Rediscovering the unusual, solitary bryozoan Monobryozoon ambulans Remane, 1936: first molecular and new morphological data clarify its phylogenetic position.

BACKGROUND: One of the most peculiar groups of the mostly colonial phylum Bryozoa is the taxon Monobryozoon, whose name already implies non-colonial members of the phylum. Its peculiarity and highly unusual lifestyle as a meiobenthic clade living on sand grains has fascinated many biologists. In particular its systematic relationship to other bryozoans remains a mystery. Despite numerous searches for M. ambulans in its type locality Helgoland, a locality with a long-lasting marine station and tradition of numerous courses and workshops, it has never been reencountered until today. Here we report the first observations of this almost mythical species, Monobryozoon ambulans. RESULTS: For the first time since 1938, we present new modern, morphological analyses of this species as well as the first ever molecular data. Our detailed morphological analysis confirms most previous descriptions, but also ascertains the presence of special ambulatory polymorphic zooids. We consider these as bud anlagen that ultimately consecutively separate from the animal rendering it pseudo-colonial. The remaining morphological data show strong ties to alcyonidioidean ctenostome bryozoans. Our morphological data is in accordance with the phylogenomic analysis, which clusters it with species of Alcyonidium as a sister group to multiporate ctenostomes. Divergence time estimation and ancestral state reconstruction recover the solitary state of M. ambulans as a derived character that probably evolved in the Late Cretaceous. In this study, we also provide the entire mitogenome of M. ambulans, which-despite the momentary lack of comparable data-provides important data of a unique and rare species for comparative aspects in the future. CONCLUSIONS: We were able to provide first sequence data and modern morphological data for the unique bryozoan, M. ambulans, which are both supporting an alcyonidioidean relationship within ctenostome bryozoans.

Alcyonidium kuklinskii sp. nov., a new species of Antarctic ctenostome bryozoan with a key to all Antarctic species of the genus.

Recent surveys of Antarctic waters in the Terra Nova Bay (Ross Sea) revealed numerous bryozoan species including ctenostome bryozoans. Whereas cheilostome bryozoans are well-studied in these latitudes, ctenostomes remain highly neglected. Large ctenostomes are easily recognized by their lack of calcified skeletons, but this lack also renders them difficult and tedious to identify. As a result, histology and reconstructions of internal soft tissues are required to classify this group of bryozoans. Thanks to the availability of new specimens from Terra Nova Bay, a detailed analysis of growth form, gut morphology and tentacle number of two colonies, initially ascribed to the ctenostome bryozoan genus Alcyonidum Lamouroux, 1813, turned out to be a new species, Alcyonidium kuklinskii sp. nov., which we described in this study. These specimens were also barcoded (COI) and sequences compared to available ones. Together with the new species described here, a total of ten species of Alcyonidium is now known for the Southern Ocean, accounting for one eighth of the entire genus diversity. All Southern Ocean species appear to be endemic. In order to speed the identification of the Antarctic Alcyonidium species, we provide an identification key and a distribution map of all type species. In brief, colony morphology, zooidal size and, in particular tentacle number represent the most suitable characters for identifying species within this genus. Supplementary Information: The online version contains supplementary material available at 10.1007/s13127-023-00629-4.

Digging into boring bryozoans: new characters and new species of Immergentiidae.

Immergentia is an endolithic genus of ctenostome bryozoans and the sole member of the Immergentiidae. Etchings of their typical spindled-shaped and sometimes enantiomorphic borehole aperture in calcium carbonate substrates are accomplished by chemical dissolution. The tentacle crown of the bryozoan is essentially the only body part that extends beyond the shell surface when protruded. Previously, species were mainly described using external colony and zooidal characteristics or whole mounts, with partial histological sections conducted on a single species in 1947. Modern approaches, however, are hitherto missing. We examined the soft body morphology of Immergentia from different locations with confocal laser scanning microscopy and the production of 3D reconstructions. In addition, zooidal characteristics such as tentacle number, size, tubulets, and interzooidal distances were used to distinguish and describe species. The combination of conventional and modern methods revealed the presence of a cardiac constrictor and intercalary kenozooids that can interpose between the cystid appendages, something not previously reported in immergentiids, thus necessitating an amendment of the family diagnosis. The polypide typically has eight to ten tentacles, and the anus is positioned in the low or mid-lophophoral area. In addition, sequence data, including the mitogenome and the nuclear ribosomal genes (18S and 28S) of four species from five locations, are presented for the first time. Based on molecular and morphological data, a novel intertidal immergentiid from France, Immergentia stephanieae sp. nov., and a subtidal species from New Zealand, I. pohowskii sp. nov., are described. This work supplements the rather sparse existing knowledge on Immergentiidae and proposes additional characteristics to complement existing descriptions in order to enhance future species identification. Supplementary Information: The online version contains supplementary material available at 10.1007/s13127-024-00645-y.

Genomic and transcriptomic survey of bryozoan Hox and ParaHox genes with emphasis on phylactolaemate bryozoans.

BACKGROUND: Bryozoans are mostly sessile aquatic colonial invertebrates belonging to the clade Lophotrochozoa, which unites many protostome bilaterian phyla such as molluscs, annelids and brachiopods. While Hox and ParaHox genes have been extensively studied in various lophotrochozoan lineages, investigations on Hox and ParaHox gene complements in bryozoans are scarce. RESULTS: Herein, we present the most comprehensive survey of Hox and ParaHox gene complements in bryozoans using four genomes and 35 transcriptomes representing all bryozoan clades: Cheilostomata, Ctenostomata, Cyclostomata and Phylactolaemata. Using similarity searches, phylogenetic analyses and detailed manual curation, we have identified five Hox genes in bryozoans (pb, Dfd, Lox5, Lox4 and Post2) and one ParaHox gene (Cdx). Interestingly, we observed lineage-specific duplication of certain Hox and ParaHox genes (Dfd, Lox5 and Cdx) in some bryozoan lineages. CONCLUSIONS: The bryozoan Hox cluster does not retain the ancestral lophotrochozoan condition but appears relatively simple (includes only five genes) and broken into two genomic regions, characterized by the loss and duplication of serval genes. Importantly, bryozoans share the lack of two Hox genes (Post1 and Scr) with their proposed sister-taxon, Phoronida, which suggests that those genes were missing in the most common ancestor of bryozoans and phoronids.

Dedifferentiated Chondrosarcoma: Diagnostic Controversies and Emerging Therapeutic Targets.

PURPOSE OF REVIEW: The pathogenesis of dedifferentiated chondrosarcoma is controversial, and no genetic abnormality has consistently been identified in the disease. Focusing on the diagnostic challenges encountered in dedifferentiated chondrosarcoma, the following review aims at summarizing the tumor's active neoplastic pathways while highlighting therapeutic modalities that could potentially be explored to enhance patient survivorship. RECENT FINDINGS: Owing to the challenging examination of small needle biopsy sampling as well as the disease's overlapping morphological and immunohistochemical features with other bone and soft-tissue sarcomas, the diagnosis of dedifferentiated chondrosarcoma can be problematic. While combined doxorubicin- and cisplatin-based regimens remain the first-line systemic chemotherapy in the disease, ~50% of tumors carry EXT1/2 or IDH1/2 mutations, advancing EXT or IDH inhibitors as potential alternative therapies, respectively. Despite systemic chemotherapy, dedifferentiated chondrosarcoma remains an aggressive tumor with dismal prognosis and limited survival. A multidisciplinary collaboration across multiple cancer centers is warranted to yield an accurate diagnosis, understand the disease's underlying pathogenesis, develop adequate treatment, and improve patient survivorship.

Manganese-cobalt oxide as an effective bifunctional cathode for rechargeable Zn-air batteries with a compact quad-cell battery design.

Metal-air batteries, which are economical and ecological alternatives to Li-ion batteries, have become an important energy storage system. In this study, bimetallic oxides of widely accepted transition metal oxides like MnCo2O4 and NiFe2O4 have been explored to fabricate an efficient rechargeable Zn-air battery. The synthesis of these materials involves a single step direct decomposition of constituent metallic salts using polyvinyl pyrrolidone as a stabilizer cum nanostructure growth modifier by a simple open-air spray pyrolysis. The well characterized materials are used as cathodes in the assembly of a Zn-air battery that delivers a decent specific capacity of 780.1 mA h g-1. It also offers long term charge-discharge for more than 900 cycles with a week-long break-free operational stability under a small voltage gap (0.65-0.73 V). Finally, a unique and compact quad-cell solid state battery design has been introduced using these cathodes and chemically modified anodes resembling the commercial lithium-ion mobile phone battery. This tiny portable Zn-air battery displays an open circuit potential (OCP) of 4.46 V.

Deep Brain Stimulation for Chronic Cluster Headaches: A Systematic Review and Meta-Analysis.

BACKGROUND: Chronic cluster headache (CCH) is a severe and debilitating sub-type of trigeminal autonomic cephalalgia that can be resistant to medical management and associated with significant impairment in quality of life. Studies of deep brain stimulation (DBS) for CCH have provided promising results but have not been assessed in a comprehensive systematic review/meta-analysis. OBJECTIVE: The objective was to perform a systematic literature review and meta-analysis of patients with CCH treated with DBS to provide insight on safety and efficacy. METHODS: A systematic review and meta-analysis were performed according to PRISMA 2020 guidelines. 16 studies were included in final analysis. A random-effects model was used to meta-analyze data. RESULTS: Sixteen studies reported 108 cases for data extraction and analysis. DBS was feasible in >99% of cases and was performed either awake or asleep. Meta-analysis revealed that the mean difference in headache attack frequency and headache intensity after DBS were statistically significant (p < 0.0001). Utilization of microelectrode recording was associated with statistically significant improvement in headache intensity postoperatively (p = 0.006). The average overall follow-up period was 45.4 months and ranged from 1 to 144 months. Death occurred in <1%. The rate of major complications was 16.67%. CONCLUSIONS: DBS for CCHs is a feasible surgical technique with a reasonable safety profile that can be successfully performed either awake or asleep. In carefully selected patients, approximately 70% of patients achieve excellent control of their headaches.

Green Synthesis of Silver Nanoparticles Using Jacobaea maritima and the Evaluation of Their Antibacterial and Anticancer Activities.

Much attention has been gained on green silver nanoparticles (green-AgNPs) in the medical field due to their remarkable effects against multi-drug resistant (MDR) microorganisms and targeted cancer treatment. In the current study, we demonstrated a simple and environment-friendly (i.e., green) AgNP synthesis utilizing Jacobaea maritima aqueous leaf extract. This leaf is well-known for its medicinal properties and acts as a reducing and stabilizing agent. Nanoparticle preparation with the desired size and shape was controlled by distinct parameters; for instance, temperature, extract concentration of salt, and pH. The characterization of biosynthesized AgNPs was performed by the UV-spectroscopy technique, dynamic light scattering, scanning electron microscopy, X-ray diffraction, and Fourier-transform infrared. The successful formation of AgNPs was confirmed by a surface plasmon resonance at 422 nm using UV-visible spectroscopy and color change observation with a particle size of 37± 10 nm and a zeta potential of -10.9 ± 2.3 mV. SEM further confirmed the spherical size and shape of AgNPs with a size varying from 28 to 52 nm. Antibacterial activity of the AgNPs was confirmed against all Gram-negative and Gram-positive bacterial reference and MDR strains that were used in different inhibitory rates, and the highest effect was on the E-coli reference strain (MIC = 25 µg/mL). The anticancer study of AgNPs exhibited an IC50 of 1.37 µg/mL and 1.98 µg/mL against MCF-7 (breast cancer cells) and A549 (lung cancer cells), respectively. Therefore, this green synthesis of AgNPs could have a potential clinical application, and further in vivo study is required to assess their safety and efficacy.

Non-operative management of pilonidal sinus disease; classification and outcome.

The characteristics of the pilonidal sinus that are associated with recurrence have scarcely been investigated in the literature. This study aims to evaluate the outcomes of patients with sacrococcygeal pilonidal sinus disease who were managed by a non-operative technique using Salih's preparation. This study also tries to classify the patients according to the features that determine the outcome of the intervention. This is a single-group cohort study that enrolled consecutive patients that had pilonidal sinus. All the patients were managed using Salih's preparation. The patients were seen at the clinic 6 weeks after the intervention to record data of recurrence. The Statistical Package for the Social Sciences (SPSS) Version 25 was used for coding and analysing the data. Test of significance and odds ratio were calculated for all of the features. The total number of patients receiving Salih's preparation was 12 123 cases, of which only 3529 patients were included in this study. The mean age of the participants was 26.95 years, ranging from 14 to 55 years. The most significant factor related to the recurrence was the presence of an abscess. After summation of all odd ratios, the percentage of each one from the total was calculated, and accordingly, the patients were divided into three classes. Non-operative methods using a preparation with antimicrobial and sclerosing properties can be an alternative for surgical intervention with a lower risk of recurrence. Classification of patients based on specific criteria can give clinicians and even patients themselves a vision of the chance of recurrence and treatment success.

Prescription patterns of quetiapine for multiple drug abuse, depression, and psychosis: A retrospective study.

Background: Quetiapine is an atypical antipsychotic prescribed for schizophrenia, bipolar disorder, multiple drug abuse (MDA), generalized anxiety disorder, severe depression, dementia, and mood disorders. Prescription of quetiapine varies according to use, with side effects increasingly reported with higher doses. Many previous case reports highlighted the misuse of the drug. Here we studied the prescribing patterns of quetiapine in multiple drug abuse (MDA), depression, and psychosis patients in the Madinah region in Saudi Arabia. Methods: This is a retrospective single-center study carried out in the main referral hospital for mental health in Madinah, Saudi Arabia for the period December 2020 till December 2021. Results: A total of 158 patients were included in this study. The mean age of the patients was 30.5 ± 10.1 years. Male presented for 89.9 % of the patients. In terms of quetiapine indications, 46.2 % of patients used it for MDA, 29.7 % for psychosis, and 24.1 for depression. For all patients, quetiapine was used with a mean daily dose of 285.2 ± 222 mg and for a mean duration of 13.9 ± 15.4 weeks. Quetiapine was prescribed with a mean of 2.1 ± 2.2 prescriptions. Comparison between different indications shows that quetiapine was more frequently prescribed for MDA (p < 0.001). The MDA patients were significantly younger than in other groups (p = 0.001). All patients who received quetiapine for MDA were males. However, MDA patients received a smaller dose of quetiapine than other indications (p < 0.001). There were no significant differences between groups in terms of the number of prescriptions, duration, and whether the patient was on other medications or not. These results have been confirmed by regression analysis, where male and younger ages represented a significant contributing factor to MDA compared to psychosis, 95 % CI: 8 x107 (8 x107 - 8 x107) and 0.943 (0.900---0.987), respectively. Conclusion: Quetiapine was prescribed more frequently in MDA patients and younger individuals. Low dose was predominant in those patients, indicating a probability of drug abuse.

GL67 lipid-based liposomal formulation for efficient siRNA delivery into human lung cancer cells.

The efficient delivery of small interfering RNA (siRNA) to the targeted cells significantly affects the regulation of the overexpressed proteins involved in the progression of several genetic diseases. SiRNA molecules in naked form suffer from low internalization across the cell membrane, high susceptibility to degradation by nuclease enzyme and low stability, which hinder their efficacy. Therefore, there is an urge to develop a delivery system that can protect siRNA from degradation and facilitate their uptake across the cell membrane. In this study, the cationic lipid (GL67) was exploited, in addition to DC-Chol and DOPE lipids, to design an efficient liposomal nanocarrier for siRNA delivery. The physiochemical characterizations demonstrated that the molar ratio of 3:1 has proper particle size measurements from 144 nm to 332 nm and zeta potential of -9 mV to 47 mV that depends on the ratio of the GL67 in the liposomal formulation. Gel retardation assay exhibited that increasing the percentage of GL67 in the formulations has a good impact on the encapsulation efficiency compared to DC-Chol. The optimal formulations of the 3:1 M ratio also showed high metabolic activity against A549 cells following a 24 h cell exposure. Flow cytometry findings showed that the highest GL67 lipid ratio (100 % GL67 and 0 % DC-Chol) had the highest percentage of cellular uptake. The lipoplex nanocarriers based on GL67 lipid could potentially influence treating genetic diseases owing to the high internalization efficiency and safety profile.

Phylogenomics reveals deep relationships and diversification within phylactolaemate bryozoans.

Bryozoans are mostly sessile colonial invertebrates that inhabit all kinds of aquatic ecosystems. Extant bryozoan species fall into two clades with one of them, Phylactolaemata, being the only exclusively freshwater clade. Phylogenetic relationships within the class Phylactolaemata have long been controversial owing to their limited distinguishable characteristics that reflect evolutionary relationships. Here, we present the first phylogenomic analysis of Phylactolaemata using transcriptomic data combined with dense taxon sampling of six families to better resolve the interrelationships and to estimate divergence time. Using maximum-likelihood and Bayesian inference approaches, we recovered a robust phylogeny for Phylactolaemata in which the interfamilial relationships are fully resolved. We show Stephanellidae is the sister taxon of all other phylactolaemates and confirm that Lophopodidae represents the second offshoot within the phylactolaemate tree. Plumatella fruticosa clearly falls outside Plumatellidae as previous investigations have suggested, and instead clusters with Pectinatellidae and Cristatellidae as the sister taxon of Fredericellidae. Our results demonstrate that cryptic speciation is very likely in F. sultana and in two species of Plumatella (P. repens and P. casmiana). Divergence time estimates show that Phylactolaemata appeared at the end of the Ediacaran and started to diverge in the Silurian, although confidence intervals were large for most nodes. The radiation of most extant phylactolaemate families occurred mainly in the Palaeogene and Neogene highlighting post-extinction diversification.

SNP-PCR genotyping links alterations in the GABAA receptor (GABRG3: rs208129) and RELN (rs73670) genes to autism spectrum disorder among peadiatric Iraqi Arabs.

INTRODUCTION: Autism spectrum disorder (ASD) is an increasing concern among the Iraqi Arab population. The genetic alterations that cause ASD are likely to converge at the synapse. This study investigated polymorphisms in the GABAA receptor subunit (GABRG3) and the RELN gene as putative biomarkers of ASD in a pediatric population in Iraq. METHODS: The case control study included 60 patients with a clinical diagnosis of ASD (mild, moderate, or severe) according to DSM-IV criteria and matched healthy controls (n = 60). Blood samples were collected for DNA genotyping of SNPs rs736707 and rs208129 for RELN and GABRG3 using allele specific PCR. Assessment of genotype and allele distributions in patient groups used odd ratios (OR) with 95% confidence intervals and the Chi-square test. All statistical analysis was performed used SPSS software. RESULT: The patient cohort was highly consanguineous, with increased ratio (p > 0.05) of males to females (3:1) in both ASD (mean age, 6.66 ± 3.05) and controls (mean age, 5.76 ± 2.3). Both GABRG3 rs208129 genotypes TT (OR 4.33, p = 0.0015) and TA (OR 0.259, P = 0.008), and the T and A alleles were significantly associated with ASD. The RELN rs736707 TC genotype (OR 2.626, P = 0.034) was the only significant association with ASD. CONCLUSION: GABRG3 SNP rs208129 is a leading biomarker to predict genetic vulnerability to ASD in Iraqi Arabs. Expanded SNP panels and increased sample sizes are required for future GABRG3 studies, and to reach a consensus on RELN utility. Future ASD screening programs in Iraq should include genetic metrics in addition to clinical phenotype assessments.

The Spectrum of Malignant Neoplasms among Liver Transplant Recipients: Sociodemographic Factors, Mortality, and Hospital Burden.

Objective: To determine the nationwide prevalence of malignant neoplasms (excluding hepatocellular carcinoma-HCC) in hospitalized liver transplant recipients and to study the hospital utilization, and mortality to the incidence of malignancies. To the best of our knowledge, few epidemiological studies addressed outcomes in post-liver transplant patients, such as the annual number of hospitalizations, mortality, patient characteristics regarding malignancies. Methods: NIS database was queried between 2016 and 2018 to retrieve records of patients admitted with a principal or secondary diagnosis of liver transplant following the International Classification of Diseases, tenth Revision (ICD-10). The population was divided into case and control groups according to the presence and absence of malignant neoplasm (MN) except for HCC. We also compared the incidence of MN in LTX patients and non-LTX matched cohort. Results: A total of 7.28% admissions were associated with malignant neoplasms (except HCC) in LTX patients. Lymphomas, respiratory, gastrointestinal (excluding HCC), leukemia, and head/neck were commonest cancers with estimated admission rates of 0.97%, 0.90%, 0.80%, 0.53%, and 0.49%, respectively. Lung cancer was the most frequent malignant neoplasm among White and Black racial/ethnic groups (15.78% and 14.8%), whereas lymphoma was pervasive among Hispanics (20.3%). Lung cancer had the highest in-hospital mortality (10.55%), followed by the cancer of the nervous system (9.09%). The LTX and non-LTX cohort comparison showed that LTX patients are at increased risk of head and neck cancers, skin cancers, lymphomas, tumors, and Myelodysplastic syndrome. According to a multivariate analysis, a statistically significant association existed between malignant neoplasms in LTX patients and the following factors: increasing age (P < .001), higher mortality (P < .001), females with 29% lesser odds than males (P < .001), Black race and Hispanic ethnicity with 20% and 26% lesser odds as compared to White (P < .05). Clinical factors included smoking, Alcoholic cirrhosis, Hepatitis B, and Hepatitis C, were statistically significant risk factors of post-liver transplantation malignancies. Conclusions: Malignancies were frequent among elderly patients and predominantly in males. Lymphoproliferative diseases were the most prevalent malignancy types, followed by respiratory/lung cancer- which showed the highest mortality risk of all cancers. LTX patients are at increased risk of head and neck cancers, skin cancers, lymphoma, tumors, and Myelodysplastic syndrome compared to non-LTX patients.

Traumatic low lumbar fractures: How often MRI changes the fracture classification or clinical decision-making compared to CT alone?

PURPOSE: To determine the impact of magnetic resonance imaging (MRI) on fracture classification for low lumbar fractures (LLFs) compared to CT alone. METHODS: This study was a retrospective review of 41 consecutive patients with LLFs who underwent CT and MRI within 10 days of injury. Three reviewers classified all fractures according to AOSpine Classification and the Thoracolumbar Injury Classification (TLISS). Posterior ligamentous complex (PLC) injury in MRI was defined by black stripe discontinuity and in CT by the presence of: vertebral body translation, facet joint malalignment, horizontal laminar or spinous process fracture, and interspinous widening. The proportion of patients with AO type A/B/C and with TLISS < 5 and ≥ 5 was compared between CT and MRI. We examined the overall accuracy and individual CT findings for PLC injury. RESULTS: AO classification using CT was: AO type A in 26 patients (61%), type B in 7 patients (17%), and type C in 8 patients (22%). Seventeen patients (41%) had a TLISS ≥ 5 while 24 (59%) had TLISS < 5. The addition of MRI after CT changed the AO classification in only 2 patients (4.9%, 95% CI (0.6-16.5%) due to upgrade of type A to type B or vice versa, but did not change TLISS from < 5 to ≥ 5 [p< 0.0001; 95% CI (0.59, 0.77)]. CONCLUSIONS: CT was highly accurate (95%) for diagnosis of PLC injury in LLFs. Addition of MRI after CT did not change the AO classification or TLISS, compared to CT alone, thus suggesting limited additional value of MRI for PLC assessment or fracture classification.

No-slip billiards with particles of variable mass distribution.

Astute variations in the geometry of mathematical billiard tables have been and continue to be a source of understanding their wide range of dynamical behaviors, from regular to chaotic. Viewing standard specular billiards in the broader setting of no-slip (or rough) collisions, we show that an equally rich spectrum of dynamics can be called forth by varying the mass distribution of the colliding particle. We look at three two-parameter families of billiards varying both the geometry of the table and the particle, including as special cases examples of standard billiards demonstrating dynamics from integrable to chaotic, and show that markedly divergent dynamics may arise by changing only the mass distribution. Furthermore, for certain parameters, billiards emerge, which display unusual dynamics, including examples of full measure periodic billiards, conjectured to be nonexistent for the standard billiards in Euclidean domains.

Putative Biosynthesis of Talarodioxadione & Talarooxime from Talaromyces stipitatus.

Polyesters containing 2,4-dihydroxy-6-(2-hydroxypropyl)benzoate and 3-hydroxybutyrate moieties have been isolated from many fungal species. Talaromyces stipitatus was previously reported to produce a similar polyester, talapolyester G. The complete genome sequence and the development of bioinformatics tools have enabled the discovery of the biosynthetic potential of this microorganism. Here, a putative biosynthetic gene cluster (BGC) of the polyesters encoding a highly reducing polyketide synthase (HR-PKS) and nonreducing polyketide synthase (NR-PKS), a cytochrome P450 and a regulator, was identified. Although talapolyester G does not require an oxidative step for its biosynthesis, further investigation into the secondary metabolite production of T. stipitatus resulted in isolating two new metabolites called talarodioxadione and talarooxime, in addition to three known compounds, namely 6-hydroxymellein, 15G256α and transtorine that have never been reported from this organism. Interestingly, the biosynthesis of the cyclic polyester 15G256α requires hydroxylation of an inactive methyl group and thus could be a product of the identified gene cluster. The two compounds, talarooxime and transtorine, are probably the catabolic metabolites of tryptophan through the kynurenine pathway. Tryptophan metabolism exists in almost all organisms and has been of interest to many researchers. The biosynthesis of the new oxime is proposed to involve two subsequent N-hydroxylation of 2-aminoacetophenone.

CT Perfusion collateral index in assessment of collaterals in acute ischemic stroke with delayed presentation: Comparison to single phase CTA.

BACKGROUND & PURPOSE: Perfusion collateral index (PCI) has been recently defined as a promising measure of collateral status. We sought to compare collateral status assessed via CT-PCI in comparison to single-phase CTA and their relationship to outcome measures including final infarction volume, final recanalization status and functional outcome in ELVO patients. METHODS: ELVO patients with anterior circulation large vessel occlusion who had baseline CTA and CT perfusion and underwent endovascular treatment were included. Collateral status was assessed on CTA. PCI from CT perfusion was calculated in each patient and an optimal threshold to separate good vs insufficient collaterals was identified using DSA as reference. The collateral status determined by CTA and PCI were assessed against 3 measured outcomes: 1) final infarction volume; 2) final recanalization status defined by TICI scores; 3) functional outcome measured by 90-day mRS. RESULTS: A total of 53 patients met inclusion criteria. Excellent recanalization defined by TICI ≥2C was achieved in 36 (68%) patients and 23 patients (43%) had good functional outcome (mRS ≤2). While having good collaterals on both CTA and CTP-PCI was associated with significantly (p<0.05) smaller final infarction volume, only good collaterals status determined by CTP-PCI was associated with achieving excellent recanalization (p = 0.001) and good functional outcome (p = 0.003). CONCLUSION: CTP-based PCI outperforms CTA collateral scores in determination of excellent recanalization and good functional outcome and may be a promising imaging marker of collateral status in patients with delayed presentation of AIS.

Recent advances in mitochondrial diseases: From molecular insights to therapeutic perspectives.

Mitochondria are double-membraned cytoplasmic organelles that are responsible for the production of energy in eukaryotic cells. The process is completed through oxidative phosphorylation (OXPHOS) by the respiratory chain (RC) in mitochondria. Thousands of mitochondria may be present in each cell, depending on the function of that cell. Primary mitochondria disorder (PMD) is a clinically heterogeneous disease associated with germline mutations in mitochondrial DNA (mtDNA) and/or nuclear DNA (nDNA) genes, and impairs mitochondrial structure and function. Mitochondrial dysfunction can be detected in early childhood and may be severe, progressive and often multi-systemic, involving a wide range of organs. Understanding epigenetic factors and pathways mutations can help pave the way for developing an effective cure. However, the lack of information about the disease (including age of onset, symptoms, clinical phenotype, morbidity and mortality), the limits of current preclinical models and the wide range of phenotypic presentations hamper the development of effective medicines. Although new therapeutic approaches have been introduced with encouraging preclinical and clinical outcomes, there is no definitive cure for PMD. This review highlights recent advances, particularly in children, in terms of etiology, pathophysiology, clinical diagnosis, molecular pathways and epigenetic alterations. Current therapeutic approaches, future advances and proposed new therapeutic plans will also be discussed.

A fusion of data science and feed-forward neural network-based modelling of COVID-19 outbreak forecasting in IRAQ.

BACKGROUND: Iraq is among the countries affected by the COVID-19 pandemic. As of 2 August 2020, 129,151 COVID-19 cases were confirmed, including 91,949 recovered cases and 4,867 deaths. After the announcement of lockdown in early April 2020, situation in Iraq was getting steady until late May 2020, when daily COVID-19 infections have raised suddenly due to gradual easing of lockdown restrictions. In this context, it is important to develop a forecasting model to evaluate the COVID-19 outbreak in Iraq and so to guide future health policy. METHODS: COVID-19 lag data were made available by the University of Anbar through their online analytical platform (https://www.uoanbar.edu.iq/covid/), engaged with the day-to-day figures form the Iraqi health authorities. 154 days of patient data were provided covering the period from 2 March 2020 to 2 August 2020. An ensemble of feed-forward neural networks has been adopted to forecast COVID-19 outbreak in Iraq. Also, this study highlights some key questions about this pandemic using data analytics. RESULTS: Forecasting were achieved with accuracy of 87.6% for daily infections, 82.4% for daily recovered cases, and 84.3% for daily deaths. It is anticipated that COVID-19 infections in Iraq will reach about 308,996 cases by the end of September 2020, including 228,551 to recover and 9,477 deaths. CONCLUSION: The applications of artificial neural networks supported by advanced data analytics represent a promising solution through which to realise intelligent solutions, enabling the space of analytical operations to drive a national health policy to contain COVID-19 pandemic.