Biogeographical partitioning of ecological communities has been renewed in recent decades to illustrate broad distributional patterns. In the oceans, observational datasets have grown substantially and open new access to test bioregional patterns beyond the classical fixed thresholds of endemism to differentiate regions. This work combines a recently collated dataset of 29 different scientific bottom trawl surveys spanning 21 years with network-based clustering to illustrate biogeographical partitions of vast tracts of the northern hemisphere’s continental shelf seas. Our work contributes to testing bioregionalization patterns in demersal fishes using observational data, totaling >2.5 million species records and >2000 species, with bipartite network clustering weighted by species occurrence frequencies. We propose eight major bioregions across shelf seas which fall along the longest geographical axis in each shelf region and against continua of species richness gradients, endemicity, and phylogenetic turnover rates. These patterns capture known biogeographical boundaries (e.g., North Sea–Baltic Sea, Cape Hatteras) alongside potential transition areas deduced from uncertainty estimates based on shared network nodes between bioregions. The most species-rich areas include the Southeast US Shelf, Temperate Pacific, Northeast Atlantic Shelf, and the Outer European Shelf— corresponding to relatively high endemicity. However, the relatively species-poor partitions including the Baltic Sea and the North & Celtic Seas display comparatively low endemicity (<8%), illustrating apparent statistical differences in partitions captured by bipartite networks and occurrence frequencies that would otherwise be missed using a fixed endemic criterion. Our proposed bioregionalization can be compared against the growing availability of species occurrence data, dispersal limitations, or other quantitative observations of ecological communities.

Algorithm for the management of Primary Diffuse Chronic RhinosinusitisW.J. Fokkens1, , E. de Corso2 , P.W.Hellings3,4, R. J. Harvey5,6, C. Hopkins7, S. Reitsma11 Amsterdam UMC, University of Amsterdam, Department of Otorhinolarynogology, Amsterdam2. Unit of Otorhinolaryngology and Head-Neck Surgery, ”A. Gemelli” University Hospital Foundation IRCCS, 00168 Rome, Italy.3. University of Leuven, Department of Otorhinolaryngology, Leuven,4.The European Forum for Research and Education in Allergy and Airway Diseases Scientific Expert Team Members, Brussels, Belgium.5. Rhinology and Skull Base Research Group, St Vincent’s Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.6. Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.7. King’s College London, London, UK.

Valproate-containing medicines (VPA) are first-line treatment for epilepsy; however, they pose teratogenic risks, restricting their use in women of childbearing age. We aimed to estimate the secular trends in use of VPA and alternative treatments in young women, and to characterise dose/strength, treatment duration and indication in new VPA users We conducted a population-based cohort study using primary care records from the Netherlands, Spain and the UK, primary and outpatient specialist care records from Germany and Belgium (and hospital records from Finland, all mapped to the OMOP Common data model. All women present in the databases aged ≥12 years and ≤55 years on 1st of January of each year in the period 2010-2022 (or latest available), with at least 365 days of prior observation were included. Incidence and prevalence of VPA use in young women decreased between 2010 and 2021, while prevalence of the alternative treatments pregabalin and gabapentin increased, especially in CPRD (it rises from 0.5% to 1.5%). Median age of new VPA users ranged between 40-43 years. Anxiety and depressive disorder were frequent comorbidities, and use of hormonal contraceptives low. Average treatment duration varied substantially across databases . Incidence and prevalence of use of VPA among young women declined since 2015. Conversely, alternative antiepileptics have increased in uptake, particularly gabapentinoids. The use of standardized federated analytics allowed for a rapid assessment of VPA utilisation, supporting the regulatory agencies in their decision making and improving patient safety across Europe.

We study in this article the blow-up of solutions to a coupled semilinear wave equations which are characterized by linear damping terms in the scale-invariant regime, time-derivative nonlinearities, mass and Tricomi terms. The latter are specifically of great interest from both physical and mathematical points of view since they allow the speeds of propagation to be time-dependent ones. However, we assume in this work that both waves are propagating with the same speeds. Employing this fact together with other hypotheses on the aforementioned parameters (mass and damping coefficients), we obtain a new blow-up region for the system under consideration, and we show a lifespan estimate of the maximal existence time.

With the global biodiversity loss, it is crucial to protect the threatened species. While endemic species not only are important components of regional biodiversity, also the ecological niche of one has significant implication for ecosystem. The low genetic diversity of the endemic species is highly vulnerable to extinction. However, conservation of threatened or endemic species is relatively weak. It is urgent to formulate appropriate protection strategies. In this paper, based on chloroplast DNA sequencing, the 3,133 base pairs (bp) of combining 5 chloroplast genes (ycf13125-ycf14381, ycf11205-ycf12402, psbA-trnH, trnD-psbM and trnL-trnF) were analyzed from 6 populations of M. adenophora, a vulnerable and endemic tree growing in forests or at forest edges in China, detecting only 5 haplotypes with 4 polymorphic sites (0.13%). The total haplotype diversity (Hd) and nucleotide diversity (π) was 0.234 and 0.0001, respectively. It is shown that the extremely low genetic diversity in the species and thus 49 individuals shared common haplotype H1. The results of haplotype network, haplotype geographical distribution analysis and neutrality tests supported that populations had experienced recent expansion. The low genetic diversity values found in the present study raise considerable concern about the conservation status of M. adenophora and highlight the need to further protect genetic diversity to strengthen their resilience against further decline.

A document by Ilir Sharka. Click on the document to view its contents.

Introduction BK polyomavirus-associated nephropathy (BKPyVAN) is a well-known complication of kidney transplantation (KTx).The mainstay of prevention is reduction of immunosuppression upon detection of BK polyomavirus (BKPyV) viremia, which precedes BKPyVAN. However, this reduction may inadvertently increase the risk of alloimmunity particularly in patients with a high BKPyV load, where significant immunosuppression reduction is often necessary. This single-center, retrospective cohort study assesses the risk of de novo donor-specific antibodies (dnDSA) development and biopsy-proven acute rejection (BPAR) following high and low BKPyV viremia. Methods All patients who underwent KTx at Leiden University Medical Center between 2011 and 2020 were included. Patients were grouped according to high (maximum BKPyV serum load >10E4 copies/ml), low (maximum serum BKPyV load <10E4 copies/ml) and absent BKPyV viremia, and analyzed for the development of dnDSA and BPAR, using Cox regression. Results Of 1076 KTx recipients included, 108(10%) developed a BKPyV viremia with a maximum serum load below 10E4 copies/ml, whereas 121(11.2%) developed a BKPyV viremia exceeding 10E4 copies/ml. The risk of dnDSA development was higher in patients with a high BKPyV viremia, compared to patients without viremia (adjusted Hazard Ratio of 1.9(95% CI1.1-3.2, p=0.017). No significant difference in dnDSA risk was observed between patients with low and absent BKPyV viremia. Risk of BPAR did not differ between groups. Conclusion Our study shows that higher BKPyV loads in KTx patients are associated with a higher risk for dnDSA development, highlighting the importance of exploring additional strategies for the prevention and treatment of BKPyV infections in KTx recipients.

Key Clinical Message :Endometriosis, though typically a pelvic disease, can rarely present with small bowel obstruction due to involvement of the terminal ileum. Awareness of this possibility can aid in accurate diagnosis with appropriate imaging modalities and surgical management, potentially avoiding extensive resections.

Mining High-Utility Itemsets (HUIs) stands as a pivotal task in database analysis, like customer transactions, to identify itemsets of high importance. Despite the development of several traditional algorithms over the years for this purpose, they often produce an excessive number of High Utility Itemsets (HUIs). Unfortunately, many of these HUIs lack meaningful correlations between their items, making them unreliable for decision-making as their high utility might be due to random chance. To tackle this issue, our paper introduces the Correlated High Utility Itemset Miner (CHUIM). CHUIM utilizes the concept of productivity in both normal and exclusive domains to eliminate HUIs that occur randomly without genuine item correlations. Experimental evaluation on benchmark databases demonstrates that CHUIM efficiently prunes HUIs lacking inherent item correlations, thereby enhancing the reliability of the generated results.

Stevens-Johnson Syndrome as an initial presentation of Systemic Lupus Erythematosus with Antiphospholipid Syndrome: Case ReportAhmed K. A. Yasin, MD (a), Ma’in Abumuhfouz, MD (b), Rana A. Mohammed, MD (c), Mohammed Almadani, MD (d)

TITLE: Diagnosis and treatment of idiopathic bone cavity in the mandible: a case report  

Title: “Venom and Vision- Unilateral Subhyaloid Hemorrhage as an Unusual Snake Bite Sequela”

Title: Antineutrophil cytoplasmic antibodies (ANCA)-Associated Vasculitis in Chronic Hepatitis B: Unraveling the Immune Puzzle” A RARE CASE REPORT WITH REVIEW OF LITERATURE

A document by Andreas Boldt. Click on the document to view its contents.

Organic soils, particularly peatlands, are important carbon sinks. In Europe, almost half of its area has been drained and is primarily used for agriculture as grasslands. In Poland, 86% of the drained peatland area causes problems with high carbon dioxide emissions due to organic matter oxidation. The aim of the study was to analyze changes in organic soils between 1975 and 2017 using data from 476 reference soil profiles. The results showed a significant decrease in organic soils (≥12% SOC) from 62% to 35%, and an increase in organo-mineral (6.0-12.0% SOC) and non-humose mineral soils (≤1.75% SOC) by a similar percentage. The depth of SOC rich layers also decreased significantly, with deep soils (>100 cm) dropping from 20% to 5% and shallow soils (21-50 cm) increasing from 24% to 58%. The average SOC stock loss was almost 273 Mg C·ha -1 (from 500.42 Mg C·ha -1 to 228.04 Mg C·ha -1), with the median being four times lower. A decrease in SOC stock was observed in 64% of sites, while an increase was seen in 36%. The most significant decrease in SOC stock, by 64.67% compared to 1975, occurred in organic soils (from 762.19 Mg C·ha -1 to 269.26 Mg C·ha -1). There was an increase in SOC stock in organo-mineral, humose, and non-humose mineral soils, although it was not statistically significant. Moreover, the results indicated that continuous grassland use on organic soils does not offset carbon losses from organic matter oxidation due to drainage.

Aims: TPN171, a novel phosphodiesterase 5 (PDE5) inhibitor, is under development for the treatment of male erectile dysfunction (ED) and pulmonary arterial hypertension (PAH) in China. Kidney clearance is a major drug elimination pathway. A pharmacokinetic study of TPN171 in patients with impaired renal function is necessary. Methods: To investigate the pharmacokinetics (PK) properties and safety of TPN171 in individuals with severe renal impairment and normal renal function, an open-label, single-dose, parallel-group phase 1 study was conducted in 8 volunteers with severe renal impairment and 8 volunteers having normal renal function, who received TNP171 tablets (10 mg) in the fasting state. TPN171 plasma concentrations were measured up to 72 h thereafter. The maximum plasma concentration (Cmax), the area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC0-t) and AUC extrapolated to infinite time (AUC0-∞) were calculated and compared between groups. Results: As compared with those with normal renal function, the elimination half-life (t1/2) of volunteers with severe renal impairment, was prolonged, resulting in a decrease in clearance rate. The geometric mean ratios (GMRs) for Cmax, AUC0-t and AUC0-∞ were 74.25% (90% confidence interval [CI], 56.18%–98.13%, p = 0.081), 138.06% (90% CI, 107.82%–176.78%, p = 0.037), and 137.31% (90% CI, 107.53%–175.33%, p = 0.038), respectively, and the adverse reaction rate showed no significant difference. All adverse events were mild intensity, and no volunteer was discontinued in this study. Conclusions: No TPN171 dosage adjustment is required for patients with mild to severe renal impairment.

Joint prevention and control of transboundary pollution in multi-regional basins has been the focus of the international community. This paper explores a joint decision problem of transboundary water pollution involving three regions based on differential game theory. The pollution control strategies assumed by three differential game models, independent, two-party joint and three-party cooperation, and the emission trading system is taken into consideration. We found that strengthening inter regional alliance cooperation in the basin is conducive to reducing pollution emissions and releasing more investment potential for pollution control, so as to optimize the decision-making purpose of transboundary pollution prevention and control. For the reduction strategy of pollution stock, the correlation between participants is more important than the strength of the alliance, and the strategy selection of downstream areas plays an important role in the effect of joint prevention and control of pollution in river basins. Policy suggestions on joint multi-regional transboundary pollution control based on different target time periods are put forward.

By increasing smart objects as high-potential computing devices and 5G technology, the Internet of Things (IoT) has emerging technology to provide a data-centric infrastructure for detecting safe device-to-device communications by supporting security and privacy issues. As 5G-enabled communication technology, Vehicle-to-Vehicle (V2V) communication provides a wirelessly exchange information connection between smart vehicles, intelligent devices and cloud-edge computing environment. This connection should be established with a safe and secured run-time protection system to avoid many critical anomalies and misbehavior problems. Detecting run-time malicious transformations with data-centric misbehaving reactions is a main challenge for autonomous vehicle communications with 5G-enabled communication technology. This paper provides a hybrid Genetic Algorithm-based Ensemble Bagged Trees (GA-EBT) algorithm for a data-centric misbehavior detection approach to support the V2V communications against malicious and misbehavior transactions. For evaluation of the proposed algorithm, four real test-cases are applied for messaging injection attacks in the V2V environments with compare to the state-of-the-art machine learning algorithms. The experimental results show that the proposed hybrid approach can achieve to optimal high rate accuracy factor with 99.999, precision and recall factors with 100% and F1-Score factor with 100% to detect unexpected cyber-attacks for the V2V communications in the IoT environment.

CYCLIC THROMBOCYTOPENIA TREATED WITH PLATELET TRANSFUSION AND ORAL PREPARATION CONTAINING HYALURONIC ACID (ORALVISC®)M. Benjamin1, R. Kotchetkov2*1University of Ottawa, Faculty of Science, Ottawa, ON, Canada, K1N 6N52Royal Victoria Regional Health Centre, Barrie, Ontario, Canada, L4M 6M2Short Title: A case of cyclic thrombocytopenia*Corresponding Author: Rouslan Kotchetkov, M.D., Ph.D.Royal Victoria Regional Health Centre, Barrie, Ontario, Canada L4M 6M2Tel: +1-705-728-9090;Fax: +1-705-739-5630;Email: KotchetkovR@rvh.on.caNumber of Tables: 0Number of Figures: 1Word count: 1495Key words: thrombocytopenia, cyclic, anti-inflammatory, transfusion, hyaluronic acid, OralviscKEY CLINICAL MESSAGECyclic thrombocytopenia is a rare disorder characterized by periodic platelet fluctuation with amplitude from low to high. There are no standardized treatment guidelines. We present a patient who had resolution of mucocutaneous bleeding with platelet transfusion at platelet nadir, normalization of platelets with an oral preparation containing hyaluronic acid (Oralvisc®).INTRODUCTIONCyclic thrombocytopenia (CTP) is a rare disorder characterized by intense fluctuations of platelet counts in a cyclical pattern repeating on an average of a 3-week basis.1 Platelet nadir can be complicated by hemorrhage, and thrombocytosis can cause hypercoagulable state and thrombosis. Initially, most CTP patients are typically misdiagnosed as having primary immune thrombocytopenia (ITP). Currently it is considered to be heterogenous in cause. Clinical presentation is similar to immune thrombocytopenia (ITP), however most treatments seem to be ineffective or even harmful if applied to patients with CTP. CTP is a diagnosis of exclusion and is usually established, if at all, much later, often at a time when ITP-specific therapies have failed. Due to its rarity, in addition to the lack of research and documentation surrounding it there are no standardized guidelines on treatment. Here we present a case of chronic CTP, who reached significant improvement in quality of life after initiation of supportive platelet transfusions at platelet nadir. Moreover, platelet count fluctuations decreased and eventually normalized after application of oral preparation containing hyaluronic acid (Oralvisc®) for concomitant arthropathy. With this case we want to illustrate challenging aspects of non-standard management for such a rare disease.CASE HISTORY / EXAMINATION64-year-old female was referred to our institution for management of chronic CTP. She was diagnosed at the age of 45, initially as ITP, when routine blood work was performed prior to minor surgery. Past medical history included calcium pyrophosphate deposition disease (CPPD), hypertension, hearing impairment, myopia, peripheral neuropathy, atrial fibrillation, chronic back pain, cholecystectomy, and excised squamous cell carcinoma on floor of mouth. There was no history of alcohol or substance abuse. She had 20 pack year history of smoking, quit one year before CTP diagnosis. Family history was unremarkable. Platelet fluctuations were not synchronized with patient’s menstrual cycle. At the time of initial assessment at our institution her platelet count fluctuated from mild thrombocytosis (~600,000 x 109/L) to severe thrombocytopenia (5,000 x 109/L) as shown in Figure 1. Bone marrow examination at diagnosis did not reveal myelodysplastic changes, abnormal lymphoid or plasma cell population. There was mild megakaryocytic hypoplasia. At the time of diagnosis, she was asymptomatic, but after 12 months started developing muco-cutaneous bleeding around nadir time of the platelet. She has no major bleeding, including hemarthroses, hematuria, hematoschezia.METHODS (TREATMENT)Given CHADS2 score of 1 at diagnosis of atrial fibrillation, she was anticoagulated with warfarin. However, due to bleeding episodes it was switched to low molecular dose heparin, and later to apixaban. That allowed a better balance of bleeding and thrombosis risks during thrombocytopenia and thrombocytosis.After taking Prednisone 1 mg/kg she achieved partial response but discontinued it due to recurrent mouth thrush. She switched to a pulse dose of dexamethasone; however it was stopped because of vaginal pain and bleeding, and feeling generally unwell. She had normalization of platelet count on oral cyclophosphamide 100 mg daily and was able to stop it. However, she relapsed shortly after discontinuation and had no significant clinical response following restarting of cyclophosphamide. Next line of therapy was course of intravenous infusion of Rituximab, 375 mg/m2 weekly x4. There was no platelet improvement, but she developed significant daily headaches, visual hallucinations, and blue vision discoloration. She declined splenectomy and was on active surveillance until bleeding symptoms at her platelets nadir progressed and started significantly affect her quality of life . High doses of tranexamic acid (1,000mg three times a day) were given at platelet nadir to improve symptomatic bleeding, but the patient had only marginal improvement and it was discontinued. Due to risk of thrombosis at platelet high, we considered it unsafe to administer thrombopoietin receptor agonists, like eltrombopag or romiplostim.OUTCOMEDue to lack of other options, we offered her platelet transfusion around nadir time which led to marked improvement in bleeding episodes. Since the timing of nadir was quite predictable, platelet transfusion improved quality of life. When the patient required dental extraction, we chose a time when the patient had a normal platelet count which resulted in an unremarkable procedure with no bleeding or thrombosis. After 2 years of platelet transfusion, the patient started taking oral preparation containing hyaluronic acid (Oralvisc®) for worsening hip and knee arthropathy. After five months her platelet count fluctuations improved, ranging from 100,000 to 150,000 x 109/L and she became transfusion independent. After 26 months the patient discontinued Oralvisc® due to supply issues and switched to colchicine. For over 19 months platelet count remains within the same range, and she remains asymptomatic and transfusion independent. Her physical examination is unremarkable.DISCUSSIONITP or immune thrombocytopenia is a platelet disorder defined by a low platelet count thought to be a result of the immune system destroying platelets either alone or in conjunction with thrombopoeisis inhibition. Common symptoms include skin and mucocutaneous hemorrhage, bruising, fatigue. ITP is diagnosis of exclusion and requires an extensive work up to rule out secondary causes and other platelet disorders. Corticosteroids (prednisone or dexamethasone) are standard frontline therapy. Platelet transfusions are not usually effective, since there is rapid destruction of transfused platelets. For relapsed disease rituximab, steroid-sparing immunosuppressants, or splenectomy are used.CTP is a similar platelet disorder however it is characterized by periods of low and high platelet counts in a reoccurring wave-like pattern every few weeks. Currently CTP is considered to be heterogenous in cause and the pathophysiology is largely unknown1. Germline heterozygous loss-of-function thrombopoietin receptor MPL mutation and pathogenic somatic gain-of-function (GOF) variants in signal transducer and activator of transcription 3 (STAT3) were shown in two patients with CTP. Interesting that 2 patients had also clonal T-cell populations. It was suggested that these mutations along with clonal T cells trigger exaggerated persistent thrombopoiesis oscillations of their intrinsic rhythm upon homeostatic perturbations2.Many patients are usually treated for ITP initially prior to diagnosis3. Two clinical features relatively unique to CTP besides periodic thrombocytopenia are rebound thrombocytosis unrelated to recent splenectomy and platelet nadirs occurring during menses4. To establish a proper diagnosis, platelet count needs to be measured every week over a period of 1-3 months to establish the presence of a cyclical pattern to diagnose CTP, however it is usually a diagnosis of exclusion. Currently it is considered to be heterogenous in cause.1Due to rarity of disease and alternating thrombocytopenia and thrombocytosis the treatment options for CTP are limited. In addition to detailed medical history and physical examination to rule out secondary causes, in non-bleeding patients serial blood count check to establish the platelet profile is recommended. In a patient with active bleeding, platelet transfusion with post-transfusion blood count check would be beneficial to assess whether platelets are actively destroyed as seen in ITP or maintain the count, which would ne more suggestive as CTP. For asymptomatic patients active surveillance is recommended until they develop clinically significant and recurrent hemorrhage affecting organ function or quality of life. Patients with CTP generally do not respond to standard ITP treatments, including corticosteroids, splenectomy, and intravenous immunoglobulin1,4. A recent publication showed normalization of platelet count in a female patient treated with danazol5. Hormonal contraceptive showed efficacy in alleviating patient’s symptoms6.Platelet transfusions in ITP patients are generally reserved for critical bleeding when there is a need to raise the platelet count immediately7. Due to antiplatelet antibodies that destroy circulating platelets and megakaryocytes in the bone marrow the response is transient and attenuated8. Based on our experience, supportive single platelet transfusion per cycle at the nadir of platelet is efficacious in long-term management of CTP. It helps to minimize bleeding and improve quality of life. Given predictable pattern of platelet count fluctuation, it is feasible to arrange blood count check and transfusions. Transfusion of platelets does not increase risk pf thrombosis. In contrast to ITP, there is not rapid platelet destruction in CTP patients and the longevity of transfused platelet is longer. This approach could also be used perioperatively prior to major or minor surgeries. The sustained response to platelet transfusion in CTP patient preoperatively was shown recently9.Efficacy of anti-inflammatory medications in ITP has not been shown. Oralvisc® is an anti-inflammatory oral preparation containing hyaluronic acid that reduces the levels of pro-inflammatory mediators leptin and bradykinin10. Bradykinin receptors exist in chondrocytes and on stimulation increase Interleukin-1. Bradykinins are known to participate in innate immunity, inflammation, and pain11. Hence, evidence of reduction in bradykinin levels is clinically relevant. Though prior to starting Oralvisc® the patient had no elevated markers of inflammation (C-reactive protein, erythrocyte sedimentation rate, fibrinogen and ferritin were normal), the anti-inflammatory effect may have contributed to normalization of platelet count and clinical improvement. Alternatively, in our case Oralvisc® may triggered spontaneous recovery, a feature previously described in CTP1.CONCLUSIONCTP is a rare disease, different from ITP, however it should be considered at the initial presentation. In patients with recurrent fluctuation in their platelet count, CTP should be considered. Serial blood count check is recommended to establish a proper diagnosis and avoid unnecessary therapies used for ITP but not effective in CTP. Supportive platelet transfusion at the nadir of thrombocytopenia is an effective management option in some symptomatic patients. Anti-inflammatory medications, suppressing bradykinin and leptin may be applied to alleviate platelet fluctuation and improve symptoms.AUTHOR CONTRIBUTIONSMarek Benjamin: Writing – original draft; writing – review and editing. Rouslan Kotchetkov: Writing – review and editing, Supervision.ACKNOWLEDGMENTSNone.FUNDING INFORMATIONThis research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors.CONFLICT OF INTEREST STATEMENTNone Declared.CONSENTComplete written informed consent was obtained from the patient for the publication of this study and accompanying images.FIGURE LEGENDFigure 1: Fluctuating platelet count/µL over a period of the last 5 years. Arrow represents the point at which the patient started Oralvisc®. Red line – lower limit of norm, grey line – upper limit of norm

Object to investigate moxibustion’s role and mechanism in the treatment of noise-induced tinnitus. Methods C57 mice were exposed to white noise (100 dB L, 2 h) to generate animal model of tinnitus. Moxibustion, which bakes acupoints with burning moxa wool, was set on particular acupoints such as Ermen (TW21)/Tinggong (SI19). GPIAS detection was performed to identify the mice with tinnitus behavior, and the GPIAS detection was conducted after moxibustion management to estimate the changes of tinnitus behavior. Hearing function was evaluated using ABR, Immunostaining was applied to examine alterations of cochlear ribbon synapses. The RNA-seq has been utilized to explore the singling pathways responsible to the changes of tinnitus. Results Significant differences of inhibition rates of GPIAS have been found seen among control, noise exposure, and moxibustion treated group. The inhibition rates decreased after noise exposure, and moxibustion treatment was able to increase the inhibition rate. Hearing function was not significantly affected in consistent with the changes of GPIAS inhibition rates, cochlear ribbon synapses showed a similar alteration with noise and moxibustion treatment. Further, we conducted at the whole cochlea RNA-seq analysis, and we found that Npas4 might be responsible for moxibustion’s effect on tinnitus and synaptic alterations. Conclusions moxibustion on Ermen (TW21)/Tinggong (SI19) acupoints can alleviate the noise-induced tinnitus through specific repair of cochlear ribbon synapses.

javascript:void(0) The northern Humboldt Current System (nHCS) is an area with high environmental variability that impacts key demographic and community-scale processes. Understanding the role and ecological implications of these interannual or long-term events is crucial in describing the dynamics of the nHCS community. Using catch data from pelagic assessment surveys from 1983 to 2019 and the community trajectory analysis framework, we tested and characterised the patterns and compositional dynamics of the nHCS pelagic fish community over space and time. Spatially, changes were evaluated for ecological regions with similar community composition identified through hierarchical clustering with spatial constraint. We found that the community is in constant inter-annual variability consistent with the long-term warm and cold periods of the system. A long trajectory segment suggests a community regime shift between 1994 and 1999, years associated with a change in the average oceanographic conditions in the system and an extreme El Niño event (1997-98). After 1999, we identified a period where the community was constantly changing and dominated by coastal species. These long-term community changes were not homogeneous over the ecological areas, finding a lower temporal variability in the coastal area than in the northern and offshore. The main factor controlling the spatial and temporal dynamics of the nHCS pelagic fish community seems to be the long and short-term environmental conditions in the system. This study helps to understand the magnitude and direction of pelagic fish community changes and define the community’s recovery process after an event-driven change.

javascript:void(0) Neurodevelopmental disorders (NDDs) are identified as inability in the field of cognition, emotion and motor development, as the outcome of complex interactions between nature and nurture. Evidence from human epidemiological studies has supported the association between NDDs and maternal inflammation. Typically, exposure to pathogens (including viruses, bacteria, fungi, and parasites) induced maternal immune activation (MIA) revealed a novel perspective in the pathogenesis of NDDs in the prenatal stage, which could be attributed to maternal inflammation, altered microbiota etc. In this review, we highlight the primary mechanisms underlying MIA-induced NDDs caused by pathogens and/or pathogen-derived agents. Moreover, we outline therapeutic strategies to mitigate pathogen-induced MIA-associated neurological disorders, with the primary goal of preventing or managing pathogen exposure during pregnancy and minimizing the long-term effects on the offspring.

IntroductionEisenmenger syndrome was initially described in 18971, when Eisenmenger reported a patient with dyspnea and cyanosis since childhood that later developed heart failure and hemoptysis, dying. His autopsy revealed a ventricular septal defect. This syndrome represents the most severe phenotype of pulmonary arterial hypertension in patients with congenital heart disease. A left-to-right shunt triggers a severe growth of pulmonary vascular resistance, which with time results in shunt reversal and cyanosis. It can lead to multiorgan disease, with cardiac, hematological, neurological, respiratory, gastrointestinal, urinary, immunological, musculoskeletal and endocrinological manifestations2. A multidisciplinary approach is the best strategy to those patients3, with both prevention and management of complications at the core of treatment. The improvement of exercise tolerance, a better quality of life and longevity are the main goals and supportive measures, in order to reduce symptoms and prevent complications, have an extraordinary importance. Complications related to hypoxaemia, coagulation disorders and congestive heart failure are among the most common. However, anticoagulants and antiplatelets are not usually prescribed, unless in some cases (with specific indications). Diuretics and pulmonary hypertension therapies are the most commonly used - bosentan, macitentan, sildenafil and prostanoids are some examples. The definitive treatment for Eisenmenger syndrome is lung transplantation and shunt closure or heart-lung transplantation.Our case report aims to mark the importance of being aware of subtle signs of cardiorespiratory distress in young patients.

Objective: To evaluate the relationship between serum mineral levels in pregnant women during the second and third trimesters and the risk of developing gestational diabetes mellitus (GDM). Design: Retrospective cohort study. Setting: A tertiary hospital in China. Population: Unselected women with singleton pregnancies who developed GDM. Methods: Maternal demographic data and serum mineral concentration information from the mid and late stages of pregnancy were collected through the hospital information system. Analyses were conducted using restricted cubic spline models and multivariate logistic regression models. Main outcome measures: The prevalence of GDM，specific serum mineral levels，gestational age at delivery. Results: Among 17 224 singleton pregnancies, the prevalence of GDM in this study was 15.07%. Chloride (P for overall = 0.01; P for nonlinear = 0.373; OR (95% CI) = 1.03 (1.01, 1.05)) showed a significant linear positive association with GDM. Additionally, serum levels of calcium (P for nonlinear < 0.001), potassium (P for nonlinear = 0.036), and magnesium (P for nonlinear < 0.001) were found to have nonlinear relationships with the risk of GDM. The interactions between calcium and magnesium (OR (95% CI) = 0.05 (0.01, 0.27), P for interaction < 0.001), potassium and magnesium (OR (95% CI) = 0.11 (0.03, 0.37), P for interaction < 0.001), and potassium and chloride (OR (95% CI) = 1.06 (1.01, 1.11), P for interaction < 0.001) were significant. Conclusions: The study indicates that specific serum mineral levels in pregnant women are closely associated with the risk of gestational diabetes mellitus. A deeper understanding of the mechanisms and interactions of these minerals could aid in developing effective prevention and treatment strategies, thereby reducing the incidence of GDM and improving pregnancy outcomes.