Complex transformer models have become popular in practice, however, they function as “black boxes”. Therefore, there is a growing need for the quantitative evaluation of existing explainability techniques. This evaluation becomes challenging when there are no ground-truth explanations available in the text data. We address this by exploring evaluation approaches for local explainability techniques in Turkish text classification tasks. We use BERT-based models, specifically BERTurk and TurkishBERTweet, and apply SHAP, LIME, and Integrated Gradients (IG). We evaluate the explainability techniques based on their ability to preserve the original text’s prediction probability when their most important tokens are used during inference. We employ evaluation approaches like Mean of Probabilities and Incremental Deletion to compare the explainability techniques with a baseline approach, aiming to measure the faithfulness of the explanations. Our results demonstrate that the gradient-based technique, IG, effectively identifies salient tokens that correlate with the class of the original text. We conclude that the IG method is effective in computing the saliency scores of the explanations when using an encoder-based model for Turkish text classification tasks. In understanding Turkish morphological complexity, it captures and highlights the nuanced contributions of context-dependent words and phrases.

Understanding the mechanisms that constrain or promote the evolution of species’ geographic ranges has emerged as a fundamental question at the intersection of evolution, ecology, and conservation. A long-held, empirically understudied idea is that asymmetrical gene flow from a more densely populated range center may restrict species’ geographic ranges by preventing local adaptation and the expansion of populations at the range edge. In this study, we use ecophysiology, population genetics, and niche modeling to evaluate whether asymmetrical gene flow from the range center toward the range edge swamps out physiological differentiation in peripheral populations preventing local adaptation. Our focal species, the plethodontid salamander Plethodon ouachitae, is isolated among six mountaintops (sky islands) in the Interior Highlands of the United States that differ in climate across mountaintop isolates and along elevational gradients within mountains. Within mountaintop isolates we found no genetic structure, uniformly high rates of gene flow, and no evidence of physiological divergence along elevational gradients. Although population density peaked at mid- to high-elevations, inferred gene flow was not consistently biased from high- to low-density sites. We found significant genetic differentiation among mountains and evidence for divergence in the environmental niche across mountains separated by low-elevation barriers to dispersal. Despite variation in climate among mountains and the potential for adaptive divergence, we found no evidence for differentiation in ecophysiology among populations isolated on different mountains. Our findings do not support asymmetric gene flow as a force restricting local physiological adaptation and expansion at the range edge, although uniformly high estimated gene flow within mountains could play such a role. However, a lack of physiological differentiation among sky-island populations that differ in climate provides additional support for the idea that gene flow does not limit local adaptation in this species.

Functional traits affect how plants respond to environmental changes, providing crucial insights into plant adaptation strategies under global climate change. Yet, there remains a lack of empirical evidence on how phenotypic plasticity and integration functionally coordinate in response to coupled light and water adaptations. In nursery experiments, we investigated the variations of plant functional traits and the correlation between phenotypic plasticity and integration in seedlings of two oak species (Quercus dentata Thunb and Quercus variabilis Blume.) subjected to four light and three water treatments. We found that a reduction in soil moisture shifted the growth patterns of seedlings towards resource conservation, including improved leaf dry matter content (LDMC) and leaf tissue density (LTD), coupled with a decrease in photosynthetic performance as measured through fluorescence (Fv/Fm), carbon uptake (Pn), and water loss (Gs). Moreover, we observed that moderate shading (25 and 50% of full light) might enhance seedling photosynthetic capacity and efficiency by inducing the optimization of leaf functional traits. However, excessive light (full light) and shade (25% of full light) were found to have detrimental effects on leaf morphology and physiological traits, consequently impeding resource acquisition efficiency (p<0.05). The functional traits of the two oak species had similar phenotypic plasticity index of water (PIW) and light (PIL). Furthermore, our findings indicate that phenotypic plasticity does not limit trait integration; instead, it is positively correlated in two oak species. Specifically, under varying light and water coupling conditions, greater plasticity in plant functional traits is associated with increased integration of these traits with others. In summary, we highlighted that plant functional traits can quickly adjust to variations in light and water treatments, while the coordination between seedling phenotypic plasticity and integration is key in facilitating the adaptation of two oak species to fluctuations in the light-water environment.

Use of synthetic microbial communities (SynComs) is a promising approach that harness nature-based solutions to support soil fertility and food security, mitigate climate change impacts and restore terrestrial ecosystems. Several microbial products are in the market and, many others are at different stages of development and commercialization. Yet, we are still far from being able to fully harness the potential and successful applications of such biotechnological tools. The limited field efficiency and efficacy of SynComs and other microbial tools have significantly constrained commercial opportunities, resulting in market growth falling below expectations. To overcome these challenges and manage expectations, it is critical to address current limitations, failures, and potential environmental consequences of SynComs. Here, we discuss the current status of SynComs and identify the next steps needed to develop and deploy the next generation tools to boost their ability to support multiple ecosystem services, including food security and environmental sustainability.

Color in flowers and fruits carries multiple functions, from attracting animal partners (pollinators, dispersers) to mitigating abiotic environmental stress (cold, drought UV-B) through changes in pigment production. However, with research primarily focusing on biotic interactions as selective agents, it remains unclear whether flower and fruit colors underlie the same abiotic stressors and vary jointly across large spatial scales. In light of climate change and biodiversity loss, it is high time to evaluate global color-environment associations. Leveraging a dataset of 2815 animal-pollinated and animal-dispersed species from 51 plant clades, we here show that the distribution and diversity of flower and fruit colors is globally decoupled and shaped by different factors. Fruit color diversity is generally higher and peaks in tropical areas where the diversity of animal mutualists is highest. Flower color diversity, in contrast, peaks in areas of high abiotic environmental stress, with distinct flower colors associating with distinct abiotic factors.

Freezing tolerance plays a pivotal role in shaping the distribution and diversification of organisms. We investigated the dynamics of adaptation to climate and potential trade-offs between stem freezing tolerance and growth rate in 48 Quercus species. Species from colder regions exhibited higher freezing tolerance, lower growth rates and higher winter-acclimation potential than species from warmer climates. Despite an evolutionary lag, freezing tolerance in oaks is closely aligned with its optimal state. Deciduous species showed marked variability in freezing tolerance across their broad climatic range while evergreen species, confined to warm climates, displayed low freezing tolerance. Annual growth rates were constrained in all deciduous species but those that evolved in warm latitudes lost freezing tolerance precluding a trade-off between freezing tolerance and growth. We provide evidence that capacity to adapt to a wide range of thermal environments was critical to adaptive radiation and current dominance of the North American oaks.

RationaleFinancial relationships between healthcare professionals (HCPs), healthcare organizations (HCOs), and the medical device industry in Japan may lead to conflicts of interest. Limited transparency in these relationships has raised concerns regarding their potential influence on clinical decision-making and patient care. Aims and ObjectivesThis study aimed to assess the scope and magnitude of financial payments from medical device companies to HCPs and HCOs in Japan, focusing on publicly disclosed data from the 2022 fiscal year. MethodsA cross-sectional analysis of publicly available payment disclosures from 169 medical device companies, including all members of the Japan Federation of Medical Devices Associations (JFMDA) and several major non-JFMDA affiliated companies, was conducted. Descriptive statistics were calculated to summarize payment data. ResultsOf the 169 medical device companies, 33.7% (57 companies) did not disclose payment information, leaving 108 companies for analysis. In total, $245.2 million in payments were made in 2022, with only 23.9% ($58.7 million) to research and development. Of the total, 34.6% ($84.9 million) was allocated to non-research payments to HCOs for sponsoring HCOs’ activities, and 19.6% ($49.0 million) were paid for lecturing and consulting fees, typically to individual HCPs. More than 80% of companies allocated a greater share of payments to non-research activities than to research. ConclusionThis study reveals substantial financial relationships between medical device companies and HCPs/HCOs in Japan, predominantly for non-research purposes. Improved transparency regulations, including a uniform, government-run database, are necessary to better oversee these financial interactions with medical device industry in Japan. 

Introduction: Celiac disease (CeD) is an autoimmune condition characterized by a reversible inflammatory reaction in the mucous membrane of the small intestine. Nevertheless, there is a limited availability of efficient control approaches. Prior research has demonstrated that pharmacological targets supported by genetic evidence can greatly enhance the efficacy of drug development. Hence, the study aims to integrate transcriptomic and proteomic information to identify candidate targets for CeD. Methods: The study employed proteome-wide Mendelian randomization (MR) analysis of circulating plasma proteins to investigate their causal association with CeD. The candidate targets for CeD were further assessed employing colocalization analysis, transcriptome-wide summary-data-based Mendelian randomization (SMR) analysis, multimarker analysis of genomic annotation (MAGMA) gene-based analysis, and bulk RNAseq-based differential expression analysis. For the proteins that were identified, extended Phenome-wide association studies (PheWAS) were conducted to assess their side-effect profiles, while the DGIdb database provided information on the approved or investigated drugs for candidate targets. Results: Systematic MR analysis identified 22 candidate targets for CeD. Among the proteins analyzed, BTN2A1 passed all subsequent verification analyses. Additionally, three proteins, including CatH, IL-18R1, and PTPRC, passed the majority of the subsequent verification analyses. The other 18 proteins were also candidate targets (Trehalase, CD226, SH2B3, ICOSLG, ULK3, Park7, ALDH2, RABEP1, TNFRSF9, COL11A2, GNPDA1, IL-1RL1, B3galt6, TNFSF11, CCL21, BTN3A3, OLFM2 and Colipase). Conclusions: The study employed a combination of human transcriptomic and proteomic information, employing several analytical methods. As a result, 22 proteins, divided into four tiers, were identified as prospective therapeutic targets for CeD.

Following wildfires, riverine water quality in forested watersheds is prone to degradation, impacting drinking water treatment and potentially causing increased emissions because of additional electricity consumption. We explore the potential for climate-based financing to support wildfire mitigation and watershed restoration and thereby reduce potential water treatment energy demand within the Provo River watershed of Utah, USA. Pre-and post-wildfire erosion and water quality in the Provo River is modeled using GeoWEPP. Energy data from the Don A. Christiansen Regional Water Treatment Plant in the watershed and related literature data are used to estimate the increase in energy use for treating degraded water. We find that most watershed areas are not subject to large treatment demand changes, but a few hotspots are prone to increased sediment. In the Provo River watershed, on average, a fire in a single 12-digit hydrologic unit code sub-watershed corresponds to an additional 350 metric tonnes of carbondioxide-equivalent emissions for one year following a wildfire event due to increased energy by the water treatment plant. If wildfire risk is reduced, the avoided emissions can generate a potential of $88,500 annually in carbon credit revenue (at $10/CO2e credit) for the HUC8 subbasin contributing to water treatment. Synopsis This study demonstrates a method for modeling pre-and post-fire erosion and connects the impacts to energy use and emissions associated with a downstream drinking water treatment plant.

Background: Monitoring patients and achieving adherence in chronic diseases is an important problem. Allergic rhinitis (AR) happens to be one of the most common chronic and lifelong conditions of today. As such, it proves to be an excellent model for identifying the determinants of app use in the monitoring of adherence to treatment and assessment of health status during treatment. The use of Mask-air® app supports clinical decision-making by actively involving the patient in the process of observing symptoms and by promoting adherence to therapy. The main objective of the study was to identify the defining characteristics of a Mask-air® user, describe their disease phenotype, satisfaction with app use, as well as potential reasons for abandoning it. Material and Methods: The study included adult patients receiving care in an allergy outpatient clinic. In the course of a routine visit they were offered to participate in a trial involving the Mask-air® app. By means of surveys/questionnaires investigators collected data regarding their symptoms, administered treatment and clinical evaluation results. At a follow-up visit, these were compared, and patients was queried about their satisfaction with app use. Additionally, patients presented and discussed their app records. Those who refused to install or utilize the app were asked to indicate their reasons in a questionnaire. Results: The study found no distinguishing characteristics of Mask-air® app users, compared to those who refused the app. Readiness to use software was analyzed according to age, economic status, disease advancement and severity, presence of allergic comorbidities and therapeutic modality used. Respondents fell into the following categories in the context of app use: those who did not install the app (11.6%), those who installed it, but did not use it (22.2%), and those who installed and evaluated it (66.2%), but did not produce symptom monitoring records (15.6%). Satisfaction ratings for app use were high, but patients were critical of the therapeutic aspect included in the app. Conclusions: No distinguishing features of the Mask -air ® user were identified, suggesting that the Mask -air ® app can be recommended to all patients regardless of gender, economic and educational status, or disease phenotype.

Response to letter re: ‘Premature Ventricular Complexes after Catheter Ablation for Atrial Fibrillation: Accounting For Regression to the Mean’William Whang, MD1 and Alex Choy, MD21Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY; william.whang@mountsinai.org2Department of Medicine, University of Chicago, Chicago, IL; a.choy10@gmail.comCorresponding author: William Whang, MD (william.whang@mountsinai.org)One Gustave Levy PlaceNew York, NY 10029212-241-7114We thank Dr. Wang for his interest in our research letter. He questions whether the endpoint used in our study, frequency of premature ventricular complexes (PVC) as a percentage of total complexes measured pre- versus post-ablation, is a valid indicator due to the skewed distribution and lack of granularity. Although we did not use absolute number of PVCs per day from a 24-hour Holter for our endpoint, we would argue that PVC percentage is a valid indicator of arrhythmia burden that has been associated in a dose-dependent manner with outcomes such as cardiomyopathy and mortality in cohorts such as the community-based Cardiovascular Health Study.1 In addition, in our study the median duration of monitoring (6 days) was longer than in prior studies of atrial fibrillation (AF) ablation and PVCs. A recent study that used commercially available event monitors concluded that longer monitoring periods resulted in significantly reduced mean measured error of PVC burden.2We sought to approach the measure for significant PVC burden (≥1000/day) mentioned by Dr. Wang, with a proxy threshold of ≥1% PVCs. In our sample 21.5% of patients had ≥1% PVCs pre-ablation and 19.2% had ≥1% PVCs post-ablation (p=0.76, chi-squared test), again suggesting lack of significant association between AF ablation and PVC burden. We agree with Dr. Wang that prospective studies would be worthwhile to assess the true impact of AF ablation on PVCs, and would stress that inclusion of samples unrestricted by PVC burden pre-ablation could help clarify this question.1. Dukes JW, Dewland TA, Vittinghoff E, Mandyam MC, Heckbert SR, Siscovick DS, Stein PK, Psaty BM, Sotoodehnia N, Gottdiener JS, Marcus GM. Ventricular Ectopy as a Predictor of Heart Failure and Death.Journal of the American College of Cardiology . 2015;66:101–109. 2. Krumerman A, Di Biase L, Gerstenfeld E, Dickfeld T, Verma N, Liberman L, Amara R, Kacorri A, Crosson L, Wilk A, Ferrick KJ. Premature ventricular complexes: Assessing burden density in a large national cohort to better define optimal ECG monitoring duration. Heart Rhythm . 2024;21:1289–1295.

BACKGROUND AND AIMS: There is scarce information about pediatric lymphoblastic lymphoma (LLy) in low and middle-income countries. We describe the clinical characteristics, treatment and outcome of a cohort of children and adolescents with LLy in Latin America (LA). METHODS: Retrospective study analyzing pediatric patients with LLy in 10 institutions of the St. Jude Global Alliance from nine LA countries between 2007 and 2017. RESULTS: One-hundred and twenty-six patients were included. Sixty (47.6%) had T-LLy, 49 (38.9%) B-LLy and in 17 (13.5%) the immunophenotype was unknown. Ninety-seven (77%) presented with stage III/IV disease, and 42 (33.3%) in critical conditions. In 30 cases (23.8%), the results of pathology diagnosis exceeded 15 days from biopsy, and 23 patients (18%) required a review at another institution. The EFS and OS at 5 years were 73% (SE 0.047) and 78% (SE 0.0435), respectively. Five-year abandonment-sensitive EFS and OS were 65% (SE 0.0477) and 70% (SE 0.0459), respectively. Events included relapse/progression (n=22), refractory disease (n =1) abandonment (n=11), induction death (n=4), death in complete remission (n=4), and second malignancies (n=1). CONCLUSIONS: A balanced proportion of LLy-T and B phenotypes was observed. Diagnosis was a challenge. Most of the patients presented with high-risk disease, and many in critical conditions. Toxic deaths and abandonment represented nearly half of the events. Improvements in diagnosis, supportive measures and follow up are imperative to improve the outcomes of pediatric LLy in Latin America.

This study investigated the relationship between relational integration and semantic processing in numerical inductive reasoning using event-related potentials (ERPs). Participants were required to identify hidden rules in three-digit sequences and judged whether fourth probes were congruent with these rules. The experiment manipulated relational complexity: simple and hierarchical rules (e.g., ”12, 13, 14, 15” or ”12, 13, 15, 18”) shared identical first two numbers but differed in the third, in order to isolate the relational integration process. The type of cue was also manipulated: the no-cue condition presented only a fixation point, providing no rule information; the part-cue condition introduced operands (such as “+” or “–”) to ensure rules could be identified after presenting second numbers and confirmed after the onset of third numbers. Both the time domain and mass univariate ERP results locked to the third numbers revealed independent main effects of relational complexity and cue type on both the Late Negative Component (LNC) . The independent effects especially on the LNC implies that high-order numerical reasoning distinct from semantic processing.

Under the global Sustainable Development Goals initiative, the pursuit of well-being is gradually shifting from wealth to sustainable development. Re-examining the contribution of regional economic, ecological, and social development to the common creation of well-being, analyzing their deep connections, will help us understand the multidimensional concepts and processes of development, and provide ideas for further promoting the construction of a more equitable and sustainable world. China is moving from comprehensive prosperity to common prosperity, and the continuous improvement of sustainable well-being provides effective samples for our research. This study focuses on 46 counties in the Qinba Mountains region of China, and constructs a coupled performance indicator system for sustainable well-being in mountain villages. The Super SBM model is used to evaluate the matching performance of input and output factors, with Economic capital, Ecological capital, and Social capital as explanatory variables and Sustainable Happiness Index as the expected output. Research has found that: (1) There is a mismatch between the input and output factors of sustainable well-being in the Qinba Mountain area, and management techniques are a key factor hindering the improvement of the coupling performance level of sustainable well-being in the Qinba Mountain area; (2) The coupling performance level of sustainable happiness in the Qinba Mountain area is showing a downward trend, and only adjusting the input-output relationship by about 1.02% can achieve optimization and growth in performance level; (3) There is a significant shortage of input factors, with 87% of counties experiencing insufficient economic capital, about 76% experiencing insufficient arable land, and 41% experiencing insufficient social capital. To solve these problems, it is necessary to strengthen the sustainable management level of each county in terms of ecology, economy, and social integration, continue to promote capital investment in mountainous areas to improve economic level, strictly use arable land, optimize land use structure, strengthen social governance level, improve residents’ satisfaction level, and thus enhance sustainable happiness level. This will provide useful reference for achieving sustainable development goals in similar regions of the world.

a newborn with cleft palate associated to PTEN-Hamartoma-Tumor syndromeUlf Nestler1, Daniel Gräfe2, Vincent Strehlow3, Robin-Tobias Jauss3, Andreas Merkenschlager4, Annika Schönfeld5 and Florian Wilhelmy11Department of Neurosurgery, University Hospital, Leipzig, Germany2Institute for Pediatric Radiology, University Hospital, Leipzig, Germany3Institute for Medical Genetics, University Hospital, Leipzig, Germany4Division of Neuropediatrics, University Hospital, Leipzig, Germany5Department of Oral and Maxillofacial Surgery, University Hospital, Leipzig, Germanyulf.nestler@medizin.uni-leipzig.de daniel.graefe@medizin.uni-leipzig.de vincent.strehlow@medizin.uni-leipzig.de robin-tobias.jauss@medizin.uni-leipzig.de andreas.merkenschlager@medizin.uni-leipzig.de annika.schoenfeld@medizin.uni-leipzig.de florian.wilhelmy@medizin.uni-leipzig.dePTEN Hamartoma Tumor Syndrome (PHTS) encompasses a range of syndromes, including Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome and Lhermitte-Duclos disease. These syndromes are caused by loss-of-function and null variants in the phosphatase and tensin homolog (PTEN) tumor suppressor gene on chromosome 10q23.31, leading to a lifelong predisposition for tumor development.1 The genotype-phenotype correlation is weak, the penetrance is age-dependent and the description of phenotype expression is still evolving.2,3Initial description of Cowden syndrome included orofacial dysmorphism, and facial and oral examinations can reveal aberrations in about one third of cases.4,5 Recent pediatric publications have primarily focused on skin stigmata, macrocephaly and developmental delay, partly influenced by the subspecialty of the initially examining physician (Tab. 1). Here we report on the phenotypic spectrum with a case of cleft palate associated to PHTS in a newborn.The male infant was born by planned cesarean section at 38 weeks of gestation due to polyhydramnios and macrocephaly. Birth weight was 3972 g (1.5 z), length 52 cm (0.4 z) and head circumference 40 cm (3.6 z).The patient is the third child of non-consanguineous parents. His 6-year-old brother had suffered from a single epileptic seizure with suspected self-limited focal epilepsy of childhood (“Rolandic”). The 4-year-old sister and the father are healthy, while the mother has ulcerative colitis and a cousin of the maternal grandmother had a cleft palate and lip.Postnatal respiratory adaptation was prolonged and complicated by hypoglycemic episodes. A cleft soft palate was detected shortly after birth, and together with macrocephaly prompted genetic counseling. Whole exome sequencing (WES) with subsequent segregation analysis of the parents revealed a heterozygous, de novo , null variant c.184A>T, p.(Lys62*) in the PTEN gene. The variant has previously been reported as pathogenic (ClinVar-ID: 1069915).The child was referred to an oromaxillofacial surgeon who scheduled surgical closure at 10 months and initiated MR-Imaging to rule out hydrocephalus before surgery (Fig. 1). Examination at 10 months revealed brown skin patches on both knees and soles, without penile freckling. Head circumference was 50 cm (2.8 z), and no partial overgrowth was observed. A persistent foramen ovale and ductus arteriosus, and mild mitral insufficiency were noted. Despite starting to roll over since 6 months of age, the boy was showing mild motor development delay, not yet being able to sit. A detailed diagnostic work-up for PHTS-related symptoms, including thyroid abnormalities, gastrointestinal polyposis and autism spectrum disorder was planned according to German guidelines.6PTEN Hamartoma Tumor Syndrome presents a diagnostic challenge. On one hand, patients have tumor predisposition with a 6% risk of developing a malignant tumor in childhood. On the other hand, screening for cancer or benign neoplasms in young children poses additional risks by repeated anesthesia or invasive procedures. Thus the appropriate timing of routine, guideline-driven diagnostic evaluations remains a matter of debate.7Macrocephaly is often an obvious symptom and can be observed prenatally. Transfontanellar ultrasonography, and cerebral MRI in older children are indicated to rule out hemorrhage, hydrocephalus or tumors. Although MRI findings are characteristic and present in up to 40 % of patients, they are not specific for PHTS (Fig. 1).7 Hydrocephalus in the setting of cranial dysmorphism in pediatric PHTS can result from Chiari malformation or arise secondary from dysplastic cerebellar gangliocytoma in Lhermitte-Duclos disease. However, in review of the 159 patients in table 1, only one ventriculo-peritoneal shunt procedure for pseudotumor cerebri was reported (0.6%).8Skin stigmata, such as lipoma, hemangioma or hamartoma, trichilemmoma and café-au-lait spots are detectable by inspection. These signs are generally well-documented, examination results appear in 155 from 159 patients. The occurrence of subcutaneous lipoma, which is a rare finding in children, particularly when combined with macrocephaly, should raise suspicion of PHTS and prompt genetic testing.5Reports of PTEN-associated cleft palate are scarce, although orofacial dysmorphism and a high-arched palate are present in 27% to 34% of cases. A single case of bifid uvula was described in 2007.9 Considering that up to 31% of cases present with oral mucosal papillomatosis, and that oral hyperkeratosis was described as part of Cowden syndrome, oral examination is an important adjunct in diagnosing PHTS.10 However, our overview suggests that oral signs are less frequently emphasized in the diagnostic process compared to the more prominent symptoms, with oral findings reported in only 24 cases from 159.Data collection and analysis in PHTS are limited by the retrospective nature of most case reports and reviews. It remains difficult to predict tumor risk during infancy or to estimate, how many patients live with a pathogenic variant in PTEN , without ever requiring medical attention. We advocate for broad genetic testing like WES with a low threshold of suspicion, to anticipate developmental delays, to potentially detect tumor growth at an early stage and to support patients and families in managing this rare, burdensome disease.CONFLICT OF INTERESTThe authors declare that there is no conflict of interest.ETHICAL STATEMENTThe mother of the patient has given written consent to the scientific publication of the case.REFERENCES1. Leibowitz MS, Zelley K, Adams D, et al. Neuroblastoma and cutaneous angiosarcoma in a child with PTEN hamartoma tumor syndrome.Pediatr Blood Cancer. 2022;69(10):e29656. doi:10.1002/pbc.296562. Macken WL, Tischkowitz M, Lachlan KL. PTEN Hamartoma tumor syndrome in childhood: A review of the clinical literature. Am J Med Genet C Semin Med Genet. 2019;181(4):591-610. doi:10.1002/ajmg.c.317433. Martinez-Rios C, De Leon Benedetti LS, Tierradentro-Garcia LO, Kilicarslan OA, Caro-Dominguez P, Otero HJ. Imaging findings of children with PTEN-related hamartoma tumor syndrome: a 20-year multicentric pediatric cohort. Pediatr Radiol. 2024;54(7):1116-1127. doi:10.1007/s00247-024-05922-84. LLOYD KM 2nd, DENNIS M. Cowden’s disease. A possible new symptom complex with multiple system involvement. Ann Intern Med. 1963;58:136-142. doi:10.7326/0003-4819-58-1-1365. Martin H, Bessis D, Bourrat E, et al. Cutaneous lipomas and macrocephaly as early signs of PTEN hamartoma tumor syndrome.Pediatr Dermatol. 2020;37(5):839-843. doi:10.1111/pde.142656. Plamper M, Gohlke B, Woelfle J. PTEN hamartoma tumor syndrome in childhood and adolescence-a comprehensive review and presentation of the German pediatric guideline. Mol Cell Pediatr. 2022;9(1):3. Published 2022 Feb 21. doi:10.1186/s40348-022-00135-17. Smpokou P, Fox VL, Tan WH. PTEN hamartoma tumour syndrome: early tumour development in children. Arch Dis Child. 2015;100(1):34-37. doi:10.1136/archdischild-2014-3059978. Plamper M, Born M, Gohlke B, et al. Cerebral MRI and Clinical Findings in Children with PTEN Hamartoma Tumor Syndrome: Can Cerebral MRI Scan Help to Establish an Earlier Diagnosis of PHTS in Children?.Cells. 2020;9(7):1668. Published 2020 Jul 10. doi:10.3390/cells90716689. Yotsumoto Y, Harada A, Tsugawa J, et al. Infantile macrocephaly and multiple subcutaneous lipomas diagnosed with PTEN hamartoma tumor syndrome: A case report. Mol Clin Oncol. 2020;12(4):329-335. doi:10.3892/mco.2020.198810. Fardal Ø, Nevland K, Johannessen AC, Vetti HH. The PTEN hamartoma tumor syndrome: how oral clinicians may save lives. Clin Adv Periodontics. 2023;13(1):21-26. doi:10.1002/cap.1019611. Bregvadze K, Jabeen S, Rafi SM, Tkemaladze T. The complexity of phosphatase and tensin homolog hamartoma tumor syndrome: A case report.SAGE Open Med Case Rep. 2024;12:2050313X241245317. Published 2024 Apr 6. doi:10.1177/2050313X24124531712. Martín-Valbuena J, Gestoso-Uzal N, Justel-Rodríguez M, et al. PTEN hamartoma tumor syndrome: Clinical and genetic characterization in pediatric patients. Childs Nerv Syst. 2024;40(6):1689-1697. doi:10.1007/s00381-024-06301-213. Ciaccio C, Saletti V, D’Arrigo S, et al. Clinical spectrum of PTEN mutation in pediatric patients. A bicenter experience. Eur J Med Genet. 2019;62(12):103596. doi:10.1016/j.ejmg.2018.12.00114. Plamper M, Gohlke B, Schreiner F, Woelfle J. Phenotype-Driven Diagnostic of PTEN Hamartoma Tumor Syndrome: Macrocephaly, But Neither Height nor Weight Development, Is the Important Trait in Children.Cancers (Basel). 2019;11(7):975. Published 2019 Jul 11. doi:10.3390/cancers1107097515. Kato K, Mizuno S, Inaba M, et al. Distinctive facies, macrocephaly, and developmental delay are signs of a PTEN mutation in childhood.Brain Dev. 2018;40(8):678-684. doi:10.1016/j.braindev.2018.04.00816. Hansen-Kiss E, Beinkampen S, Adler B, et al. A retrospective chart review of the features of PTEN hamartoma tumour syndrome in children.J Med Genet. 2017;54(7):471-478. doi:10.1136/jmedgenet-2016-10448417. Busa T, Milh M, Degardin N, et al. Clinical presentation of PTEN mutations in childhood in the absence of family history of Cowden syndrome. Eur J Paediatr Neurol. 2015;19(2):188-192. doi:10.1016/j.ejpn.2014.11.012LEGENDSTABLE 1: Childhood PTHS symptoms reported over the last ten years, listed according to the number of patients examined for each specific symptom

Today, we talk about the topic of Basic Networking & Static Routing!Let’s take a look at the network scenario as an example showing the concept of Networking and Routing!For this example, Our goal is : We need to send some digital files like PDF documents from laptop A to laptop B or in the reverse direction!This is the most common things we always do everyday!It is similar to send a message from the APPS of smartphone A to another smartphone B!Do you know how the technology behind it helps us to make it happen!We are going to demonstrate all the technical steps how to achieve this goal!—————————————————————————In order to transfer data between 2 user terminals, we need to make a connection between them first. There are 2 Scenarios of connection between 2 end points!

Today, we talk about the topic of Basic Networking & Static Routing!Let’s take a look at the network scenario as an example showing the concept of Networking and Routing!For this example, Our goal is : We need to send some digital files like PDF documents from laptop A to laptop B or in the reverse direction!This is the most common things we always do everyday!It is similar to send a message from the APPS of smartphone A to another smartphone B!Do you know how the technology behind it helps us to make it happen!We are going to demonstrate all the technical steps how to achieve this goal!—————————————————————————In order to transfer data between 2 user terminals, we need to make a connection between them first. There are 2 Scenarios of connection between 2 end points!

Avian influenza virus (AIV) remains a significant global threat, with periodic reemergence in Iraq. This study presents the first molecular characterization of the highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b in seagulls. The H5N1 AIV was identified during outbreaks in 2024 at Dukan Lake in Sulaimani province. Phylogenetic analysis of the HA gene revealed that the Dukan Lake strain belongs to subclade 2.3.4.4b, clustering closely with Kazakhstan strains (A/mute swan/Mangystau and A/Arakol Lake) with DNA identities of 99.38% and 98.82%, respectively. Genetic analysis showed a polybasic amino acid cleavage site motif (PLREKRRKRGLF) in the HA gene. Additionally, receptor binding domain (RBD) analysis indicated a preference for the avian α-2, 3 SA receptor over the mammalian α-2, 6 SA receptor. The NA gene analysis revealed amino acid residues D199, I223, S247, and H275, which are susceptible to antiviral drugs. These findings demonstrate the genetic evolution of the H5N1 2024 Dukan Lake seagull strain, distinguishing it from other strains in Iraq. Rapid communication of virological and genetic data is essential for implementing customized preventative measures and enhancing public health awareness.

The outbreak of Mpox in China has rendered the promotion of effective preventive measures among susceptible populations particularly crucial. The study team investigated 2,403 men who have sex with men (MSM) for whether they would get a Mpox vaccine. The participants were randomly split into a training set and a testing set in a ratio of 3:1 with R software. The variables were screened by the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Then, the prediction model, including important variables, used a multivariate logistic regression analysis and presented as a nomogram. The Receiver Operating Characteristic (ROC) curve, Calibration curve, Kolmogorov-Smirnov (K-S) test, Lift test and Population Stability Index (PSI) were performed to test the validity and stability of the model. 87.1% of the participants had vaccination intentions. Five of the thirty-one screened variables, i.e., Mpox knowledge, social support, vaccination internal rewards, vaccination external rewards and vaccination response efficacy, were included in the prediction model. The results indicated that the model has a high predictive power and is highly stable. The government should design targeted public health strategies, integrating social engagement and leveraging peer and community education for Mpox vaccine promotion.

Long Covid is a multisystemic syndrome that can affect various systems, presenting signs and symptoms that can be disabling and significantly impact the quality of life of those affected. Objectives: This study aimed to translate, adapt, and validate the psychometric properties of the C19-YRSm in Spanish for the Mexican population. Method: A total of 889 participants were recruited from February to November 2023. Invitations were extended through social media to Mexican men and women over 18 years old who had experienced COVID-19 symptoms at any point, to participate in this study by completing the C19-YRSm. Data collection took place from February to November 2023. Results: The C19-YRSm instrument demonstrated adequate scale characteristic properties. Item-total correlations ranged from 0.28 to 0.67 for SS and 0.45 to 0.75 for FD, with good internal reliability (Cronbach’s alpha of 0.87 for SS and 0.82 for FD). Convergent validity showed a strong positive association between SS and FD. Factor analysis supported a two-factor structure of SS and FD. Conclusions: The evidence presented in this research project, along with findings reported by other authors in different validations of the C19-YRSm, suggests it is a specific, valid, and reliable tool for assessing and monitoring Long Covid.

Background & Aim: This study aims to evaluate the prevalence of undiagnosed hepatitis delta in southern Spain (Andalusia) and assess the effectiveness and cost-efficiency of implementing reflex testing for hepatitis D detection in HBsAg-positive patients. Patient & Methods: A multicenter ambispective study was conducted in 17 hospitals in Andalusia. The retrospective phase analyzed diagnostic processes for hepatitis delta from January 2018 to June 2022, focusing on HBsAg-positive patients. The prospective phase, from October 2022 to March 2023, implemented reflex testing, performing anti-HDV serology on all HBsAg-positive patients without prior testing. HDV RNA testing was conducted on those who tested positive for anti-HDV. Results: In the retrospective phase, out of 18,583 HBsAg-positive patients, anti-HDV tests were performed on 3,436 (18%), identifying 205 (6%) positive cases. HDV RNA was tested in 158 (77%) anti-HDV-positive patients, with 69 (44%) testing positive. In the prospective phase, out of 2,384 HBsAg-positive patients without prior anti-HDV testing, 2,293 (96%) were tested, identifying 109 (4.7%) positive cases. HDV RNA was analyzed in 97 (89%) anti-HDV-positive patients, with 30 (31%) testing positive. Reflex testing increased anti-HDV detection by 77%, resulting in a fourfold increase in detecting anti-HDV-positive patients and a threefold increase in detecting HDV RNA-positive patients, reducing undiagnosed HDV RNA-positive cases to 4% compared to 45% with clinical practice. Cost analysis indicated a saving of €265,954 with reflex testing. Discussion: Reflex testing significantly improves HDV detection and reduces healthcare costs. It simplifies the diagnostic process, increasing the detection rate of hidden chronic hepatitis delta patients and proving to be an efficient strategy for managing chronic hepatitis B patients.

Titli Bhattacharjee1, Raj Ahmad Rain2*, Prayushi Patel3, Mohit Badhai4, G. Anil K. Reddy5

A document by Dr.Vaishnavi Rajaraman. Click on the document to view its contents.

Unmasking the Wolf in Sheep’s Clothing: Atypical Presentation of Pulmonary Embolism as Acute Abdomen - A Case Report1st and Corresponding Author: Dr. Lolwa Al-Khulaifi, Emergency Medicine Resident, Medical Education.Hamad Medical Cooperation.Email: alkhulaifi.l@outlook.com2nd Author: Dr. Mohammed Elgassim, Emergency Medicine Resident, Medical Education.Hamad Medical Cooperation.Email: Moelgassim@gmail.com3rd Author: Dr. Waleed Salem, Emergency Medicine Senior Consultant, Hamad Medical Education.Email: wsalem@hamad.qaAuthor’s contributions: The authors confirm contribution to the paper as followsLiterature review: 1st Author.Draft Manuscript preparation: 1st and 2nd Authors.Draft manuscript revision: 1st, 2nd,and 3rd Authors.Project supervision: 3rd Author.The patient has consented in a written form for the following information to be published and released; written information is provided.Keywords:Pulmonary Embolism (PE), Epigastric pain, Right heart strain, Anticoagulation.Introduction:Pulmonary embolism (PE) is defined as the blockage of the pulmonary artery or its branches by material that was created elsewhere in the body, such as thrombus, tumor, fat, or air [1]. There are multiple risk factors that can provoke the development of PE. There are all combined in one triad called Virchow’s triad, which include venous stasis, endothelial injury, and hypercoagulable status [2,3]. PE is considered one the common diseases and a fatal one too. It is thought to be responsible for 50,000-200,000 deaths yearly [4].The variety of its presenting features can range from no symptoms at all, to sudden death. Current resources consider dyspnea as the most common presenting feature for PE. Other common presentation includes chest pain, hemoptysis, syncope, or symptoms of deep venous thrombosis [5]. However, the uncommon presentation of PE is not well illustrated. And this may lead to misdiagnosis of this fatal disease. Herein, we present this case of one the uncommon presentation of PE in clinical practice.History and physical examination:A 40-year-old previously healthy Sri-Lankan male was referred to the emergency department from a private clinic due to epigastric pain and abnormal ECG, mainly to rule out myocardial infarction. The patient had abdominal pain localized to the epigastric area, sharp in nature, started suddenly today at around 4 hours prior to presentation. The non-radiating, with no exacerbating/alleviating factors. There was no history of chest pain, shortness of breath palpitations, dizziness, or syncope. The patient also denied any additional gastrointestinal or genitourinary symptoms. He had an appendectomy done 10 years back, otherwise he does not suffer from any chronic medical illnesses. His family history was unremarkable. He is smoker and drinks alcohol occasionally with no use of illicit drugs. And lastly, he works as a laundry business and no recent travel history.The ECG that was done in the clinic that raise the suspicion of MI had no changes compared to the ECG done in the emergency department, showing normal sinus rhythm, heart rate of 100, with T- wave inversion in lead V1-V3. No other remarkable findings were found. During his emergency department stay, he was initially calm and not in respiratory distress, with normal vital sings. Then when he was re-examined, vital signs were Temperature: 36.9 °C, Heart Rate: 119 bpm, Respiratory Rate: 27 bpm, Blood Pressure: 147/107, SpO2: 97%. Upon physical examination, the remarkable findings were epigastric tenderness with no obvious peritoneal signs. Cardiovascular and respiratory examinations were normal. In addition, point of care ultrasound (POCUS) was done by a POCUS subspeciality expert and showed normal heart contractility and function, no right ventricular dilation, no pericardial fluid, with normally sized abdominal aorta.Methods:Laboratory and imaging investigation were done to rule out the possibility of MI or a perforated viscus. These included complete blood count, complete metabolic panne, cardiac enzymes (Troponin-T), venous blood gas, chest x-ray (figure 1) and repeat ECG (figure 2). The remarkable results were leukocytosis and Troponin T of 9, then second set of 11. The patient status has progressed further with tachypnea and sweating; however, the pain was less after analgesia. This has prompted the physician to proceed with CT Abdomen to look for a possible perforated viscus. The result of that imaging showed that the visualized lower chest section has features concerning of bilateral pulmonary embolism. The next step after this report was to have an CT pulmonary angiography (figure 3 and 4), that confirmed the presence of bilateral pulmonary artery thromboembolism with right ventricular strain.Conclusion:After the confirmed diagnosis the patient received the therapeutic dose of anticoagulation (enoxaparin) and disposition to medical intensive care unit has been made, where he received thrombolysis. Further workup and observation have been done. The patient’s stay was uneventful, he was stepped down to the medical ward, then discharged home.Discussion:This case presents a diagnostic challenge, initially raising suspicion of myocardial infarction due to epigastric pain and abnormal ECG findings. The patient’s journey underscores the importance of a comprehensive diagnostic approach. The timely utilization of imaging played a pivotal role in steering the diagnostic process. The CT Abdomen, though initially sought to investigate a potential perforated viscus, revealed features concerning bilateral pulmonary embolism. Subsequent confirmation through CT pulmonary angiography provided critical insights into the extent of pulmonary artery thromboembolism. In the management of this case, swift initiation of therapeutic anticoagulation (enoxaparin) and subsequent medical intensive care unit admission for thrombolysis showcased the impact of prompt decision-making on positive patient outcomes.A comprehensive literature review revealed similar cases, emphasizing a 6.7% incidence of pulmonary embolism presenting with abdominal pain [6]. It hypothesizes possible mechanisms that may explain abdominal pain in PE, such as hepatic congestion due to right heart strain, diaphragmatic irritation, and tension on the parietal pleura nerve endings [6-9]. This enhances our understanding of atypical presentations. It is crucial to acknowledge the mortality risk associated with missed or untreated pulmonary embolism, estimated at around 30% [10]. Also, around 70% of misdiagnosed PEs were discovered postmortem [4]. Unfortunately, traditional learning resources often overlook unusual presentations [9]. Therefore, presenting this case contributes to existing literature, urging physicians to consider pulmonary embolism in patients with abdominal pain.The strengths in our case management include effective triaging, considering the patient’s clinical status, and the initial use of POCUS. However, areas for improvement include advocating for a broader initial differential diagnosis and recognizing the potential benefits of serial POCUS examinations.Lastly, this case serves as a reminder of the diagnostic intricacies surrounding pulmonary embolism, particularly its atypical presentations. By incorporating such cases into educational materials, we hope to enhance physician awareness, prompt further research, and ultimately reduce misdiagnosis and mortality rates associated with pulmonary embolism.Key clinical message:This case highlights the importance of implementing a systematic approach and keeping a wide differential when encountering nonspecific symptoms. Along with the other similar cases, here we remind the physicians to have high index of suspicion of PE, especially with uncommon symptoms such as abdominal pain. This realization could lead to a lifesaving decision in clinical practice.References:Rali, P., Gandhi, V., & Malik, K. (2016). Pulmonary embolism. Critical Care Nursing Quarterly, 39(2), 131–138. doi:10.1097/cnq.0000000000000106.Bagot, C. N., & Arya, R. (2008). Virchow and his triad: A question of attribution. British Journal of Haematology, 143(2), 180–190. doi:10.1111/j.1365-2141.2008.07323.Coon, W. W., & Willis, P. W. (1959). Deep venous thrombosis and pulmonary embolism. The American Journal of Cardiology, 4(5), 611–621. doi:10.1016/0002-9149(59)90145-6.Derr, C., Gantner, J., & Keffeler, J. (2013). Pulmonary embolism: An abdominal pain masquerader. Journal of Emergencies, Trauma, and Shock, 6(4), 280. doi:10.4103/0974-2700.120376.Stein, P. D., Terrin, M. L., Hales, C. A., Palevsky, H. I., Saltzman, H. A., Thompson, B. T., & Weg, J. G. (1991). Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease. Chest, 100(3), 598–603. doi:10.1378/chest.100.3.598.Israel, H. L., & Goldstein, F. (1957). The varied clinical manifestations of pulmonary embolism. Annals of internal medicine, 47(2), 202–226. doi:10.7326/0003-4819-47-2-202.Kounis N. G. (1979). Pulmonary embolism with neurological and abdominal manifestations. The Practitioner, 223(1333), 115–116.Gorham, L. W. (1961). A study of pulmonary embolism. Archives of Internal Medicine, 108(2), 189. doi:10.1001/archinte.1961.03620080021003.Han, Y., & Gong, Y. (2019). Pulmonary embolism with abdominal pain as the chief complaint. Medicine, 98(44). doi:10.1097/md.0000000000017791.Carson, J. L., Kelley, M. A., Duff, A., Weg, J. G., Fulkerson, W. J., Palevsky, H. I, Terrin, M. L. (1992). The clinical course of pulmonary embolism. New England Journal of Medicine, 326(19), 1240–1245. doi:10.1056/nejm199205073261902.Images: