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Reaffirming the true identity of Passiflora foetida var. nigelliflora, and uncovering...
J.R. Kuethe

J.R. Kuethe

August 30, 2024
The convoluted species complex surrounding Passiflora foetida and its segregates has overshadowed many new and interesting species. It was found in particular that the South American Passiflora foetida var. nigelliflora exhibited two different forms, found in very different habitats without a lateral distribution present. An in-depth study of the original source material was needed to identify the true identity of the plant belonging to the given taxon, as well as uncover a new species restricted to the south Brazilian states of Rio Grande do Sul and Santa Catarina. True Passiflora foetida var. nigelliflora was found to be native to mainly Argentina and Paraguay, with only questionable records found in southern Brazil, whereas the new species, here assigned as Passiflora coroniforma sp.nov., is endemic to the coastal regions of south-eastern Brazil. Both taxa are herein further described and illustrated, and their interim relation discussed.
Laccaria friesii sp. nov. (Hydnangiaceae), a new species from Northwestern Himalaya o...
Shikha Choudhary
Yash Pal Sharma

Shikha Choudhary

and 2 more

August 30, 2024
Laccaria friesii sp. nov. is proposed here as a new species based on morphological characteristics and phylogenetic analyses of the nuclear rDNA internal transcribed spacer region. The combination of morphological and molecular data confirmed the novelty of the species and its infrageneric placement within the genus Laccaria. This species was found in association with Rhododendron arboreum and Quercus leucotrichophora and is characterized by large basidiome (17–90 µm pileus diam.), convex to campanulate pileus with a central depression, wavy margins, pink fleshy brown distant lamellae, presence of versiform cheilocystidia and trichoderm type pileipellis.
Plasmodium Falciparum and Immune Phagocytosis: Characterization of the Process
Dia Aldeen Alfaki
Mohamed Elbasheir

Dia Aldeen Alfaki

and 1 more

August 30, 2024
Phagocytosis is an immunological characteristic that assists the host immune defense in recognizing and responding effectively to foreign pathogenic molecules and other self-antigens. Understanding the phagocytic activities against malaria infection in the context of Plasmodium falciparum infection which represents a major public health concern in many countries is crucial for developing effective interventions to prevent and control malaria, and improving the overall notion about the importance of this mechanism in the protective immune response. Previous studies have shown that various factors such as the type of phagocyte cells, plasma molecules, and the evasion of tactics by Plasmodium falciparum pathogens influence the phagocytic process. However, the mechanisms underlying phagocytic activity during Plasmodium falciparum infection are still not fully understood. This review aims to provide a comprehensive insight into the current state of knowledge on phagocytic activities in Plasmodium falciparum infection, highlighting the significant involvement of different active phagocyte cells, influences on phagocytosis, and giving perspective on the therapeutic approach and implications of this immunological activity in malaria infection clearance.
Physiological responses of artificially cultivated biocrust under addition of sacchar...
H.R. Ren
L. Tao

H.R. Ren

and 3 more

August 30, 2024
The medium for artificial culture is very important for the survival and development of biocrusts. The physiological responses of biocrusts to the addition of saccharides and growth regulators were investigated to evaluate the optimal cultivation method. The research results suggested that MDA was the lowest and chlorophyll-a, soluble protein, and soluble sugar were the highest under the addition of 0.5 mg/L sucrose and glucose (10 mg/L). The MDA content of the biocrusts decreased with increasing 2,4-D and 6-BA concentrations. Chlorophyll-a, soluble protein, and soluble sugar of the biocrusts were the most abundant when the additions of 2,4-D and 6-BA were both 0.5 mg/L. The chlorophyll-a concentration of the biocrusts always increased with the addition of sucrose and glucose. The maximum tolerance of biocrust to sucrose was 40 mg/L. The excessive sugar in the medium had an inhibitory effect on the growth and reproductive cycles and resulted in greater damage to moss cells in biocrusts as sugar concentrations increased. The appropriate addition of saccharides and growth regulators can promote the survival and growth of desert biocrusts.
Suicidal Ideation in Asian American Young Adults: Integrating Interpersonal and Socio...
Christina S. Lee
Nari Yoo

Christina S. Lee

and 3 more

August 30, 2024
Introduction. This study integrated sociocultural and psychological factors to explain suicidal ideation among Asian American young adults. We investigated pathways to suicidal ideation from two major sociocultural stressors—racial discrimination and intergenerational cultural conflict—through interpersonal theory constructs (i.e., perceived burdensomeness, thwarted belongingness) and interpersonal shame (i.e., family shame, external shame). Methods. Participants were 396 East Asian Americans aged 18 to 30. Structural equation modeling examined whether the associations between sociocultural stressors and suicidal ideation were sequentially mediated first by interpersonal shame, then by interpersonal theory constructs. Results. Perceived burdensomeness had the strongest direct effect on suicidal ideation across all models. The indirect paths from both stressors (i.e., racial discrimination, intergenerational cultural conflict) to family shame to perceived burdensomeness to suicidal ideation were significant. The indirect paths from both stressors to suicidal ideation solely through perceived burdensomeness were not significant. Conclusion. Our findings expand interpersonal theory by illuminating the sociocultural stressors that contribute to perceptions of burdensomeness, which in turn are proximally associated with East Asian American young adults’ suicidal ideation. Findings also contextualize their suicidal ideation pathways by highlighting the culturally salient experience of family shame as a mediator in the links between sociocultural stressors and perceived burdensomeness.
Sexual health education for young adults diagnosed with severe mental illness, intell...
Miriam Belluzzo
Veronica Giaquinto

Miriam Belluzzo

and 5 more

August 30, 2024
Background: Young adults diagnosed with severe mental illness (SMI), intellectual disability (ID), and developmental disability (DD) often face challenges in accessing comprehensive sexual health education. The educational Intervention and Training Program on Sexuality and Affectivity (eITPoSA) aims to address this gap by providing tailored psycho-educational interventions. Methods: A pilot study was conducted with 15 participants diagnosed with SMI, ID, and DD. The program comprised six sessions focusing on body knowledge, genital sexuality, privacy awareness, privacy protection, and hygiene and personal care. Pre- and post-intervention evaluations were carried out using monitoring and evaluation grids. Data were analyzed using descriptive statistics, paired-samples t-tests with bootstrapped confidence intervals, and Cohen’s d to assess effect sizes. Additional valuable insights were gained from the open-ended questions designed for Modules 1, 2, and 6, as well as from the qualitative analysis of the Circles in Module 5. Results: The program demonstrated significant improvements in all areas evaluated. Mean scores for body knowledge increased from 31.43% (SD = 25.18) to 86.65% (SD = 23.98), genital sexuality from 15% (SD = 34.81) to 90% (SD = 24.00), privacy awareness from 82.94% (SD = 25.10) to 98.75% (SD = 7.16), privacy protection from 86.11% (SD = 29.65) to 95.95% (SD = 14.45), and hygiene and personal care from 47.27% (SD = 38.23) to 96.36% (SD = 12.06). All improvements were statistically significant with large effect sizes for body knowledge, genital sexuality, and hygiene and personal care. Conclusion: The eITPoSA program significantly enhances sexual and relational knowledge among young adults with SMI, ID, and DD. These results support the efficacy of tailored sexual health education programs. However, further research with larger, more diverse samples is needed to generalize these findings.
Raptor: Distributed Scheduling for Serverless Functions
Kevin Exton
Maria Read

Kevin Exton

and 1 more

August 30, 2024
To support parallelizable serverless workflows in applications like media processing, we have prototyped a distributed scheduler called Raptor that reduces both the end-to-end delay time and failure rate of parallelizable serverless workflows. As modern serverless frameworks are typically deployed to extremely large scale distributed computing environments by major cloud providers, Raptor is specifically designed to exploit the property of statistically independent function execution that tends to emerge at very large scales. To demonstrate the effect of horizontal scale on function execution, our evaluation demonstrates that mean delay time improvements provided by Raptor for RSA public-private key pair generation can be accurately predicted by mutually independent exponential random variables, but only once the serverless framework is deployed in a highly available configuration and horizontally scaled across three availability zones.
Analysis and review of more than 7 million prescriptions in medical institutions in B...
Sitong LIU
Jing Bian

Sitong LIU

and 5 more

August 30, 2024
Abstract Aim To analyze prescription review results in Beijing and to provide references for improving prescription rationality. Methods This study included outpatient prescriptions which were randomly extracted in Beijing from 2020 to 2022. Drug names were used as search keywords. The changes in prescriptions number and irrationality rate over the past three years were analyzed. Drugs associated with irrational prescriptions were sampled and the reasons for their irrational use were analyzed. Results Approximately 1.9 million prescriptions were sampled for 2020-2021, and more than 4 million prescriptions were sampled for 2022. The proportion of Modern medicine (abbreviated medicine) prescriptions of oncology treatment gradually increased while the proportion of Traditional Chinese Medicine(TCM) prescriptions gradually decreased from 2020 to 2022. The irrationality rate of medicine prescriptions briefly decreased in 2021 before increasing again in 2022. The irrationality rate of TCM prescriptions gradually decreased, and the average irrationality rate of medicine prescriptions was higher than that of TCM. Notably, the rationality of several drugs didn’t improve over the past three years, which included fluorouracil (injection), lobaplatin,bleomycin,Goserelin Acetate Sustained-release Depot ,Pabolizumab,vaginal preparations of recombinant human interferon. Conclusion Prescription review can improve prescription rationality and systematically identify off-label drug use, becoming an important way to expand drug clinical use and improve drug regulatory policies. The use of TCM in oncology treatment is becoming more rational, while the rational use of medicine still needs to be improved. Doctors should regulate their prescribing behavior and strive to increase the rationality of prescriptions.
The role of climate and species interactions in determining the distribution of two e...
Alexandra Coconis
Kenneth Nussear

Alexandra Coconis

and 4 more

August 30, 2024
The relative importance of abiotic and biotic factors in determining species distributions has long been of interest to ecologists but is often difficult to assess due to the lack of spatially and temporally robust occurrence records. Furthermore, locating places where potentially highly competitive species co-occur may be challenging but would provide critical knowledge into the effects of competition on species ranges. We built species distribution models for two closely related species of small mammals (Neotoma) that are largely parapatric along mountainsides throughout the Great Basin Desert using extensive modern occurrence records. We hindcasted these models to the mid-Holocene to compare the response of each species to dramatic climatic change and used paleontological records to validate our models. Model results showed species co-occurrence at mid-elevations along select mountain ranges in this region. We confirmed our model results with fine-scale field surveys in a single mountain range containing one of the most extensive survey datasets across an elevational gradient in the Great Basin. We found close alignment of both species’ realized distributions to their respective abiotic species distribution model predictions, despite the presence of the congener, indicating that climate may be more influential than competition in shaping distribution at the scale of a single mountain range. Our models also predict differential species responses to historic climate change, leading to reduced probability of species interactions during warmer and dryer climatic conditions. Our results emphasize the utility of examining species distributions with regards to both abiotic variables and species interactions and at various spatial scales to make inferences about the mechanisms underlying distributional limits.
Extremum seeking without transient misdirection: An adaptive high-pass filter-based a...
Zilong Li
Libin Wang

Zilong Li

and 3 more

August 30, 2024
Extremum seeking (ES) addresses the control problems concerned with a nonlinear plant or objective function, aiming at finding and maintaining an unknown optimal operating condition that either maximizes or minimizes the nonlinearity. The transient behavior of an ES system being regulated away from its optimal operating condition is referred to as transient misdirection. This phenomenon not only results in the depression of control efficiency but is also undesirable in many practical applications. This article focuses on transient misdirection in a basic ES scheme and proposes a novel modification on the high-pass filter (HPF). The core methodology is to introduce an adaptive HPF with a time-varying cut-off frequency that is high during transients and low during steady states. The adaptive HPF-based ES scheme is applied to both static and Hammerstein plants, and a semi-global stability result of the obtained system is presented by performing a Lyapunov analysis. The proposed approach can considerably reduce transient misdirection without sacrificing the convergence rate, as illustrated through simulation examples, demonstrating its effectiveness, practical prospect, and advantage over nonadaptive approaches.
Memory-Dynamic Event-Based Controller with Additive-Memory Time-Delay for Cyber-Physi...
Qing Zhu
Kaibo Shi

Qing Zhu

and 4 more

August 30, 2024
This paper tackles the challenge of designing a memory-dynamic event-triggered output feedback controller for cyber-physical systems (CPSs) under distributed denial of service (DDoS) attacks. First, we consider the impact of hybrid time delays on communication networks and focus on DDoS attacks that can continuously paralyze network. Second, with limited bandwidth communication resources, a memory-dynamic event-triggered scheme (MDETS) that efficiently utilizes the bandwidth resources as well as mitigates the network-induced phenomena is proposed. In addition, to ensure the safe operation of CPSs, an output feedback controller with memory is designed based on time delay states in the measurement channel. Then, selecting the proper multi-area Lyapunov-Krasovskii functionals (LKFs), criteria for sufficient exponentially mean-square H ∞ stability condition is formulated. Finally, an illustrative example is used to demonstrate the effectiveness and applicability of the designed strategies.
Identification, analysis, and drug prediction of key genes related to endoplasmic ret...
Huiwei Ye
Laifa Kong

Huiwei Ye

and 1 more

August 30, 2024
Pancreatitis, as a common exocrine pancreatic disease, poses a daunting challenge to patients’ health and the medical system. Endoplasmic reticulum stress (ERS) plays an essential role in the pathological process of pancreatitis. However, its mechanism is not fully understood. Therefore, this project was designed to deepen the understanding of the pathogenic mechanism of the disease by screening key ERS-related genes (hub genes) associated with pancreatitis. Through differential analysis and network analysis, we identified 4 hub genes (CCND1, BCL2, PIK3R1, and BCL2L1) from public databases. The receiver operation characteristic (ROC) curves indicated that they possessed good diagnostic capabilities. Subsequently, hub genes, especially BCL2 and PIK3R1, were elucidated to have strong interactions with 24 differentially expressed pancreatitis-related genes through differential analysis, Venn analysis, and correlation analysis. Further research revealed that these hub genes were closely linked to the immune microenvironment of pancreatitis, exhibiting negative correlations with Macrophages and Neutrophils, as well as a positive correlation with B_cells, CD8+_T_cells, and Tfh immune cells. Finally, we predicted potential miRNAs, lncRNAs, and compounds targeting these hub genes, providing reliable research directions for targeted studies on pancreatitis. In summary, this investigation not only further supports the function of ERS in pancreatitis development but also provides new perspectives and directions for the development of biomarkers for pancreatitis.
A rare but important side-effect of Cilostazol: A case-report
sara mohammadnia
Soheil Ebrahimpour

Sara Mohammadnia

and 2 more

August 30, 2024
Manuscript title:
Simultaneity of Tuberculosis and CLL : A Case Report
Zeinab Mohseni Afshar
Babak Sayad

Zeinab Mohseni Afshar

and 4 more

August 30, 2024
Title: Simultaneity of Tuberculosis and CLL : A Case Report
Modeling the Tumor Microenvironment In Vitro in Prostate Cancer: Current And Future P...
Kedi Yuan
Xinxing  Du

Kedi Yuan

and 4 more

August 30, 2024
Prostate cancer is the most common cancer in over 50% of the countries and the third most common malignancy worldwide. The tumor microenvironment denotes the non-cancerous cells and components present in the tumor, including the molecules they produce and release. Prostate cancer proliferation, angiogenesis, metastasis and drug resistance are closely associated with the tumor microenvironment. With the continuous development of in vitro tumor models, they have gradually become an important tool for recapitulating parental tumors in vivo and studying the reciprocal interactions between tumors and their microenvironment. In this review, we describe significant in vitro models of prostate cancer, analyze the research results on incorporating the tumor microenvironment into these models, and compare their advantages and disadvantages. Furthermore, we highlight the future developmental direction of prostate cancer in vitro model research according to the hotspots of in vitro model research in other cancer types to facilitate precision medicine in prostate cancer.
B Cells as a host of Persistent Salmonella Typhimurium
Alonso D. Cruz-Cruz
Jocelyn C. Pérez-Lara

Alonso D. Cruz-Cruz

and 4 more

August 30, 2024
Salmonella enterica serovar Typhimurium ( S. Tm) can colonize different intracellular niches, either actively dividing or remaining dormant to persist. Bacterial persisters are phenotypic variants that temporarily enter a non-replicative state. This allows them to evade host cell defenses and antibiotics, leading to chronic infections. We previously reported that during chronic periods, Salmonella remains within B cells in the bone marrow and spleen. However, the dynamics of Salmonella replication and the formation of antibiotic tolerance in infected B cells have not been studied. Here we show that B cells are a favorable reservoir for bacterial persistence. In vitro and in vivo experiments identified non-replicating, persistent Salmonella subsets in splenic B cells. These non-replicative Salmonella are tolerant to antibiotics (cefotaxime and ciprofloxacin), while replicative bacteria remain susceptible. Infected mice demonstrated viable, non-replicative Salmonella in spleen B cells, maintaining antibiotic tolerance. Although acid intravacuolar pH and SPI-2 regulators (SsrA/SsrB) are not necessary for Salmonella persistence in B cells, the SehA/B toxin-antitoxin system facilitates the formation of the persistent phenotype in Salmonella. Overall, we show that B cells are a reservoir for non-replicating, antibiotic-tolerant Salmonella.
Influence of Structural Engineering Design Software and Fees on Cost Certainty of Hig...
Simiyu Waswa
Fuchaka Waswa

Simiyu Waswa

and 1 more

August 30, 2024
In investigating the influence of structural engineering design software and fees on cost certainty of High-rise building, data was collected from 150 consulting civil engineers drawn from the Engineers Board of Kenya register using a web-based structured questionnaire survey. Descriptive and inferential statistics were used in data analysis and interpretation. Results showed that the greatest influence design software has on cost certainty of building projects is the accuracy of the pre-tender cost estimates used for procurement. Further only 9.4% of engineers used modern integrated design software because of the high purchase and licencing costs. Consequently, inaccuracies in pre-tender documents are perpetuated through limitations in modelling complex buildings, inflexibility in effecting design changes, and updating and synchronizing project documentation. Therefore incentives to discard stand-alone engineering design software in favour of integrated ones merit consideration. Although expensive, integrated software significantly reduce the risk of cost overruns. As such, they should be viewed as a necessary investment that enhances efficiency and overall quality of work. Further, whereas various approaches exist for paying the consultants, negotiations as dictated by free market systems are becoming popular, which calls for fidelity to professional ethics from contract signing and through the entire project cycle.
Diversity and abundance of the species of arboreal mammals in a tropical rainforest i...
J. Rojas-Sánchez
Rosamond Coates

J. Rojas-Sánchez

and 4 more

August 30, 2024
Habitat loss threatens biodiversity worldwide being particularly detrimental in tropical rainforest where a cumulative deforestation expands for decades. Tropical rainforests harbor a rich mammal diversity with a wide range of species using different habitats, ranging from forest-dwelling to arboreal species. Recent techniques as camera trapping have proven useful to study the ecology of arboreal mammals. Here we assessed the overall community structure of arboreal mammals in a protected area by analyzing patterns of diversity and abundance and their spatial and seasonal variations. A total of 21 camera-trapping stations were set in clusters in three zones. Spatial and seasonal alpha diversity, and community evenness patterns were estimated using Hill’s numbers, and Sørensen’s dissimilarities were used as a proxy to estimate beta diversity. A relative abundance index was calculated for each species, at each site and season. To estimate the influence of spatial and tree-morphology on arboreal use by mammals, linear regressions were performed for species richness, evenness, and abundance; logistic regression were used to test correlations with presence/absence data. We observed a high species richness (14 species) of arboreal mammals. Species richness remained similar between sites, although shifts in abundances, and a decreasing gradient in community evenness related to distance of camera trap station located in each site were observed. We observed a high and low diversity dissimilarity between camera trap stations and between sites, respectively. Seasonality showed no significant effect over abundance, alpha and beta diversities. Linear and logistic regression of arboreal use by mammals was determined by several environmental variables. This protected area holds the natural habitat conditions to ensure the persistence of this rich arboreal mammal community.
Exploring inter-brain coherence between fathers and infants during maternal storytell...
Xin Zhou
Xuancu Hong

Xin Zhou

and 2 more

August 30, 2024
The current study examined the inter-brain coherence (IBC) between 34 dyads of fathers and infants 7-9 months of age using functional near-infrared spectroscopy (fNIRS). We specifically focused on father-infant IBC to broaden the empirical base beyond the mother-infant connections, as the former has received limited attention. There were three conditions: a baseline condition, and two task conditions when the infant and the adult participant jointly listened to maternal storytelling in Cantonese in infant-directed speech (IDS) and adult-directed speech (ADS). Father-infant IBC was compared with stranger-infant IBC in the same experimental settings. Our results found that father-infant IBC was greater in the baseline and ADS conditions but not in the IDS condition, compared to stranger-infant IBC. Further, stranger-infant dyads showed greater IBC in the IDS condition than in the ADS condition, with no significance in father-infant IBC between the two speech conditions. These results identified different IBC mechanisms between the two dyads. The IBC pattern in stranger-infant dyads is driven by neural entrainment to mothers’ speech, whereas father-infant IBC is more resistant to mothers’ behaviors in the co-presence of both parents.
Flow matters: Unravelling the interactive influences of flow alterations and non-nati...
Olivia R. Hore
Jonathan Tonkin

Olivia R. Hore

and 3 more

August 30, 2024
Understanding the interactive effects of non-native species and alterations to flow regimes is important to combat threats to freshwater communities. Low-flow conditions may either exacerbate or offset influences of non-natives but the mechanisms determining the direction are poorly understood. We evaluated how stream drying affected interactions between vulnerable native non-migratory galaxiids and non-native trout in Aotearoa - New Zealand. We electrofished (December – March) paired perennial and drying reaches containing galaxiids ( Galaxias vulgaris and G. paucispondylus) to compare abundance and growth rates in streams with high abundance (n=2), low abundance (n=2) or no brown trout (n=3; Salmo trutta). Low flows greatly reduced trout abundance and size, likely reducing predatory threats to galaxiids since risk is size-related. Galaxiid densities were consistently lower in drying compared to perennial reaches of troutless streams. However, galaxiids were less affected by low flows than trout, setting the scene for an interaction between trout and low flow. In streams with high numbers of trout, galaxiid numbers were very low in perennial reaches, whereas they were moderate in drying reaches. That meant galaxiid numbers increased with decreasing flow in streams with many trout, an indirect positive effect, although their abundance never reached the high levels of trout-free perennial reaches. In low-density trout streams, there were no clear differences in galaxiid abundance between reaches of different flow type. Thus, the effects of trout on galaxiids depended on the flow regime, likely driven by harsh low-flow conditions suppressing large trout, which were more sensitive to low flow than galaxiids. Growth advantages for galaxiids possibly enhanced this interaction because galaxiids grew fastest when trout were present at low densities. Overall, although low-flow conditions likely reduced predatory effects of non-natives, populations of natives were also suppressed by low flow. Such interactive effects of flow reduction are likely common and appear controlled by relative vulnerability and size-structured interactions. Balancing maintenance of natural flows with minimising effects of non-native sports fish poses a difficult challenge, but managers should aim to both protect natural flow regimes to maintain suitable fish habitat, and actively manage non-native species in harmful situations to conserve native fish.
Living with Alveolar capillary dysplasia with misalignment of the pulmonary veins --...
Renata Cohen
Flavio Sztajnbok

Renata Cohen

and 9 more

August 30, 2024
Title: Living with Alveolar capillary dysplasia with misalignment of the pulmonary veins – case reportAuthorsRenata Wrobel Folescu CohenInstituto Fernandes Figueira IFF/FIOCRUZ Rio de Janeiro, RJ, BrazilUniversidade do Estado do Rio de Janeiro (UERJ) Rio de Janeiro, RJ, BrazilFlavio SztajnbokUniversidade Federal do Rio de Janeiro (UFRJ) Rio de Janeiro, RJ, BrazilUniversidade do Estado do Rio de Janeiro (UERJ) Rio de Janeiro, RJ, BrazilEvanice Lima de MarcaHospital Pediátrico Jutta Batista, Rede Dor Rio de Janeiro, RJ, BrazilVera Luiza CapelozziUniversidade do Estado de São Paulo, São Paulo, SP, BrazilDafne Dain Gandelman HorovitzInstituto Fernandes Figueira IFF/FIOCRUZ, Rio de Janeiro, RJ, BrazilEloa NunezHospital Pediátrico Jutta Batista, Rede Dor, Rio de Janeiro, RJ, BrazilHenrique de Campos Reis GalvãoDiagnósticos da América S.A., DASA, São Paulo, SP, Brazil.Joselito SobreiraDiagnósticos da América S.A., DASA, São Paulo, SP, Brazil.Diana Carolina Salazar BermeoDiagnósticos da América S.A., DASA, São Paulo, SP, Brazil.Tania Wrobel FolescuInstituto Fernandes Figueira IFF/FIOCRUZ, Rio de Janeiro, RJ, BrazilTo the editor,Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) is a rare and lethal disorder mainly involving the vascular development of the lungs. The clinical presentation is characterized by respiratory distress and cyanosis caused by severe pulmonary hypertension (PH) and insufficient oxygen uptake. 95% of ACD/MPV patients are born at full term with normal Apgar scores and develop symptoms within the first 24 hrs of life. In up to 80% of the cases, associated malformations are found, for which surgery is occasionally needed1. These malformations predominantly affect the gastrointestinal tract, but also may affect the cardiovascular and urogenital systems. The mortality of ACD/MPV is almost 100%1. Atypical, milder cases of ACD/MPV patients that present after 24 hrs of life or survive beyond the neonatal period have occasionally been described2. The current gold standard to unambiguously diagnose ACD/MPV is histological examination of the lungs. In most studies, cases were diagnosed postmortem by autopsy3.It is postulated that the milder phenotype of atypical ACD/MPV patients, including late presenters and long-term survivors, is correlated with the extent of affected lung tissue. A recent study showed a heterogeneous non-uniform distribution of histological findings in all atypical ACD/MPV patients4.Recently, Sen et al5 have reported genomic deletions and point mutations in the FOXF1 gene (OMIM 601089) in chromosome 16q24.1 in unrelated patients with histopathological verified ACD/MPV. So far, 42 FOXF1 variants and 24 genomic and genic deletions identified in the 16q24.1 region have been reported. All patients have died in the first 4 months of life.This case report describes a patient as a late presenter and long-term survivor of ACD/MPV with a non previously described de novo variant in FOXF1. Informed consent statement was obtained from parents. Written informed consent to participate in this study was provided by the participant legal guardian. This study was approved by the Instituto Fernandes Figueira Ethical Committee, under the ethical approval number 59963822.0.2001.5269 (chILD - RJ).CASE REPORT:Full-term female born to non-consanguineous parents. GII/PII mother was 38yo and pregnancy was uneventful; Apgar scores 9/10, phototherapy needed for 4 days due to jaundice. There was no respiratory distress, nor congenital abnormalities were detected. Pulse oximetry was 98% (upper end lower limbs), transfontanelle and doppler ultrasound were normal. Family history negative for congenital cardiac or lung disease.At nine months she presented cough and wheezing and received salbutamol and prednisolone at home. At 14mo, there was a new respiratory distress, with no response to Salbutamol, Prednisolone and antibiotics, requiring her first ICU admission: Her weight was 8.4kg; pulse oximetry:96% with oxygen therapy support. She presented increased AP diameter, intercostal retraction, reduced air flow with crackling sounds in both lungs and hepatosplenomegaly.On admission, laboratorial exams revealed: Hb:10.6g/dL; Hto:34%; RDW:18,4%; platelets:196000/mm3; WBC:2100/mm3; Reticulocytes:13,4%; Serum iron:17mcg/dL; Ferritin:24ng/ml; Transferrin:267mg/dL; HIV and mycoplasma serology were negative. Nasopharyngeal material was negative for SARASCOV2, RSV, Influenza A and B. Immunoglobulin and lymphocytes were normal for age.Echocardiogram presented situs solicitus; levocardia; concordant atrioventricular and arterial ventricle connections; intact interatrial and interventricular septa; pulmonary trunks and branches were confluent and without obstruction; pulmonary venous drainage to the right atrium; dilation of the right cavities; significant right ventricular (RV) systolic overload; mild RV systolic dysfunction, normal left ventricular function. Systolic pressure in the pulmonary artery (SPPA) was 70mmHg. Inferior vena cava with normal caliber.Thorax high resolution computed tomography (HRCT) showed extensive diffuse ground-glass opacity in both lungs (FIG1-A,B). Bronchoscopy revealed: hyperemia and moderate mucosal edema with thick and yellowish secretion in the main bronchi. The secretion collected from bronchial lavage was negative for pyogenic germs, fungi, mycobacteria, andPneumocystis jirovecci. She was discharged home using sildenafil, captopril, furosemide + hydrochlorothiazide, spironolactone and carvedilol.She progressed with worsening respiratory pattern and hypoxemia, being readmitted at 16mo. New exams showed negative viral and SARSCOV-2 panel; negative blood cultures; echocardiogram: SPPA 88-100mmHg. Salbutamol, fluticasone, sildenafil, Captopril furosemide, hydrochlorothiazide, spironolactone and carvedilol were maintained. A new HRCT scan detected ground-glass opacities affecting both lungs (FIG1-C,D), with the appearance of septal thickening and diffuse thickening of the bronchial walls.After this, she underwent a lung biopsy and the histopathological report (FIG2) showed muscular hypertrophy of the middle layer of medium and small pulmonary arteries; reduction of capillary loops in the microcirculation along the alveolar septa; ectasia and tortuosity of pulmonary veins and lymphatics; misalignment of pulmonary veins adjacent to the terminal bronchiole; discrete inflammatory infiltrate represented mainly by small lymphocytes; there were no signs of malignancy. Perls staining was positive for macrophages with hemosiderin. Electron microscopy showed abnormal lamellar bodies of varying shapes and sizes with dense inclusions inside. Heteromorphic mitochondria with cristae fusion. There was no evidence of glycogenosis or storage diseases. No ciliary abnormalities were detected.She was discharged with regular monitoring by a pediatric cardiologist and pulmonologist, and receiving sildenafil, captopril and furosemide, spironolactone, carvedilol, hydrochlorothiazide, salbutamol and fluticasone.In parallel, exome analysis was carried out. A heterozygous variant in the FOXF1 gene was identified (NM_001451.3: c.359A>T; p.(His120Leu)), classified as probably pathogenic, considering that the variant is absent on populational databases, in silico algorithms predict damaging impact of the variant on protein function, parental testing for the variant was negative and this indivudual phenotype is highly specific for the disease.Thus, the diagnosis of alveolar-capillary dysplasia with misalignment of pulmonary vessels was confirmed.During the last two years, she has been receiving the same medication, and was admitted in hospital por 3 times due to respiratory exacerbation following viral infection. She needed during admission period, oxygen supplementation, non invasive ventilation, antibiotics and systemic corticosteroids. Cardiac catheterization at 3yo showed a high pulmonary artery pressure (100mmHg) and Bosentana was started after this exam.CONCLUSIONInfants affected with ACD/MPV usually develop respiratory distress and severe pulmonary hypertension, have no sustained response to supportive treatments, and die early in life. Few patients with ACD/MPV have been reported beyond the neonatal period. One report describing two siblings shows that a patient with less severe symptoms has a patchy pattern of capillary deficiency and abnormal distal air space, which may be correlated with the late onset. All infants with pathogenic/probably pathogenic variants in the FOXF1 gene, responsible for ACD/MPV, have died in the first 4 months of life. Our case, however, shows a 3yo girl with ACD/MPV carrying a de novo variant in FOXF1, which configurates quite a long survival with ACD/MPV. This is a missense mutation, absent in population databases with predicted in silico impact in the protein function. Based in normal parental investigation and compatible pathologic study, we considered it as phenotype-causing. Further studies will be needed to clarify the phenotypic difference between the above patient and the previously reported cases. Although phenotypical differences are present, genetic testing could contribute to earlier detection and allows adequate consultation about the prognosis and the process of decision-making.
Mosaic Trisomy 16 in a Preterm Newborn with Intrauterine Growth Restriction, Hypoglyc...
Hussein Khalifeh
Lea Chokr

Hussein Khalifeh

and 3 more

August 30, 2024
Trisomy 16, responsible for 1-2% of first-trimester losses, poses diagnostic dilemmas in reproductive medicine. While total trisomy 16 is typically lethal, mosaic trisomy 16 cases exhibit diverse phenotypes, often featuring intrauterine growth retardation and cardiac anomalies. Postnatal survival with high levels of mosaic trisomy 16 is rare, with most affected pregnancies ending in spontaneous abortion between 8 and 15 weeks of gestation. However, recent data suggest that select prenatally diagnosed mosaic trisomy 16 patients manifest a mild phenotype and favorable outcomes. Confined placental mosaicism, commonly detected during Chorionic Villus Sampling, underscores the intricate nature of this condition. We present a case of mosaic trisomy 16 in a neonate with atrial tachycardia, emphasizing the complexities and treatment strategies in pediatric care. Notably, our management approach involved the novel use of Ivabradine alongside propranolol. This case highlights the imperative for ongoing research and collaborative efforts to deepen our understanding and tailor care for the diverse clinical spectrum of mosaic trisomy 16, ensuring comprehensive monitoring and support for affected individuals
A Fragmentation Study of Disaccharide Flavonoid C-Glycosides Using Triple Quadrupole...
Bin Huang
Fangjun Chen

Bin Huang

and 7 more

August 30, 2024
Rationale: Flavonoid C-glycosides have a wide range of pharmacological activities. However, there are few mass spectrometric research on C,O-disaccharide flavonoid C-glycosides and di-C,O-saccharide flavonoid C-glycosides. Their fragmentation pattern and differences have not been reported, and the fragment ion library is incomplete. Therefore, it was essential to elucidate the fragmentation patterns of disaccharide flavonoid C-glycosides, which is described in this study. Methods: Four disaccharide flavonoid C-glycosides such as vitexin-4″- O-glucoside were analyzed by ultra performance liquid chromatography-triple quadrupole tandem mass spectrometer (UPLC-MS/MS) in both positive and negative ion modes. each ion and its proposed fragmentation pathways of the four disaccharide flavonoid C-glycosides were analyzed comprehensively. Finally, Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and the established fragmentation patterns have been used to identify disaccharide flavonoid C-glycosides in Odontosoria Chinensis. Results: The fragmentation pathways of C,O-disaccharide flavonoid C-glycosides and di-C,O-saccharide flavonoid C-glycosides. are similar. they both have the mass spectrometric characteristics of O-glycoside and C-glycoside. Fragment ions after mixed pathways of neutral fragments such as saccharide ring fragment, O-glycosides, H 2O and CH 2O detraction appeared in both types of flavonoid C-glycosides, but their relative abundances are significantly different. According to the established fragmentation patterns, di-C,O-saccharide flavonoid glycosides were also found in Odontosoria Chinensis. Conclusion: The fragment ions of m/z 431, 413, 341, 311, 293, 282 in negative ion mode and m/z 293, 282, 577, 559, 541, 523, 529 and 499 in positive ion mode can serves as the main characteristics for identifying C,O-disaccharide flavonoid C-glycosides and di-C,O-saccharide flavonoid C-glycosides.
Investigating Plant Growth Promoting Properties of Trichoderma Species for Sustainabl...
Kemal Karaca
Rengin Eltem

Kemal KARACA

and 1 more

August 30, 2024
The sustainability and productivity of agriculture can be significantly enhanced through the use of Plant Growth Promoting Microorganisms (PGPM). Trichoderma species are well-known Plant Growth Promoting Fungi (PGPF) with proven capabilities in promoting plant growth, and they have been studied for many years as soil microorganisms. The utilization of Trichoderma species in sustainable agricultural systems can potentially to increase soil fertility, thereby contributing to environmentally friendly farming practices. In this study, Trichoderma strains (n=62) isolated from various soil and fungal compost samples were investigated for their PGPM properties. These properties include antagonistic effects against phytopathogens, lytic enzyme activities, siderophore and IAA production, phosphate solubilization, and potassium mobilization. Three Trichoderma isolates showing high PGPF activity were identified, and their molecular characterization was conducted. Two isolates of Trichoderma koningiopsis and one isolate of T. harzianum were identified.
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