Unravelling the novel sex determination genotype with 'ZY' and a distinctive 2.15-2.95 Mb inversion among poplar species through haplotype-resolved genome assembly and comparative genomics analysis.

Populus tomentosa, an indigenous tree species, is widely distributed and cultivated over 1,000,000 km2 in China, contributing significantly to forest production, ecological conservation and urban-rural greening. Although a reference genome is available for P. tomentosa, the intricate interspecific hybrid origins, chromosome structural variations (SVs) and sex determination mechanisms remain confusion and unclear due to its broad and even overlapping geographical distribution, extensive morphological variations and cross infiltration among white poplar species. We conducted a haplotype-resolved de novo assembly of P. tomentosa elite individual GM107, which comprises subgenomes a and b with a total genome size of 714.9 Mb. We then analysed the formation of hybrid species and the phylogenetic evolution and sex differentiation across the entire genus. Phylogenomic analyses suggested that GM107 likely originated from a hybridisation event between P. alba (♀) and P. davidiana (♂) approximately 3.8 Mya. A total of 1551 chromosome SVs were identified between the two subgenomes. More noteworthily, a distinctive inversion structure spanning 2.15-2.95 Mb was unveiled among Populus, Tacamahaca, Turaga, Aigeiros poplar species and Salix, highlighting a unique evolutionary feature. Intriguingly, a novel sex genotype of the ZY type, which represents a crossover between XY and ZW systems, was identified and confirmed through both natural and artificial hybrids populations. These novel insights offer significant theoretical value for the study of the species' evolutionary origins and serve as a valuable resource for ecological genetics and forest biotechnology.

The harms of promoting the lab leak hypothesis for SARS-CoV-2 origins without evidence.

Science is humanity's best insurance against threats from nature, but it is a fragile enterprise that must be nourished and protected. The preponderance of scientific evidence indicates a natural origin for SARS-CoV-2. Yet, the theory that SARS-CoV-2 was engineered in and escaped from a lab dominates media attention, even in the absence of strong evidence. We discuss how the resulting anti-science movement puts the research community, scientific research, and pandemic preparedness at risk.

Edaphoclimatic variation and harvest seasonality as determining factors of multidimensional quality in avocado cv. hass grown in the tropics.

The increase in cultivated areas in tropical zones such as Colombia for avocado cv. Hass and the lack of knowledge on edaphoclimatic relationships with factors associated with quality led to the present research. The aim of this research was to establish the relationship of soil, climatic, spatial factors (plot location), and harvest seasonality (principal and transitory) with the multidimensional quality of avocado cv. Hass planted under tropical conditions. This research was carried out on eight farms located in three producing subregions. Soil, environmental and harvest data were recorded for three years (2015-2017) in each plot. Avocado fruit samples were used to determine the parameters of macronutrient, fatty acids, minerals, and vitamin E. Descriptive, inferential statistics, multivariate analysis, effect size, second-order exponential model, and causal relationships were used to determine variables associated with soil, climate, harvest seasonality, and spatial location, and to determine quality parameters. The results established a relationship between nutritional quality and the origin region. Similarly, it was possible to identify parameters associated with differential quality with a robust statistical methodology to propose origin as a differentiating factor for quality. This study provided useful information for the value chain that selected the best areas for avocado crops according to market expectations and nutritional quality criteria.

Clinico-Epidemiological Profile of Patients with Chronic Kidney Diseases of Unknown Etiology: A Hospital-Based, Cross-Sectional Study from Central India.

Background: Chronic kidney disease (CKD) not associated with known risk factors, called CKD of unknown etiology (CKDu), has been reported from several geographically distinct regions across the world. This study reports the clinical and epidemiological profile of patients with CKDu from a new hotspot in central India. Materials and Methods: This cross-sectional study describes the sociodemographic, clinical, and laboratory profile of the patients diagnosed with CKDu visiting a tertiary care public hospital in the state of Chhattisgarh in central India between June 2019 and June 2021. CKDu was diagnosed as progressive CKD, minimal proteinuria, absence of hematuria, diabetes, severe hypertension, systemic illness, glomerulonephritis or other urinary tract diseases, and presence of symmetrically contracted kidneyon ultrasound. Results: A total of 166 (3.1%) out of 5365 patients with CKD were diagnosed with CKDu. The mean age was 53.6 ± 11.8 years. The patients were predominantly male (n = 113, 68.1%), belonged to rural areas (n = 147, 88.6%), and were engaged in farming (n = 105, 63.3%). The estimated glomerular filtration rate (eGFR) at presentation was 21.5 ± 15.1 ml/min/1.73m2. Forty-four (26.5%) had stage 3 CKD, 57 (34.3%) had stage 4 CKD, and 65 (39.2%) had stage5 CKD. There was an over-representation of CKDu cases in patients with CKD from Gariyaband (36.0%) and Mahasamund (25%) districts of Chhattisgarh and Nuapada (35.0%) and Balangir (30.0%) districts of Odisha. Conclusion: The study suggests clustering of cases of CKDu in certain districts of Orissa and Chhattisgarh.

Optimization of headspace high-capacity tool coupled to two-dimensional gas chromatography-mass spectrometry for mapping the volatile organic compounds of raw pistachios. A proof-of-concept on the classification ability by geographic origin.

An optimized procedure for extracting and analyzing raw pistachio volatiles was developed through headspace sampling with high-capacity tools and subsequent analysis using comprehensive two-dimensional gas chromatography coupled with mass spectrometry. The examination of 18 pistachio samples belonging to different geographic areas led to the identification of a set of 99 volatile organic compounds (VOCs). Molecules were putatively identified using linear retention index, mass spectra similarity, and two-dimensional plot location. The impact of preprocessing and processing techniques on the aligned data matrix from a set of samples of different geographical origins, after removing contaminants, was evaluated. The combination of scaling with log-transformation, normalization with z-score, and data reduction with random forest machine learning algorithm generated a panel of 16 discriminatory VOC molecules. As a proof of concept, raw pistachios' VOC profile was employed for the first time to tentatively classify them based on their geographical origin.

Pyrexia of Unknown Origin in a Young Male: Unmasking Melioidosis in a Tuberculosis-Endemic Setting.

A young male, plantation worker from Southeast Asia, presented with a non-productive cough, intermittent high-grade fever with chills, and significant weight loss over two months. Prior investigations were non-contributory, despite various antibiotics, his symptoms persisted. Physical examination and routine investigations, including an extensive microbiological workup for fever were non-contributory. A positron emission tomography-computed tomography (PET-CT) scan performed for pyrexia of unknown origin (PUO) revealed pulmonary consolidation, mediastinal lymphadenopathy, and splenic microabscesses. Material aspirated via endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) from the left interlobar lymph node was positive for Burkholderia pseudomallei on conventional nested polymerase chain reaction (PCR), confirming a diagnosis of melioidosis. Following appropriate antibiotic therapy, there was a complete resolution of symptoms. This case underscores the diagnostic challenges and the need for advanced techniques in identifying melioidosis, which can mimic tuberculosis.

Acvr1b loss increases formation of pancreatic precancerous lesions from acinar and ductal cells of origin.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) can develop from precursor lesions, including pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). Previous studies indicated that loss of Acvr1b accelerates the Kras-mediated development of papillary IPMN in the mouse pancreas, however, the cell type predominantly affected by these genetic changes remains unclear. METHODS: We investigated the contribution of cellular origin by inducing IPMN associated mutations- KRASG12D expression and Acvr1b loss - specifically in acinar (Ptf1aCreER;KrasLSL-G12D;Acvr1bfl/fl mice) or ductal (Sox9CreER;KrasLSL-G12D;Acvr1bfl/fl mice) cells in mice. We then performed MRI imaging and a thorough histopathological analysis of their pancreatic tissues. RESULTS: The loss of Acvr1b increased the development of PanIN and IPMN-like lesions when either acinar and ductal cells expressed a Kras mutation. MRI, immunohistochemistry and histology revealed large IPMN-like lesions in these mice that exhibited features of flat, gastric epithelium. In addition, cyst formation in both mouse models was accompanied by chronic pancreatitis. Experimental acute pancreatitis accelerated the development of large mucinous cysts and PanIN when acinar, but not ductal, cells expressed mutant Kras and lost Acvr1b. CONCLUSION: These findings indicate that loss of Acvr1b in the presence of the Kras oncogene promotes the development of large and small precancerous lesions from both ductal and acinar cells. However, the IPMN-like phenotype was not equivalent to that observed when these mutations were made in all pancreatic cells during development. Our study underscores the significance of the cellular context in the initiation and progression of precursor lesions from exocrine cells.

Complex Genomes of Early Nucleocytoviruses Revealed by Ancient Origins of Viral Aminoacyl-tRNA Synthetases.

Aminoacyl-tRNA synthetases (aaRSs), also known as tRNA ligases, are essential enzymes in translation. Owing to their functional essentiality, these enzymes are conserved in all domains of life and used as informative markers to trace the evolutionary history of cellular organisms. Unlike cellular organisms, viruses generally lack aaRSs because of their obligate parasitic nature, but several large and giant DNA viruses in the phylum Nucleocytoviricota encode aaRSs in their genomes. The discovery of viral aaRSs led to the idea that the phylogenetic analysis of aaRSs can shed light on ancient viral evolution. However, conflicting results have been reported from previous phylogenetic studies: one posited that nucleocytoviruses recently acquired their aaRSs from their host eukaryotes, while another hypothesized that the viral aaRSs have ancient origins. Here, we investigated 4,168 nucleocytovirus genomes, including metagenome-assembled genomes (MAGs) derived from large-scale metagenomic studies. In total, we identified 780 viral aaRS sequences in 273 viral genomes. We generated and examined phylogenetic trees of these aaRSs with a large set of cellular sequences to trace evolutionary relationships between viral and cellular aaRSs. The analyses suggest that the origins of some viral aaRSs predate the last common eukaryotic ancestor. Inside viral aaRS clades, we identify intricate evolutionary trajectories of viral aaRSs with horizontal transfers, losses, and displacements. Overall, these results suggest that ancestral nucleocytoviruses already developed complex genomes with an expanded set of aaRSs in the proto-eukaryotic era.

Subsequent fracture risk in Norwegians and immigrants with an index forearm fracture: a cohort study.

The current study investigated subsequent fracture risk following a forearm fracture in three country of birth categories: Norway, Europe and North America, and other countries. Subsequent fracture risk was modestly higher in Norwegian-born individuals compared to the two other groups. Secondary fracture prevention should be recommended regardless of country background. BACKGROUND: Fracture risk is higher in patients with a previous fracture, but whether subsequent fracture risk differs by origin of birth is unknown. This study explores subsequent fracture risk in patients with an index forearm fracture according to region of birth. METHODS: Nationwide data on forearm fractures in patients ≥ 18 years in 2008-2019 were obtained from the Norwegian Patient Registry and Statistics Norway. Index fractures were identified by ICD-10 code S52, whereas subsequent fractures included any ICD-10 fracture code. Data on country of birth were from Statistics Norway and included three regional categories: (1) Norway, (2) other Europe and North America and (3) other countries. Direct age standardization and Cox proportional hazard regression were used to analyse the data. RESULTS: Among 143,476 individuals with an index forearm fracture, 35,361 sustained a subsequent fracture. Norwegian-born forearm fracture patients had the highest subsequent fracture rates (516/10,000 person-years in women and 380 in men). People born outside Europe and North America had the lowest rates (278/10,000 person-years in women and 286 in men). Compared to Norwegian-born individuals, the hazard ratios (HRs) of subsequent fracture in individuals from Europe and North American were 0.93 (95% CI 0.88-0.98) in women and 0.85 (95% CI 0.79-0.92) in men. The corresponding HRs in individuals from other countries were 0.76 (95% CI 0.70-0.84) in women and 0.82 (95% CI 0.74-0.92) in men. CONCLUSION: Individuals born outside Norway had a lower subsequent fracture risk than Norwegian-born individuals; however, subsequent fracture risk increased with age in all groups. Our results indicate that secondary fracture prevention should be recommended regardless of region of origin.

Mechanistic study of fructus aurantii (Quzhou origin) in regulating ileal reg3g in the treatment for NASH.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a critical stage in the progression of non-alcoholic fatty liver disease (NAFLD), characterized by obvious inflammation and fibrosis. Because of its high incidence rate and serious consequences, NASH is becoming a global health problem. The influence of endotoxin translocation on NASH is receiving attention. As a traditional Chinese herb that effectively improves hepatic inflammation, Fructus Aurantii (Quzhou origin, FAQ) is widely used in the clinical treatment of NASH. However, the intervention mechanism of FAQ on reg3g and related endotoxin translocation remains unclear. AIM: To study the mechanism of the impact by which ileal regenerating family member 3 gamma (reg3g) deficiency and subsequent endotoxin translocation impact the progression of NASH; To elucidate the efficacy and mechanism of FAQ in the treatment of NASH. METHODS: Clinical serum, ileal tissue, and dynamic NASH model-related analyses collectively confirmed that reg3g is a pivotal gene associated with NASH. Reg3g-/- mice were used to assess the impact of reg3g on liver injury, inflammation, and fibrosis, as well as the underlying mechanism involved. In vitro studies elucidated the regulatory effects of FAQ on reg3g, intestinal barrier function, and intestinal permeability. Subsequently, the efficacy of FAQ was investigated in NASH mouse models. Pathological examinations combined with Western blotting (WB), immunohistochemistry (IHC), and multiplex immunohistochemical (mIHC) analyses were used to evaluate the effects of FAQ on mucosal repair and barrier function. Transepithelial electrical resistance (TEER), fluorescein isothiocyanate-dextran 4 (FD-4) experiments, coupled with enzyme linked immunosorbent assay (ELISA) and chromogenic LAL endotoxin assay were used to confirm intestinal permeability and endotoxin translocation. The results of WB and mIHC reflected the levels of endotoxin recruitment and M1 macrophage polarization in the liver. Parameters such as body weight, transaminases, and cholesterol were utilized to assess the metabolic effects of FAQ. RESULTS: Decreased expression of reg3g was associated with the progression of NASH. Ileal deficiency in reg3g resulted in damage to the intestinal barrier and permeability, leading to the recruitment of endotoxins via the 'gut-liver' axis to the liver, causing the polarization of M1 macrophages, release of inflammatory factors, excessive inflammation, and activation of hepatic stellate cells (HSCs), leading to fibrosis. FAQ significantly upregulated ileal reg3g expression and the expression of intestinal barrier-related proteins tight junction protein 1 (ZO-1) and occludin (OLCN) in mice (p < 0.05), thereby improving intestinal barrier function and permeability. Reduced intestinal permeability led to decreases in endotoxins entering the bloodstream and accumulating in the liver (p < 0.05). The expression of CD68 suggested reduced polarization of M1 macrophages. Expression levels of actin alpha 2, smooth muscle actin (α-SMA) and extracellular matrix (ECM)-related proteins also decreased, indicating improved liver fibrosis. CONCLUSION: FAQ ameliorates NASH by upregulating the expression of reg3g. The upregulation of reg3g contributes to the repair of the intestinal barrier and permeability, reducing the recruitment of endotoxins and subsequent polarization of M1 macrophages, excessive inflammation, and fibrosis.

Prenatal origin of NUTM1 gene rearrangement in infant B-cell precursor acute lymphoblastic leukaemia.

Rearrangement of NUTM1 gene (NUTM1r) is one of the most frequent aberrations occurring in infants (younger than 1 year at diagnosis) with B-cell precursor Acute Lymphoblastic Leukaemia (BCP-ALL). In this study we had the unique opportunity to analyze the umbilical cord blood (UCB) sample from one infant patient with NUTM1r BCP-ALL. Herein we reported for the first time that NUTM1r infant ALL arise prenatally, as both the patient-specific CUX1::NUTM1 fusion gene, as well as two IG/TR leukaemic markers were already present and detectable in the patient's UCB at birth. Our results clearly demonstrate the prenatal origin of NUTM1r infant BCP-ALL.

Mesenchymal stromal/stem cell tissue source and in vitro expansion impact extracellular vesicle protein and miRNA compositions as well as angiogenic and immunomodulatory capacities.

Recently, therapies utilizing extracellular vesicles (EVs) derived from mesenchymal stromal/stem cells (MSCs) have begun to show promise in clinical trials. However, EV therapeutic potential varies with MSC tissue source and in vitro expansion through passaging. To find the optimal MSC source for clinically translatable EV-derived therapies, this study aims to compare the angiogenic and immunomodulatory potentials and the protein and miRNA cargo compositions of EVs isolated from the two most common clinical sources of adult MSCs, bone marrow and adipose tissue, across different passage numbers. Primary bone marrow-derived MSCs (BMSCs) and adipose-derived MSCs (ASCs) were isolated from adult female Lewis rats and expanded in vitro to the indicated passage numbers (P2, P4, and P8). EVs were isolated from the culture medium of P2, P4, and P8 BMSCs and ASCs and characterized for EV size, number, surface markers, protein content, and morphology. EVs isolated from different tissue sources showed different EV yields per cell, EV sizes, and protein yield per EV. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of proteomics data and miRNA seq data identified key proteins and pathways associated with differences between BMSC-EVs and ASC-EVs, as well as differences due to passage number. In vitro tube formation assays employing human umbilical vein endothelial cells suggested that both tissue source and passage number had significant effects on the angiogenic capacity of EVs. With or without lipopolysaccharide (LPS) stimulation, EVs more significantly impacted expression of M2-macrophage genes (IL-10, Arg1, TGFß) than M1-macrophage genes (IL-6, NOS2, TNFα). By correlating the proteomics analyses with the miRNA seq analysis and differences observed in our in vitro immunomodulatory, angiogenic, and proliferation assays, this study highlights the trade-offs that may be necessary in selecting the optimal MSC source for development of clinical EV therapies.

Daily and Ethnic Discriminatory Experiences and Cognitive Control in Mexican-Origin Bilingual Language Brokers.

Few studies have considered bilingualism's impact on cognitive development within the sociolinguistic and cultural context of the immigrant communities where bilingualism is commonly practiced. In the United States, many Mexican-origin bilingual youth practice their bilingual skills by brokering (i.e., translating/interpreting between languages) for their immigrant parents who have low English proficiency. Meanwhile, these youth may also experience discrimination in their daily life. The present study focuses on Mexican-origin bilingual youth brokers (N=334) in order to examine how discriminatory experiences (i.e., daily and ethnic discrimination) and bilingual brokering experiences captured by profiles are related to cognitive control performance (i.e., attentional control and inhibition). We found no significant direct influence of either bilingual broker profiles or discriminatory experiences on cognitive control. However, the associations between discriminatory experiences and cognitive control performance depended upon brokering experiences. Specifically, greater discrimination was associated with lower cognitive control performance among moderate brokers (with moderate bilingual experiences), but the association was attenuated among efficacious brokers (with positive bilingual experiences). Findings highlight the need to consider the sociolinguistic heterogeneity of both discriminatory experiences and language use when investigating cognitive control performance in bilinguals.

Prebiotic thiol-catalyzed thioamide bond formation.

Thioamide bonds are important intermediates in prebiotic chemistry. In cyanosulfidic prebiotic chemistry, they serve as crucial intermediates in the pathways that lead to the formation of many important biomolecules (e.g., amino acids). They can also serve as purine and pyrimidine precursors, the two classes of heterocycle employed in genetic molecules. Despite their importance, the formation of thioamide bonds from nitriles under prebiotic conditions has required large excesses of sulfide or compounds with unknown prebiotic sources. Here, we describe the thiol-catalyzed formation of thioamide bonds from nitriles. We show that the formation of the simplest of these compounds, thioformamide, forms readily in spark-discharge experiments from hydrogen cyanide, sulfide, and a methanethiol catalyst, suggesting potential accumulation on early Earth. Lastly, we demonstrate that thioformamide has a Gibbs energy of hydrolysis ( Δ G r ∘ ) comparable to other energy-currencies on early Earth such as pyrophosphate and thioester bonds. Overall, our findings imply that thioamides might have been abundant on early Earth and served a variety of functions during chemical evolution.

Comparative transcriptomics analysis-guided metabolic engineering of Yarrowia lipolytica for improved erythritol and fructooligosaccharides production.

Currently, fructooligosaccharides (FOS) are converted from sucrose by purified enzymes or fungal cells, but these methods are costly and time-consuming. Here, the optimal fermentation conditions for strain E326 were determined through fermentation optimization: initial glucose 200 g/L, NaCl 25 g/L, inoculum volume 20 %, dissolved oxygen 20-30 %, pH 3, and glucose feeding concentration 100 g/L, which increased erythritol titer by 1.5 times. The co-expression of HGT1 and APC11 genes alleviated the erythritol synthesis stagnation, shorten the fermentation time by 16.7 %, and increased the erythritol productivity by 17.2 %. The episomal plasmids based on yeast mitochondrial replication origins (mtORIs) were constructed to surface display fructosyltransferase, effectively utilizing waste yeast cells generated during erythritol fermentation. Under the conditions of 60℃ and pH 6, the FOS yield reached 65 %, which to our best of knowledge is so-far the highest yield of FOS obtained. These findings will contribute to the industrial production of erythritol and FOS.

Pediatric Tumors as Disorders of Development: The Case for In Vitro Modeling Based on Human Stem Cells.

Despite improvements in patient outcomes, pediatric cancer remains a leading cause of non-accidental death in children. Recent genetic analysis of patients with pediatric cancers indicates an important role for both germline genetic predisposition and cancer-specific somatic driver mutations. Increasingly, evidence demonstrates that the developmental timepoint at which the cancer cell-of-origin transforms is critical to tumor identity and therapeutic response. Therefore, future therapeutic development would be bolstered by the use of disease models that faithfully recapitulate the genetic context, cell-of-origin, and developmental window of vulnerability in pediatric cancers. Human stem cells have the potential to incorporate all of these characteristics into a pediatric cancer model, while serving as a platform for rapid genetic and pharmacological testing. In this review, we describe how human stem cells have been used to model pediatric cancers and how these models compare to other pediatric cancer model modalities.

Today, pediatric cancer is a leading cause of non-accidental death in children. In order to further improve outcomes, it is important for researchers and clinicians alike to recognize how pediatric cancers are distinct from adult cancers. Inherited risk of cancer may play a greater role in pediatric cancer risk, and subsequent tumor-specific acquired driver mutations initiate tumor formation. However, there is substantial interaction between inherited and acquired mutations, which supports consideration of both simultaneously. Recent advancements in biotechnology, have improved matching between early cells of development and pediatric cancer cells, although cell-of-origin for certain pediatric central nervous system tumors remain elusive. Increasingly, evidence, particularly in pediatric medulloblastoma, demonstrates that the developmental timepoint at which the cancer cell-of-origin transforms is critical to tumor identity and therapeutic response. Therefore, future therapeutic development would be bolstered by the use of disease models that faithfully recapitulate the genetic context, cell-of-origin, and developmental window of pediatric cancers. Human stem cells have the potential to incorporate all of these characteristics into a pediatric cancer model, while serving as a platform for rapid genetic and pharmacological testing. In this review, we describe how human stem cells have been used to model pediatric cancers, how human these models compare to other pediatric cancer model modalities, and how these models can be improved in the future.

Enhanced data preprocessing with novel window function in Raman spectroscopy: Leveraging feature selection and machine learning for raspberry origin identification.

In this study, a simple and accurate approach is proposed for enhancing the origin identification of raspberry samples using a combination of innovative Raman spectral preprocessing techniques, feature selection, and machine learning algorithms. Window function was creatively introduced and combined with baseline removal technique to preprocess the Raman spectral data, reducing the dimensionality of the raw data and ensuring the quality of the processed data. An optimization process was conducted to determine the optimal parameter for the window function, resulting in a binning window width of 5 that yielded the highest accuracy. After applying three feature selection techniques, it was found that the information gain model had the best performance in extracting discriminative spectral features. Finally, ten different machine learning algorithms were employed to construct predictive models, and the optimal models were selected. Linear Support Vector Classifier (LinearSVC), Multi-Layer Perceptron Classifier (MLPClassifier), and Linear Discriminant Analysis (LDA) achieve accuracy, precision, recall, and F1 values above 0.96, while the Random Vector Functional Link Network Classifier (RVFLClassifier) surpasses 0.93 for these performance metrics. These results demonstrate the effectiveness of the proposed approach in identifying the origin of raspberry samples with high accuracy and robustness, providing a valuable tool for agricultural product authentication and quality control.

Anomalous Origin of the Right Coronary Artery From the Pulmonary Artery: Advantages of Multimodality Imaging.

Coronary anomalies are one of the most surprising yet challenging pediatric cardiology diagnoses. The anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is frequently underdiagnosed due to a lack of typical signs or symptoms. We present a case of ARCAPA in a healthy six-month-old girl during follow-up of a newly detected heart murmur. Echocardiography raised the suspicion of a coronary anomaly, but the diagnosis was unclear, so cardiac catheterization and computed tomography were performed, which posteriorly confirmed the diagnosis. The patient underwent surgical repair, and the short-term follow-up has been uneventful. Regular monitoring is essential due to the potential long-term complications of ARCAPA, including myocardial ischemia, heart failure, and sudden cardiac death, underscoring the importance of early diagnosis and continuous management.

Misconception of 'malignant' and 'scissor-like compression' of interarterial course in anomalous aortic origin of a coronary artery: a case series.

Background: The notion that the 'interarterial' segment of anomalous aortic origin of a coronary artery (AAOCA) is 'malignant' and 'scissor-like' compressed between the aorta and pulmonary artery (PA) is debated, owing to the lower pressure in the pulmonary system compared with that in the coronary system. However, data supporting or refuting this belief under stress conditions are lacking. Case summary: Three cases of right AAOCA with interarterial/intramural courses (52, 66, and 51 years old) were assessed. Invasively measured fractional flow reserve (FFR) under dobutamine was 0.85, 0.82, and 0.81, respectively. Intravascular ultrasound illustrated lateral vessel compression of the intramural course with a decrease of minimal lumen area (MLA) (i.e. 5.71-3.47 mm2, 5.88-4.00 mm2, and 5.85-4.06 mm2) under stress conditions with heart rates of 130, 140, and 150 b.p.m., respectively. Pulmonary artery pressure (PAP) increased from rest {s/d (m) [systolic/diastolic (mean)] 22/11 (15), 15/2 (5), and 24/6 (14) mmHg} to stress [s/d (m) 47/24 (36), 30/3 (11), and 36/22 (24) mmHg] and remained below aortic peak pressure (blood pressure, BP) rest [s/d (m) 116/64 (91), 94/48 (71), 99/53 and (62) mmHg]; BP stress [s/d (m) 142/63 (80), 123/63 (88), and 86/46 (62) mmHg]; coronary pressure (CoP) rest [s/d (m) 100/59 (80), 80/45 (62), and 83/47 (63) mmHg]; and CoP stress [s/d (m) 95/60 (69),101/54 (72), and 70/32 (50) mmHg]. Conclusion: This case series challenges the assumption that the interarterial segment of AAOCA is scissor-like compressed by both the aorta and PA. The decrease in MLA and FFR under stress is due to the aorta's unidirectional lateral compression on the intramural segment. Additionally, the term 'malignant' should not be universally applied to all AAOCA cases with an interarterial course, as not all result in haemodynamic significance.

Origins of Life: The Protein Folding Problem all over again?

How did specific useful protein sequences arise from simpler molecules at the origin of life? This seemingly needle-in-a-haystack problem has remarkably close resemblance to the old Protein Folding Problem, for which the solution is now known from statistical physics. Based on the logic that Origins must have come only after there was an operative evolution mechanism-which selects on phenotype, not genotype-we give a perspective that proteins and their folding processes are likely to have been the primary driver of the early stages of the origin of life.