsy.

Methods

Ten patients with IBD-associated cancers and high-grade dysplasia (HGD) with preserved tumor tissue and blood were included. Tumor and non-tumor tissues were analyzed for 48 cancer-related genes using next-generation sequencing. Simultaneously, circulating tumor DNA (ctDNA) was analyzed for mutations in the target genes using digital PCR.

Results

Out of 10 patients, seven had IBD-related cancer and three had IBD-related HGD. Two patients had carcinoma in situ; moreover, three had stageII and two had stage III. To avoid false positives, the mutation rate cutoff was set at 5% based on the control results; seven of 10 (70%) tumor tissue samples were mutation-positive. Mutation frequencies for each gene were as follows: TP53 (20.9%; R136H), TP53 (25.0%; C110W), TP53 (8.5%; H140Q), TP53 (31.1%; R150W), TP53 (12.8%; R141H), KRAS (40.0%; G12V), and PIK3CA (34.1%; R 88Q). The same mutations were detected in the blood of these seven patients. However, no mutations were detected in the blood of the remaining three patients with no tumor tissue mutations. The concordance rate between tumor tissue DNA and blood ctDNA was 100%.

Conclusion

Blood liquid biopsy has the potential to be a new method for non-invasive diagnosis of IBD-associated neoplasia.
Patient and health system factors associated with pretreatment loss to follow up among patients diagnosed with tuberculosis using Xpert® MTB/RIF testing in Uganda
Authors: Zawedde-Muyanja Stella , Katamba Achilles , Cattamanchi Adithya , Castelnuovo Barbara , Manabe Yukari C.
Published: December 2020

Background

In 2018, Uganda started only 65% of persons with incident tuberculosis on treatment. Pretreatment loss to follow up is an important contributor to suboptimal treatment coverage. We aimed to describe the patient and health facility-level characteristics associated with pretreatment loss to follow up among patients diagnosed with pulmonary tuberculosis at public health facilities in Uganda.

Methods

At ten public health facilities, laboratory register data was used to identify patients aged ≥ 15 years who had a positive Xpert®MTB/RIF test. Initiation on TB treatment was ascertained using the clinical register. Factors associated with not being initiated on TB treatment within two weeks of diagnosis were examined using a multilevel logistic regression model accounting for clustering by health facility.

Results

From January to June 2018, 510 patients (61.2% male and 31.5% HIV co-infected) were diagnosed with tuberculosis. One hundred (19.6%) were not initiated on TB treatment within 2 weeks of diagnosis. Not having a phone number recorded in the clinic registers (aOR 7.93, 95%CI 3.93–13.05); being HIV-infected (aOR 1.83; 95% CI: 1.09–3.26) and receiving care from a high volume health facility performing more than 12 Xpert tests per day (aOR 4.37, 95%CI 1.69–11.29) and were significantly associated with pretreatment loss to follow up.

Conclusion

In public health facilities in Uganda, we found a high rate of pretreatment loss to follow up especially among TBHIV co-infected patients diagnosed at high volume health facilities. Interventions to improve the efficiency of Xpert® MTB/RIF testing, including monitoring of the TB care cascade should be developed and implemented.
A multisite longitudinal evaluation of patient characteristics associated with a poor response to non-surgical multidisciplinary management of low back pain in an advanced practice physiotherapist-led tertiary service
Authors: O’Leary Shaun , Raymer Maree , Window Peter , Swete Kelly Patrick , Lee Darryl , Garsden Linda , Tweedy Rebecca , Phillips Ben , O’Sullivan Will , Wake Anneke , Smith Alison , Pahor Sheryl , Pearce Luen , McLean Rod , Thompson David , Williams Erica , Nolan Damien , Anning Jody , Seels Ian , Wickins Daniel , Marks Darryn , Diplock Brendan , Parravicini Vicki , Parnwell Linda , Vicenzino Bill , Comans Tracy , Cottrell Michelle , Khan Asaduzzaman , McPhail Steven
Published: December 2020

Background

Non-surgical multidisciplinary management is often the first pathway of care for patients with chronic low back pain (LBP). This study explores if patient characteristics recorded at the initial service examination have an association with a poor response to this pathway of care in an advanced practice physiotherapist-led tertiary service.

Methods

Two hundred and forty nine patients undergoing non-surgical multidisciplinary management for their LBP across 8 tertiary public hospitals in Queensland, Australia participated in this prospective longitudinal study. Generalised linear models (logistic family) examined the relationship between patient characteristics and a poor response at 6 months follow-up using a Global Rating of Change measure.

Results

Overall 79 of the 178 (44%) patients completing the Global Rating of Change measure (28.5% loss to follow-up) reported a poor outcome. Patient characteristics retained in the final model associated with a poor response included lower Formal Education Level (ie did not complete school) (Odds Ratio (OR (95% confidence interval)) (2.67 (1.17–6.09),p = 0.02) and higher self-reported back disability (measured with the Oswestry Disability Index) (OR 1.33 (1.01–1.77) per 10/100 point score increase,p = 0.046).

Conclusions

A low level of formal education and high level of self-reported back disability may be associated with a poor response to non-surgical multidisciplinary management of LBP in tertiary care. Patients with these characteristics may need greater assistance with regard to their comprehension of health information, and judicious monitoring of their response to facilitate timely alternative care if no benefits are attained.
Comparison of health care utilization among patients affiliated and not affiliated with healthcare professionals in China
Authors: Si Yafei , Zhou Zhongliang , Su Min , Hu Han , Yang Zesen , Chen Xi
Published: December 2020

Background

Doing “more” in healthcare can be a major threat to the delivery of high-quality health care. It is important to identify the supplier-induced demand (SID) of health care. This study aims to test SID hypothesis by comparing health care utilization among patients affiliated with healthcare professionals and their counterpart patients not affiliated with healthcare professionals.

Methods

We used coarsened exact matching to compare the health care utilization and expenditure between patients affiliated and not affiliated with healthcare professionals. Using cross-sectional data of the China Labour-force Dynamics Survey (CLDS) in 2014, we identified 806 patients affiliated with healthcare professionals and 22,788 patients not affiliated with healthcare professionals. The main outcomes were outpatient proportion and expenditure as well as inpatient proportion and expenditure.

Results

The matched outpatient proportion of patients not affiliated with healthcare professionals was 0.6% higher (P = 0.754) than that of their counterparts, and the matched inpatient proportion was 1.1% lower (P = 0.167). Patients not affiliated with healthcare professionals paid significantly more (680 CNY or 111 USD, P < 0.001) than their counterparts did per outpatient visit (1126 CNY [95% CI 885–1368] vs. 446 CNY [95% CI 248–643]), while patients not affiliated with healthcare professionals paid insignificantly less (2061 CNY or 336 USD, P = 0.751) than their counterparts did per inpatient visit (15583 CNY [95% CI 12052–19115] vs. 17645 CNY [95% CI 4884–30406]).

Conclusion

Our results lend support to the SID hypothesis and highlight the need for policies to address the large outpatient care expenses among patients not affiliated with healthcare professionals. Our study also suggests that as the public becomes more informed, the demand of health care may persist while heath care expenditure per outpatient visit may decline sharply due to the weakened SID. To address misbehaviors and contain health care costs, it is important to realign provider incentives.
Birth attendants’ hand hygiene compliance in healthcare facilities in low and middle-income countries: a systematic review
Authors: Gon Giorgia , de Barra Mícheál , Dansero Lucia , Nash Stephen , Campbell Oona M. R.
Published: December 2020

Background

With an increasing number of women delivering in healthcare facilities in Low and Middle Income Countries (LMICs), healthcare workers’ hand hygiene compliance on labour wards is pivotal to preventing infections. Currently there are no estimates of how often birth attendants comply with hand hygiene, or of the factors influencing compliance in healthcare facilities in LMICs.

Methods

We conducted a systematic review to investigate the a) level of compliance, b) determinants of compliance and c) interventions to improve hand hygiene during labour and delivery among birth attendants in healthcare facilities of LMICs. We also aimed to assess the quality of the included studies and to report the intra-cluster correlation for studies conducted in multiple facilities.

Results

We obtained 797 results across four databases and reviewed 71 full texts. Of these, fifteen met our inclusion criteria. Overall, the quality of the included studies was particularly compromised by poorly described sampling methods and definitions. Hand hygiene compliance varied substantially across studies from 0 to 100%; however, the heterogeneity in definitions of hand hygiene did not allow us to combine or compare these meaningfully. The five studies with larger sample sizes and clearer definitions estimated compliance before aseptic procedures opportunities, to be low (range: 1–38%). Three studies described two multi-component interventions, both were shown to be feasible.

Conclusions

Hand hygiene compliance was low for studies with larger sample sizes and clear definitions. This poses a substantial challenge to infection prevention during birth in LMICs facilities. We also found that the quality of many studies was suboptimal. Future studies of hand hygiene compliance on the labour ward should be designed with better sampling frames, assess inter-observer agreement, use measures to improve the quality of data collection, and report their hand hygiene definitions clearly.
Gut microbiome as a response marker for pancreatic enzyme replacement therapy in a porcine model of exocrine pancreas insufficiency
Authors: Ritz Sabrina , Hahn Daniela , Wami Haleluya T. , Tegelkamp Karin , Dobrindt Ulrich , Schnekenburger Juergen
Published: December 2020

Background

Exocrine pancreatic insufficiency (EPI) is characterized by the loss of active pancreatic enzymes and a resulting severely reduced food digestion. EPI therapy requires orally applied pancreatic enzyme replacement. The gut microbiome is a known mediator of intestinal diseases and may influence the outcome of EPI and the effects of a pancreatic enzyme replacement therapy (PERT). Here, we analyzed the effects of EPI and PERT on the gut microbiome in the model of pancreatic duct ligated minipigs.

Results

The microbial community composition in pig feces was analyzed by next generation sequencing of 16S rRNA amplicons. The data were evaluated for α- and β-diversity changes and changes at the different Operational Taxonomic Unit (OTU) levels by Shannon–Wiener and inverse Simpson index calculation as well as by Principal Coordinates Analysis based on Bray–Curtis dissimilarity. Microbial α-diversity was reduced after EPI induction and reverted to nearly healthy state after PERT. Analysis of microbial composition and β-diversity showed distinctive clusters of the three study groups and a change towards a composition comparable to healthy animals upon PERT. The relative abundance of possible pathobionts likeEscherichia/Shigella,AcinetobacterorStenotrophomonaswas reduced by PERT.

Conclusion

These data demonstrate that EPI-induced dysbiosis could be reverted by PERT to a nearly healthy state. Elevated α-diversity and the reduction of bacterial overgrowth after PERT promises benefits for EPI patients. Non-invasive microbiome studies may be useful for EPI therapy monitoring and as marker for response to PERT.
Intestinal region-specific Wnt signalling profiles reveal interrelation between cell identity and oncogenic pathway activity in cancer development
Authors: Adam Ronja S. , van Neerven Sanne M. , Pleguezuelos-Manzano Cayetano , Simmini Salvatore , Léveillé Nicolas , de Groot Nina E. , Holding Andrew N. , Markowetz Florian , Vermeulen Louis
Published: December 2020

Background

Cancer results from the accumulation of mutations leading to the acquisition of cancer promoting characteristics such as increased proliferation and resistance to cell death. In colorectal cancer, an early mutation leading to such features usually occurs in theAPCorCTNNB1genes, thereby activating Wnt signalling. However, substantial phenotypic differences between cancers originating within the same organ, such as molecular subtypes, are not fully reflected by differences in mutations. Indeed, the phenotype seems to result from a complex interplay between the cell-intrinsic features and the acquired mutations, which is difficult to disentangle when established tumours are studied.

Methods

We use a 3D in vitro organoid model to study the early phase of colorectal cancer development. From three different murine intestinal locations we grow organoids. These are transformed to resemble adenomas after Wnt activation through lentiviral transduction with a stable form of β-Catenin. The gene expression before and after Wnt activation is compared within each intestinal origin and across the three locations using RNA sequencing. To validate and generalize our findings, we use gene expression data from patients.

Results

In reaction to Wnt activation we observe downregulation of location specific genes and differentiation markers. A similar effect is seen in patient data, where genes with significant differential expression between the normal left and right colon are downregulated in the cancer samples. Furthermore, the signature of Wnt target genes differs between the three intestinal locations in the organoids. The location specific Wnt signatures are dominated by genes which have been lowly expressed in the tissue of origin, and are the targets of transcription factors that are activated following enhanced Wnt signalling.

Conclusion

We observed that the region-specific cell identity has a substantial effect on the reaction to Wnt activation in a simple intestinal adenoma model. These findings provide a way forward in resolving the distinct biology between left- and right-sided human colon cancers with potential clinical relevance.
LACCASE14 is required for the deposition of guaiacyl lignin and affects cell wall digestibility in poplar
Authors: Qin Shifei , Fan Chunfen , Li Xiaohong , Li Yi , Hu Jian , Li Chaofeng , Luo Keming
Published: December 2020

Background

The recalcitrance of lignocellulosic biomass provided technical and economic challenges in the current biomass conversion processes. Lignin is considered as a crucial recalcitrance component in biomass utilization. An in-depth understanding of lignin biosynthesis can provide clues to overcoming the recalcitrance. Laccases are believed to play a role in the oxidation of lignin monomers, leading to the formation of higher-order lignin. In plants, functions of only a few laccases have been evaluated, so little is known about the effect of laccases on cell wall structure and biomass saccharification.

Results

In this study, we screened a gain-of-function mutant with a significant increase in lignin content from Arabidopsis mutant lines overexpressing a full-length poplar cDNA library. Further analysis confirmed that a Chinese white poplar (Populus tomentosa) laccase gene PtoLAC14 was inserted into the mutant, and PtoLAC14 could functionally complement the Arabidopsis lac4 mutant. Overexpression of PtoLAC14 promoted the lignification of poplar and reduced the proportion of syringyl/guaiacyl. In contrast, the CRISPR/Cas9-generated mutation of PtLAC14 results in increased the syringyl/guaiacyl ratios, which led to integrated enhancement on biomass enzymatic saccharification. Notably, the recombinant PtoLAC14 protein showed higher oxidized efficiency to coniferyl alcohol (precursor of guaiacyl unit) in vitro.

Conclusions

This study shows that PtoLAC14 plays an important role in the oxidation of guaiacyl deposition on cell wall. The reduced recalcitrance of the PtoLAC14-KO lines suggests that PtoLAC14 is an elite target for cell wall engineering, and genetic manipulation of this gene will facilitate the utilization of lignocellulose.
Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi
Authors: Silva Marta G. , Bastos Reginaldo G. , Stone Doggett J. , Riscoe Michael K. , Pou Sovitj , Winter Rolf , Dodean Rozalia A. , Nilsen Aaron , Suarez Carlos E.
Published: December 2020

Background

The most common apicomplexan parasites causing bovine babesiosis are Babesia bovis and B. bigemina, while B. caballi and Theileria equi are responsible for equine piroplasmosis. Treatment and control of these diseases are usually achieved using potentially toxic chemotherapeutics, such as imidocarb diproprionate, but drug-resistant parasites are emerging, and alternative effective and safer drugs are needed. The endochin-like quinolones (ELQ)-300 and ELQ-316 have been proven to be safe and efficacious against related apicomplexans, such as Plasmodium spp., with ELQ-316 also being effective against Babesia microti, without showing toxicity in mammals.

Methods

The inhibitory effects of ELQ-300 and ELQ-316 were assessed on the growth of cultured B. bovis, B. bigemina, B. caballi and T. equi. The percentage of parasitized erythrocytes was measured by flow cytometry, and the effect of the ELQ compounds on the viability of horse and bovine peripheral blood mononuclear cells (PBMC) was assessed by monitoring cell metabolic activity using a colorimetric assay.

Results

We calculated the half maximal inhibitory concentration (IC50) at 72 h, which ranged from 0.04 to 0.37 nM for ELQ-300, and from 0.002 to 0.1 nM for ELQ-316 among all cultured parasites tested at 72 h. None of the parasites tested were able to replicate in cultures in the presence of ELQ-300 and ELQ-316 at the maximal inhibitory concentration (IC100), which ranged from 1.3 to 5.7 nM for ELQ-300 and from 1.0 to 6.0 nM for ELQ-316 at 72 h. Neither ELQ-300 nor ELQ-316 altered the viability of equine and bovine PBMC at their IC100 in in vitro testing.

Conclusions

The compounds ELQ-300 and ELQ-316 showed significant inhibitory activity on the main parasites responsible for bovine babesiosis and equine piroplasmosis at doses that are tolerable to host cells. These ELQ drugs may be viable candidates for developing alternative protocols for the treatment of bovine babesiosis and equine piroplasmosis.

Graphical Abstract
Synthesis of aligned porous polyethylene glycol/silk fibroin/hydroxyapatite scaffolds for osteoinduction in bone tissue engineering
Authors: Yang Yuchao , Feng Yanting , Qu Rongmei , Li Qingtao , Rong Dongming , Fan Tingyu , Yang Yiting , Sun Bing , Bi Zhenyu , Khan Asmat Ullah , Deng Ting , Dai Jingxing , Ouyang Jun
Published: December 2020

Background

The physical factors of the extracellular matrix have a profound influence on the differentiation behavior of mesenchymal stem cells. In this study, the effect of the biophysical microenvironment on rat bone marrow mesenchymal stem cell (BMSC) osteogenesis was studied both in vitro and in vivo.

Methods

To prepare cell culture scaffolds of varying stiffness, increasing amounts of hydroxyapatite (HAp) were mixed into a polyethylene glycol/silk fibroin (PEG/SF) solution. The amount of HAp ranged from 25 to 100 mg, which provided for different ratios between HAp and the PEG/SF composite. In vitro, the effect of stiffness on the osteogenic differentiation of rat BMSCs was studied. The outcome measures, which were verified in vivo, included the protein expression of runt-related transcription factor 2 and osteocalcin, alkaline phosphatase activity, and the mRNA expression of osteogenesis-related markers.

Results

Increasing amounts of HAp resulted in an increased elastic modulus of the cell culture scaffolds. The PEG/SF/HAp fabricated with HAp (50 mg) significantly increased cell adhesion and viability (p < 0.05) as well as the expression of all the osteogenesis-related markers (p < 0.05).

Conclusions

We developed a novel cell culture scaffold and demonstrated that substrate stiffness influenced the osteogenic differentiation of rat BMSCs.
ReactionCode: format for reaction searching, analysis, classification, transform, and encoding/decoding
Authors: Delannée Victorien , Nicklaus Marc C.
Published: December 2020

In the past two decades a lot of different formats for molecules and reactions have been created. These formats were mostly developed for the purposes of identifiers, representation, classification, analysis and data exchange. A lot of efforts have been made on molecule formats but only few for reactions where the endeavors have been made mostly by companies leading to proprietary formats. Here, we present ReactionCode: a new open-source format that allows one to encode and decode a reaction into multi-layer machine readable code, which aggregates reactants and products into a condensed graph of reaction (CGR). This format is flexible and can be used in a context of reaction similarity searching and classification. It is also designed for database organization, machine learning applications and as a new transform reaction language.
Evaluation of [13N]ammonia positron emission tomography as a potential method for quantifying glutamine synthetase activity in the human brain
Authors: Egerton Alice , Dunn Joel T. , Singh Nisha , Yu Zilin , O’Doherty Jim , Koychev Ivan , Webb Jessica , Claridge Simon , Turkheimer Federico E. , Marsden Paul K. , Hammers Alexander , Gee Antony
Published: December 2020

Purpose

The conversion of synaptic glutamate to glutamine in astrocytes by glutamine synthetase (GS) is critical to maintaining healthy brain activity and may be disrupted in several brain disorders. As the GS catalysed conversion of glutamate to glutamine requires ammonia, we evaluated whether [13N]ammonia positron emission tomography (PET) could reliability quantify GS activity in humans.

Methods

In this test–retest study, eight healthy volunteers each received two dynamic [13N]ammonia PET scans on the morning and afternoon of the same day. Each [13N]ammonia scan was preceded by a [15O]water PET scan to account for effects of cerebral blood flow (CBF).

Results

Concentrations of radioactive metabolites in arterial blood were available for both sessions in five of the eight subjects. Our results demonstrated that kinetic modelling was unable to reliably distinguish estimates of the kinetic rate constantk3(related to GS activity) fromK1(related to [13N]ammonia brain uptake), and indicated a non-negligible back-flux of [13N] to blood (k2). Model selection favoured a reversible one-tissue compartmental model, and [13N]ammoniaK1correlated reliably (r2 = 0.72–0.92) with [15O]water CBF.

Conclusion

The [13N]ammonia PET method was unable to reliably estimate GS activity in the human brain but may provide an alternative index of CBF.
Opportunities for diversifying and enriching our article mix
Authors: Rosen Bruce , Schoenbaum Stephen C. , Israeli Avi
Published: December 2020

As 2020 comes to a close, the Israel Journal of Health Policy Research (IJHPR) will soon be starting its tenth year of publication. This editorial compares data from 2012 (the journal’s first year of publication) and 2019 (the journal’s most recent full year of publication), regarding the journal’s mix of article types, topics, data sources and methods, with further drill-downs regarding 2019.

The analysis revealed several encouraging findings, including a broad and changing mix of topics covered. However, the analysis also revealed several findings that are less encouraging, including the limited number of articles which assessed national policy changes, examined changes over time, and/or made secondary use of large-scale survey data. These findings apparently reflect, to some extent, the mix of studies being carried out by Israeli health services researchers.

As the senior editors of the IJHPR we are interested in working with funders, academic institutions, the owners and principal users of relevant administrative databases, and individual scholars to further understand the factors influencing the mix of research being carried out, and subsequently published, by Israel’s health services research community. This deeper understanding could then be used to develop a joint plan to diversify and enrich health services research and health policy analysis in Israel. The plan should include a policy of ensuring improved access to data, to properly support information-based research.
Binaural speaker identification using the equalization-cancelation technique
Authors: Geravanchizadeh Masoud , Ghalamiosgouei Sina
Published: December 2020

In real applications, environmental effects such as additive noise and room reverberation lead to a mismatch between training and testing signals that substantially reduces the performance of far-field speaker identification. As a solution to this mismatch problem, in this paper, a new binaural speaker identification system is proposed which employs the well-known equalization-cancelation technique in its structure. The equalization-cancelation algorithm is employed to enhance the input test speech and alleviate the detrimental effects of noise and reverberation in the speaker identification system. The performance of the proposed speaker identification system is compared with unprocessed identification systems and a traditional binaural speaker identification system from the literature. The proposed system is evaluated in both anechoic and reverberant conditions using different types of noise at various azimuthal positions. Simulation results show the superiority of the proposed method in all experimental conditions.
CSO (Canadian Society of Otolaryngology - Head & Neck Surgery) position paper on rhinologic and skull base surgery during the COVID-19 pandemic
Authors: Chan Yvonne , Banglawala Sarfaraz M. , Chin Christopher J. , Côté David W. J. , Dalgorf Dustin , de Almeida John R. , Desrosiers Martin , Gall Richard M. , Gevorgyan Artur , Hassan Hassan A. , Janjua Arif , Lee John M. , Leung Randy M. , Mechor Bradford D. , Mertz Dominik , Monteiro Eric , Nayan Smriti , Rotenberg Brian , Scott John , Smith Kristine A. , Sommer Doron D. , Sowerby Leigh , Tewfik Marc A. , Thamboo Andrew , Vescan Allan , Witterick Ian J.
Published: December 2020

Healthcare services in many countries have been partially or completely disrupted by the Coronavirus (COVID-19) pandemic since its onset in the end of 2019. Amongst the most impacted are the elective medical and surgical services in order to conserve resources to care for COVID-19 patients. As the number of infected patients decrease across Canada, elective surgeries are being restarted in a staged manner. Since Otolaryngologists – Head & Neck Surgeons manage surgical diseases of the upper aerodigestive tract where the highest viral load reside, it is imperative that these surgeries resume in a safe manner. The aim of this document is to compile the current best evidence available and provide expert consensus on the safe restart of rhinologic and skull base surgeries while discussing the pre-operative, intra-operative, and post-operative care and tips. Risk assessment, patient selection, case triage, and pre-operative COVID-19 testing will be analyzed and discussed. These guidelines will also consider the optimal use of personal protective equipment for specific cases, general and specific operative room precautions, and practical tips of intra-operative maneuvers to optimize patient and provider safety. Given that the literature surrounding COVID-19 is rapidly evolving, these recommendations will serve to start our specialty back into elective rhinologic surgeries over the next months and they may change as we learn more about this disease.
Correction to: The “State of Implementation” Progress Report (SIPREP): a pilot demonstration of a navigation system for implementation
Authors: Miech Edward J. , Larkin Angela , Lowery Julie C. , Butler Andrew J. , Pettey Kristin M. , Rattray Nicholas A. , Penney Lauren S. , Myers Jennifer , Damush Teresa M.
Published: December 2020

An amendment to this paper has been published and can be accessed via the original article.
Emotion processing in depression and anxiety disorders in older adults: systematic review
Authors: Gray Vanessa , Douglas Katie M. , Porter Richard J.
Published: December 2020

Background

Emotional cognition and effective interpretation of affective information is an important factor in social interactions and everyday functioning, and difficulties in these areas may contribute to aetiology and maintenance of mental health conditions. In younger people with depression and anxiety, research suggests significant alterations in behavioural and brain activation aspects of emotion processing, with a tendency to appraise neutral stimuli as negative and attend preferentially to negative stimuli. However, in ageing, research suggests that emotion processing becomes subject to a ‘positivity effect’, whereby older people attend more to positive than negative stimuli.

Aims

This review examines data from studies of emotion processing in Late-Life Depression and Late-Life Anxiety to attempt to understand the significance of emotion processing variations in these conditions, and their interaction with changes in emotion processing that occur with ageing.

Method

We conducted a systematic review following PRISMA guidelines. Articles that used an emotion-based processing task, examined older persons with depression or an anxiety disorder and included a healthy control group were included.

Results

In Late-Life Depression, there is little consistent behavioural evidence of impaired emotion processing, but there is evidence of altered brain circuitry during these processes. In Late-Life Anxiety and Post-Traumatic Stress disorder, there is evidence of interference with processing of negative or threat-related words.

Conclusions

How these findings fit with the positivity bias of ageing is not clear. Future research is required in larger groups, further examining the interaction between illness and age and the significance of age at disease onset.