A document by Théophile Perrod. Click on the document to view its contents.

Dynamic flux balance analysis (FBA) allows estimation of intracellular reaction rates using organism-specific genome scale metabolic models (GSMM) and by assuming instantaneous pseudo steady states for processes that are inherently dynamic. This technique is well-suited for industrial bioprocesses employing complex media characterized by a hierarchy of substrate uptake and product secretion. However, knowledge of exchange rates of many components of the media would be required to obtain meaningful results. Here, we performed spent media analysis using mass spectrometry (MS) coupled with liquid (LCMS) and gas chromatography (GCMS) for a fed-batch, high cell density cultivation of E. coli BL21(DE3) expressing a recombinant protein. Time course measurements thus obtained for 246 metabolites were converted to instantaneous exchange rates. These were then used as constraints for dynamic FBA using a previously reported GSMM, thus providing insights into how the flux map evolves through the process. Changes in TCA cycle fluxes correlated with the increased demand for energy during recombinant protein production. The results show how amino acids act as hubs for the synthesis of other cellular metabolites. Our results provide a deeper understanding of an industrial bioprocess and will have implications in further optimizing the process.

In this paper, Long Short-Term Memory (LSTM) networks and multilayered feedforward neural networks (FFNNs) were combined with first principles equations in a hybrid workflow to describe human embryonic kidney 293 (HEK293) culture dynamics. Experimental data of 27 extracellular state variables in 20 fed-batch HEK293 cultures were collected in a parallel high throughput 250 mL cultivation system. The adaptive moment estimation method (ADAM) with stochastic regularization and cross-validation were employed for deep learning. A total of 784 hybrid models with varying deep neural network (DNN) architectures, depths, layers sizes and node activation functions were compared. In most scenarios, hybrid LSTM models outperformed hybrid FFNN models in terms of training and testing error. Hybrid LSTM models revealed to be less sensitive to data resampling than FFNN hybrid models. As disadvantages, Hybrid LSTM models are in general more complex (higher number of parameters) and have a higher computation cost than FFNN hybrid models. The hybrid model with the highest prediction accuracy consisted in a LSTM network with 7 internal states connected in series with dynamic material balance equations. This hybrid model correctly predicted the dynamics of the 27 state variables (R 2=0.93 in the test data set), including biomass, key substrates, amino acids and metabolic by-products for around 10 cultivation days.

Biological invasions represent an extraordinary opportunity to study evolution. This is because accidental or deliberate species introductions have taken place for centuries across large geographical scales, in natural and anthropogenic environments. Until recently however, the utility of invasions as evolutionary experiments has been hampered by the limited information on the makeup of populations that were part of earlier invasion stages. Now, developments in ancient and historical DNA technologies, as well as the quickening pace of digitization for millions of specimens that are housed in herbaria and museums globally promise to help overcome this obstacle. In this review, we first introduce the types of temporal data that can be used to study invasions, highlighting the timescale captured by each approach, and their respective limitations. We then discuss how ancient and historical specimens as well as data available from prior invasion studies can be used to answer questions on mechanisms of (mal)adaptation, rates of evolution, or community-level changes during invasions. By bridging the gap between contemporary and historical invasive populations, temporal data can help us connect pattern to process in invasion science. These data will become increasingly important if invasions are to achieve their full potential as experiments of evolution in nature.

Zooplankton undergo a vertical migration which exposes them to gradients of light, temperature, oxygen and food availability on a predictable daily schedule. Anticipating and responding to these environmental conditions, which independently are known to influence metabolic rates, likely has an appreciable effect on the delivery of waste products to the distinctly different daytime (deep) and nighttime (surface) habitats. Disentangling the co-varying and potentially synergistic interactions on metabolic rates has proven difficult, despite the importance of this migration to oceanic biogeochemical cycling. This study examines the transcriptomic and proteomic profile of the circumglobal migratory copepod, Pleuromamma xiphias, over the diel cycle. The transcriptome showed a large number of up-regulated genes during the middle of the day – the period often considered to be of lowest metabolic activity. There were proteomic and transcriptomic peaks in oxidative stress response and muscle proteins after the periods of migration, suggestive of a physiological consequence of migration. There were changes in metabolic pathways over time, with increased ammonium production signals during the evening and chitin synthesis and degradation pathways during the day. Comparisons of patterns across the paired datasets suggest that 1) estimates of physiological rates made in the laboratory in steady state conditions that don’t account for time of day may not be adequate to predict in situ phenotypes 2) use of ‘omics datasets to predict organismal phenotypes must be done cautiously as highly dynamic patterns in the transcriptome and proteome are often dampened and sometimes asynchronous at the enzyme or organismal level.

Cerebral toxoplasmosis in a human immunodeficiency virus (HIV) seronegative patient with liver cirrhosis.1Elroy Patrick Weledji, 2Frank Zouna1Department of Surgery, Faculty of Health sciences, University of Buea, Cameroon, W/Africa; Regional hospital Limbe, S.W. Region, Cameroon. E-mail: elroypat@yahoo.co.uk2Department of Medicine, Faculty of Health Sciences, University of Buea, Cameroon , W/Africa, Regional Hospital Limbe, S.W. Region, Cameroon. Email: zounafrank@yahoo.frCorresponding author : EP Weledji, Holy family foundation, Livanda Kongo Hill, lumpsum quarters, PO Box 126, Limbe, Cameroon. Tel 237699922144. Email: elroypat@yahoo.co.uk

Background: The role of Component Resolved Diagnostics (CRD) in the diagnosis of cow’s milk allergy (CMA) remains highly controversial. In this systematic review, we aimed to evaluate the accuracy of CRD in diagnosing CMA in children. Methods: We searched four electronic databases (EMBASE, PubMed, the Cochrane Library, and Web of Science) from January 1, 2000, to March 27, 2023, for studies that utilized milk composition and oral food challenges (OFC) as a reference standard in patients with suspected milk allergy. The quality of the included studies was assessed using QUADAS-2. Due to the heterogeneity of the studies, a meta-analysis could not be performed, and a narrative synthesis of the findings was conducted. Results: Our analysis included 5 prospective studies, 2 retrospective studies, and 2 case-control studies, with a total of 958 children. The sensitivity of Bos d 4 ranged from 0.50 to 0.82, and specificity from 0.78 to 0.98. Bos d 5 sensitivity 0.24-1.0, and specificity 0.58-0.98. Bos d 6 sensitivity 0.09, and specificity 0.94. Bos d 8 sensitivity 0.34-0.90, specificity 0.79-0.98. CONCLUSION: The specific IgE (sIgE) of the Bos d 4, Bos d 6, and Bos d 8 components of milk is highly specific but not sensitive in diagnosing cow’s milk allergy in children. The use of CRD for the diagnosis of CMA in children may reduce the need for OFC.

Background: The need for echocardiograms among patients with long COVID is debatable. Our aim was to evaluate the prevalence of left ventricular (LV) dysfunction and identify predictors. Methods: We conducted a cross-sectional study and included all consecutive patients enrolled in our post-COVID clinic. We included patients who had an echocardiogram and had no previous known heart disease. We defined LV dysfunction as a low ejection fraction or grade II to grade III diastolic dysfunction on an echocardiogram with evidence of elevated filling pressures. We calculated the prevalence of heart disease and predictors of heart disease using logistic regression. Results: We included 217 post-COVID patients enrolled in the clinic. The prevalence of LV dysfunction is 24%;95% CI 18-30. Predictors of heart disease include older age and a previous history of hypertension and diabetes or having a intermediate or high ASCVD score. Patients with low ASCVD score did not have low ejection fraction on the screening echocardiograms. Conclusion: Our study found a considerable number of patients with LV dysfunction. Older patients with cardiovascular risk factors are at risk of long COVID associated heart disease.

Basal amygdala (BA) neurons projecting to nucleus accumbens core/shell (NAc) are primarily glutamatergic and are integral to the circuitry of emotional processing. Several recent mouse studies have addressed whether neurons in this population(s) respond to reward, aversion, or both emotional valences. The focus has been on processing of physical emotional stimuli and here we extend this to salient social stimuli. In male mice, an iterative study was conducted into engagement of BA-NAc neurons in response to estrous female (social reward, SR) and/or aggressive-dominant male (social aversion, SA). In BL/6J mice, SR and SA activated c-Fos expression in a high and similar number/density of BA-NAc neurons in the anteroposterior intermediate BA (int-BA), whereas activation was predominantly by SA in posterior (post-)BA. In Fos-TRAP2 mice, compared with SR-SR or SA-SA controls, exposure to successive presentation of SR-SA or SA-SR, followed by assessment of tdTomato reporter and/or c-Fos expression, demonstrated that many int-BA-NAc neurons were activated by only one of SR and SA; these SR/SA monovalent neurons were similar in number and present in magnocellular and parvocellular int-BA subregions. In freely moving BL/6J mice exposed to SR, bulk GCaMP6 fibre photometry provided confirmatory in vivo evidence for engagement of int-BA-NAc neurons during social and sexual interactions. Therefore, populations of BA-NAc glutamate neurons are engaged by salient rewarding and aversive social stimuli in a topographic and valence-specific manner; this novel evidence is important to the overall understanding of the roles of this pathway in the circuitry of socio-emotional processing.

Aims: To compare the outcomes of real-world Japanese patients with nonvalvular atrial fibrillation who are ineligible for phase III trials of direct oral anticoagulants with those of eligible patients. Methods: In retrospective cohort design, consecutively registered patients with nonvalvular atrial fibrillation who had taken warfarin were followed up and assessed eligibility of patients for phase III trials of direct oral anticoagulants. The effects of the ineligibility of patients on outcomes were estimated using Cox proportional hazards models to calculate the hazard ratio (HR) and 95% confidence interval. Results: We registered 7826 Japanese patients with nonvalvular atrial fibrillation from 71 hospitals. Nearly half (48.2%, n=3772) of these patients were ineligible for phase III trials of direct oral anticoagulants, mainly because of low CHADS2 scores (26.4%), renal dysfunction (9.5%), anemia (6.4%), and chronic treatment with nonsteroidal anti-inflammatories (4.0%). After excluding patients with a CHADS2 score <2 (n=2064, 26.4%) from total ineligible patients, the remaining ineligible patients (n=1708) exhibited significantly greater risks of major bleeding (unadjusted hazard ratio 2.00, 95% confidence interval 1.63–2.44, p<0.0001), stroke/systemic embolism (unadjusted hazard ratio 1.53, 95% confidence interval 1.17–1.98, p=0.0016), and all-cause mortality (unadjusted hazard ratio 2.84, 95% confidence interval 2.36–3.43, p<0.0001) compared to the eligible patients. Conclusions: The benefits and risks of direct oral anticoagulants suggested by phase III trials may not necessarily apply to patients ineligible for Phase III trials. This gap between evidence and practice is an issue in the real-world safety and efficacy of anticoagulants.

The rapid growth of the live streaming industry brought about the VTuber trend, where content creators use character avatars to stream. One of the most accessible way to move a character in real time is by using a vision-based facial motion capture technique. However, previous works still suffer from jittering issues, which hinder the quality of the character’s movements. This work aims to develop a smoothed facial motion capture system that works with a live2D VTuber model. The system combines Mediapipe Face Mesh and OpenCV solutions to capture facial landmarks, which are then used to calculate head pose estimation using the Perspective-n-Point (PnP) function. In addition, the system uses EAR and MAR functions to detect facial features. The motion values obtained from this process are then filtered using a Kalman filter. Finally, the filtered motion data is sent to the Unity engine, which drives the Live2D VTuber model by adjusting the character’s motion parameters. The developed system successfully captures and drives the Live2D VTuber model with smoother motion, overcoming the jitter problem prevalent in previous facial motion capture approaches. The system’s improved motion capture quality makes it a more viable option for a wide range of potential uses.

Prolonged drug provocation with an initial full therapeutic dose to diagnose serum sickness-like reactions (SSLR) to β-lactams in childrenMarcel M Bergmanna,b,c, Eva Gomesd, Natalia Blanca-Lópeze, Jean-Christoph Caubeta, Philippe A Eigenmanna , Giulia Liccioli f, Francesca Morif, Marina Atanaskovic Markovicga Pediatric allergy unit, Department of women, children and adolescents, University Hospitals of Geneva, Geneva, Switzerlandb Centro Pediatrico del Mendrisiotto, Mendrisio, Switzerlandc Faculty of Biomedical Science, Università della Svizzera Italiana (USI), Lugano, Switzerlandd Serviço de Imunoalergologia, Centro Hospitalar Universitário do Porto, Porto, Portugale Servicio de Alergia, Laboratorio de Investigación, Hospital Universitario Infanta Leonor, Madrid, Spainf Allergy Unit, Meyer Children’s University Hospital, IRCCS, Florence, Italyg University of Belgrade Faculty of Medicine, University Children’s Hospital, Belgrade, Serbia

This paper is devoted to analysing a kind of fractional neutral stochastic system (FNSS). Firstly, by introducing the notion of newly defined two-parameter Mittag-Leffler matrix function, we derive the solution of the corresponding linear stochastic system. Subsequently, for the linear case, by virtue of the Grammian matrix, we give a suffcient and necessary condition to guarantee the relatively exact controllability for the addressed case. Furthermore, for the nonlinear one, the relatively exact controllability is obtained by fixed point and explore it via Banach contraction principle. Finally, two examples are provided to intensify our theoretical conclusions.

A document by Alexandre Buisson. Click on the document to view its contents.

A world record conversion efficiency of 26.81% has been achieved recently by LONGi team on industry-grade silicon wafer (274 cm 2, M6 size). An unparalleled high fill factor ( FF) of up to 86.59% boosted the cell performance. The theoretical FF limit has been predicted to be 89.26%, while the practical FF is far below this limit for a prolonged interval due to the constraints of recombination ( i.e., SRH recombination) and series resistance. The ideality factor ( m) in the equivalent circuit of silicon solar cells is consistently ranging from 1 to 2 and rarely falls below 1, resulting in a relatively lower FF than 85%. Here, this work complements a systematic simulation study to demonstrate how to approach the FF limit in silicon solar cell fabrication. Firstly, a diode component with an ideality factor equal to 2/3 corresponding to Auger recombination is incorporated in the equivalent circuit for LONGi’ ultra-high FF solar cell; Secondly, an advanced equivalent circuit is put forward for comprehensive analysis of bulk recombination and surface recombination on the performance, in which specific ideality factors are directly correlated with various recombination mechanisms exhibiting explicit reverse saturation current density ( J 0); Finally, we evaluate precisely the route for approaching theoretical FF in practical solar cell fabrication based on electrical design parameters using the developed model.

INTRODUCTIONVeno-venous extra-corporeal membrane oxygenation (V-V ECMO) is used in perioperative respiratory care of patients with lung abscess, considered unfit for one-lung ventilation or who are functionally inoperable, despite exploiting all conventional mechanical ventilation possibilities, including nitric oxide inhalation. V-V ECMO does not pose higher odds of postoperative mortality.1Independent lung ventilation (ILV) is a mechanical ventilation treatment for differential lung disease, used in intensive care settings. ILV is divided into anatomical and physiological lung separation. Physiological lung separation is divided into synchronous and asynchronous ventilation.2Combined use of V-V ECMO and asynchronous independent lung ventilation can have a perioperative advantage of lung abscess because in lung abscess, the right and left lungs often have different characteristics.Herein, we describe the case of a patient who received V-V ECMO for thoracic surgery for lung abscess, in whom ILV was performed to provide asynchronous treatment during the perioperative period.

Abstract Objective: To evaluate the feasibility and necessity of enhanced recovery after surgery in elderly patients with colorectal cancer by observing the inflammatory markers and postoperative complications in patients. Methods: Hospitalized Colorectal cancer patients from the Affiliated Hospital of Jiangsu University during 2021.01-2022.09 were collected and these patients were divided into two groups:ERAS group and non-ERAS group. Postoperative inflammatory markers and complications of patients were collected. Results: 313 patients with colorectal cancer were included, There were 182 patients in the ERAS group and 131 in non-ERAS group. The patients in ERAS group was significantly shorter than the non-ERAS group in terms of postoperative hospitalization days, withdrawal time of urinary catheter, withdrawal time of drainage tube, and recovery of bowel function (P<0.05). In terms of hospitalization expenses, the patients in ERAS group were lower than non-ERAS group, the distinction was statistically significant (P<0.05).However, the level of procalcitonin and TNF-α in ERAS group was significantly lower than non-ERAS group on the post-operative day 1, 3 (P<0.05), the level of IL-6 and IL-10 in ERAS group was significantly lower than non-ERAS group on the 1st ,3rd and 5th day after operation (P<0.05). The levels of CRP and WBC in ERAS group were lower than non-ERAS group on the post-operative day 3, 5 (P<0.05). However,hemoglobin levels did not differ significantly(P>0.05). Albumin levels did not differ significantly between the two groups before surgery (P>0.05), but the level of albumin in ERAS group was higher than non-ERAS group on the post-operative day3,5 (P<0.05). ERAS patients had a lower level of albumin after surgery compared to non-ERAS patients (P<0.05). Conclusion: ERAS leads to a series of perioperative optimization measures, thereby reducing the postoperative stress response of elderly colorectal cancer patients and reducing the occurrence of perioperative complications.

Background: N1-methyladenosine (m1A) is a recently identified mRNA modification. It is still unclear, though, whether m1A alteration affects how colorectal cancer (CRC) develops. Methods: We retrospectively analyzed 398 CRC patients and 39 normal controls using the TCGA database to evaluate m1A modification patterns regarding tumor immune microenvironment (TIME) in CRC. The m1Ascore was developed using principal component analysis. And its clinical value in prognosis of CRC was further explored. Results: We revealed 12 key m1A-related DEGs including CLDN3, MUC2 and CCDC85B which are identified associated with invasion and metastasis in CRC. The most important biological processes linked to a weak immune response and a poor prognosis were the regulation of RNA metabolism and RNA biosynthesis. Furthermore, we found that compared to CRC patients with low m1A scores, those with high m1A scores had a higher percentage, a larger tumor burden, and a worse prognosis for survival. Conclusion: Significantly diverse m1A modification patterns can be seen in CRC. Through its impact on TIME and immunological dysfunction, the heterogeneity of m1A alteration patterns influences the prognosis of CRC. This study provided novel insights into the m1A modification in CRC which might promote the development of personalized immunotherapy strategies.