The fifth modeling workshop (5MW) was held in June 2023 in Favrholm, Denmark and sponsored by Recovery of Biological Products Conference Series. The goal of the workshop was to assemble modeling practitioners to review and discuss the current state, progress since the last fourth mini modeling workshop (4MMW), gaps and opportunities for development, deployment and maintenance of models in bioprocess applications. Areas of focus were four categories: biophysics and molecular modeling, mechanistic modeling, computational fluid dynamics (CFD) and plant modeling. Highlights of the workshop included significant advancements in biophysical/molecular modeling to novel protein constructs, mechanistic models for filtration and initial forays into modeling of multi-phase systems using CFD for a bioreactor and mapped strategically to cell line selection/facility fit. A significant impediment to more fully quantitative and calibrated models for biophysics is the lack of large, anonymized data sets. A potential solution would be the use of specific descriptors (ex. patch sizes and types mapped to a homology model) in a database that would allow for detailed analyses without sharing proprietary information. Another gap identified was the lack of a consistent framework for use of models that are included or support a regulatory filing beyond the high-level guidance in ICHQ8-Q11. One perspective is that modeling can be viewed as a component or precursor of machine learning (ML) and Artificial Intelligence (AI). Recent requests for feedback from health authorities on use of ML and AI may provide an opportunity for more clarity regarding expectations for use and deployment. Two specific additional outcomes of the workshop were alignment on a key definition for “mechanistic modeling” and the acknowledgement/realization that modeling can have a significant impact on improving sustainability of bioprocessing through elimination of experiments both during development and manufacturing. Feedback from the participants was that there was progression in all of the fields of modeling within scope of the conference. Some areas (e.g. biophysics and molecular modeling) have opportunities for significant research investment to realize full impact. However, the need for ongoing research and development for all model types does not preclude the application to support process development, manufacturing and use in regulatory filings. Analogous to ML and AI, given the current state of the four modeling types, a prospective investment in educating inter-disciplinary subject matter experts (SMEs) (e.g. data science, chromatography) is essential to advancing and maintaining the modeling community.

Objectives: To assess the ability of left atrial(LA) strain parameters to discriminate patients with elevated left atrial pressure(LAP) from patients with atrial fibrillation(AF). Methods and results: A total of 142 patients with non-valvular AF who underwent first catheter ablation(CA) between November 2022 and November 2023 were enrolled in the study. Conventional and speckle-tracking echocardiography（STE）were performed in all patients within 24 hours before CA，and LAP was invasively measured during the ablation procedure. According to mean LAP,the study population was classified into 2 groups of normal LAP(LAP＜ 15 mmHg, n=101) and elevated LAP（LAP≥15 mmHg, n=41)．Compared with the normal LAP group, elevated LAP group showed significantly reduced LA reservoir strain (LASr) [9.14 ( 7.97 -11.80 ) vs 20(13.59-26.96), p < 0.001], and increased LA filling index[9.60 ( 7.15 -12.20 ) vs 3.72 ( 2.17 -5.82 )，p<0.001], LA stiffness index[1.13 ( 0.82-1.46 ) vs 0.47( 0.30 -0.70 )，p<0.001]. LASr, LA filling index and LA stiffness index were independent predictors of elevated LAP after adjusted by the type of AF, EDT, E/e’, mitral E and Peak acceleration rate of mitral E velocity. The receiver-operating characteristic curve (ROC) analysis showed LA strain parameters (area under curve [AUC] 0.794 to 0.819) could provide similar or greater diagnostic accuracy for elevated LAP, as compared to conventional echocardiographic parameters. Furthermore, the novel algorithms built by LASr, LA stiffness index, LA filling index and LA emptying fraction（LAEF）, was used to discriminate elevated LAP in AF with good accuracy (AUC 0.880, accuracy of 81.69%, sensitivity of 80.49%, specificity of 82.18%), and much better than 2016 ASE/EACVI algorithms in AF. Conclusion: In patients with AF，LA strain parameters could be useful to predict elevated LAP and non-inferior to conventional echocardiographic parameters. Besides, the novel algorithm built by LA strain parameters combined with conventional parameters would improve the diagnostic efficiency.

Interdisciplinary integration is a superior method to improve the optimization algorithm. In this paper, control theory and optimization are combined, and the optimization algorithm is regarded as a control process. Based on the premise of optimal control, the state equation corresponding to Lagrange Algorithm is established with the Karush-Kuhn-Tucker (KKT) conditions as the objective. As an optimal control method, Linear Quadratic Regulator (LQR) is utilized to control the calculation process, and an innovative LQR-Lagrange Algorithm is proposed. The Lyapunov stability criterion is applied to analyze the convergence, and it is proved that the proposed LQR-Lagrange Algorithm is bound to converge as long as the parameter matrices and are positive definite. The analysis indicates that the influence of parameters in LQR-Lagrange Algorithm on the calculation speed is monotonic, and the elements in and has no effect on the convergence. Therefore, the proposed algorithm has a monotonic and user-friendly parameter tuning strategy. The significance and advantages of interdisciplinary integration with control theory and optimization are discussed in the end.

Bronchial foreign body presenting as pneumothorax and pneumomediastinum in a young child.Rajendra Shilpakar1, Nipun Shrestha1, Dhruba Shrestha1*1 Siddhi Memorial Hospital (For Women and Children), Bhaktapur, Nepal.Keywords: Foreign body aspiration, Pneumomediastinum, Pneumothorax, Subcutaneous emphysema

摘要： 破骨细胞是骨质疏松症发展不可或缺的一部分 （OP）及其在氧化应激（OS）条件下的产生 涉及多种途径。但是，通过具体机制 天然抗氧化剂山奈酚（KAE）减轻了OS的影响 破骨细胞仍然有些不确定。为了评估 KAE对OS下破骨细胞形成的影响及探讨其可能性 机制。在这项研究中，斑马鱼被用来观察 OP 和 OS 上的 KAE。 OP 和 OS“双重疾病靶点”网络 采用药理学预测KAE的作用靶点及机制 在操作系统下的 OP 上。KAE对破骨细胞分化的影响 使用 LPS 诱导的 RWA264.7 细胞评估 OS。阐明 潜在机制，为了阐明其可能的机制， 诱导过程中相关因子和靶基因的表达量为 检测。结果：KAE的存在显示出改善的潜力 斑马鱼的 OP 和 OS 状况。KAE可以降低RAW的操作系统 264.7 细胞受 LPS 刺激，抑制破骨细胞的形成，以及 改变OS相关因素水平，减少OS增加 陷阱。网络药理学和靶基因表达的利用 分析显示，KAE对 原癌基因酪氨酸蛋白激酶 （SRC） 的表达，核 因子 κ-B （NF-κB）、丝氨酸/苏氨酸激酶-1 （AKT1）、一氧化氮 合酶 3 （NOS3） 和基质金属肽酶-2 （MMP2）。基于这些 研究结果，可以得出结论，KAE可以有效地缓解OS和 通过 SRC/NF-ΚB-AKT/NOS3 阻碍破骨细胞的形成 轴。

“UNUSUAL COEXISTENCE: A CASE OF MIXED SMALL AND LARGE CELL NEUROENDOCRINE TUMOR IN A BLADDER PREVIOUSLY AFFECTED BY BILHARZIAL CYSTITIS”1Mohammed Saleh E. Khalifa SALEM,1Abdulhamid ALHEREK, 1Martin VAN ROOYEN, 1Alain Mwamba MUKENDI1University of the Witwatersrand, Division of Urology, Department of Surgery, Klerksdorp Hospital, Klerksdorp, Northwest, South Africa.*Corresponding AuthorAlain Mwamba MukendiCel: 0027711576350E-mail: alainmwamba2006@yahoo.fr

Cutaneous leishmaniasis mimicking psoriasis: a case report

A document by Mohammad Dalili. Click on the document to view its contents.

1. Widely used methods to assess population genetic structure and differentiation rely on independence of marker loci. Following the assumption, the common metrics, for example FST, evaluate genetic structure by averaging across loci. Common metrics do not use information in the associations among loci at the individual level and are often criticized for failing to measure true differentiation even when loci segregate independently. 2. We introduce a new concept to measure β-variation (Effective Number of Different Populations, ENDP). It requires the following steps: (a) calculation of a proper dissimilarity between genetic profiles of all individuals; (b) calculation of suitable pairwise distances between the samples based on the dissimilarities between individuals; (c) calculation of diversity (in terms of Hill numbers) and dispersion of samples based on the pairwise distances between samples; (d) ENDP is then estimated as a combination of the diversity and dispersion. ENDP estimates β-variation independently of within-sample α-variation. This new concept differs from the existing standard where β-diversity is estimated based on the ‘partition of variation’ scheme (beta=gamma-alpha or beta=gamma/alpha). 3. Estimates of ENDP are obtained by evaluating information in the available genetic profiles of individuals including association of loci. Therefore, ENDP can be used even in an absence of panmixia. 4. We illustrate the use of this concept by analyzing the population genetic structure of a sexual species (a trematode parasite) occupying connected populations across a broad geographic area. Analysis is complicated by two coexisting cryptic sister clades and the potentially mixed-mating system of this hermaphroditic parasite.

Because of the soft dynamic performance of the fuel cell stack, the battery is usually integrated in the power system in fuel cell hybrid electric vehicles. In this paper, a real time energy management strategy considering thermal constraints based on speed prediction with neuron network is proposed. The main principle of the proposed control strategy is to get the future power requirement with model predictive control based on the historic speed information, and then optimize the objective function according to the state variables. The objective function is set to minimize the equivalent fuel consumption of the vehicle and extend the life span of the fuel cell stack based on thermal constraints. Contrasting with the control strategy without thermal constraints under the WLTC driving cycle, the proposed energy management is 0.9% higher, but the temperature of the fuel cell stack and the battery can be limited within an appropriate range. The total equivalent fuel consumption is 3.9% lower than dynamic programming control strategy, which proves the availability of the proposed control strategy can reduce the equivalent fuel consumption while prolonging the fuel cell stack life span. Hardware in loop (HIL) experiment is implemented to testify the real time application of the proposed control strategy.

IntroductionForeign body aspiration (FBA) is common at both extremes of age and is a potentially life-threatening event(1). Advanced age, alcohol intoxication, psychiatric illness, seizure disorders, stroke, neuromuscular disorders, sedative or hypnotic drugs, and chronic debilitating conditions predispose the elderly to FBA(2). Common foreign bodies (FBs) aspirated include metallic objects, organic substances, dentures, chicken or fish bones, and peas(3). FBA in the elderly poses a diagnostic and therapeutic challenge due to several factors. These include the masking of respiratory symptoms post-aspiration, atypical imaging findings, the patient’s inability to recall the aspiration event, and the challenges encountered during bronchoscopy(4). FBA usually follows a choking event, often during feeding. The patient might present with dyspnea, hemoptysis, cough, a fall in oxygen saturation, anxiety, etc.(5). The signs and symptoms depend on the size of the foreign body and the level of obstruction. Small objects lodged in distal airways seldom produce acute symptoms, while the opposite is true for larger FBs lodged in larger airways. Stridor is present if FBs are lodged in trachea(6). FBA results in collapse/hyperinflation of lungs aerated by the airway. If there is chronic obstruction, obstructive pneumonia, bronchiectasis, and lung abscess can develop(2). FBs generally lodge in the right middle and lower lobe bronchi(4). FBA causing acute airway obstruction and respiratory failure requiring urgent intervention.

Background: The JPLT3-S (Japanese study group for Pediatric Liver Tumors) 3 study, conducted cisplatin (CDDP) monotherapy for young children (< 3 years old) with standard risk hepatoblastoma (HB) evaluated central review system in Japan. In the previous JPLT2 study, cases with resectable tumors without any annotation factors in the PRETEXT classification (standard risk HB) showed favorable outcomes by the therapies consisted of CDDP and pirarubicin, but showed toxicities and late complications. In this JPLT3-S trial, less intensity regimen consisted of CDDP alone were evaluated in the young children (< 3 years old) with standard risk HB. Methods: Patients who were less than three years of age, who had PRETEXT I, II, or III HB without any annotation factors (e.g., E1, E1a, E2, E2a, H1, N1, P2, P2a, V3, and V3a) were eligible for inclusion in this study. In this trial, we introduced central radiological and pathological reviews of all patients. The primary outcome was 3-year progression-free survival (PFS). Results: A total of 38 patients (23 female) were included. The median patient age was 12 (range, 2-34) months. Two patients discontinued treatment because of progressive disease, and five patients discontinued treatment for other reasons. The 3- year PFS rate was 93.9% (95% confidence interval [CI], 86.4 to 100). All 38 patients survived (follow-up period 38-98 months), and the OS rate was 100% (confidence interval, 100). There were no cases with late complication without ototoxicity. Conclusion: CDDP monotherapy regimen is feasible in young patients with localized HB classified by central review.

Introduction Arteriovenous fistulas (AVFs) are a form of arteriovenous malformations clinically characterized by anomalous communications between arterial and venous systems that bypass the normal anatomic capillary beds (1). Broadly it can be divided into two forms based on the cause: acquired or congenital. Surgery, penetrating trauma, and percutaneous catheterization are the most common causes of acquired AVFs. Rarely AVFs can be formed in the absence of a clear cause and are called spontaneous AVFs which are rare with very few case reports in the literature (2-4). The anatomy of the fistula depends on the location in the body and where the causative factor was applied. Greater than 50% of traumatic AVFs happen in the lower extremity, and about one-third occur in the femoral vessels, while 15% take place in the popliteal vessels but AVF can occur at any site (5-8).AVFs present clinically with progressively growing pulsatile mass on each respective site associated with or without complications including infection, thrombosis, aneurysm, hypertension, and heart failure demanding timely intervention (9).

A document by Simeon Mengistu. Click on the document to view its contents.

In this paper, we trace the emergence of what we term the digital plant humanities—abbreviated as DPH throughout—as an evolution of burgeoning botanical interest among environmental and digital humanists. We argue that DPH coalesces the theoretical and methodological frameworks of the three research areas of plant humanities, environmental humanities, and digital humanities. After conceptualising DPH, we analyse three projects representative of the emergent field—the Native American Ethnobotany Database; Herbaria 3.0; and Microcosms: A Homage to Sacred Plants of America—while referring to a broader range of formative projects including the Plant Humanities Lab.

Papaverine Effect on Superficial Vein in Thumb Replantation Procedure: A Case Study

Bees and moths are globally important pollinators. Xeric barrens in the largely mesic northeastern USA support high levels of pollinator diversity, including rare bees and moths. We investigated the response of bee vs moth communities to abiotic and vegetation drivers in barrens across the region. We sampled environment, vegetation, bees, and moths for 2-4 years in 20 preserves. Employing random forest analysis, we tested the role of 26 abiotic and vegetation predictors of bee vs moth abundance, species richness, Shannon-Wiener Diversity Index, evenness, and species composition. Variables related to climate, canopy cover, and soils were the most important predictors of abundance, diversity, and species composition for both bees and moths. Vegetation variables, such as species richness of shrubs and hostplants, were also important for bees. The direction of these relationships contrasted sharply between bees and moths: bees were more abundant and species rich in more open, sandy sites and moths the opposite. Surprisingly, bee-moth contrasts in diversity did not hold for Shannon-Wiener Diversity. Habitat preferences for a subset of moth xeric specialists were much more similar to bees than to other moths, with a preference for open, sandy conditions. Contrasts between bees and moths in habitat preferences likely stemmed from differences in life history: bees rely on flowers for feeding and porous substrates for nesting, whereas most moth adults rely on flowers but many moth caterpillars use woody plants as hosts. The contrast between bees and moths for species richness vs. Shannon-Wiener Diversity raises important general questions about the conservation value of these two metrics. Our results suggest that, because of differences in habitat preferences among pollinators, barrens management for spatial and temporal heterogeneity is likely to promote the highest abundance and diversity of resident pollinator communities.

The mutual interactions of ER resident proteins in the ER maintain its functions, prompting the protein folding, modification, and transportation. Here, a new method, named YST-PPI (YESS-based Split fast TEV protease System for Protein-protein Interaction) was developed, targeting the characterization of protein interactions in ER. YST-PPI method integrated the YESS system, split-TEV technology and endoplasmic reticulum retention signal peptide (ERS) to provide an effective strategy for studying ER in situ PPIs in a fast and quantitative manner. The interactions among 15 ER resident proteins of S. cerevisiae were explored using the YST-PPI system, and their interaction network map was constructed, in which more than 74 interacting resident protein pairs were identified. Our studies also showed that Lhs1p plays a critical role in regulating the interactions of most of the ER resident proteins, expect the Sil1p, indicating its potential role in controlling the ER molecular chaperones. Moreover, the mutual interaction revealed by our studies further confirmed that the ER resident proteins perform their functions in a synergetic way and multimer complex might be formed during the process.