IntroductionMultiple causes could alter liver functions including infections, biliary disorders, viral or non-viral hepatitis, autoimmunity, and drugs. Brucellosis, zoonotic infection, presents with unspecific varied signs and symptoms affecting multiple organs (1). This infection is widely prevalent in both animals and humans (2). The liver is commonly involved in both acute and chronic cases of Brucellosis. When infected, patients may experience a slight increase in transaminase levels and mild swelling of both the liver and spleen. Occasionally, acute hepatitis can occur, but it’s usually not the only symptom of infection (3). Conjugated hyperbilirubinemia along with normal liver transaminase, serum alkaline phosphatase (ALP), and jaundice highly suggest Dubin-Johnson syndrome (DJS). Patients less likely present with mild abdominal pain, pruritus, nausea, or vomiting. DJS is a rare, chronic mainly autosomal recessive disease caused by mutations in the gene encoding for proteins involved in hepatobiliary transport of non-bile salt organic anions, leading to conjugated hyperbilirubinemia (4). Mutations in the multidrug resistance-associated protein-2 (MRP-2) gene are responsible for this disorder (4). The diagnosis of this benign condition is important to avoid unnecessary anxiety or intervention (5). Herein, for the first time, we report a case of a 35-year-old man presenting with jaundice for the first time in his life caused by brucella hepatitis, that lead to the diagnosis of concomitant DJS.

A document by Muhammad Sharjeel. Click on the document to view its contents.

jabbrv-ltwa-all.ldf jabbrv-ltwa-en.ldfLupus Disguised as Chorea: Uncommon Presentation of a Common Disease

Note: Nanowires are quasi-dielectronic nanostructures with high aspect ratio and large area, where radial strain uniformity allows for unusable combinations of semiconductor materials.  It enables countless applications of nanowires in electronics, optics and quantum technologies in general.In the multiplication of nanowire particles, they are synthesized in air by calculating the nanowire particles embedded in the alumina pattern.  The morphology and phases of nanowires/nanotubes are investigated by transmission electron microscope (TEM) and X-ray diffraction (XRD), respectively.   Electron reaction of nanowire particles between oxidation plays a role in the formation of such Nanowire nanostructures.

Ransomware attacks have grown increasingly sophisticated, leveraging advanced encryption techniques and evolving rapidly to bypass traditional detection mechanisms. The need for real-time, autonomous detection systems has never been more critical, and the Hybrid Entropic Behavior Monitoring (HEBM) framework addresses this challenge through a novel combination of entropy deviation monitoring and dynamic behavioral profiling. By detecting significant changes in file entropy and correlating them with behavioral anomalies, HEBM offers a robust solution for identifying both known and novel ransomware variants without reliance on predefined signatures. Experimental results demonstrate that the duallayered approach of HEBM not only enhances detection accuracy but also reduces false positives compared to existing methods. Its machine learning-based behavioral analysis ensures adaptability to new ransomware tactics, while maintaining computational efficiency. The proposed system operates autonomously, providing scalable ransomware protection for a wide range of real-world applications. Additionally, areas for future improvement, such as integrating memory analysis for fileless attacks and optimizing computational overhead, present exciting avenues for extending the framework's capabilities.

Stimulus-responsive organic room temperature phosphorescence (RTP) materials with luminescence properties changed with force, heat, etc., have drawn increasing attentions. Especially, the hydrostatic pressure effects on excited state properties of RTP molecules are conspicuous, corresponding theoretical investigations are highly desired. Herein, on the basis of density functional theory and time-dependent density functional theory, combined with the quantum mechanics/molecular mechanics and the thermal vibration correlation function methods, the influence of methyl substitution effect and hydrostatic pressure effect on the photophysical properties of five isomers is investigated theoretically. Results reveal that molecules with quasi-equatorial conformation have superior spin-orbit coupling (SOC) effects and more restricted geometric changes than molecules with quasi-axial conformation. In particular, the O-PTZ-H-1Me (eq) molecule has the minimum reorganization energy due to strong intermolecular interactions, significantly inhibits the non-radiative transition process, and exhibits a maximum intersystem crossing (ISC) rate for efficient triplet exciton generation. In addition, the quantum efficiency and lifetime are impressively improved by applying high hydrostatic pressure. Because of the small reorganization energy and SOC constant, the minimum non-radiative rate is achieved, resulting in a 64-fold (44.24%) increase in quantum efficiency and a 76-fold (21.12 ms) increase in lifetime compared to the unpressurized state.

Attention allows individuals to prioritize and effectively process relevant information while ignoring task-irrelevant distractions. It plays a critical role in task performance, learning and creativity. This study examines how varying levels of workload influence auditory attention, cognitive resource allocation, and the experience of flow. Thirteen participants engaged in a game-based electroencephalographic study designed to induce states of mental underload, overload and flow. To assess available attentional resources, an implicit auditory oddball task was integrated as a secondary task. Spatiotemporal cluster analyses revealed significant differences in event-related potentials when comparing flow and overload to underload. Multivariate pattern analysis successfully decoded all three conditions above chance level, particularly in centroparietal regions. Subjective measures, including the NASA Task Load Index and Flow Short Scale, along with behavioral performance metrics, confirmed the effective induction of flow and distinct levels of workload. Notably, participants demonstrated significantly higher performance and subjectively perceived valence during the flow condition compared to the overload condition, albeit with similar levels of neural engagement. Our results support the notion that experiencing flow may act as a "shielding mechanism," enhancing the effective allocation of attentional resources to the game and improving task engagement and performance efficiency.

The topic of genetic influence is an understudied area in play research. We argue that play research can draw on behavioural genetics methodologies to investigate individual differences in children's play. Studies applying behavioural genetic methods seek to understand how genes and the environment work together to impact behaviour and this is an area that remains relatively unexplored in play research. In doing so, we can extend what is known about the forms, functions and origins of play in child development. To invite play researchers to consider behavioural genetics methods, we share an overview of quantitative genetic methods like twin studies, genome-wide association studies, and polygenic studies and present possible applications to play research. We suggest that variables related to children, their parents, and their genetic propensities can be used to explore linkages between play, child development outcomes and the environment.

Occam’s Razor is a philosophy used widely in medicine. Often, it is referred to as the law of parsimony. However, there are different interpretations to how Occam’s razor is applied in the clinical diagnostic process. There have also been discussions around the application of Occam’s razor in medicine and concerns were raised on the accuracy of the diagnosis. This paper discusses the different interpretations used, their advantages and risks, and when we should apply the principle of Occam’s razor.

Authors' Names and AffiliationsTatsuya Koreedaa,*, Hiroshi Hondab, and Jun-ichi Onamica CLINIC FOR Group, Nagisa Terrace 4F, 3-1-32 Shibaura, Minato-ku, Tokyo 108-0023, Japanb Kao Corporation, Bunka, Sumida-ku, Tokyo 131-8501, Japanc RIKEN BioResource Research Center, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan*: correspondenceCorrespondence:  Tatsuya Koreeda – ta.koreeda@gmail.com

Although the negative impact of human-induced environmental effects on bird populations has been widely demonstrated, the question of whether adaptive adjustments may potentially arise as a result of unforeseen challenges is still unclear. Despite their obvious pervasive effect, human-induced challenges may activate, under certain circumstances, physiological and behavioural compensatory mechanisms that allow organisms to cope better with an altered and distressful environment. In this viewpoint, we highlight that understanding such compensatory responses (or the lack of them) requires adopting an ontogenetic and transgenerational perspective, as well as a multidisciplinary approach that integrates physiology, ageing biology, molecular processes and behaviour. Given the outstanding capacity for plasticity during development, we focus on how early-life (human-induced) experiences potentially shape, even prenatally, specific physiological and molecular processes (i.e., protection against oxidative damage and telomere maintenance mechanisms), and lifelong reproductive strategies (i.e., maternal allocation into eggs), which may in turn activate physiological and behavioural adjustments across generations. To test whether such adjustments in the developmental trajectory allow individuals to make “the best of a bad situation” or even increase their performance or that of their offspring in human-altered environments, we call for studies using a lifelong approach and that explore transgenerational effects. We thus propose experimental designs that could help the advancement in the field.

Washover deposits formed by overwash are important deposits for evaluating the stratigraphy and evolution of coastal environments. Examination of preserved washover fans also provide a palaeotempestological record that can used to inform on past and recent coastal risk with a view to predicting future coastal risk. To evaluate coastal systems and accurately recognise past washover deposits, requires detailed knowledge of the internal structure of recent deposits including washover fans. We used very high frequency Ground Penetrating Radar and satellite imagery to examine the internal architecture of the 31 st December 2011 Cyclone Thane surge-generated washover deposit on the beach that blocked the Then Pennai River at Thazhamkuda, near Cuddalore in Tamil Nadu Province, southeastern India. Cyclone Thane overwash overtopped the beach and deposited sediments on the contemporary beach and behind the beach within the former channel of the blocked river. The modern washover fan thus contains sediments that are preserved subaqueously Manuscript File Click here to view linked References and subaerially. We demonstrate that the internal architecture of the fan at Thazhamkuda is largely controlled by the pre-existing topography, and erosional and depositional processes as the cyclone washed sediment inland. At the landward margin of the fan, terminal foreset bedding is preserved and this sedimentary structure remains one of the only features that can discriminate storm and over tsunami deposits.

Revised Manuscript with No changes Marked (Clean copy of the revised paper)

Fault-bounded sag pond sediment records are commonly found to be excellent archives of palaeoearthquakes and more rarely, they can provide robust evidence of local environment and climate change. We examined the sedimentary and geomorphological record of the Aksay Pond within the Karachingar Valley along the southern margin of the Altai Mountain Range in northwestern China. This pond is associated to a shutter ridge resulting from cumulative deformation associated with successive earthquakes along the Fuyun Fault, including the most recent 11 August 1931 Mw7.9 Manuscript Click here to view linked References earthquake. However, detailed chronology based on 14 C Accelerator Mass Spectrometry, 210 Pb and 137 Cs dating suggests that only deformation related to the 1931 earthquake have been preserved at the pond site. A small wedge of sediments comprising cobble and gravel sized clasts are separated by two palaeosoil deposits suggesting that very minor sediment could accumulate prior to 1931. In the northern part of the pond, sediment was deposited predominantly from a colluvial fan that has periodically been mobilised from the steep mountain slopes to the east. In the southern part of the pond we find that the dry climate of the region has experienced periodic storms that have resulted in the deposition of 11 fining upwards packages formed by remobilised and deposited sand to mud-sized sediments within the pond. Associated with these fining upward cycles are two colluvial wedges that emanate from the fault scarp. The upper wedge is dated at approximately 1986 CE and coincides with a high precipitation event recorded at the Fuyun Meteorological Station in 1986. The middle wedge may be related to an earlier high precipitation event, but due to challenges in obtaining accurate ages, cannot be verified. Alternatively, these two colluvial wedges could coincide with minor ca. Mw5 earthquakes in the region. Importantly, these wedges are not associated with large scale rupturing similar to the 1931 earthquake. Based on the sedimentary and geomorphological evidence of the Aksay Pond, we propose a model for the sequential formation of sag ponds highlighting the influence of both climatic and tectonics processes.

Cannabinoid receptor 1 (CB1R) is widely expressed in central auditory system and play important roles in synaptic plasticity and sensory processing. However, the function of CB1R in specific neuronal subtypes in the central auditory system is largely unclear. In the current study, we investigated whether CB1R deficiency in the parvalbumin (PV)-expressing interneurons, a major class of GABAergic interneurons, affect hearing function. We fist systematically examined the neuronal localization and distribution of CB1R in mice central auditory system using double-label immunofluorescence and confocal laser scanning microscopy, and found that CB1R showed a wide distribution in the central auditory system, especially highly expressed in the cochlear nucleus (CN), superior olivary complex (SOC) and lateral lemniscus (LL). Furthermore, we established a CB1R conditional knockout mice specifically in PV interneurons, and measured auditory function using the auditory brainstem response (ABR) test. Surprisingly, analysis of ABR indicated that conditional deletion of CB1R specifically from PV interneurons significantly elevated the physiological hearing threshold, prolongated the latency of I waves, and decreased the amplitudes of I–V waves. Collectively, these results indicate that CB1R is highly expressed in CN and SOC, as well as deleting CB1R specifically from PV interneurons resulted in partial hearing loss and abnormal brainstem response. Our finding provides an anatomical basis for further investigating CB1R’s function in auditory system, and suggest that CB1R expression in inhibitory PV interneurons is essential for hearing function.

jabbrv-ltwa-all.ldf jabbrv-ltwa-en.ldfEP Rounds

jabbrv-ltwa-all.ldf jabbrv-ltwa-en.ldf Background and Objectives: Transcranial alternating current stimulation(tACS) has been demonstrated to improve cognition. In this study, we investigate the impact of accelerated high-definition (HD) tACS on craving and cognition in synthetic cannabinoid use disorder (SCUD). Methods: We conducted an accelerated HD-tACS on a patient with SCUD (N=1). Results: After the intervention, the patient showed reduced pathological attention bias, drug-craving, impulsivity, and risk-taking behavior. Discussion and Conclusions: Our study demonstrates the efficacy of accelerated HD-tACS in SCUD. Scientific Significance: This study provides evidence for the feasibility, safety, and efficacy of accelerated HD-tACS in a drug-dependent patient and encourages further systematic investigation.

The use of subcutaneous implantable cardioverter defibrillators has been steadily increasing during the last decade. They serve multiple benefits, including freedom from lead-related complications and preservation of vasculature. However, subcutaneous implantable cardioverter defibrillators---specific complications have been starting to emerge and are currently threatening the potential benefit achieved by subcutaneous implantable cardioverter defibrillators over transvenous implantable cardioverter defibrillators. We present a case of T wave over sensing during sinus rhythm, resulting in an inappropriate shock therapy leading to malignant tachycardia in a patient with generation three subcutaneous implantable cardioverter defibrillators.

jabbrv-ltwa-all.ldf jabbrv-ltwa-en.ldf Background Plasmablastic myeloma (PBM) is a rare, aggressive subtype of multiple myeloma (MM) with poor prognosis. On the other hand, plasmablastic lymphoma (PBL) is also an aggressive large B-cell lymphoma with plasmacytic phenotype, which is generally treated with anti-lymphoma drugs. Importantly, PBM is difficult to distinguish from PBL, because clinical features of both diseases closely overlap. We report two cases of PBM accompanied by apparent extramedullary lesions. Case Case1: A 38-year-old female complained of fatigue. She presented pancytopenia, splenomegaly, the soft tissue lesion over the chest wall and multiple osteolytic lesions. Initially, pathology of the soft tissue established a diagnosis of PBL. She received two cycles of EPOCH, leading to considerable improvement. She then received daratumumab (Dara) and Lenalidomide (Len), achieving remission for two years. Case2: A 60-year-old-male was evaluated for multiple tumors of pancreas and retroperitoneum. Biopsy of pancreatic tumor identified plasmacytoid cells, whereas biopsy of bone marrow showed no evidence of plasma cells. Therefore, he was initially diagnosed as multiple plasmacytoma, and received 3 cycles of chemotherapy with Bortezomib (Bor), lenalidomide, and dexamethasone, but in vain. Once Bor was replaced to Dara, he rapidly developed panperitonitis and ascites filled with plasmablasts, and eventually died of multiple organ failure. Conclusion As there has been no standard care for PBM, our cases raise a possibility that combination therapy of anti-myeloma and anti-lymphoma drugs from the first may provide good outcome. In addition, Ki-67 proliferation index is an useful finding to diagnose as PBM. Keywords plasmablastic myeloma (PBM), plasmablastic lymphoma (PBL), Ki-67

Structure-preserving two-step linearly implicit exponential integrators are constructed for Hamiltonian partial differential equations with linear constant damping combining exponential integrators and polarization of the polynomial Hamiltonian function. We also construct an exponential version of the well-known one-step Kahan’s method by polarizing the quadratic vector field. These integrators are applied to one-dimensional damped Burger’s, Korteweg-de Vries, and nonlinear Schrödinger equations. Preservation of the dissipation rate is demonstrated for linear, quadratic conformal invariants and of the Hamiltonians by numerical experiments.

Background & aim: Children and young people (CYP) with severe, sub-optimally controlled asthma and co-existing allergic sensitisation to indoor aeroallergens, such as pet dander and house dust mite (HDM), would likely benefit from reduced allergen exposure. Multiple allergen remediation interventions exist and are often suggested to families in secondary care asthma clinics in the United Kingdom. Evidence suggests remediation uptake is low or partial but there is sparse evidence to explain why. This study aims to explain how families in this situation make decisions about home-based allergen remediations. Methods: In-depth qualitative interviews with CYP and mothers were analysed, and a grounded theory approach was used to develop a theory to explain decision-making processes and behaviours. Results: Ten CYP aged 11-15 years and 11 mothers were interviewed. The core finding was that families iteratively respond to changes in how certain they are in their asthma management decisions and actions. For allergen remediation uptake, this certainty varied depending on seeing an outcome-exposure relationship, understanding asthma severity, variability, and asthma control at the time of remediation decision-making. Understanding the mechanistic role of allergen exposures in asthma was challenging for families, and ongoing bi-directional communication with clinicians was essential in supporting long-term decision-making. Conclusion: The theory explains the often elongated, reactive process of allergen remediation decision making and implementation. It also explains other elements of family management of asthma, and their interconnections. Families’ iterative responsiveness suggests opportunities to intervene and promote earlier, preventative behaviour change.

Objective: This study aimed to delineate the clinical and genetic features of late-onset congenital central hypoventilation syndrome (LO-CCHS) in four children. Methods: Clinical data from four children with LO-CCHS, including presentations, genetic testing, and follow-up results, were collected and analyzed at the Department of Respiratory Medicine at Beijing Children’s Hospital, China, from December 2019 to December 2023. Results: Four children (two males, two females) with PHOX2B mutations and LO-CCHS diagnosis were included. Ages of disease onset were 0.75, 4.2, 10.3, and 0.4 years, corresponding diagnostic ages were 6.5, 5.8, 11.3, and 1.6 years, and diagnostic delays ranged from one to five years. All patients exhibited nocturnal bradypnea and hypercapnia. patient 1 presented with pulmonary artery hypertension (PAH) as the initial symptom. Patient 2 experienced recurrent pulmonary hemorrhage (PH) after respiratory infections and genetic testing conformed a CCHS diagnosis. patient 3 exhibited hypersomnia due to increased respiratory resistance triggered by swimming, and patient 4 experienced recurrent cyanosis and lethargy followed by convulsions a year later. Four different PHOX2B mutations were identified: three polyalanine repeat mutations (PARMs) and one non-polyalanine repeat mutation (NPARM). Two of these were de novo mutations and two were respectively inherited from asymptomatic mother. For one to three years follow-up, three of them were in stable condition with oxygen supplement while one (patient 4) dead of respiratory failure. Conclusions: PAH could be as significant phenotypes of LO-CCHS when diagnosis was delayed and PH may be as relevant manifestations of LO-CCHS in children with PHOX2B mutations.

Following the ’8.8’ earthquake, many geological hazards, including landslides and collapses, are dispersed around the Jiuzhai gully. Susceptibility evaluation has been demonstrated to assist in reducing the chance of hazards and social and financial losses when developing mitigation plans for geological hazards, which are essential for risk management and hazard prevention. After the earthquake, as vegetation continues to recover, the temperature and precipitation fluctuate periodically, leading to regular changes in the amount and scale of geological hazards. We generated the geological hazards susceptibility mapping of Jiuzhai gully after the earthquake based on the variation trend slope of precipitation and vegetation, CIM-ANN, and CIM-LR ensemble models. The results of this research were validated using the area under the curve (AUC) and proportion. The study showed that, when comparing the CIM-LR and CIM-ANN, the AUC is 0.94 and 0.937, the accumulative cover area proportion of the geological hazards of MS, HS, and EHS is 40.86% and 55.79%, and the accumulative cover area proportion of the watershed is 55.79% and 37.24%, respectively. The geological hazards susceptibility obtained using the variation trend slope model has high applicability and AUC values that are relatively high compared to previous studies on the susceptibility in Jiuzhai gully. These results can be effectively used to assess the susceptibility of geological hazards in Jiuzhai Gully. Lastly, we anticipate that the susceptibility mapping produced can effectively protect people’s lives and property by serving as a reference and source of guidance for dynamic geological hazards assessment in high-seismic-intensity mountainous locations.

[Abstract] Objective: To summarize the surgical indications, complication management and perioperative management of pulmonary mucormycosis in children .Methods: The diagnosis and treatment of 3 children with pulmonary mucormycosis in Wuhan Children’s Hospital from 2023 to 2024 were retrospectively analyzed, and the surgical indications of 3 children were summarized, and relevant literatures were reviewed. Results: All three cases were children with bone marrow suppression after chemotherapy, and neutrophils decreased significantly.Enhanced CT showed lung infection and necrosis, including occlusion of the left pulmonary artery in one case.Fiberoptic bronchoscopy and mNGS showed mucor mycosis infection and were treated with esaconazole or Posaconazole, but the improvement was not obvious.Three cases underwent surgery, one of which suffered massive bleeding after returning to ICU on the same day after surgery, and had thoracotomy for hemostasis again. Postoperative examination confirmed the pulmonary mucor infection.There was no re-infection in the lung during 6-12 months of follow-up. Conclusions: Mucor has strong invasion in blood vessels easily, bronchus and lung tissues, often leading to hemoptysis, airway obstruction, tissue necrosis, etc. While actively treating underlying diseases, if the lesions are relatively limited, surgery can be performed as soon as possible after evaluation by a multidisciplinary team, including local debridement, removal of infected tissues or organs, which has positive effects on infection control and reducing the duration of antifungal drug use.