Key Clinical MessageParoxysmal hypertension, especially when associated with a negative workup for pheochromocytoma, should prompt consideration of pseudopheochromocytoma. This diagnosis requires careful exclusion of other secondary causes of hypertension and highlights the complexity of managing unexplained hypertensive episodes. Clinicians should avoid unnecessary tests and adopt a tailored approach to diagnosis and management.IntroductionSymptomatic paroxysmal hypertension is the hallmark of a pheochromocytoma, a type of neuroendocrine tumor that releases catecholamines, triggering the symptomatic episodes associated with these tumors. Despite the frequently reflexive association between the two, only 2% with this presentation have a pheochromocytoma.1 In the absence of negative radiologic laboratory and radiologic workups, symptomatic paroxysmal hypertension is known as pseudopheochromocytoma.In the current report, we detail a case of pseudopheochromocytoma in a 22-year-old man, which has been a diagnostic conundrum. The case is reported after obtaining informed consent from the patient.Case HistoryA 22-year-old Caucasian male with a PMHx of Lyme Disease, hypermobility, MTHFR mutation, COVID-19 and s/p appendectomy presented to the office to establish care with a primary care provider. At the time of presentation, the patient had been experiencing five months of symptomatic hypertensive episodes for which extensive workup by multiple providers had begun. These episodes consisted of dizziness, palpitations, headache, chest pain, and/or tinnitus, often prompting evaluation in the emergency department, where blood pressures ranged from 173-196/89-110. Outside of these spells, the patient reported posterior headaches, which he likened to a pressure sensation, that worsened when supine and were occasionally accompanied by pulsatile tinnitus. He found that his headaches and elevated blood pressure worsened after eating and drinking. He was also experiencing episodes of dizziness. He denied diarrhea, flushing, weight loss, hypotensive episodes. Baseline blood pressures in office averaged in the 130s/70s. Various workups had been done by providers in the emergency department and in specialty offices in attempt to unearth a diagnosis.Methods (differential diagnosis, investigations and treatment)The patient had multiple EKGs, notable for PVCs, and cardiology evaluation with echocardiogram, holter monitor, and treadmill stress test. Stress testing was normal, the echocardiogram revealed trace tricuspid regurgitation, and the holter study revealed a 0.5% PVC burden. Given the episodic nature of the patient’s symptoms and severe hypertension, workup for a pheochromocytoma was started during an ED visit. CT of the abdomen and pelvis was negative for masses, plasma metanephrines were within normal limits, and CT of the head was unremarkable. The patient traveled home to seek further evaluation with his hometown primary care provider. 24 hour urine collection was done which revealed the following elevations: Vanillylmandelic Acid (VMA) at 10.3 (ULN 7.5), dopamine at 701 (ULN 510), and 5-HIAA at 79 (ULN 14.9). The patient sought evaluation with endocrinology, where further imaging and labs were ordered for concern of a neuroendocrine tumor and workup of secondary hypertension. CT soft tissue of the neck and CT of the chest, both with contrast, were unremarkable. MRI of the abdomen and pelvis was unremarkable. Renal artery ultrasound showed no evidence of stenosis. Renal panel, plasma renin activity, aldosterone, serum plasma metanephrines, IGF-1, chromogranin A, ANA profile, ANCA profile, and sedimentation rate were all within normal limits. To rule out carcinoid, a colonoscopy was done which was unremarkable except for gastropathy.68Ga-DOTATATE PET was negative for evidence of pheochromocytoma or paraganglioma. Tilt table testing was suggestive of POTS, with concurrent transcranial doppler ultrasound showing impaired cerebral blood flow in the left middle cerebral artery.Throughout the course of multiple workups, the patient trialed multiple medications for his hypertensive episodes. Amlodipine worsened his symptoms. Prazosin was ineffective. At the time of writing, the patient was on a regimen of Toprol and Olmesartan. This case remains ongoing with further imaging planned to evaluate both the cervical spine and cervical and cerebral blood flow. Given the negative workup for a catecholamine-secreting tumor, dysautonomia remains a leading working diagnosis for this case.DiscussionPseudopheochromocytoma presents a diagnostic challenge for the clinician. Prior to making this diagnosis, a catecholamine-secreting tumor, such as a pheochromocytoma or a paraganglioma, must be ruled out. Initial workup entails evaluation for significant elevations in plasma fractionated metanephrines and urine fractionated metanephrines and catecholamines.6 Though not observed at the level expected with a catecholamine secreting tumor, mild elevations in catecholamines are commonly observed with pseudopheochromocytoma. It has been proposed that these patients have increased sympathetic tone at baseline, thus explaining these laboratory findings which may be falsely interpreted as a catecholamine-secreting tumor.2 Not only do these elevations have the potential to cloud the clinical picture, but they may also trigger a cascade of unnecessary testing. Observation of urine catecholamines greater than twice the upper limit of normal, urine normetanephrine > 900 μg, urine metanephrines > 400μg or a “significant increase” in fractionated plasma metanephrines warrants imaging, often through adrenal/abdominal MRI or CT.6In the case of a negative workup, pseudopheochromocytoma must be considered in addition to other conditions which may manifest as paroxysmal hypertension: hyperthyroidism, hyperdynamic beta-adrenergic circulatory state, migraine headaches, coronary insufficiency, renovascular hypertension, central nervous system lesions, anxiety, baroreflex failure, carcinoid, and panic disorder.2,4Hypertensive paroxysms associated with pseudopheochromocytoma are unprompted and severe, with blood pressure peaking up to > 200/ > 100 during an episode and accompanied by chest pain, headache, lightheadedness, nausea, palpitations, and flushing.2-5 Episodes may last less than 10 minutes and up to 2 days, occurring daily or less than once a month.2 The exact pathophysiology of these paroxysms remains unclear. Sharabi et. al found that patients with pseudopheochromocytoma showed higher baseline plasma concentrations of epinephrine as well as an exaggerated epinephrine response to glucagon when compared to controls, thus suggesting a component of adrenomedullary hyperfunction in these patients.3 Mann et. al suggested repressed emotions as being an element of the cause of hypertensive paroxysms. In a case series of 10 patients with hypertensive paroxysms and a negative workup for pheochromocytoma, 8 of the patients reported a history of significant emotional trauma (such as being abused as a child or the death of a spouse). It was suggested that repressed emotions may trigger an adrenomedullary response.5 It is worth noting that paroxysmal hypertensive episodes seen in pseudopheochromocytoma can be associated with various etiologies2 and thus no single underlying mechanism can be solely responsible.Once a tumor has been ruled out, the major question becomes: how do we manage these patients? Without a clear etiology, the proper course of management can be vague and often a process of trial and error. As with the case in our patient, multiple medications were trialed and failed. This appears to be a shared experience in patients with pseudopheochromocytoma. Mann et. al reported similar findings in a case series of pseudopheochromocytoma, where multiple patients had failed various antihypertensives, both alone and in combination.4 The same case series reported a successful treatment outcome using both an alpha and beta blockade. Some patients found control through this blockade combination alone whereas others required the addition of a tricyclic antidepressant or selective serotonin reuptake inhibitor.4 Sertraline specifically has been studied for paroxysmal hypertension. Vaclavik et. al studied the effect of sertraline in 47 patients experiencing hypertensive paroxysms. Patients were given 50mg sertraline once a day, to be taken in addition to current medications. After 3 months of sertraline therapy, 28 patients (59.6%) reported full and 14 patients (29.8%) reported partial resolution of their symptoms of paroxysmal hypertension (such as nausea, headache, dyspnea). However, a majority of the patients involved in this study had chronic hypertension at baseline, requiring an average of 3.1 antihypertensives, and were experiencing paroxysmal exacerbations of their blood pressure.7 Though these findings are poorly generalizable to normotensive individuals, the symptomatic improvement observed provides notable support for Mann et. al’s proposition that repressed emotions may play a role in the pathophysiology behind these unexplained hypertensive paroxysms.5ConclusionThe presented case underscores the diagnostic challenge of symptomatic paroxysmal hypertension in the setting of a negative neuroendocrine tumor workup. Symptom etiology often remains elusive despite thorough, sometimes unnecessary, testing. We hope that this case heightens awareness of pseudopheochromocytoma as a differential diagnosis.AuthorshipSarah E. Goodrich, B.S.: Conceptualization; investigation; methodology; project administration; supervision; visualization; writing – original draftDr. Jason P. Browder, D.O.: supervisionReferencesPacak K, Linehan WM, Eisenhofer G, Walther MM, Goldstein DS. Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma. Ann Intern Med. 2001;134(4):315-329.Mann SJ. Severe Paroxysmal Hypertension (Pseudopheochromocytoma). In: Berbarie AE, Mancia G, eds. Disorders of Blood Pressure Regulation: Phenotypes, Mechanisms, Therapeutic Options. Cham, Switzerland: Springer International Publishing; 2018:525-540.Sharabi Y, Goldstein DS, Bentho O, et al. Sympathoadrenal function in patients with paroxysmal hypertension: pseudopheochromocytoma. J Hypertens. 2007;25(11):2286-2295.Mann SJ. Severe paroxysmal hypertension (pseudopheochromocytoma): Understanding the cause and treatment. Arch Intern Med. 1999;159(7):670-674.Mann SJ. Severe paroxysmal hypertension. An automatic syndrome and its relationship to repressed emotions. Psychosomatics. 1996;37(5):444-450.Young WF. Endocrine Hypertension. In: Melmed S, Auchus RJ, Goldfine AB, Koenig RJ, Rosen CJ, eds. Williams Textbook of Endocrinology. Philadelphia, PA: Elsevier; 2020:542-572.Vaclavik J, Krenkova E, Vaclavik T, Kamasova M. Effect of sertraline in paroxysmal hypertension. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2018;162(2):116-120.

Seagrasses are globally declining due to direct human impacts and climate change. Effective measures of seagrass conservation, management, and restoration require an understanding of the variation in reproductive strategies. Here, we examine how reproductive strategies differ between core and range-edge populations for the widely distributed but regionally threatened seagrass species Enhalus acoroides, spanning more than 5000 km. We fill an important gap in geographic coverage by including western Pacific islands, a region often overlooked in Indo-Pacific seagrass genetic studies. Specifically, we assess genotypic diversity, clonal structure, and genetic connectivity for thirty-six populations across islands or small island groups throughout Southeast Asia and Micronesia. Near the range edge, exceptionally low genotypic richness was found for geographically isolated islands in Micronesia (Guam and Saipan), with a millennia-old clone being prevalent across all meadows and shared between islands at more than 200 km distance, a phenomenon not previously documented for Indo-Pacific seagrass species. In contrast, core populations around small islands in Southeast Asia, that are in close vicinity to the mainland or large islands, exhibited high genotypic diversity and small clonal sizes. We propose that limited long-distance dispersal of propagules to isolated islands near the species’ range edge drives reduced levels of sexual reproduction and facilitates extreme clonality in E. acoroides. The strong variation in genotypic diversity and clonal structure between core and range-edge populations suggest regional differences in the resilience of E. acoroides meadows, highlighting the need for targeted conservation measures and restoration efforts.

Phosphorus (P) is a limiting element in highly-weathered subtropical/tropical soils. Depending on lithology, tropical soils differ strongly in soil chemistry and aggregate structure but little is known about how this controls P speciation and distribution and hence P supply for the forests. We compared the distribution of organic and inorganic P fractions as well as microbial biomass P (MBP) and enzymatic activities in bulk soils and soil aggregates of two adjacent subtropical forests, one on an acidic red soil and one on a limestone soil. The red soil was poor in total P (TP) and exchangeable P (Ex-P) but rich in iron-bound (Fe-P) and MBP, phosphorus in the limestone soil was more evenly distributed among different P fractions conveying an overall larger P availability. We found major differences in P abundance and distribution in macro- and micro- aggregates between the soils: 1) red soil was dominated by stable organic P which was slightly enriched in macro-aggregates, while limestone soil held higher proportion of labile organic P with organic P fractions being more equally distributed across aggregate sizes. 2) MBP was more abundant in red soil and, like organic P, concentrated in macro-aggregates, while MBP in limestone soil was concentrated in micro-aggregates. MBP correlated positively with other P forms in the macro-aggregates of the red soil, whereas it correlated negatively in the macro-aggregates of the limestone soil. 3) Phosphatase and phytase activities correlated positively with organic P forms in both macro- and micro-aggregates of the red soil but not in the limestone soil. Together, these findings indicate that microorganisms mediate a tighter P cycle in the P-poor red soil. In the P-rich limestone soil, macro-aggregates appear to protect P from microbial uptake by calcium adsorption and occlusion, hence contribute to P sequestration. Our study highlights the key role of lithology for controlling P storage and supply in subtropical forest soils, which is relevant for forest conservation and restoration.

Rare Complication of Intrauterine Device Migration to the Bladder: A Case Report

Navigating the Needles: Unveiling the Risks of Acupuncture, A Case ReportHarkesh Arora1, Dhiran Sivasubramanian2, Sinduja Sivakumar 3, Sivaguha Yadunath4, Sreekanth Avula5(corresponding author)1Lovelace Medical Center, 601 Dr. Martin Luther King Jr Ave NE, Albuquerque, NM USA 871022Christian Medical College and Hospital Vellore3Burrell College of Osteopathic Medicine4Mercy Catholic Medical Center - Mercy Fitzgerald Campus5University of Minnesota, Twin Cities, PWB, 516 Delaware St SE 6-207, Minneapolis, MN, USA 55455; avula015@umn.edu

A document by Jonathan Harris. Click on the document to view its contents.

The purpose of this study is to clarify the mechanism of Government Embedment and Organizational Environment on the supervisory effectiveness in collective governance of Rural Residential Land, and to provide decision-making reference for optimizing the order of Rural Residential Land utilization and promoting the effective implementation of collective governance of Rural Residential Land. The research employs various models including OLS model, Tobit model, mediated effect model and moderated mediated effect model. The research results show that 1) Government Embedment can significantly enhance the supervisory effectiveness in collective governance of Rural Residential Land. 2) The Technical and Cultural Environments in the Organizational Environment can significantly enhance the supervisory effectiveness in collective governance of Rural Residential Land, but the Resource Environment has a negative effect on the supervisory effectiveness in collective governance of Rural Residential Land, the Technical Environment and the Cultural Environment play a partially mediating effect, and Resource Environment plays a masking effect. 3) Anonymous whistleblowing mechanism positively moderates the positive effect of Technical Environment and Cultural Environment on the supervisory effectiveness in collective governance of Rural Residential Land. 4) There is locational heterogeneity in the influence of Government Embedment and Organizational Environment on the supervisory effectiveness in collective governance of Rural Residential Land. In conclusion, our research underscores the need to build a supervision and sanction mechanism for coordination between towns and villages, promote the integration and complementarity of formal and informal systems, establish and improve an anonymous whistle-blowing mechanism for the use of illegal Rural Residential Land. These strategies will enhance the supervisory effectiveness of Collective Governance, so as to promote the effective implementation of collective governance of Rural Residential Land, and break the dilemma of Rural Residential Land governance.

Epstein-Barr virus (EBV) is a ubiquitous human ɣ-herpesvirus implicated in various malignancies, including Burkitt’s lymphoma and gastric carcinomas. In most EBV-associated cancers, the viral genome is maintained as an extrachromosomal episome by the EBV nuclear antigen-1 (EBNA1). EBNA1 is considered to be a highly stable protein that interacts with the ubiquitin-specific protease 7 (USP7). Here, we show that pharmacological inhibitors and small interfering RNA (siRNA) targeting USP7 reduce EBNA1 protein levels. The USP7 inhibitor GNE6776 altered EBNA1 protein interactions, including disrupting its ability to bind to USP7. GNE6776 also inhibited EBNA1 binding to EBV oriP DNA and reduced viral episome copy number. GNE6776 selectively inhibited EBV + gastric and lymphoid cell proliferation in cell culture and slowed EBV+ tumor growth in mouse xenograft models. Transcriptomic studies revealed that USP7 inhibition differentially affected EBV + cancer cells compared to EBV - cells with a significant effect on chromosome segregation and mitotic cell division pathways. Our findings indicate that USP7 inhibition perturbs EBNA1 stability and function and can be exploited to target EBV + cancer cells selectively.

Background Huddling is a behavioral strategy for small rodents to save energy and improve the survival rate under cold environments and in winter. Brown adipose tissue (BAT) is the main site of non-shivering thermogenesis (NST) in small mammals, playing an important role in maintaining body temperature and energy balance. However, the behavioral regulation in BAT thermogenesis in small mammals is rarely illustrated. We used male Brandt’s voles (Lasiopodomys brandtii) to explore the possible regulation mechanisms in BAT thermogenesis by the way of cold acclimation and huddling behavior. Results Results showed that there is a strong relationship between huddling behavior and NST in BAT. The hypothalamus, which is impacted by huddling behavior, influences PPAR signaling pathway in the BAT, and induces thermogenesis through Calcium signaling pathway. PPAR pathway causes crosstalk among NF-κB signaling pathway, Thermogenesis and Fatty acid metabolism to perform thermogenesis functions. Conclusions The results suggest that huddling behavior can modulate adaptive thermogenesis in BAT. Cold acclimation and huddling had a synergistic effect on the regulation of thermogenic function. In BAT, the specific pathway of thermogenesis is as follows: TRAF6-PPARγ-UCP1-SUCLG1.

Inferring community composition from shotgun sequencing of environmental DNA is highly dependent on the completeness of reference databases used to assign taxonomic information as well as the pipeline used. While the number of complete, fully assembled reference genomes is increasing rapidly, their taxonomic coverage is generally too sparse to use them to build complete reference databases that span all or most of the target taxa. Low-coverage, whole genome sequencing, or skimming, provides a cost-effective and scalable alternative source of genome-wide information in the interim. Without enough coverage to assemble large contigs of nuclear DNA, much of the utility of a genome skim in the context of taxonomic annotation is found in its short read form. However, previous methods have not been able to fully leverage the data in this format. We demonstrate the utility of wholeskim, a pipeline for the indexing of k-mers present in genome skims and subsequent querying of these indices with short DNA reads. Wholeskim expands on the functionality of kmindex, a software which utilizes Bloom filters to efficiently index and query billions of k-mers. Using a collection of thousands of plant genome skims, wholeskim is the only software that is able to index and query the skims in their unassembled form. We also explore the effects of taxonomic and genomic completeness of the reference database on the accuracy and sensitivity of read assignment.

Biodiversity monitoring based on DNA metabarcoding depends on primer performance. Here, we develop a new metabarcoding primer pair that targets a ~ 318 bp fragment of the 28S rRNA gene. We validate the primer pair in assessing sponges, a notoriously challenging group for coral reef metabarcoding studies, by using mock and natural complex reef communities to examine its performance in species detection, amplification efficiency, and quantitative potential. Mock community experiments revealed a high number of sponge species (n = 94) spanning a broad taxonomic scope (15 orders), limited taxon-specific primer biases (only a single species exceeded a two-fold deviation from the expected number of reads), and its suitability for quantitative metabarcoding – there was a significant relationship between read abundance and visual percent coverage of sponge taxa (R = 0.76). In the natural complex coral reef community experiments, commonly used COI metabarcoding primers detected only 30.9% of sponge species, while the new 28S primer increased detection to 79.4%. These new 28S primers detect a broader taxonomic array of species across phyla and classes within the complex cryptobiome of coral reef communities than the Leray-Geller COI primers. As biodiversity assessments using metabarcoding tools are increasingly being leveraged for environmental monitoring and guide policymaking, these new 28S rRNA primers can improve biodiversity assessments for complex ecological coral reef communities.

Fault injection attacks can compromise cryptographic operations with out the necessity of physical alteration, thereby potentially disclosing private keys, which poses a grave threat to the security of elliptic curve digital signature algorithms. This letter presents an efficient and prac tical lattice-based fault injection attack on the SM2 digital signature algorithm (SM2-DSA), along with the corresponding defense strategy. The proposed attack method significantly reduces the moment precision requirements compared to existing lattice-based fault attacks, while also demonstrating computational advantages over other fault attacks. From the defensive perspective, the proposed strategy effectively defend against the lattice-based fault injection attacks while minimizing both time and spatial overheads. Specifically, our countermeasure incurs only a 0.8% time overhead and the area overhead for secure design does not exceed 1%. Our research provides valuable insights for evaluating the security of hardware implementations of SM2-DSA.

Mesenchymal stem cells (MSCs) derived exosomes, as a cell-free therapy to replace MSCs, have higher safety and great potential in regenerative medicine. The isolation of exosomes is a challenge that complicates their application. The commonly used ultracentrifugation and tangential flow filtration methods are inconvenient due to the need for expensive instruments and ultrafilter membranes. The cost of commercial kits limits their application in handling large samples. PEG precipitation is convenient and cost-effective. However, there is a need for optimized and standardized isolation methods based on PEG precipitation in different cell types or liquids to ensure consistent quality and yield. In this work, we optimized the PEG precipitation method for exosomes isolation and compared its effectiveness to two commonly used methods: ultracentrifugation (UC) and commercial exosome isolation kits (ExoQuick). The recovery rate of the optimized PEG method ( about 61.74%) was comparable to that of the commercial ExoQuick kit (about 62.19%), which was significantly higher than UC (about 45.80%). Exosome cargo analysis validated no significant differences in miRNA and protein profiles associated with the proliferation and migration of exosomes isolated by UC and PEG precipitation, which was confirmed by gap closure and CCK8 assays. These findings suggest that PEG-based exosomes isolation could be a highly efficient and high-quality method and may facilitate the development of exosome-based therapies for regenerative medicine.

Optimisation of isoamylase production in Escherichia coli under different nutrient limitation conditions

not-yet-known not-yet-known not-yet-known unknown The study of parameter-dependent partial differential equations (parametric PDEs) with countably many parameters has been actively studied for the last few decades. In particular, it has been well known that a certain type of parametric holomorphy of the PDE solutions allows the application of deep neural networks without encountering the curse of dimensionality. This paper aims to propose a general framework for verifying the desired parametric holomorphy by utilizing the bounds on parametric derivatives. The framework is illustrated with examples of parametric elliptic eigenvalue problems (EVPs), encompassing both linear and semilinear cases. As the results, it will be shown that the ground eigenpairs have the desired holomorphy. Furthermore, under the same conditions, improved bounds for the mixed derivatives of the ground eigenpairs are derived. These bounds are well known to take a crucial role in the error analysis of quasi-Monte Carlo methods.

Wheeze is the musical continuous sound produced by oscillations in any critically narrowed airways, and heard mostly on expiration. It is common in preschool age, about half of all children will experience an episode of wheezing by their sixth birthday. Asthma is usually characterized by cough, wheeze, chest tightness and fast breathing. It is a significant global health issue and affects both children and adults. The prevalence is on the increase, especially in LMIC. Studies from different populations have revealed the key role influencing the progression from preschool wheezing to childhood asthma. Recurrent wheezing is four or more episodes in the preceding year and has a spectrum of phenotypes and with heterogeneous features. Phenotypes of wheezing were proposed to facilitate the identification of young children who are at risk of subsequent development of asthma. The epidemiology and environmental determinants of recurrent wheezing and asthma are discussed.

not-yet-known not-yet-known not-yet-known unknown Pneumonia is an infection affecting the lower airway, where the air sacs are filled with mucus and pus; and typically presents with cough, fever, and fast breathing. Pneumonia is estimated to be the leading cause of mortality in children under five worldwide with 120 million episodes result in one million deaths globally. 1 The Low-Income and Middle-Income Countries (LMICs) are more affected. In a study in southeast Nigeria, 2 bronchopneumonia accounted for 41.9%, of the cases admitted in the tertiary hospitals and in another hospital based study among children, 3 pneumonia had the highest respiratory admission rates at 34.0%. Pneumonia can be caused by various organisms: Bacterial (Streptococcus, staphylococcus etc), Viral (RSV) and recently COVID 19 pneumonia. RSV has been noted globally to be a major cause of childhood lower respiratory tract infection, with morbidity/mortality occurring in 99% of (LMICs). 4 Some of the long term sequalae are discussed

Formaldehyde and Polyvinylpyrrolidone and characterized by high-end techniques is reported. MFP delves into design and modelling stoichiometric framework with dopants elucidating thermal interactions. Frameworks encompass diverse dopant structures exhibiting unique heat response by synchronizing eigenenergies with valence and conduction bands. The objective was to investigate different hysteresis assessing Frequency Resonance Energy Transfer (FRET). Thermal energy investigated structural frameworks via thermal curve. Experimentation and theoretical modelling have found effect of dopant on thermal properties through conjugative structural energies. Thermal behavior highlights intricate interplay between dopants and framework via FRET synchronizing energy to tailor dopant interactions and experimental optimizing FRET efficiency. Dynamic of dopant-framework interactions offered insights for energy transfer enhancing material performance in diverse applications. Intensified thermal studies have determined decomposition, activation energy (Ea), order of reaction, frequency factor, enthalpy change (H), entropy change (S) and Gibbs free energy (G). Thermodynamics predict stability as heating weaken cohesive forces to kinetic energy of intacting structure. From TGA/DTA, thermodynamic parameters are calculated by modern Coats – Redfern and Madhusudanan – Krishnan – Ninan equations. Calculations have elucidated HOMO-LUMO high temperature doped and coated interstities. Stability of MFP doped with metallic and graphene oxide nanoparticles as single energy ensemble gaining single valued wavefunction.

Objective: The purpose of this study is to investigate the clinical efficacy of the combination therapy of sorafenib and DOAP (doxorubicin, vincristine, cytarabine, and prednisone) in the treatment of a case of Langerhans cell sarcoma (LCS) negative for BRAF V600E mutation. Furthermore, we aim to retrospectively analyze the clinical characteristics, diagnosis, treatment, and prognosis of LCS. Methods: We conducted a retrospective analysis of the clinical data, pathological examination, and treatment of a patient with LCS, along with a review of relevant literature both domestic and international. Results: After four cycles of sorafenib combined with DOAP chemotherapy, the patient underwent sequential local radiotherapy, resulting in complete remission of the disease. The treatment-related side effects were manageable, and the patient tolerated the treatment well. The patient has survived for 40 months. Conclusion: LCS is a highly rare and aggressive malignancy that can involve various organs throughout the body. It presents with complex and diverse clinical manifestations, progresses rapidly, and has a poor prognosis. Treatment options include surgery, radiotherapy, chemotherapy, targeted therapy, and hematopoietic stem cell transplantation. However, there is currently no universally recognized optimal treatment protocol, and personalized treatment is necessary. Targeted therapy offers new hope for LCS patients.

Background: The differential diagnosis of supraventricular tachycardias(SVTs) is essential during radiofrequency(RF) ablation. The Extracardiac Vagal Stimulation(ECVS), introduced in 2015, offers new insights for electrophysiologic studies and ablation by allowing a controlled vagal effect on the heart. Methods: A prospective study of 625 patients with SVT ablation indication. ECVS was performed using a regular electrophysiology catheter to study atrioventricular(AV) and ventriculo-atrial(VA) conduction and their effects on tachycardia. Baseline ECVS was performed to determine the optimal position for right or left ECVS, near the jugular foramen. ECVS was repeated during atrial and ventricular pacing(VP) to monitor the procedure’s progression and ensure successful endpoints. Results: ECVS was successful in 611/625 patients(98%), 381(62.3%) had AV node reentry tachycardia(AVNRT), and 230(37.6%) Accessory Pathway(AP), including 135(58.7%) manifest AP(WPW) and 95(41.3%) concealed AP. ECVS+VP in 33 patients with atypical AVNRT yielded VA block in 32(97%), suggesting VA conduction solely via the AV node. In contrast, 57 patients with concealed para-septal AP maintained VA conduction during ECVS, confirming AP. ECVS proved to be a fast, reliable, and practical additional EP tool: VA block indicated AVNRT, while persitent VA conduction suggested AP. Additionally, ECVS was highly effective in revealing and confirming successful AP ablation by demonstrating absence of AV and VA anomalous conduction. Conclusion: ECVS was a valuable tool in the diagnosis and ablation of SVTs. It allowed reproducible AV and VA block through normal pathways, easily identifying AVNRT and concealed, intermittent, or subtle AP. It was particularly useful in complex cases involving concealed AP and atypical AVNRT tachycardia.

The transmission of monkeypox is studied using a stochastic model taking into account the biological aspects, the contact mechanisms and the demographic factors together with the intrinsic uncertainties. Our results provide insight into the interaction between stochasticity and biological elements in the dynamics of monkeypox transmission. The rigorous mathematical analysis determines threshold parameters for disease persistence. For the proposed model, the existence of a unique global almost sure non-negative solution is proven. Conditions leading to disease extinction are established. Asymptotic properties of the model are investigated such as the speed of transmission.

This clincal report presents the case of a six-month-old male infant with suspected left testicular torsion and right cryptorchidism, who exhibited prolonged activated partial thromboplastin time (aPTT) and prothrombin time (PT), microcytic anemia, and elevated plasma levels of aspartate aminotransferase (AST). Physical examination revealed pale skin and small subcutaneous hematomas, but no significant signs of cholestasis or other abnormalities. The family history included unspecified coagulation disorders. After treating the anemia with iron supplements, repeated coagulation tests confirmed deficiencies in multiple coagulation factors, with normal or elevated FVIII levels. Major genetic and autoimmune causes were initially ruled out, and other potential conditions, such as vitamin K deficiency and liver disease, were considered but not confirmed. At age six, the patient was hospitalized again due to macrohematuria. Further testing showed persistent coagulation abnormalities and elevated AST levels. Whole-exome sequencing identified a de novo heterozygous variant in the SLC37A4 gene, associated with glycosylation disorders and liver dysfunction. Additionally, congenital malformation of the C1 vertebra was discovered. Glycosylation analysis of transferrin revealed a marked alteration, supporting the involvement of the SLC37A4 variant in the patient’s condition. This case highlights the importance of considering glycosylation disorders in patients presenting with coagulopathy, liver dysfunction, and skeletal abnormalities. It also emphasizes the role of genetic testing in diagnosing rare disorders and the potential implications of glycosylation in the regulation of coagulation factor activity.

This paper discusses an analytical framework to model one-and two-ports in a way which avoids prioritizing either the voltage or the current as model variables. This approach allows for a truly general symbolic treatment of such circuits, avoiding the need to perform repetitive analyses in different working scenarios, and also displays a number of benefits from a theoretical point of view. The key ingredient is a homogeneous version of the Thévenin-Norton theorem for one-ports which possibly include controlled sources and coupling effects. This paves the way for the introduction of a comprehensive form for the transfer functions and the driving point immitances of two-ports, accounting for all possible impedance/admittance descriptions of the devices connected at the ports and also of the internal devices. Our framework allows e.g. for a universal definition of reciprocity but also for a straightforward derivation of Middlebrook's formulae in the context of the extra element theorem. Several examples illustrate the results.

Abstract: Background: The transesophageal echocardiogram (TEE) is the standard imaging modality for confirming the presence or absence of patent foramen ovale. There is a causal association between PFO and unexplained stroke. It seems that 3D-TEE can present a high-risk PFO morphological feature, which seems to show more than just being easier to open. Methods: In total 134 consecutive patients with cryptogenic stroke or migraine who had suspected PFO and underwent c-TCD, TTE, and c-TEE were included in this study. TEE confirmed the PFO. The right-to-left shunt (RLS) grade of PFO at rest and abdominal compression Valsalva maneuver was detected by c-TEE. Results: The long diameter of FO (1.74±0.3 vs. 1.60±0.4, P=0.039), the short diameter of FO (1.12±0.3 vs. 1.00±0.3, P=0.036), perimeter of FO (4.62±0.7 vs. 4.22±1.0, P=0.026) and area (1.80±0.8 vs. 1.35±0.8, P=0.05) of the FO were significantly larger in the larger RLS group. The cut-off value calculated by ROC for the diagnosis of high-risk PFO was that the length of the PFO tunnel was 12 mm and Left funnelform combined with multiple exits of left atrial (sensitivity was 92%, specificity was 90%). Conclusions: A larger oval fossa can be more easily activated and cause a large right-to-left shunt. The left funnelform, a longer length of the PFO tunnel, and multiple exits of the tunnel of LA increase the risk of CS in anatomical of PFO respect. TEE can precisely visualize the specific morphological characteristics of PFO. These features on TEE have a strong correlation with CS.