bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive analysis of angiogenesis subtype of squamous cell carcinoma
Authors: Qin Fanglu , Lin Shenghua , Deng Kun , Qin Junqi , Xu Zhanyu , Yuan Liqiang , Wei Jiangbo , Sun Yu , Zheng Tiaozhan , Li Shikang
Published: September 2021

Background

Squamous cell carcinoma (SCC) is a disease with distinct management complexities as it displays a remarkably heterogeneous molecular subtype. However, the landscape of angiogenesis for SCC is not fully investigated.

Method and materials

The angiogenesis-related subtypes of SCC were established by using the ConsensusClusterPlus package based on angiogenesis-related genes and TCGA data. We analyzed the alteration of genes and miRNAs as well as pathways associated with angiogenesis subtypes. Next, the regulation network, the correlation with genomic characteristics, immune microenvironment, and clinical features of the angiogenesis subtypes were further investigated. Finally, the prognostic impact of the angiogenesis-related subtypes for SCC was also analyzed.

Results

A total of 1368 SCC samples were included in this study. Two angiogenesis subtypes were then identified based on the one hundred and sixty-three angiogenesis-related genes with subtype1 (angiogenesis subtype) of 951 SCC patients and subtype2 (non-angiogenesis subtype) of 417 SCC. GSEA revealed that angiogenesis and epithelial-mesenchymal transition, inflammatory response, and hypoxia were enriched in the angiogenesis subtype. Eight of the 15 immune checkpoints (ADORA2A, BTLA, CD276, CYBB, HAVCR2, SIGLEC7, SIGLEC9, and VTCN1) were significantly upregulated while C10orf54 were significantly downregulated in the angiogenesis subtype. The survival analysis revealed that the patients in the angiogenesis subtype have poorer survival outcomes than those in the non-angiogenesis subtype (P = 0.017 for disease-free interval and P = 0.00013 for overall survival).

Conclusion

Our analysis revealed a novel angiogenesis subtype classification in SCC and provides new insights into a hallmark of SCC progression.
Sequential cleavage and blastocyst embryo transfer and IVF outcomes: a systematic review
Authors: Zhang Jianeng , Wang Chong , Zhang Huanhuan , Zhou Yan
Published: September 2021

Background

Sequential embryo transfer has been proposed as a way to improve embryo implantation in women forin vitrofertilization (IVF), but the effect on pregnancy outcomes remains ambiguous. This systematic review was conducted to investigate the efficacy of sequential embryo transfer on IVF outcomes.

Methods

A literature search was performed in the PubMed, Web of Science, Cochrane Library, ScienceDirect and Wanfang databases. Data were pooled using a random- or fixed-effects model according to study heterogeneity. The results are expressed as relative risks (RRs) with 95% confidence intervals (CIs). Heterogeneity was evaluated by the I2statistic. The study protocol was registered prospectively on INPLASY, ID: INPLASY202180019.

Results

Ten eligible studies with 2658 participants compared sequential embryo transfer and cleavage transfer, while four studies with 513 participants compared sequential embryo transfer and blastocyst transfer. The synthesis results showed that the clinical pregnancy rate was higher in the sequential embryo transfer group than in the cleavage embryo transfer group (RR 1.42, 95% CI 1.26–1.60,P< 0.01) for both women who did experience repeated implantation failure (RIF) (RR 1.58, 95% CI 1.17–2.13,P< 0.01) and did not experience RIF (Non-RIF) (RR 1.44, 95% CI 1.20–1.66,P< 0.01). However, sequential embryo transfer showed no significant benefit over blastocyst embryo transfer.

Conclusion

The current systematic review demonstrates that sequential cleavage and blastocyst embryo transfer improve the clinical pregnancy rate over conventional cleavage embryo transfer. For women with adequate embryos, sequential transfer could be attempted following careful consideration. More high-grade evidence from prospective randomized studies is warranted.
Colchicine – an effective treatment for children with a clinical diagnosis of autoinflammatory diseases without pathogenic gene variants
Authors: Welzel Tatjana , Wildermuth Anna L. , Deschner Norbert , Benseler Susanne M. , Kuemmerle-Deschner Jasmin B.
Published: September 2021

Background

Autoinflammatory diseases (AID) are rare chronic conditions with high disease burden, affecting children and adults. Clinically and genetically confirmed, AID can be effectively treated with targeted cytokine inhibition. In contrast, for patients with clinical AID symptoms without pathogenic gene variants, no treatment recommendations are available. Colchicine is approved and established as effective, safe and low-cost first-line therapy in Familial Mediterranean Fever. Up to now, efficacy data for colchicine in children with a clinical AID diagnosis without pathogenic gene variants are rare. This pilot study was performed to evaluate the effectiveness of colchicine in children with a clinical diagnosis of AID without pathogenic gene variants.

Methods

A pilot cohort study of consecutive children with active clinical AID without pathogenic gene variants treated with colchicine monotherapy was performed between 01/2009 and 12/2018. Demographics, clinical and laboratory characteristics were determined serially. Colchicine dosing and safety were documented. Physician estimate of disease activity was captured on visual analogue scales (VAS). Primary outcome: Complete response (PGA ≤2 plus CRP ≤0.5 mg/dL and/or SAA ≤10 mg/L) at last follow-up. Secondary outcomes: partial/no response, flare characteristics and requirement for rescue therapies. Analysis: Nonparametric comparison of disease activity measures.

Results

A total of 33 children were included; 39% were female. Median age at colchicine start was 3.8 years, median follow-up was 14.1 months. Clinical AID diagnoses included CAPS (24%), FMF (27%), PFAPA (43%) and unclassified AID (6%). At baseline, overall disease activity was moderate (PGA 4), inflammatory markers were elevated (CRP 12.1 mg/dL; SAA 289.2 mg/L), and 97% reported febrile flares. Outcome: 55% achieved complete response, 35% showed partial response and 58% had no febrile flares at last follow-up. Inflammatory markers (SAA: p < 0.0001, CRP: p < 0.005) and disease activity (p < 0.0001) decreased significantly. Overall, 93% of children experienced improvement of flare characteristics.

Conclusion

Colchicine was found to be effective and safe in children with a clinical AID diagnosis in the absence of pathogenic gene variants. Colchicine is a low-cost treatment option for non-organ threatening AID.
Attitude theory and measurement in implementation science: a secondary review of empirical studies and opportunities for advancement
Authors: Fishman Jessica , Yang Catherine , Mandell David
Published: September 2021

Background

Implementation science studies often express interest in “attitudes,” a term borrowed from psychology. In psychology, attitude research has an established methodological and theoretical base, which we briefly summarize here. We then review implementation studies designed to measure attitudes and compare their definitions and methods with those from psychology.

Methods

A recent review identified 46 studies empirically examining factors associated with implementation. For each of these studies, we evaluated whether authors included attitudes as a construct of interest, and if so, whether and how the construct was defined, measured, and analyzed.

Results

Most of the articles (29/46 [63%]) mention attitudes as an implementation factor. Six articles include a definition of the construct. Nineteen studies were designed to measure attitudes but lacked clarity in describing how attitudes were measured. Those that explained their measurement approach used methods that differed from one another and from validated methods in social psychology. Few articles described associated analyses or provided results specific to attitudes. Despite the lack of specificity regarding relevant measurement, analysis, and results, the articles often included causal conclusions about the role of attitudes.

Conclusions

Attitudes may be an important construct to implementation scientists, but studies to date are ambiguous in their definitions of attitudes and inconsistent in the methods used to measure and analyze attitudes. We discuss how implementation studies can apply psychology’s standardized definitions, validated measurement approaches, and causal models that include attitudes. This application of attitude theory and methods could offer implementation research valuable scientific opportunities.
A comparison of immediate release and delayed release cysteamine in 17 patients with nephropathic cystinosis
Authors: van Stein Christina , Klank Sabrina , Grüneberg Marianne , Ottolenghi Chris , Grebe Jürgen , Reunert Janine , Harms Erik , Marquardt Thorsten
Published: September 2021

Background

Nephropathic cystinosis is a rare and severe metabolic disease leading to an accumulation of cystine in lysosomes which especially harms kidney function. A lifelong therapy with the aminothiol cysteamine can delay the development of end-stage renal disease and the necessity of kidney transplantation. The purpose of our study was to compare the effectiveness of immediate-release and delayed-release cysteamine on cystine and cysteamine levels as well as assessing the onset of adverse effects.

Methods

We retrospectively analysed cystine and cysteamine levels of 17 patients after a single dose of immediate-release cysteamine (Cystagon®, Mylan Pharmaceuticals, Canonsburg, PA and Recordati Pharma GmbH) as well as a single dose of delayed-release cysteamine (Procysbi®; Horizon Pharma USA and Chiesi Farmaceutici S.p.A., Parma, Italy) respectively. Data were collected during a period of three years in the context of optimizing the individual treatment regimens. The dose of DR-cysteamine was reduced to 70% of the equivalent dose of IR-cysteamine. The efficacy of both formulas in depleting white blood cells’ cystine levels and their side effects were compared.

Results

Immediate (IR)- and delayed-release (DR) cysteamine effectively decreased intracellular cystine levels under the target value of 0.5 nmol cystine/mg protein, while fewer side effects occurred under DR-cysteamine. Mean maximum levels of cysteamine were reached after 60 min with IR-cysteamine and after 180 min with DR-cysteamine.

Conclusion

A therapy with DR-cysteamine is as effective as IR-cysteamine while less side effects were reported. Our data show that DR-cysteamine should be dosed higher than 70% of the equivalent dose of IR-cysteamine in order to decrease cystine levels over an extended period of time. Moreover, our data suggest increasing the dosing scheme of Procysbi® to three times daily, to prevent a rapid decrease and achieve a steadier decline in cystine levels. Due to the more convenient dosing scheme, DR-cysteamine might ameliorate therapy adherence and improve patients’ quality of life.
PRINCESS: comprehensive detection of haplotype resolved SNVs, SVs, and methylation
Authors: Mahmoud Medhat , Doddapaneni Harshavardhan , Timp Winston , Sedlazeck Fritz J.
Published: September 2021

Long-read sequencing has been shown to have advantages in structural variation (SV) detection and methylation calling. Many studies focus either on SV, methylation, or phasing of SNV; however, only the combination of variants provides a comprehensive insight into the sample and thus enables novel findings in biology or medicine. PRINCESS is a structured workflow that takes raw sequence reads and generates a fully phased SNV, SV, and methylation call set within a few hours. PRINCESS achieves high accuracy and long phasing even on low coverage datasets and can resolve repetitive, complex medical relevant genes that often escape detection. PRINCESS is publicly available at https://github.com/MeHelmy/princess under the MIT license.
Optimization of Nutrition And Medication (OptiNAM) for acutely admitted older patients: protocol for a randomized single-blinded controlled trial
Authors: Andersen Aino L. , Houlind Morten B. , Nielsen Rikke L. , Jørgensen Lillian M. , Treldal Charlotte , Damgaard Morten , Bengaard Anne Kathrine , Juul-Larsen Helle Gybel , Laursen Louise Bolvig , Iversen Esben , Kruse Marie , Pedersen Anne M. L. , Hornum Mads , Beck Anne M. , Pedersen Mette M. , Ankarfeldt Mikkel Z. , Petersen Janne , Andersen Ove
Published: September 2021

Background

Internationally, older patients (≥65 years) account for more than 40% of acute admissions. Older patients admitted to the emergency department (ED) are frequently malnourished and exposed to inappropriate medication prescribing, due in part to the inaccuracy of creatinine-based equations for estimated glomerular filtration rate (eGFR). The overall aims of this trial are to investigate: (1) the efficacy of a medication review (MED intervention) independent of nutritional status, (2) the accuracy of eGFR equations based on various biomarkers compared to measured GFR (mGFR) based on99mTechnetium–diethylenetriaminepentaacetic acid plasma clearance, and (3) the efficacy of an individualized multimodal and transitional nutritional intervention (MULTI-NUT-MED intervention) in older patients with or at risk of malnutrition in the ED.

Methods

The trial is a single-center block randomized, controlled, observer-blinded, superiority and explorative trial with two parallel groups. The population consists of 200 older patients admitted to the ED: 70 patients without malnutrition or risk of malnutrition and 130 patients with or at risk of malnutrition defined as a Mini Nutritional Assessment-Short Form score ≤11. All patients without the risk of malnutrition receive the MED intervention, which consists of a medication review by a pharmacist and geriatrician in the ED. Patients with or at risk of malnutrition receive the MULTI-NUT-MED intervention, which consists of the MED intervention in addition to, dietary counseling and individualized interventions based on the results of screening tests for dysphagia, problems with activities of daily living, low muscle strength in the lower extremities, depression, and problems with oral health. Baseline data are collected upon study inclusion, and follow-up data are collected at 8 and 16 weeks after discharge. The primary outcomes are (1) change in medication appropriateness index (MAI) score from baseline to 8 weeks after discharge, (2) accuracy of different eGFR equations compared to mGFR, and (3) change in health-related quality of life (measured with EuroQol-5D-5L) from baseline to 16 weeks after discharge.

Discussion

The trial will provide new information on strategies to optimize the treatment of malnutrition and inappropriate medication prescribing among older patients admitted to the ED.

Trail registration

ClinicalTrials.govNTC03741283. Retrospectively registered on 14 November 2018.
Advanced-stage Wilms tumor arising in a horseshoe kidney of a 9-year-old child: a case report
Authors: Farouk Abubakar Garba , Ibrahim H. A. , Farate A. , Wabada S. , Mustapha M. G.
Published: September 2021

Background

Horseshoe kidney (HK) is one of the most common renal fusion abnormalities, with an incidence of 1:400 in the normal population. However, Wilms tumor (WT) arising in an HK is a rare occurrence. We report the case of a 9-year-old boy who presented with an advanced WT in an HK and also highlight the management challenges in a resource-poor setting such as ours.

Case presentation

The patient was a 9-year-old Nigerian boy presented to the Pediatrics Outpatient Clinic of the University of Maiduguri Teaching Hospital (UMTH) with a history of progressive abdominal swelling, weight loss, abdominal pain, and cough. Abdominal examination revealed an irregular, firm, and non-tender mass in the right lumbar region. A computed tomography (CT) scan of the abdomen showed a heterogeneously dense mass that was predominantly to the right side of the abdomen and crossed the midline to the left side, where it continued with the relatively normal renal tissue. Chest CT revealed pulmonary metastases. A diagnosis of WT in an HK was made. The patient had a 6-week course of neoadjuvant chemotherapy, and a right nephrectomy and left partial nephrectomy was performed. The final histologic diagnosis of WT was made. Radiotherapy was intended but was not available in our facility, and the parents could not afford referral to another center.

Conclusions

Children with a clinically suspected HK with WT should undergo a careful imaging evaluation such as CT before any surgical intervention. Neoadjuvant chemotherapy to reduce tumor bulk might be a good treatment method to reduce surgical morbidity and aid in complete excision and potential for preserving renal function.
The combination of R2R3-MYB gene AmRosea1 and hairy root culture is a useful tool for rapidly induction and production of anthocyanins in Antirrhinum majus L
Authors: Piao Chunlan , Wu Jinguo , Cui Min-Long
Published: September 2021

Anthocyanins are the largest group of water-soluble pigments and beneficial for human health. Although most plants roots have the potential to express natural biosynthesis pathways required to produce specialized metabolites such as anthocyanins, the anthocyanin synthesis is specifically silenced in roots. To explore the molecular mechanism of absence and production ability of anthocyanin in the roots, investigated the effect of a bHLH gene AmDelila, and an R2R3-MYB gene AmRosea1, which are the master regulators of anthocyanin biosynthesis in Antirrhinum majus flowers, by expressing these genes in transformed hairy roots of A. majus. Co-ectopic expression of both AmDelila and AmRosea1 significantly upregulated the expression of the key target structural genes in the anthocyanin biosynthesis pathway. Furthermore, this resulted in strongly enhanced anthocyanin accumulation in transformed hairy roots. Ectopic expression of AmDelila alone did not gives rise to any significant anthocyanin accumulation, however, ectopic expression of AmRosea1 alone clearly upregulated expression of the main structural genes as well as greatly promoted anthocyanin accumulation in transformed hairy roots, where the contents reached 0.773–2.064 mg/g fresh weight. These results suggest that AmRosea1 plays a key role in the regulatory network in controlling the initiation of anthocyanin biosynthesis in roots, and the combination of AmRosea1 and hairy root culture is a powerful tool to study and production of anthocyanins in the roots of A. majus.
Discrete-time phytoplankton–zooplankton model with bifurcations and chaos
Authors: Khan A. Q. , Javaid M. B.
Published: September 2021

The local dynamics with different topological classifications, bifurcation analysis, and chaos control for the phytoplankton–zooplankton model, which is a discrete analogue of the continuous-time model by a forward Euler scheme, are investigated. It is proved that the discrete-time phytoplankton–zooplankton model has trivial and semitrivial fixed points for all involved parameters, but it has an interior fixed point under the definite parametric condition. Then, by linear stability theory, local dynamics with different topological classifications are investigated around trivial, semitrivial, and interior fixed points. Further, for the discrete-time phytoplankton–zooplankton model, the existence of periodic points is also investigated. The existence of possible bifurcations around trivial, semitrivial, and interior fixed points is also investigated, and it is proved that there exists a transcritical bifurcation around a trivial fixed point. It is also proved that around trivial and semitrivial fixed points of the phytoplankton–zooplankton model there exists no flip bifurcation, but around an interior fixed point there exist both Neimark–Sacker and flip bifurcations. From the viewpoint of biology, the occurrence of Neimark–Sacker implies that there exist periodic or quasi-periodic oscillations between phytoplankton and zooplankton populations. Next, the feedback control method is utilized to stabilize chaos existing in the phytoplankton–zooplankton model. Finally, simulations are presented to validate not only obtained results but also the complex dynamics with orbits of period-8, 9, 10, 11, 14, 15 and chaotic behavior of the discrete-time phytoplankton–zooplankton model.
The LRA Workbench: an IDE for efficient REST API composition through linked metadata
Authors: Serrano Diego , Stroulia Eleni
Published: September 2021

The number of Web APIs for accessing information and services is continuously increasing, and yet, no tools exist to automate the time-consuming and error-prone process of invoking those APIs and composing their responses. The recent emergence of widely-adopted, standardized, Web-API description formats and the development of Linked Data technologies for data integration have motivated our work on the LRA (Linked REST APIs) methodology [1, 2]. LRA relies on RDF service specifications to automate the development process around the usage of Web APIs. This automation represents a great opportunity to systematize and improve the quality of service-oriented application development. However, LRA’s reliance on SPARQL as the user-interaction model may hinder its adoption, because it requires developers to learn the intricacies of the unconventional graph data model and its associated datasets. In this paper we have developed the LRA Workbench ($$LRA_{Wbench}$$LRAWbench), which takes advantage of the emergent schema of Web-API specifications, in order to simplify the formulation of LRA-compliant SPARQL queries. Our empirical evaluation of the$$LRA_{Wbench}$$LRAWbench usability demonstrates that our tool significantly improves the performance of developers formulating SPARQL queries for LRA. A subsequent study on the effectiveness of the$$LRA_{Wbench}$$LRAWbench demonstrated that developers using LRA tend to produce code with considerable better structural complexity, in less time, than developers manually composing APIs.
Regional-scale data assimilation with the Spatially Explicit Individual-based Dynamic Global Vegetation Model (SEIB-DGVM) over Siberia
Authors: Arakida Hazuki , Kotsuki Shunji , Otsuka Shigenori , Sawada Yohei , Miyoshi Takemasa
Published: September 2021

This study examined the regional performance of a data assimilation (DA) system that couples the particle filter and the Spatially Explicit Individual-based Dynamic Global Vegetation Model (SEIB-DGVM). This DA system optimizes model parameters of defoliation and photosynthetic rate, which are sensitive to phenology in the SEIB-DGVM, by assimilating satellite-observed leaf area index (LAI). The experiments without DA overestimated LAIs over Siberia relative to the satellite-observed LAI, whereas the DA system successfully reduced the error. DA provided improved analyses for the LAI and other model variables consistently, with better match with satellite observed LAI and with previous studies for spatial distributions of the estimated overstory LAI, gross primary production (GPP), and aboveground biomass. However, three main issues still exist: (1) the estimated start date of defoliation for overstory was about 40 days earlier than the in situ observation, (2) the estimated LAI for understory was about half of the in situ observation, and (3) the estimated overstory LAI and the total GPP were overestimated compared to the previous studies. Further DA and modeling studies are needed to address these issues.
Introduction of Dalbergia odorifera enhances nitrogen absorption on Eucalyptus through stimulating microbially mediated soil nitrogen-cycling
Authors: Yao Xianyu , Zhang Qianchun , Zhou Haiju , Nong Zhi , Ye Shaoming , Deng Qi
Published: September 2021

Background

There is substantial evidence that Eucalyptus for nitrogen (N) absorption and increasing the growth benefit from the introduction of N-fixing species, but the underlying mechanisms for microbially mediated soil N cycling remains unclear.

Methods

We investigated the changes of soil pH, soil water content (SWC), soil organic carbon (SOC), total N (TN), inorganic N (NH4+-N and NO3−-N), microbial biomass and three N-degrading enzyme activities as well as the biomass and N productivity of Eucalyptus between a pure Eucalyptus urophylla × grandis plantation (PP) and a mixed Dalbergia odorifera and Eucalyptus plantation (MP) in Guangxi Zhuang Autonomous Region, China.

Results

Compared with the PP site, soil pH, SWC, SOC and TN in both seasons were significantly higher at the MP site, which in turn enhanced microbial biomass and the activities of soil N-degrading enzymes. The stimulated microbial activity at the MP site likely accelerate soil N mineralization, providing more available N (NH4+-N in both seasons and NO3−-N in the wet-hot season) for Eucalyptus absorption. Overall, the N productivity of Eucalyptus at the MP site was increased by 19.7% and 21.9%, promoting the biomass increases of 15.1% and 19.2% in the dry-cold season and wet-hot season, respectively.

Conclusion

Our results reveal the importance of microbially mediated soil N cycling in the N absorption on Eucalyptus. Introduction of D. odorifera enhances Eucalyptus biomass and N productivity, improve soil N availability and increased soil C and N concentration, which hence can be considered to be an effective sustainable management option of Eucalyptus plantations.
Expanding the toolbox: another auxotrophic marker for targeted gene integrations in Trichoderma reesei
Authors: Primerano Paul , Juric Melani , Mach Robert , Mach-Aigner Astrid , Derntl Christian
Published: September 2021

Background

The filamentous ascomycete Trichoderma reesei is used for the industrial production of cellulases and holds the promise for heterologous gene expression due to its outstandingly high protein secretion rates and its long-term application in industry and science. A prerequisite for successful heterologous gene expression is the ability to insert a corresponding expression cassette at suitable loci in the genome of T. reesei.

Results

In this study, we test and demonstrate the applicability of the his1 gene [encoding for the ATP phosphoribosyltransferase (EC 2.4.2.17), part of the histidine biosynthesis pathway] and locus for targeted gene insertion. Deletion of the his1 promoter and a part of the coding region leads to histidine auxotrophy. Reestablishment of the his1 locus restores prototrophy. We designed a matching plasmid that allows integration of an expression cassette at the his1 locus. This is demonstrated by the usage of the reporter EYFP (enhanced yellow fluorescence protein). Further, we describe a minimal effort and seamless marker recycling method. Finally, we test the influence of the integration site on the gene expression by comparing three strains bearing the same EYFP expression construct at different loci.

Conclusion

With the establishment of his1 as integration locus and auxotrophic marker, we could expand the toolbox for strain design in T. reesei. This facilitates future strain constructions with the aim of heterologous gene expression.
Prevalence and characteristics of Listeria species from selected African countries
Authors: Dufailu Osman Adamu , Yaqub Muneer Oladipupo , Owusu-Kwarteng James , Addy Francis
Published: September 2021

Listeriosis, caused by Listeria spp., presents varying clinical manifestations among individuals, from moderate fecal infections such as diarrhea to severe infections such as septicemia, meningitis and abortion or newborn listeriosis in perinatal patients. In Africa, listeriosis is attributed to poor sanitation and cross-contamination in food processing environments, particularly ready to eat (RTE) foods including dairy products, leafy vegetables, fish and meat. Despite the global increase in reported cases and research on listeriosis, data from Africa remains scarce and this could lead to possible underestimation of the importance of listeriosis on the continent. This paper therefore presents a comprehensive overview of currently available reports on Listeria spp. in Africa with emphasis on molecular characteristics, antimicrobial susceptibility, and prevalence in food, animal and environmental samples. The majority of studies on Listeria spp. in Africa have so far focused on the prevalence and antibiotic susceptibility of L. monocytogenes isolated from RTE foods and raw meat but rarely from humans, animals, and the environment. The overall calculated average prevalence values from the available reports are 23.7 and 22.2% for Listeria spp. and L. monocytogenes, respectively. Listeria spp. isolated from different parts of Africa are generally sensitive to ciprofloxacin, but resistant to penicillin. The majority of these studies employed conventional culture and biochemical tests to characterize Listeria spp. However, the use of modern molecular techniques such as PCR and whole-genome sequencing is on the rise. Most of the studies employing molecular tools were carried out in South Africa and Nigeria, with the predominant strain reported in South Africa being ST6. In order to provide a better understanding of the importance of listeria in Africa, there is the need for extensive and coordinated studies using modern molecular-based techniques to characterize the various Listeria species, and to assess the disease epidemiology using the one health concept.
Pre-clinical medical student cardiac point-of-care ultrasound curriculum based on the American Society of Echocardiography recommendations: a pilot and feasibility study
Authors: Jujo Satoshi , Lee-Jayaram Jannet J. , Sakka Brandan I. , Nakahira Atsushi , Kataoka Akihisa , Izumo Masaki , Kusunose Kenya , Athinartrattanapong Natsinee , Oikawa Sayaka , Berg Benjamin W.
Published: September 2021

Background

Cardiac point-of-care ultrasound (POCUS) training has been integrated into medical school curricula. However, there is no standardized cardiac POCUS training method for medical students. To address this issue, the American Society of Echocardiography (ASE) proposed a framework for medical student cardiac POCUS training. The objective of this pilot study was to develop a medical student cardiac POCUS curriculum with test scoring systems and test the curriculum feasibility for a future definitive study.

Methods

Based on the ASE-recommended framework, we developed a cardiac POCUS curriculum consisting of a pre-training online module and hands-on training with a hand-held ultrasound (Butterfly iQ, Butterfly Network Inc., Guilford, CT, USA). The curriculum learning effects were assessed with a 10-point maximum skill test and a 40-point maximum knowledge test at pre-, immediate post-, and 8-week post-training. To determine the curriculum feasibility, we planned to recruit 6 pre-clinical medical students. We semi-quantitatively evaluated the curriculum feasibility in terms of recruitment rate, follow-up rate 8 weeks after training, instructional design of the curriculum, the effect size (ES) of the test score improvements, and participant satisfaction. To gather validity evidence of the skill test, interrater and test-retest reliability of 3 blinded raters were assessed.

Results

Six pre-clinical medical students participated in the curriculum. The recruitment rate was 100% (6/6 students) and the follow-up rate 8 weeks after training was 100% (6/6). ESs of skill and knowledge test score differences between pre- and immediate post-, and between pre- and 8-week post-training were large. The students reported high satisfaction with the curriculum. Both interrater and test-retest reliability of the skill test were excellent.

Conclusions

This pilot study confirmed the curriculum design as feasible with instructional design modifications including the hands-on training group size, content of the cardiac POCUS lecture, hands-on teaching instructions, and hand-held ultrasound usage. Based on the pilot study findings, we plan to conduct the definitive study with the primary outcome of long-term skill retention 8 weeks after initial training. The definitive study has been registered in ClinicalTrials.gov (Identifier: NCT04083924).
Gonadotropin releasing hormone analogue treatment of central precocious puberty is not associated with altered prevalence of polycystic ovary syndrome: a single center cohort study
Authors: Karavani Gilad , Chill Henry H. , Schachter-Safrai Natali , Lomnitz Gan , Gillis David , Bauman Dvora
Published: September 2021

Background

There is conflicting evidence regarding an association between gonadotropin releasing hormone analogue (GnRHa) therapy and polycystic ovary syndrome (PCOS). This study aimed to compare the prevalence of endocrine disorders, primarily PCOS, between women who had been treated with GnRHa for central precocious puberty (CPP) and those who were not treated.

Methods

This was a retrospective cohort study, including women diagnosed with central precocious puberty between 1989 and 2011 in a university affiliated tertiary medical center. Data collected included demographic data, medical background, clinical presentation at diagnosis and duration of treatment (zero for non-treated). Gynecologic and endocrine long-term outcomes were compared by treatment group.

Results

Fifty-one women were included in the study, 27/51 had been treated with gonadotropin releasing hormone analogue (GnRHa). Overall prevalence of PCOS was 19.6%. No statistically significant difference in prevalence of PCOS was demonstrated between the treated and non-treated groups. Similarly, overall prevalence of either clinical or laboratory hyper-androgenism, was 29.4% and 33.3%, for the treatment and non-treatment groups respectively (p = non-significant).

Conclusions

GnRHa treatment for precocious puberty is not associated with increased risk of polycystic ovary syndrome.
The role of e-engagement and flow on the continuance with a learning management system in a blended learning environment
Authors: Goh Tiong-Thye , Yang Bing
Published: September 2021

E-learning systems are widely deployed in higher education institutions but sustaining students’ continued use of e-learning systems remains challenging. This study investigated the relationship between e-learning engagement, flow experience and learning management system continuance via a mediated moderation interaction model. The context of the study is a Moodle LMS supporting a blended learning environment. After controlling age and gender, a PLS analysis of 92 students’ samples with a reflective flow construct explained 49% of the variance in the research model. The analysis shows that flow mediates e-engagement and perceived ease of use with a direct positive impact on e-learning system continuance. Flow has an indirect impact through perceived usefulness on e-learning system continuance. However, the direct impact of flow on system continuance weakens as e-learning engagement increases. This finding may help to explain the mixed and inconsistent impact of flow in the e-learning system continuance literature. The dual effect of flow suggests that instructors must carefully balance pedagogical decisions intended to heighten flow experience to generate positive learning outcomes through e-engagement and its consequence of reduced impact on continued system use.
Pre-procedural predictors for multiple clips in percutaneous edge-to-edge mitral valve repair
Authors: El Garhy Mohammad , Lauer Bernward , Göbel Björn , Costello-Boerrigter Lisa C. , Salomon Carsten , Lapp Harald , Ohlow Marc-Alexander
Published: September 2021

Background

Percutaneous mitral valve (MV) clipping for mitral regurgitation (MR) revolutionized MV repair; however, valve anatomies and pathologies vary. Often multiple clips are required, and predicting this pre-procedurally would be useful. We evaluated pre-procedural predictors for multiple clips.

Results

We retrospectively analyzed 127 severe MR patients treated by mitral clipping between January 2011 and August 2018. Patients were grouped according to the use of a single (group I) or multiple clips (group II) and pre-procedure echocardiographs compared. No demographic differences existed except group II had more males (68.1%) than group I (48.3%). Mean left atrial diameter was larger in group II, 51 ± 9 mm, than group I, 48 ± 5 mm, p = 0.026. Mean mitral annular diameter differed: 34 ± 4mm (group II) versus 33 ± 3 mm (group I), p = 0.017. The vena contracta was broader in group II than group I (6.6 ± 1 mm vs. 6 ± 0.9 mm, p = 0.001). Severe mitral annular calcification occurred more in group I (36.2%) than group II (10.1%), p = 0.0001. On multivariate analysis, vena contracta width correlated positively with multiple clips (B 0.125, p = 0.013), but severe annular calcification correlated inversely (B − 0.35, p = 0.002).

Conclusions

Vena contracta width and severe annular calcification are factors to consider when planning MV clipping.
Congenital cystic adenomatoid malformation associated with right aortic arch with mirror image branching and absence of left pulmonary artery in an adult
Authors: Padmanaban Elamparidhi , Nibhanupudi Kamala Manogna , Amirthalingam Umamageswari , Rekha Padma , George Rintu
Published: September 2021

Background

Congenital cystic adenomatoid malformation is an uncommon developmental anomaly that is diagnosed prenatally or during early childhood and is rare to present in adulthood. Type 2 congenital cystic adenomatoid malformation is often associated with other anomalies such as congenital cardiac anomalies. We present a case of type 2 congenital cystic adenomatoid malformation in an adult male associated with absence of left pulmonary artery and right aortic arch with mirror image branching. To our knowledge, this is the first case report with the combination of all three anomalies.

Case presentation

A 33-year-old male presented to the Department of Pulmonary Medicine with high-grade fever, chills and rigor, breathlessness, and productive cough for a duration of one week. He had multiple similar self-limiting episodes in the past which did not require hospitalization. The plain radiograph showed right aortic arch and a small left hilum. CT thorax showed multiple cystic lesions of size 0.5–2.0 cm in the apico-posterior segment of the left upper lobe; anterior, posterior, and lateral segments of the left lower lobe; and the apical segment of the right upper lobe with a maximal cyst wall thickness of 2 mm. Volume of left lung was reduced with trans-thoracic herniation of the medial segment of the right middle lobe; bronchiectatic changes were seen in the apical, anterior, and posterior segments of the right upper lobe; and fibrotic strands were seen in the apical segment of the right lower lobe and the apico-posterior segment of the right upper lobe. Mediastinal window showed right-sided aortic arch with mirror image branching. The pulmonary trunk was seen to continue as the right pulmonary artery with absent left pulmonary artery.

Conclusions

Though congenital cystic adenomatoid malformation is a disease of infancy and childhood, it should also be considered in adults presenting with recurrent lower respiratory tract infections and/or pneumothorax. Radiologists must be aware of the types of congenital cystic adenomatous malformation (CCAM) and their associations, as type 2 CCAM has a high association with congenital cardiac disease. Proximal interruption of pulmonary artery should be considered if the pulmonary trunk continues as either right or left pulmonary artery.
Assessment of the relationship between hepatocellular carcinoma location and its response to transarterial chemoembolization
Authors: Elsahhar Ahmed , Abdelwahab Sameh M. , Nasser Haytham M. , Hassan Mohammed Sobhi
Published: September 2021

Background

Transarterial chemoembolization (TACE) is the recommended treatment in intermediate stage of hepatocellular carcinoma (HCC). Many indices are used to predict the outcome of the TACE. The location of the HCC has not been enough studied as a prognostic variable.

Results

We evaluated 149 HCC nodules (111 patients) and analyzed the association between the response to TACE and the nodule location. There was a significant difference between the complete response (CR) and the non-CR group in the location of the HCC regarding its segment and the response to TACE with the anterior segment lesions achieving higher rates of complete response (CR) (P .03), and the distance between the tumor and the liver capsule with the subcapsular lesions showing higher rate of non-CR (P .02). However, there was no significant difference between the CR and the non-CR groups regarding the location between the right and the left lobes (P .48) and the central versus peripheral lesions (P .41).

Conclusions

The location of the HCC can improve the prediction of the tumor response to TACE. Anterior segment tumors showed a higher rate of complete response and subcapsular lesions showed a higher rate of recurrence after TACE.
Development of a duplex real-time PCR method for the detection of influenza C and D viruses
Authors: Zhang Letian , Lu Meng , Lu Jiaxuan , Wang Ningning , Pan Zhongzhou , Su Shuo
Published: September 2021

Influenza viruses are major respiratory pathogens known to infect human and a variety of animals and are widely prevalent worldwide. Genome structure of influenza D virus (IDV) is identical to that of influenza C virus (ICV), and phylogenetic analyses suggest that IDV and ICV share a common ancestry and high homology. To date, the prevalence of ICV and IDV in China is unclear, but these viruses represent a potential threat to public health due to cross-species transmission and zoonotic potential. To efficiently monitor ICV and IDV, it is necessary to establish a dual detection method to understand their prevalence and conduct in-depth research. A duplex real-time PCR method for the simultaneous detection of ICV and IDV was developed. TaqMan fluorescent probes and specific primers targeting NP gene of ICV and PB1 gene of IDV were designed. This method exhibited good specificity and sensitivity, and the detection limit reached 1 × 101 copies/μL of plasmid standards of each pathogen. Thirty-one clinical swine samples and 10 clinical cattle samples were analyzed using this method. One positive sample of IDV was detected, and the accuracy of clinical test results was verified by conventional PCR and DNA sequencing. The duplex real-time PCR detection method represents a sensitive and specific tool to detect ICV and IDV. It provides technical support for virus research and clinical diagnosis of ICV and IDV. This information will benefit animal and human health.
Hepatectomy Followed by mFOLFOX6 Versus Hepatectomy Alone for Liver-Only Metastatic Colorectal Cancer (JCOG0603): A Phase II or III Randomized Controlled Trial
Authors: Kanemitsu Yukihide , Shimizu Yasuhiro , Mizusawa Junki , Inaba Yoshitaka , Hamaguchi Tetsuya , Shida Dai , Ohue Masayuki , Komori Koji , Shiomi Akio , Shiozawa Manabu , Watanabe Jun , Suto Takeshi , Kinugasa Yusuke , Takii Yasumasa , Bando Hiroyuki , Kobatake Takaya , Inomata Masafumi , Shimada Yasuhiro , Katayama Hiroshi , Fukuda Haruhiko ,   on behalf of the JCOG Colorectal Cancer Study Group
Published: September 2021

PURPOSE

Adjuvant chemotherapy after hepatectomy is controversial in liver-only metastatic colorectal cancer (CRC). We conducted a randomized controlled trial to examine if adjuvant modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) is superior to hepatectomy alone for liver-only metastasis from CRC.

PATIENTS AND METHODS

In this phase II or III trial (JCOG0603), patients age 20-75 years with confirmed CRC and an unlimited number of liver metastatic lesions were randomly assigned to hepatectomy alone or 12 courses of adjuvant mFOLFOX6 after hepatectomy. The primary end point of phase III was disease-free survival (DFS) in intention-to-treat analysis.

RESULTS

Between March 2007 and January 2019, 300 patients were randomly assigned to hepatectomy alone (149 patients) or hepatectomy followed by chemotherapy (151 patients). At the third interim analysis of phase III with median follow-up of 53.6 months, the trial was terminated early according to the protocol because DFS was significantly longer in patients treated with hepatectomy followed by chemotherapy. With median follow-up of 59.2 months, the updated 5-year DFS was 38.7% (95% CI, 30.4 to 46.8) for hepatectomy alone compared with 49.8% (95% CI, 41.0 to 58.0) for chemotherapy (hazard ratio, 0.67; 95% CI, 0.50 to 0.92; one-sided P = .006). However, the updated 5-year overall survival (OS) was 83.1% (95% CI, 74.9 to 88.9) with hepatectomy alone and 71.2% (95% CI, 61.7 to 78.8) with hepatectomy followed by chemotherapy. In the chemotherapy arm, the most common grade 3 or higher severe adverse event was neutropenia (50% of patients), followed by sensory neuropathy (10%) and allergic reaction (4%). One patient died of unknown cause after three courses of mFOLFOX6 administration.

CONCLUSION

DFS did not correlate with OS for liver-only metastatic CRC. Adjuvant chemotherapy with mFOLFOX6 improves DFS among patients treated with hepatectomy for CRC liver metastasis. It remains unclear whether chemotherapy improves OS.
Cleaved Delta like 1 intracellular domain regulates neural development via Notch signal-dependent and -independent pathways
Authors: Okubo Yusuke , Ohtake Fumiaki , Igarashi Katsuhide , Yasuhiko Yukuto , Hirabayashi Yoko , Saga Yumiko , Kanno Jun
Published: September 2021

Notch-Delta signaling regulates many developmental processes, including tissue homeostasis and maintenance of stem cells. Upon interaction of juxtaposed cells via Notch and Delta proteins, intracellular domains of both transmembrane proteins are cleaved and translocate to the nucleus. Notch intracellular domain activates target gene expression; however, the role of the Delta intracellular domain remains elusive. Here, we show the biological function of Delta like 1 intracellular domain (D1ICD) by modulating its production. We find that the sustained production of D1ICD abrogates cell proliferation but enhances neurogenesis in the developing dorsal root ganglia (DRG), whereas inhibition of D1ICD production promotes cell proliferation and gliogenesis. D1ICD acts as an integral component of lateral inhibition mechanism by inhibiting Notch activity. In addition, D1ICD promotes neurogenesis in a Notch signaling-independent manner. We show that D1ICD binds to Erk1/2 in neural crest stem cells and inhibits the phosphorylation of Erk1/2. In summary, our results indicate that D1ICD regulates DRG development by modulating not only Notch signaling but also the MAP kinase pathway.