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.

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

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.

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.

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.

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.

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.

Introduction Co-infection with tuberculosis (TB) is the leading cause of death in individuals infected with human immunodeficiency virus (HIV)-1. Dolutegravir and lamivudine (DTG+3TC) has recently been recommended as the preferred first-line regimen for the treatment of new and treatment-experienced HIV-infected patients. The primary objective of this study was to determine the efficacy and safety of DTG 50 mg + 3TC 300 mg in HIV-positive antiretroviral therapy (ART)-naïve patients with TB who were receiving a rifampicin- or rifabutin-based treatment regimen, and to characterize viral suppression rates at week 48. Methods A single-center retrospective observational case series, spanning January 1, 2021 to March 1, 2023, was conducted in Guiyang Public Health Treatment Center. The outcomes of interest were successful TB treatment, viral load suppression, and immunological and biochemical indexes. Results All PWH had at least 48 weeks of follow-up, and all TB treatments were successful. A total of seven PWH (100%) achieved viral suppression (VL <50 copies/mL) from a baseline VL greater than 500,000 copies/mL. Among the PWH who started DTG+3TC after the initiation of the rifabutin-based anti-TB regimen, all achieved viral suppression by week 24, except for the non-suppressed PWH. CD4+ T-cell counts were greatly improved after antiretroviral treatment. The CD4+/CD8+ ratio increased by 0.38 (P < 0.001). Serum creatinine, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels significantly increased (P = 0.054, P = 0.015, P < 0.001, and P < 0.05, respectively). There were no significant changes in body weight, alanine aminotransferase, aspartate aminotransferase, chronic kidney disease epidemiology collaboration-based serum creatinine, or triglyceride levels from baseline to week 48 (P > 0.05). No serious adverse events were observed. Conclusion This case series preliminarily validated the efficacy of DTG+3TC when combined with rifabutin-based anti-TB regimens in patients with TB and HIV.

This article explores the issues involved in developing personalized medicine as part of the KidneySign project, which aim is to mobilize translational Big Data to validate a proteomic biomarker of renal fibrosis. This research offers hope for the management of chronic kidney disease in terms of early diagnosis and treatment. This article looks at how the human and social sciences can be mobilized within the project to study the adjoining ethical, legal and social issues. By highlighting these aspects, this point of view defends a multidisciplinary approach to personalized medicine and artificial intelligence in medicine. The presentation of theoretical and methodological contributions of social sciences in the case of KidneySign offers an opportunity to better understand the integration of these disciplines into biomedical research. It allows to question the study protocol itself and to frame it through legal contributions (considering the legal aspects, consequences and challenges). Moreover, by carrying out a sociological study, one may identify key points and highlight the limits of the technophile fantasy in the representations of patients and healthcare professionals. The introduction of new technologies into medical research and practice requires particular attention to ethics.

Service-learning is one way to engage students in health professions and promote health literacy in the community. This paper describes developing and delivering a service-learning course designed to improve diabetes literacy and diabetes outcomes among a medically underserved population. The didactic component of the course introduced topics such as health literacy, health education techniques, and diabetes pathophysiology, prevention, and treatment. Later, students designed and delivered community diabetes education classes at a local free clinic. After the classes were offered, diabetes knowledge and self-efficacy scores improved for community members and students leading the classes. A subset of community members also had lower body mass index at a 6-month follow-up. Though COVID-19 interfered with student's ability to offer in-person education sessions in the last semester this course was offered, it provided an opportunity to examine differences in diabetes knowledge and self-efficacy scores between students who offered in-person courses versus those who were unable to go out to the community and developed an online class instead. Self-efficacy was significantly higher at the end of the semester compared to at the end of the didactic component of the class for only those students who delivered in-person community education and not for those who developed the online class, providing further evidence of the benefit of engaging with community members on student outcomes. Community members and students alike were delighted with the program. Student-led community classes can be a financially sustainable solution to improving health literacy that benefits community members and students alike.

not-yet-known not-yet-known not-yet-known unknown Unexpected Guillain-Barré Syndrome After Hysterectomy: A Clinical Case Report

Successful Management of Severe Unknown Snake Bite with Coagulopathy in an Intensive Care Unit (ICU) of a peripheral district hospital: A Case Report S Bijukchhe1, S Adhikari21.      Department of Anesthesia and Critical CareHetauda Hospital, Madan Bhandari Academy of Health Sciences2. Pharmacy Officer, Health Logistic Management Center, Hetauda.

IntroductionDepressive disorders are characterized by recurrent episodes and a substantial disease burden, often leading to chronic functional impairment and reduced quality of life [1, 2]. Approximately one-third of patients fail to achieve satisfactory remission despite appropriate treatment, including antidepressant medications, electroconvulsive therapy(ECT), and psychotherapy[3-5]. This results in TRD, a severely disabling psychiatric disorder that is often refractory to conventional treatments. Patients face increased treatment costs, complications, and the heightened risk of recurrent hospitalizations. TRD poses a major clinical challenge within psychiatric practice due to delayed onset of action and low remission rates following multiple antidepressant doses[6, 7].Treatment options remain limited due to the prevalence of adverse effects tied to pharmacological therapies, low accessibility to psychotherapy, and high tolerance levels for electroconvulsive therapy. New neuromodulation techniques, such as rTMS, may offer potential solutions to these limitations[8, 9]. The U.S. Food and Drug Administration (FDA) approved rTMS for TRD in 2008, and it is recognized in the latest Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines [10, 11]. However, not all patients benefit from standard rTMS regimens[10], with meta-analytic evidence indicating an average effectiveness of 29.3% for the left dorsal lateral prefrontal cortex (lDLPFC) using high-frequency rTMS [10]. The FDA-approved rTMS regimen for TRD operates at 10 Hz, with a minimum of 60,000 total pulses; higher doses of 15 Hz or 20 Hz may achieve more favorable outcomes[12].Various classes of antidepressants, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been utilized in the treatment of depression [13]. However, the estimated rate of TRD persists above 30% after treatment with multiple antidepressant classes [4]. Currently available antidepressants are effective for treating depression; however, they are often accompanied by notable limitations. These include delayed onset of action, limited therapeutic efficacy (yielding moderate effectiveness ranging from 50% to 70%), and a lack of cognitive improvement. Consequently, there is a growing clinical need for safer and more effective antidepressant options [14, 15]. In recent years, the triple monoamine reuptake inhibition hypothesis has gained significant recognition as a potentially effective strategy for treating depression. Toludesvenlafaxine, also known as Ansofaxine, LY03005, or LPM570065, is a triple reuptake inhibitor (TRI) that has been integrated into clinical settings. It functions by inhibiting the reuptake of serotonin, dopamine, and norepinephrine in the central nervous system. The simultaneous activation of all three monoamine systems is believed to have a favorable impact on mood by alleviating symptoms such as loss of pleasure, irritability, and depressive symptoms. It also supports cognitive improvement, including better attention span, learning abilities, and memory, and addresses somatic symptoms by reducing fatigue, increasing energy, and addressing insomnia in individuals with depressive disorders. Preclinical studies suggest that toludesvenlafaxine exhibits superior efficacy and a favorable safety profile compared to traditional monoamine reuptake inhibitors. It shows promise for addressing the unmet needs in the treatment of TRD by alleviating symptoms that are resistant to current standard therapies. Toludesvenlafaxine is noted for its rapid antidepressant-like effects and is considered a promising treatment option[15-18].On the other hand, previous studies have demonstrated that DTMS demonstrates beneficial therapeutic outcomes on depressed patients who are already on medication[19, 20]. Additionally, there is an urgent need for a safe and effective treatment for TRD. Therefore, this study aims to utilize a newer rTMS regimen, such as DTMS, in combination with a novel triple monoaminergic reuptake inhibitor (toludesvenlafaxine) to augment efficacy and achieve the therapeutic remission of TRD patients. By focusing on novel treatment combinations and techniques, this approach seeks to provide a safe and effective treatment strategy for managing patients with TRD who have experienced limited success with traditional treatment trials.

The analysis of natural abundance isotopes in biogenic N 2O molecules can give precious information such as the nature of their precursor. However, many uncertainties exist and further validations are necessary to confirm this method as a reliable tracer of biogeochemical cycles. In particular, current methodologies (such as the isotopocule map approach) can only estimate the combined contributions of several processes at once. In this study, we aimed to develop a new methodology capable of individually discriminating the main sources of N 2O production in soil by combining natural abundance isotopes with the use of a 15N tracer ( 15N Gas Flux method). To achieve this, we conducted parallel laboratory incubations of an agricultural soil, during which we optimized the denitrification conditions through increase of moisture and amendment of nitrate; where this nitrate was either labelled or unlabeled with 15N atoms. A new linear system combined with Monte Carlo simulation enabled the determination of N 2O source partitioning, where bacterial denitrification was identified as the dominant process (87.6%), compared to fungal denitrification (9.4%), nitrification (1.5%) and nitrifier denitrification (1.6%). This new system has been compared to a recently developed stable isotope modelling tool applying Bayesian statistics (FRAME). The results agreed generally well at the exception of lower bacterial denitrification (80%) and higher nitrifier-denitrification (9%) contributions found with the FRAME model. This new approach provides a perspective for a wider application, potentially enabling the source partitioning of nitrous oxide emissions in agroecosystems.

Protein farming, or molecular farming, is an innovative approach that utilizes plants/animals/microorganisms as biofactories to produce valuable pharmaceutical proteins, antibodies, vaccines, and other high-value bio-active molecules. This emerging field has gained significant attention due to its potential to address the growing demand for affordable and scalable biopharmaceutical production platform. Correspondingly, plants offer several advantages over traditional expression systems, including low production costs, scalability, ease of manipulation, and reduced risk of contamination by pathogens. This review provides an overview of principles underlying protein farming in plants (P-farm), including the identification and selection of host, optimization of transgene expression, and downstream processing techniques for protein purification. It also discusses recent advancements in plant biotechnology and the development of transient expression systems to use genetically modified plants (transgenic plants) in the enhancement of protein production. Additionally, the potential applications and challenges associated with molecular farming in plants are considered, including prospects of commercialization and novel opportunities to meet the growing demands of global healthcare markets.

In this paper, we conduct a thorough analysis for a group of stochastic Hilfer fractional delay differential equations (SHFDDEs) with Lipschitz parameters. By introducing innovative theoretical conditions, we successfully establish the existence and uniqueness solutions using the Carath e ̵́ odory approximation approach. Furthermore, we deduce the average principle for accordingly system by employing H o ̵̈ lder’s inequality, Jensen’s inequality, It o ˆ isometric distance, and Gronwall’s inequality. Ultimately, two demonstrative examples are undertaken to substantiate the efficacy and practical applicability of our findings.