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Iatrogenic tibial arteriovenous fistula after Fogarty balloon catheter graft thrombec...
Spyros Papadoulas
Konstantinos Moulakakis

Spyros Papadoulas

and 8 more

October 08, 2021
A 75-year-old male presented with an immediately threatened grade IIb acute ischemia of the left leg due to thrombosis of a femoro-infrapopliteal prosthetic bypass graft. After an urgent Computed Tomography Angiography, an urgent graft thrombectomy was performed using a 5 Fr Fogarty catheter, which had a troublesome distal passage.
Second Language Acquisition: Analysis of Chinese Learning Challenges and Influence of...
Dr. Okafor Miracle Uzochukwu

Okafor Miracle Uzochukwu

October 08, 2021
With the great development of China's economy, and the globalization of China, more and more Nigerian students have begun to cultivate interest in learning Chinese language. Many seek to study Chinese in Nigeria or study aboard especially in China, with the goal of learning Chinese, cross-cultural understandings, achieve personal academic goals, or obtain personal independence. For Nigerian students of Igbo origin, there are lots of problems they tend to encounter in the process of learning Chinese language. Through critical analysis, this paper finds out the influence of Igbo language on Chinese language learners of Igbo origins, and some challenges encountered in learning Chinese language which includes; pronunciation, vocabulary, grammar, Chinese character writing, and so on. According to the results of this survey, both positive interference and negative interference exist in the process of learning Chinese. Igbo language has both positive and negative effects on Chinese learners. This study also puts forward effective teaching and learning strategies for students and teachers, and theoretical suggestions for further enriching and improving Teaching Chinese Language in Nigeria. This study is quite significant as it will enrich the research on Chinese teaching, improve the Chinese level of students, provide beneficial help for the mutual translation of Chinese and Igbo, promote cultural exchanges between China and Igbo people of Nigeria, and facilitate economic and trade development.
Evaluating biological activity of folic acid-modified and 10-hydroxycamptothecin-load...
Mei-Xia Zhao
Di-Feng Chen

Mei-Xia Zhao

and 4 more

October 07, 2021
Targeted nanocarrier can selectively deliver anti-tumor drugs to cancer sites improving drug efficiency. Accordingly, a targeted nanocarrier (MSN-FA) was synthesized based on folic acid (FA) modified mesoporous silica nanoparticles (MSNs). These loaded with 10-hydroxycamptothecin (HCPT) to obtain the nano-drug MSN-FA@HCPT. These nanocarriers were characterized by transmission electron microscopy (TEM), zeta potential, ultraviolet-visible spectroscopy (UV-Vis), fourier transform infrared spectroscopy (FT-IR), and thermogravimetric analysis (TGA). Notably, the nanocarriers were nearly spherical before and after loading HCPT and exhibited good dispersibility. Also, folate receptor (FR) over-expressing HeLa cells and FR deficient HepG2 cells were used to evaluate in vitro cellular uptake and cytotoxicity of MSN-FA@HCPT and MSN@HCPT. Interestingly, FA-modified nanocarriers enhanced the cytotoxicity of HCPT by improving drug targeting to tumor cells. Also, apoptotic and mitochondrial membrane potential (MMP) reducing effects of MSN-FA@HCPT were more prominent than the MSNs without FA modification. MSN-FA@HCPT can be excellent drug carriers with profound biomedical applications.
Impact of a time-to-effect guided ablation protocol in cryoballoon ablation on durabi...
Enida Rexha
Christian Heeger

Enida Rexha

and 13 more

October 07, 2021
Background: Cryoballoon (CB) based pulmonary vein isolation (PVI) has proven to be as effective as radiofrequency (RF) based ablation. Different ablation protocols took the individual time-to-isolation (TTI) into account aiming at shorter but equally or even more effective freeze-cycles. The current study sought to assess the impact of the TTI on PVI durability in patients undergoing a repeat procedure for recurrence of atrial tachyarrhythmia (ATA). Methods and Results: In 205 patients with ATA recurrence after previous CB-based PVI a total of 806 PVs were identified. One hundred-twenty-six out of 806 PVs (16%) were previously treated with a TTI guided ablation (protocol #1; TTI+120 sec.), in 92/806 (11%) PVs TTI was only monitored (m) but fixed freeze-cycles were applied (protocol #2; mTTI) and in 588/806 (73%) a fixed freeze-cycle was applied without TTI-monitoring. There was no difference in the PV-reconduction rate between the groups (P=0.23). The right inferior pulmonary vein (RIPV) showed overall significantly higher reconduction rates compared to the other PVs (RIPV – left inferior PV (LIPV) p<0.003, -left superior PV (LSPV) p<0.001, - right superior PV RSPV p<0.013). In 21 patients (10%) only for the RIPV reconduction was assessed. Conclusions: TTI based CB ablation did not show significant differences regarding PV-reconduction rates compared to the other protocols.
Programmed intermittent epidural bolus in comparison with continuous epidural infusio...
Xiaofei Mo
Tianyun Zhao

Xiaofei Mo

and 6 more

October 07, 2021
Objective Programmed intermittent epidural bolus (PIEB) was reported to provide superior maintenance of labour analgesia with better pain relief, and less motor block than continuous epidural infusion (CEI). Whether this is also evident for uterine contraction pain relief after caesarean section remains unknown. Design Randomised, double blind, positive-control trial. Setting Guangzhou Women and Children’s Medical Center, China Population Parturients scheduled for elective caesarean section under combined spinal-epidural anaesthesia were enrolled. Methods At the end of the surgery, after a similar epidural loading dose given, patients received either PIEB (6 mL every hour) or CEI (6 mL/h) of 0.1% ropivacaine. Main outcome measures The primary outcome was the effectiveness of uterine contraction pain relief during breastfeeding assessed with visual analog scale score (VAS-UD) at the postoperative 36 h. Secondary main outcome was lower extremity motor block (defined as Bromage score > 0). Results One hundred and twenty parturients were studied (PIEB, 60; CEI, 60). The VAS-UD at the postoperative 36 h was significantly lower in the PIEB group than in the CEI group [median (IQR), 30 (20 to 40) mm] compared with the CEI group [40 (30 to 50) mm], with an estimated difference of -10 mm (95% CI -15 to -5 mm; P=0.001). Motor block was higher in the CEI group than in the PIEB group during the study period except 2 h (all P<0.05). Conclusions PIEB provides more effective uterine contraction pain relief and less motor block after caesarean section than CEI.
Commentary on Donati et al. SARS-CoV-2 infection among hospitalized pregnant women an...
James Thornton

James Thornton

October 07, 2021
Unlike many viral infections such as influenza, and the two previous incarnations of the coronavirus, SARS and MERS, Covid-19 originally appeared to be of similar severity, after adjusting for age, BMI and other co-morbidities, in the pregnant as in the non-pregnant population. Worryingly the paper from the Italian Obstetric Surveillance System COVID-19 Working Group (p …), suggests that, in pregnancy, the virus may be getting more virulent with the advent of newer variants. Specifically the need for ventilation or ICU admission was significantly increased during the second wave (alpha variant predominant) compared to the first (wild-type predominant), albeit with no maternal deaths during the first wave and only one during the second. If real, this is both unexpected and concerning. Unexpected, because viruses tend to mutate in the direction of reduced severity; it is not in the interests of the virus that the host dies. Concerning, because it suggest that the newer variants are behaving more like other viral diseases; causing more severe disease in pregnancy.The evidence from Italy is supported by at least three other sources. In August a preprint from the UK Obstetric Surveillance Service (Vousden et al. MedRxiv 2021.07.22.21261000; doi: https://doi.org/10.1101/2021.07.22.21261000 accessed 30 September) reported disease severity in pregnancy when wild type predominated, when alpha predominated and when delta predominated. In each succeeding phase disease severity in increased. On 24 September the UK Intensive Care National Audit & Research Centre reported (ICNARC 17 September 2021 https://www.icnarc.org/Our-Audit/Audits/Cmp/Reports accessed 30 September) that the absolute numbers of pregnant women admitted to critical care with Covid were significantly higher in the second (alpha) wave than the first (wild type), and looked set to be significantly higher again in the third (delta) wave. Finally a large series from Nair Hospital, the largest hospital caring for Covid in Mumbai (Mahajan et al. Obstet Gynecol: July 7, 2021 doi: 10.1097/AOG.0000000000004529), reported significantly higher maternal mortality during the second (alpha predominant) wave than the first (wild type).The lesson for women is simple, get vaccinated. Vaccines are safe and if the disease is really getting more severe, the balance of risks and benefits will be moving overwhelmingly in favour of vaccination. The lesson for obstetricians is more complicated. Encourage women to get vaccinated and take the disease seriously. Keep women with Covid out of hospital if possible, but monitor them with saturation monitors reliably, so those who deteriorate can be picked up quickly. When they need admission follow evidence-based treatment guidelines, and keep using personal protective equipment. We’re not yet done with Covid.Jim Thornton MD FRCOGEmeritus Professor of Obstetrics & Gynaecology, University of Nottingham.
Viral  infections mediate microbial controls on ecosystem responses to global warming...
Daniel J Wieczynski

Daniel J Wieczynski

and 9 more

September 09, 2022
Climate change is affecting how energy and matter flow within ecosystems, altering global carbon and nutrient cycles. Microorganisms play a fundamental role in carbon and nutrient cycling and are thus an integral link between ecosystems and climate. Here, we highlight a major black box hindering our ability to anticipate ecosystem climate responses: viral infections within complex microbial food webs. We show how understanding and predicting ecosystem responses to warming could be challenging—if not impossible—without accounting for the direct and indirect effects of viral infections on different microbes (bacteria, fungi, protists) that together perform diverse ecosystem functions. Importantly, understanding how rising temperatures associated with climate change influence viruses and virus-host dynamics is crucial to this task, yet severely understudied. In this perspective, we 1) synthesize existing knowledge about virus-microbe-temperature interactions and 2) identify important gaps to guide future investigations regarding how climate change might alter microbial food web effects on ecosystem functioning. To provide real-world context, we consider how these processes may operate in peatlands—globally significant carbon sinks that are threatened by climate change. We stress that understanding how warming affects biogeochemical cycles in any ecosystem hinges on disentangling complex interactions and temperature responses within microbial food webs.
Radiomics features for differentiating clear cell sarcoma of the kidney from Wilms’ t...
Haoru Wang
Xin Chen

Haoru Wang

and 7 more

October 07, 2021
Background: Clear cell sarcoma of the kidney (CCSK) is a rare but the second common renal malignant tumor mimicking Wilms’ tumor. Radiomics is helpful for differentiating CCSK from Wilms’ tumor preoperatively through analyzing the pixel distribution of lesions on medical images quantitatively. Procedure: In this study, the regions of interest (ROIs) of lesions were delineated on corticomedullary phase (CMP) and nephrographic phase (NP) images to extract radiomics features. Dimensionality reduction and Logistic Regression (LR) algorithm were used to construct the classification models. The area under the receiver operator characteristic curve (AUC), sensitivity and specificity were calculated for evaluation, and Delong test was used to compare the performance of the most meaningful features and LR models. Results: Lower skewness was observed in Wilms’ tumor, and higher skewness in CCSK. Skewness transformed by exponential and squareroot filters from NP images achieved moderate to good diagnostic performance for CCSK with AUCs of 0.707 (95%CI: 0.573, 0.840) and 0.705 (95%CI: 0.572, 0.839) in the training set, and 0.818 (95%CI: 0.608, 1.000) and 0.803 (95%CI: 0.585, 1.000) in the validation set, respectively. Delong test showed no significant difference between LR model, exponential-skewness and squareroot-skewness based on NP images in both training and validation sets. Conclusion: Skewness from nephrographic phase at exponential and squareroot filters is helpful to discriminate between CCSK and Wilms’ tumor in children, and higher skewness on NP images may be a potential imaging biomarker for diagnosing CCSK from Wilms’ tumor.
Childhood Interstitial and Diffuse Lung Disease in an Immunocompetent Patient Without...
saleh alharbi

saleh alharbi

October 07, 2021
Childhood interstitial and diffuse lung disease (chILD) is a heterogeneous group of rare and chronic respiratory disorders with an estimated prevalence of 1.5 cases per million children aged 0-18 years. Presented is the case of an immunocompetent young girl who presented with symptoms of recurrent cough and clubbing
Cessation of grazing causes biodiversity loss and homogenization of soil food webs
Maarten Schrama
Casper Quist

Maarten Schrama

and 9 more

October 07, 2021
There is widespread concern that cessation of grazing in historically grazed ecosystems is causing biotic homogenization and biodiversity loss. Here, we used 12 montane grassland sites along an 800-km north-south gradient across the United Kingdom, to test whether cessation of grazing affects local ɑ- and β-diversity of belowground food webs. We show that cessation of grazing leads to strongly decreased ɑ-diversity of both soil microbial and faunal diversity. In contrast, the β-diversity varied between groups of soil organisms. While soil microbial communities exhibited increased homogenization after cessation of grazing, we observed decreased homogenization for soil fauna after cessation of grazing. Overall, our results indicate that grazer exclusion from historically grazed montane grasslands has far-ranging consequences for the diversity and composition of belowground food webs, and underscore the importance of grazers for maintaining the diversity of belowground communities, which play a central role in ecosystem functioning.
Application of a Vertical “Electric Sieve” to Mitigate and Prevent Salinization in Co...
Yuehua Li
Lin Zhao

Yuehua Li

and 3 more

October 07, 2021
This study explored the application of a Vertical Electrokinetic system (V-EK) with multilayer electrodes in shallow soil to form an “Electric Sieve” to mitigate and prevent the soil salinization caused by salts rising from shallow groundwater in the coastal areas. In the model V-EK system, the electric resistances of soil column, reversely corresponding to salinity, at the applied voltages 4, 10 and 20 V were 266, 487 and 1272 Ω, respectively. Meanwhile, lower electrical conductivity (EC, between 67-230 μs/cm) were observed in the soil within 50 cm below the surface at the voltages of 10 V and 20 V, which was much lower than the minimum value (581 μs/cm) of the control with no current applied. For the control column without EK treatment (0 V), soil in the surface layer had the highest EC value at 1721 μS/cm due to the salts rising from the bottom, and the EC values of soil beneath the surface were in the range of 581-1127 μS/cm. Compared to control column, the level of ions in the surface soil significantly declined after V-EK treatment, especially for the column with voltage at 10 V and 20V. When voltage was at 20 V, Na+ was detected at a range of 0.06-0.08mg/g in the surface soil, a >99% reduction when compared to the controls. Similar efficacy was observed for chloride (Cl-), in the V-EK column with the voltages at 10 V and 20V.
PatientMatcher: a customizable Python-based open-source tool for matching undiagnosed...
Chiara  Rasi
Daniel Nilsson

Chiara Rasi

and 8 more

October 07, 2021
The amount of data available from genomic medicine has revolutionized the approach to identify the determinants underlying many rare diseases. The task of confirming a genotype-phenotype causality for a patient affected with a rare genetic disease is often challenging. In this context, the establishment of the MatchMaker Exchange (MME) network has assumed a pivotal role in bridging heterogeneous patient information stored on different medical and research servers. MME has made it possible to solve rare disease cases by “matching” the genotypic and phenotypic characteristics of a patient of interest with patient data available at other clinical facilities participating in the network. Here, we present PatientMatcher (https://github.com/Clinical-Genomics/patientMatcher), an open-source Python and MongoDB-based software solution developed by Clinical Genomics facility at the Science for Life Laboratory in Stockholm. PatientMatcher is designed as a standalone MME server, but can easily communicate via REST API with external applications managing genetic analyses and patient data. The MME node is being implemented in clinical production in collaboration with the Genomic Medicine Center Karolinska at the Karolinska University Hospital. PatientMatcher is written to implement the MME API and provides several customizable settings, including a custom-fit similarity score algorithm and adjustable matching results notifications.
Advances in the development of PubCaseFinder, including the new application programmi...
Toyofumi  Fujiwara
Jae-Moon Shin

Toyofumi Fujiwara

and 2 more

October 07, 2021
Over 7,000 rare genetic diseases have been identified, and millions of newborns are affected by severe rare genetic diseases each year. A variety of Human Phenotype Ontology (HPO)-based clinical decision support systems (CDSS) and patient repositories have been developed to support clinicians in diagnosing patients with suspected rare genetic diseases. In September 2017, we released PubCaseFinder (https://pubcasefinder.dbcls.jp), a web-based CDSS that provides ranked lists of genetic and rare diseases using HPO-based phenotypic similarities, where top-listed diseases represent the most likely differential diagnosis. We also developed a Matchmaker Exchange (MME) application programming interface (API) to query PubCaseFinder, which has been adopted by several patient repositories. In this paper, we describe notable updates regarding PubCaseFinder, the GeneYenta matching algorithm implemented in PubCaseFinder, and the PubCaseFinder API. The updated GeneYenta matching algorithm improves the performance of the CDSS automated differential diagnosis function. Moreover, the updated PubCaseFinder and new API empower patient repositories participating in MME and medical professionals to actively use HPO-based resources.
Chromosome-level genome assembly of the horned-gall aphid, Schlechtendalia chinensis...
Hongyuan Wei
Yu-Xuan Ye

Hongyuan Wei

and 6 more

October 07, 2021
The horned gall aphid Schlechtendalia chinensis, is an economically important insect that induces galls valuable for medicinal and chemical industries. S. chinensis manipulates its host plant to form well-organized horned galls during feeding. So far, more than twenty aphid genomes have been reported; however, all of those are derived from free-living aphids. Here we generated a high-quality genome assembly of S. chinensis, representing the first genome sequence of a galling aphid. The final genome assembly was 280.43 Mb, with 97% of the assembled sequences anchored into thirteen chromosomes. S. chinensis presents the smallest aphid genome size among available aphid genomes to date. The contig and scaffold N50 values were 3.39 Mb and 20.58 Mb, respectively. The assembly included 96.4% of conserved arthropod and 97.8% of conserved Hemiptera single-copy orthologous genes based on BUSCO analysis. A total of 13,437 protein-coding genes were predicted. Phylogenomic analysis showed that S. chinensis formed a single clade between the Eriosoma lanigerum clade and the Aphidini+Macrosiphini aphid clades. In addition, salivary proteins were found to be differentially expressed when S. chinensis underwent host alternation, indicating their potential roles in gall formation and plant defense suppression. A total of 36 cytochrome P450 genes were identified in S. chinensis, considerably fewer compared to other aphids, probably due to its small host plant range. The high-quality S. chinensis genome assembly and annotation provide an essential genetic background for future studies to reveal the mechanism of gall formation and to explore the interaction between aphids and their host plants.
Polyunsaturated fatty acids cause physiological and behavioral changes in Vibrio algi...
David S. Smith
Carina Houck

David S. Smith

and 7 more

October 06, 2021
Vibrio alginolyticus and Vibrio (Aliivibrio) fischeri are Gram-negative bacteria found globally in marine environments. During the past decade, studies have shown that certain Gram-negative bacteria, including Vibrio species (cholerae, parahaemolyticus, and vulnificus) are capable of using exogenous polyunsaturated fatty acids (PUFAs) to modify the phospholipids of their membrane. Moreover, exposure to exogenous PUFAs has been shown to affect certain phenotypes that are important factors of virulence. The purpose of this study was to investigate whether V. alginolyticus and V. fischeri are capable of responding to exogenous PUFAs by remodeling their membrane phospholipids and/or altering behaviors associated with virulence. Thin-layer chromatography (TLC) analyses and ultra-performance liquid chromatography-electrospray ionization mass spectrometry (UPLC/ESI-MS) confirmed incorporation of all PUFAs into membrane phosphatidylglycerol and phosphatidylethanolamine. Several growth phenotypes were identified when individual fatty acids were supplied in minimal media and as sole carbon sources. Interestingly, several PUFAs acids inhibited growth of V. fischeri. Significant alterations to membrane permeability were observed depending on fatty acid supplemented. Strikingly, arachidonic acid (20:4) reduced membrane permeability by approximately 35% in both V. alginolyticus and V. fischeri. Biofilm assays indicated that fatty acid influence was dependent on media composition and temperature. All fatty acids caused decreased swimming motility in V. alginolyticus, while only linoleic acid (18:2) significantly increased swimming motility in V. fischeri. In summary, exogenous fatty acids cause a variety of changes in V. alginolyticus and V. fischeri, thus adding these bacteria to a growing list of Gram-negatives that exhibit versatility in fatty acid utilization and highlighting the potential for environmental PUFAs to influence phenotypes associated with planktonic, beneficial, and pathogenic associations.
Expression of degQ gene and its effect on lipopeptide production as well as the forma...
Lars Lilge
Maliheh Vahidinasab

Lars Lilge

and 8 more

October 06, 2021
Bacillus subtilis is described as a promising production strain for lipopeptides. In the case of B. subtilis strains JABs24 and DSM10T, surfactin, and plipastatin are produced. Lipopeptide formation is controlled, among others, by the DegU response regulator. The activating phospho-transfer by the DegS sensor kinase is stimulated by the pleiotropic regulator DegQ, resulting in enhanced DegU activation. In B. subtilis 168, a point mutation in the degQ promoter region leads to a reduction in gene expression. Corresponding reporter strains showed a 14-fold reduced expression. This effect on degQ expression and the associated impact on lipopeptide formation was examined for B. subtilis JABs24, a lipopeptide-producing derivative of strain 168, and B. subtilis wild-type strain DSM10T, which has a native degQ expression. Based on the stimulatory effects of the DegU regulator on secretory protease formation, the impact of degQ expression on extracellular protease activity was additionally investigated. To follow the impact of degQ, a deletion mutant was constructed for DSM10T, while a natively expressed degQ version was integrated into strain JABs24. This allowed strain-specific quantification of the stimulatory effect of degQ expression on plipastatin and the negative effect on surfactin production in strains JABs24 and DSM10T. While an unaffected degQ expression reduced surfactin production in JABs24 by about 25%, a 6-fold increase in plipastatin was observed. In contrast, degQ deletion in DSM10T increased surfactin titer by 3-fold but decreased plipastatin production by 5-fold. In addition, although significant differences in extracellular protease activity were detected, no decrease in plipastatin and surfactin produced during cultivation was observed.
Comparison of swab types for collection and analysis of microorganisms
Natalie Wise
Sarah Wagner

Natalie Wise

and 4 more

October 06, 2021
The human microbiome has begun to emerge as a potential forensic tool, with varied applications ranging from unique identification to investigative leads that link individuals and/or locations. The relative abundance of the combined DNA of the microbiome, compared to human nuclear DNA, may expand potential sources of biological evidence, especially in cases with transfer or low-copy number DNA samples. This work sought to determine the optimal swab type for the collection and analysis of the microbiome. A bacterium (Proteus mirabilis) was deposited by pipette onto four swab types (cotton, flocked, dental applicators, and dissolvable), and extraction and real-time PCR quantitation of the bacterial DNA were performed, which allowed for absolute microbial DNA recovery and comparison of yields across the four sampling substrates. Flocked swabs had the highest yield (~1240 ng) compared to the cotton swabs (~184 ng), dental applicators (~533 ng), and dissolvable swabs (~430 ng). The collection efficiency was further evaluated for cotton and flocked swabs using dried microbial samples spotted onto non-porous surfaces (treated wood, glass, plastic, and tile). Flocked swabs performed consistently better across wood, glass, and tile, but showed decreased recovery from plastic. The cotton swabs failed in the recovery of P. mirabilis DNA across all surfaces. Knowing the appropriate sampling substrate will be useful as others continue to investigate the use of the microbiome as a forensics tool.
INTEGRAL REPRESENTATIONS AND INEQUALITIES OF EXTENDED CENTRAL BINOMIAL COEFFICIENTS
Chunfu Wei

Chunfu Wei

October 06, 2021
In the paper, the author presents three integral representations of extended central binomial coefficient, proves decreasing and increasing properties of two power-exponential functions involving extended (central) binomial coefficients, derives several double inequalities for bounding extended (central) binomial coefficient, and compares with known results.
Homotopy Continuation Enhanced Branch and Bound Algorithms for Process Synthesis Usin...
Yingjie Ma
Jie Li

Yingjie Ma

and 1 more

October 06, 2021
Process synthesis using rigorous unit operation models is highly desirable to identify the most efficient pathway for sustainable production of fuels and value-added chemicals. However, it often leads to a large-scale strongly nonlinear and nonconvex mixed integer nonlinear programming (MINLP) model. In this work, we propose two robust homotopy continuation enhanced branch and bound (HCBB) algorithms (denoted as HCBB-FP and HCBB-RB) where the homotopy continuation method is employed to gradually approach the optimal solution of the NLP subproblem at a node from the solution at its parent node. A variable step length is adapted to effectively balance feasibility and computational efficiency. The computational results demonstrate that the proposed HCBB algorithms can find the same optimal solution from different initial points, while the existing MINLP algorithms fail or find much worse solutions. In addition, HCBB-RB is superior to HCBB-FP due to lower computational effort required for the same locally optimal solution.
How precision medicine changes medical epistemology: A formative case from Norway
Henrik Vogt
Bjørn Hofmann

Henrik Vogt

and 1 more

October 06, 2021
Rationale and aims: Precision medicine (PM) raises a key question: How can we know what works when the number of people with a health problem becomes small or one (n=1)? We here present a formative case from Norway. The Norwegian Board of Health Supervision was faced with a cancer patient, who had improved after treatment with a drug in the private health sector but was refused continued treatment in the public health service due to lack of clinical trial evidence. The Board overturned this decision, arguing that the drug had been unambiguously documented to work in the individual case. We aim to provide an in-depth analysis of this case and The Board´s decision and thereby to illustrate and elucidate key epistemological and ethical issues and developments in PM. Method: We provide our analysis and discussion using tools of critical thinking and concepts from philosophy of science and medicine such as uncertainty, evidence, forms of inference and causation. We also examine the case in the light of the history of evidence-based medicine (EBM). Results and discussion: The case reflects an epistemological shift in medicine where PM puts greater emphasis on evidence that arises in individual patients after the treatment is provided over preexisting population-based evidence. PM may rely more heavily on abduction to decide what works and qualitative, rather than quantitative judgments. The case also illustrates a possible shift in the concept of causation from regularity accounts to mechanistic and process accounts. We discuss ethical implications of a shift from more “traditional” to “personalized EBM”. Conclusion: A framework that is more based on abductions and evidence arising in the individual case has problems in creating quantifiable, reliable, and generalizable evidence, and in promoting transparency and accountability. PM currently lacks clear criteria for deciding what works in an individual, posing ethical challenges.
Characterization of the genetic switch from phage phi13 important for Staphylococcus...
Camilla Kristensen
Anders Varming

Camilla Kristensen

and 6 more

October 06, 2021
Temperate phages are bacterial viruses that either reside integrated in a bacterial genome as lysogens or enter a lytic lifecycle. Decision between lifestyles is determined by a switch involving a phage-encoded repressor, CI, and a promoter region from which lytic and lysogenic genes are divergently transcribed. Here we investigate the switch of phage phi13 from the human pathogen Staphylococcus aureus. phi13 encodes several virulence factors and is prevalent in S. aureus strains colonizing humans. We show that the phi13 switch harbors a cI gene, a predicted mor (modulator of repression) gene, and three high-affinity operator sites binding CI. To quantify the decision between lytic and lysogenic lifestyle, we introduced reporter plasmids that carry the 1.3 kb switch region from phi13 with the lytic promoter fused to lacZ into S. aureus and B. subtilis. Analysis of beta-galactosidase expression indicated that decision frequency is independent of host factors. The white “lysogenic” phenotype, which relies on expression of cI, could be switched to a stable blue “lytic” phenotype by DNA damaging agents. We have characterized lifestyle decisions of phage phi13, and our approach may be applied to other temperate phages encoding virulence factors in S. aureus.
Trans-cuff leakage in bio-Bentall operation
Azumi Hamasaki
Kozo Morita

Azumi Hamasaki

and 3 more

October 06, 2021
We have reported a case of trans-cuff leakage that occurred in a composite graft of bio-Bentall operation. The leakage resolved several months after surgery, similar to the trans-cuff leakage seen in simple aortic valve replacement. We have proposed hypotheses on the mechanism of trans-cuff leakage during a bio-Bentall operation and suggested ways to prevent it from occurring.
What's in a Name? A Candid Assessment of a New Candida Therapy
Karl Oláh (BJOG DEBATES ONLY)

Karl Oláh (BJOG DEBATES ONLY)

October 06, 2021
A document by Karl Oláh (BJOG DEBATES ONLY). Click on the document to view its contents.
Reaping the benefits of open science in scholarly communication    

Rosaria Ciriminna

and 4 more

October 11, 2021
Regardless of multiple efforts carried out across many countries to disseminate the ideas and the practice of open science, most scholars in the early 2020s do not self-archive their research articles and do not publish research papers in preprint form. Having received no education and training on open science, researchers are often puzzled on what to do, in practice, to start reaping the benefits of open science. This study offers a succinct vademecum on how to benefit from the open science approach to scholarly communication, no matter whether in natural or in humanistic and social sciences.
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