Agricultural soil erosion is largely attributed to arable extensification and increased mechanisation. Runoff from arable land and intensively managed grassland transports sediment and contaminants across the landscape and into watercourses, causing crop loss, land degradation and water quality issues. One low-cost and low-maintenance nature-based mitigation approach is the implementation of vegetated buffer strips (VBS): grassland sited along field margins to trap sediment and contaminants, reducing transportation and diffuse pollution rates. GIS modelling using remotely sensed landscape indices and land parcel data can provide an efficient means of identifying priority areas for intervention at sub-catchment or farm system scales. We develop and test a scalable runoff risk model in the lower Rother catchment, West Sussex. The model uses the Normalised Difference Vegetation Index (NDVI) applied to satellite images as an erodibility proxy and identifies locations along pathways that are conceivably at greatest risk of sediment accumulation and transfer, guided by field observations. Current and historical field boundaries near high-risk locations are evaluated for their potential capacity to reduce runoff using an innovative ranking system. Recommendations are made for VBS implementation and utility of historical field margin restoration is discussed. Our method offers a rapid approach with minimal data requirements to identify high-risk erosion locations and priority sites for intervention. The tool has the potential to guide decision-makers responsible for targeting and implementing soil erosion control measures such as VBS, while also maximising agri-environmental and cultural benefits.

An efficient and highly stereoselective synthetic method access to polycyclic chromanes has been achieved through organocatalyzed three-component reactions involving 2-hydroxycinnamaldehydes, 2-aminochalcones, and malononitrile as substrates. The reactions underwent a quintuple process by aza-Michael/Michael/Knoevenagel/oxa-Michael/aldol-type reaction in sequence to give products bearing 3 new generated rings and 5 chiral centers in moderate to quantitative yields with excellent enantioselectivities. A novel retro-reaction mechanism was discovered in the synthetic transformations of products.

Deeply rooted in its developmental philosophy of gross national happiness (GNH), Bhutan’s healthcare system strives towards achieving a shared goal of universal health coverage (UHC). Despite being primarily financed by the government, the healthcare system faces a plethora of challenges. To overcome these hurdles and achieve UHC goals, expanding the fiscal space for health and improving operational efficiency is crucial. This policy brief aims to address Bhutan’s evolving healthcare landscape and advance the achievement of UHC through two policy options. The first policy option focuses on dual objective of improving health outcomes and promoting financial sustainability by leveraging heath taxes, while the second option emphasises reinforcing a systematic Health Technology Assessment (HTA) in the healthcare system. First, to promote financial sustainability, the proposal suggests introducing earmarked taxes on alcohol and tobacco products for the health sector. Global evidence suggests that earmarked taxes are a reliable source of revenue for health, and Bhutan’s high prevalence of tobacco and alcohol consumers assures a reliable revenue base. The Goods and Services Tax (GST) will be implemented in 2024, and it will be a good opportunity for the Ministry of Health to advocate and negotiate with Ministry of Finance (MoF) for the earmarked taxes to the health sector. Second, integration of HTA into policymaking and decision-making processes is essential for effective resource allocation in UHC. Nurturing and strengthening the existing HTA structure under MoH and establishing a dedicated multidisciplinary HTA Committee will ensure informed decision-making and resource optimization. HTA evidence should abided to revise health service standards, develop clinical guidelines, make procurement decisions, and set healthcare priorities. These policy options can assist the country in improving ensure financial sustainability, enhance effective resource allocation and utilisation, and improve healthcare delivery, aligning with its vision of GNH and ultimately accelerating progress towards achieving UHC.

Given the growing demand for new materials for supercapacitor applications, high entropy alloys (HEAs) are being extensively investigated. They are an efficient alternative to existing energy sources due to their synergistic contribution from individual element. We demonstrate the development of nanostructured HEA (FeCoNiCuMn) as a cathode material with specific capacitance (C s) of ~388 F g -1 (5 mV s -1). As anode material, green graphene (rice straw biochar) synthesized using pyrolysis shows a maximum C s of ~560 F g -1 at similar scan rate (5 mV s -1). A hybrid asymmetric liquid state device was assembled using the FeCoNiCuMn nanostructured HEA and green graphene as electrodes. Utilizing the green source, the device provided a high C s of 83.22 F g -1 at 2 A g -1. The specific energy of the device was 33.4 Wh kg -1 and specific power of 1.7 kW kg -1. The electrochemical behavior of each element in the high entropy composition was studied through post X-ray photoelectron spectroscopy and scanning electron microscopic analysis. The chemical behavior of FeCoNiCuMn is further investigated using DFT studies. The enhanced electrochemical properties and synergistic contribution of each element of the HEA is studied via of d-band theory. The current work can be utilized to develop asymmetric hybrid supercapacitors as environmental friendly energy source.

Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive sarcoma that most commonly presents in males with abdominal and peritoneal invasion. There are potential curative therapeutic options, but survival remains poor. To this day, there have only been 19 reported cases of primary renal DSRCT in the literature and thoracic DSRCT has been rarely reported with very little known about effective therapy. We present a patient with a case of thoracic relapse of DSRCT after a primary renal lesion and prior history of nodular lymphocyte predominant Hodgkin Lymphoma.

The purpose of this study was to detect the presence of HHV-6 A and HHV-6 B in genital samples of infertile men, relating these findings to alterations of normal seminal parameters, considering only those samples in which there was no co-infection with other frequent genital tract microorganisms such as Chlamydia trachomatis, Human Papillomavirus, and Herpes Simplex Virus 1 and 2. For these assays, were processed 105 semen and urethral swab samples from men with a diagnosis of infertility. Seminal parameters were determined for each of them and subsequently molecular biology tests were performed to detect DNA for HHV-6 A, HHV-6 B, HSV, HPV, and Chlamydia trachomatis Of the total samples processed, 28.5% (30/105) were positive for HHV-6 A/B of which 23.3% (7/30) corresponded to HHV-6 A and 76.7% (23/30) corresponded to HHV-6 B. No HHV-6 A and B coinfection was detected. HHV-6A co-infected with any of the pathogens studied in 14.2% samples (1/7) while HHV-6B co-infected in 26.1% samples (6/23). The odds ratio obtained was 1.44, reflecting a positive association. Statistically significant differences were observed between HHV-6 A and B when volume and morphology parameters were analyzed. Both HHV-6A and HHV-6B are associated with alterations in sperm volume, concentration, motility, mortality and morphology. The presence of HHV-6B in genital samples would be associated with alterations in sperm volume and morphology, but their true pathological role, still remains to be answered.

The Blaps rhynchopetera Fairmaire is a significant medicinal resource in southwestern China. We utilized Nanopore and Hi-C technologies in combination to generate a high-quality, chromosome-level assembly of the B. rhynchopetera genome and described its genetic features. Gene surveys revealed that B. rhynchopetera is a highly heterozygous species. The assembled genome was 379.24 Mb in size, of which 96.03% was assigned to 20 pseudochromosomes. A total of 212.93 Mb of repeat sequences were annotated and 26,824 protein-coding genes were identified. Phylogenetic analysis indicated that the divergence of the ancestors of B. rhynchopetera and its closely related species Tenebrio molitor at about 85.6 mya. The co-linearity analysis showed that some chromosomes of B. rhynchopetera may have happen fission events and it has a good synteny relationship with Tribolium castaneum. Furthermore, in GO and KEGG enrichment analyses, the gene families related to detoxification and immunity of B. rhynchopetera facilitated the understanding its environmental adaptations, which will provide research references for the prevention of some pests and the protection of beneficial insects. This high-quality reference genome will also contribute to the conservation of insect species diversity and genetic resources.

Natural Cyclic dinucleotide (CDN) is the secondary messenger involving bacterial hemostasis, human innate immunity, and bacterial antiphage immunity. Synthetic CDN and its analogues are key molecular probes and potential immunotherapeu-tics. Several CDN analogues are under clinical research for antitumor immunotherapy. A myriad of synthetic methods has been developed and reported to prepare CDN and its analogues. Chemical modifications of phosphate, ribose, and nucleo-base of natural CDN have been investigated using solid phase or solution phase strategy. However, most of the protocols take multisteps and only one CDN or its analogue could be prepared in one time. In this paper, a strategy based on a mac-rocyclic ribose phosphate skeleton containing a 1’-alkynyl group was designed and developed to prepare CDN analogues containing triazolyl C-nucleosides by Click chemistry. Combinatorial application of Click chemistry and sulfenylation cascade to the macrocyclic skeleton extended the diversity of CDN analogues. This macrocyclic skeleton strategy could rapidly and efficiently provide CDN analogues to facilitate the research of microbiology, immunology, and the development of immu-notherapeutics.

Non-perennial streams play a crucial role in ecological communities. However, the key parameters and processes involved in stream intermittence remain poorly understood. While climate conditions, geology and land use are well identified, assessing and modeling the groundwater controls on streamflow intermittence remains a challenge. In this study, we explore new opportunities to calibrate process-based 3D groundwater flow models designed to simulate stream intermittence in groundwater-fed headwaters. Streamflow measurements and stream network maps are jointly considered to constrain aquifer’s effective hydraulic properties in hydrogeological models. The simulations were then validated using visual observations presence/absence of water, provided by a national monitoring network in France (ONDE). We tested the methodology on two pilot catchments with unconfined shallow crystalline aquifer, the Canut and Nançon (Brittany, France). We found that streamflow and expansion/contraction dynamics of the stream network are both necessary to calibrate simultaneously hydraulic conductivity K and porosity θ with low uncertainties. Conversely, calibration resulted in accurate prediction of stream intermittence - in terms of flow and spatial extent. For the two catchments studied, the Canut and Nançon, hydraulic conductivity is close reaching 1.5 x 10 -5 m/s and 4.5 x 10 -5 m/s respectively. However, they differ more by their storage capacity, with porosity estimated at 0.1 % and 2.2 % respectively. Lower storage capacities lead to higher fluctuations in the water table, increasing the proportion of intermittent streams and reducing perennial flow. This new modeling framework allowing to predict streamflow intermittence in headwaters can be deployed to improve our understanding of groundwater controls in different geomorphological, geological, and climatic contexts. It will benefit from advances in remote sensing and crowdsourcing approaches that generate new observed data products with high spatial and temporal resolution.

Physical human-robot collaboration (pHRC) requires both compliance and safety guarantees since robots coordinate with human actions in a shared workspace. This paper presents a novel fixed-time adaptive neural control methodology for handling time-varying workspace constraints that occur in physical human-robot collaboration while also guaranteeing compliance during intended force interactions. The proposed methodology combines the benefits of compliance control, time-varying integral barrier Lyapunov function (TVIBLF) and fixed-time techniques, which not only achieve compliance during physical contact with human operators but also guarantee time-varying workspace constraints and fast tracking error convergence without any restriction on the initial conditions. Furthermore, a neural adaptive control law is designed to compensate for the unknown dynamics and disturbances of the robot manipulator such that the proposed control framework is overall fixed-time converged and capable of online learning without any prior knowledge of robot dynamics and disturbances. The proposed approach is finally validated on a simulated two-link robot manipulator and then extended to the simulated UR10 robot. Simulation results show that the proposed controller is superior in the sense of both tracking error and convergence time compared with the existing barrier Lyapunov functions based controllers, while simultaneously guaranteeing compliance and safety.

Background: Research indicates a relationship between nutrition, physiological characteristics, and mental health. It was already reported that Israeli-Arab adolescents consume more fast food, sweets, and candies than Jews. Higher energy drink consumption by Israeli-Arab adolescents emerged. Though, data on the topic still needs to be updated. The current study examined possible associations between energy drink consumption, anxiety, and well-being in Israeli-Arab adolescents. We also investigated these associations concerning fast food consumption, physical activity, and sleep hours. Methods: One hundred and fourteen adolescents (59 females) aged 12–18 from several cities & villages in northern Israel were recruited to study. A cross-sectional exploratory study assessed adolescents’ energy drink consumption, nutritional and lifestyle habits, well-being, and anxiety using self-reported questionnaires. Anthropometric measurements - weight, height, and waist circumference were also assessed. Results: Gender and energy drink consumption were associated with psychological status. Energy drink consumers reported a lower well-being index and a higher anxiety index than non-consumers. Energy drink consumers ate significantly more fast food per week than non-consumers. In addition, sleep hours were correlated with anxiety levels. These results differed between genders. Conclusions: Our study shows complex associations between energy drink consumption and mental health indices. These associations can serve as a basis for further research into this topic.

Short-Patch Double Illegitimate Recombination (SPDIR) has been recently identified as a rare mutation mechanism. During SPDIR, ectopic DNA single-strands anneal with genomic DNA at microhomologies and get integrated in the course of DNA replication, presumably acting as Okazaki fragments. The resulting microindel mutations are highly variable in size and sequence. In the soil bacterium Acinetobacter baylyi, SPDIR mutations are tightly controlled by genome maintenance functions including RecA. In this study, we investigate the roles of DprA, RecFOR and RecBCD, which are cytoplasmic functions that load DNA single-strands with RecA. All three functions suppress SPDIR mutations in wildtype to levels below the detection limit. While SPDIR mutations are slightly elevated in the absence of DprA alone, they are strongly increased in the absence of both DprA and RecA. This SPDIR-avoiding function of DprA is not related to its role in natural transformation. These results suggest an antimutational function for DprA and offer an explanation for the ubiquity of dprA in the genomes of non-transformable bacteria.

An Unusual case of Crusted Scabies in an Immunocompetent Adult: A Case ReportMartin Agyei1,2, Priscilla Abrafi Opare-Addo1, Afua Ofori1, Gloria Kyem1, Solomon Gyabaah1, Serwaa Asare-Bediako11 Komfo Anokye Teaching Hospital, Kumasi, Ghana2 Kwame Nkrumah University of Science and Technology

Cave adapted animals evolve a suite of regressive and constructive traits that allow survival in the dark. Most studies aiming at understanding cave animal evolution have focused on the genetics and environmental underpinnings of regressive traits, with special emphasis on vision loss. However, cave-associated constructive traits, like compensations from non-visual sensory systems, have been relatively overlooked. In blind cavefish of the Mexican tetra, Astyanax mexicanus, a major non-visual sensory system that compensated through morphological expansions is the mechanosensory lateral line. Although this system has been studied and described in A. mexicanus for over decades, there are still many unknowns about the developmental origin, synaptic plasticity, and overall adaptive value of expanded lateral lines. This review provides a snapshot of the current state of knowledge of lateral line adaption in A. mexicanus, with an emphasis on anatomy, synaptic plasticity, and behavior. Multiple open avenues for future research in this system, and how these can be leveraged as tools for both evolutionary biology and evolutionary medicine, are discussed.

Social Dissonance is then, both a form of practice, an effect of that practice- the furthering of the already present socially dissonant effect/affect-, and a specific score, proposing possible kinds of action to an audience to bring about the consciousness of their own unfreedom- or, more radically, the consciousness of their unconsciousness. But this program has two insufficiencies: 1. The circuit through which the risen consciousness of an unfree state may translate into forms of action is not provided. 2. Even if one has successfully elicited the experience of unfreedom, the transmission of that feeling of unfreedom within a localized social milieu- typically enclosed within an art gallery, a concert hall, or a punk venue- to the consciousness of the unfreedom of the social world at large is, in the least, problematic. The first insufficiency relates to the problem of the theoretical conditions of practice, or what kinds of influence can a theoretically gained description have upon practice - a very classical problem. The second insufficiency is more specific to Mattin and one would say amounts to the influence one practice may have upon other practices. But this last formulation is a superficial one, being maybe more fruitfully described as the problem of the traction one form of action may have upon the practical conditions of conceptual representation- once we understand the dialectics between action and conception that seems to be implicit in Mattin’s account, and much of the present text will be dealing with exactly that.

Objective: To investigate the distribution characteristics of HPV16 E6 gene 295T/G and E7 gene 647A/G variants in different cervical tissues in Xinjiang, to study the effects of these two loci on the expression of molecules in IFNκ and its pathway, to explore the molecular mechanism of their roles, and to analyse the relationship between these two variants and the occurrence and development of cervical cancer. Methods: (1) A total of 461 cervical paraffin-embedded tissue samples were collected and tissue DNA was extracted to detect the type of HPV infection by PCR, and the distribution of HPV16 viral E6-T295G and E7-A647G variants in cervical tissues was analysed by Sanger sequencing. Immunohistochemistry was used to detect the expression of IFNκ and molecules on its pathway including IFNκ, STAT1, IRF9, IFI27, IFI44L,OAS1 in cervical cancer and normal cervical tissues. Results: (1) The HPV16 infection rate of cervical paraffin-embedded tissue samples from women in Xinjiang region was 64.0% by PCR. And the HPV16 infection rate of Uyghur was 75.7%, of which the infection rate of Uyghur CIN1 and CIN2 with HPV16 was 60.6%, and the infection rate of CIN3 and cervical cancer was 82.9%. The HPV16 infection rate of Han ethnic group was 54.5%, among which the infection rate of Han ethnic group CIN1 and CIN2 of HPV16 was 34.0%, and the infection rate of CIN3 and cervical cancer was 66.5%. (2) The variant rate of Uyghur CIN1 patients presenting with E6-295T/G variant was 41.7%, and the variant rate of squamous cervical cancer patients presenting with E6-295T/G variant was 43.4%. The variant rate of Han ethnic group CIN1 patients presenting with the E6-295T/G variant was 33.3%, and the variant rate of squamous cervical cancer patients presenting with the E6-295T/G variant was 16.1%. The variant rate of Uyghur CIN1 patients presenting with the E7-647A/G variant was 41.7%, and the variant rate of squamous cervical cancer patients presenting with the E7-647A/G variant was 9.2%. The variant rate of E7-647A/G variant was 45.8% in Han ethnic group of CIN1 patients and 50.0% in squamous cervical cancer patients. (3) The results showed that the expression of IFNκ, IRF9, OAS1, IFI27, and IFI44L molecules on the IFNκ pathway was higher in normal cervical tissues uninfected with HPV than that of CIN1 with HPV infection, and the difference was statistically significant ( P<0.05). The expression of IFNκ, STAT1, IRF9, OAS1, IFI27, IFI44L molecules in CIN3, moderately differentiated, poorly differentiated cervical squamous carcinoma and adenocarcinoma were higher than that of CIN1, and the molecular expression of IFN-κ and its pathway in cervical squamous cell carcinoma and adenocarcinoma was higher than that in normal tissues, and the difference was statistically significant ( P<0.05). Conclusion: The rate of E6-295T/G variation in cervical cancer patients infected with HPV16 in Uyghur is higher than that in Han, while the rate of E7-647A/G variation in cervical cancer patients infected with HPV16 in Han is higher than that in Uyghur.

Audiovisual conflict control is an important cognitive function in humans. However, it was not clear whether there was a defect in audiovisual conflict control in Parkinson’s disease (PD) patients, nor was it clear how it was reflected at periods of perception and response in the cognitive process. We recruited 27 PD patients and 22 healthy controls (HC) to complete audiovisual matching task to investigate the audiovisual conflict in PD patients at different processing periods and its relationship with cortical thickness. Behavioral results showed that HC group showed stronger visual interference at both periods of perception and response. But in PD patients, there was no significant difference between visual interference and auditory interference at period of perception, indicating the abnormal audiovisual conflict. In addition, the cortical thickness of left middle frontal gyrus (MFG) in PD patients was positively correlated with the sensory interference (visual interference > auditory interference) at period of perception, and the thinner the left MFG was, the weaker sensory interference was. The abnormal audiovisual conflict in PD patients was reflected at period of perception, and was associated with the cortical thickness of the left MFG, revealing the important role of the left MFG in conflict control in PD patients.

Abstract CSF-contacting neurons are involved in detecting changes in the cerebrospinal (CSF) circulation and recent studies report their role in nociception. Using neuronal tracers (Fluoro-Gold™, Cholera toxin subunit B, BDA), immunofluorescence (Anti-FG, Anti-OT-neurophysin, Anti-vasopressin, Anti-GABA, Anti-OTR) and electron microscopy, we describe oxytocinergic and vasopressinergic CSF-contacting neurons within the hypothalamic paraventricular nucleus (PVN) and their projections towards the rostral agranular insular cortex (RAIC). Our results show the presence of CSF-contacting neurons along the PVN that are labelled by oxytocin (OT) or/and vasopressin (AVP) and could secrete these peptides into CSF by dendritic projections. Besides, we report some oxytocinergic CSF-contacting neurons that send projections towards the RAIC. Inside the RAIC, our ultrastructural analysis shows that axons from PVN sustain synaptic connections with cortical GABAergic neurons that express oxytocin receptor (OTR) where we identify OT molecules as well. These findings support the possible role of CSF-contacting neurons in the neuronal modulation by releasing neuromodulators both at CSF and synaptic levels. Also, our results signal the extended means of oxytocinergic transmission, including its release inside RAIC promoting local GABAergic activity and its secretion towards CSF probably modulating many areas close to the ventricles, that can be involved in different conditions as nociception modulation.

A document by Karin Vadovičová. Click on the document to view its contents.

Current studies suggest a role of the medial habenula (MHb) and interpeduncular nucleus (IPN) in stress, anxiety, depression and addiction. These regions were found to have increased glucose intake during anesthesia (Herkenham, 1981), and MHb has the densest μ-opioid receptors (MORs) in the brain (Gardon and Faget, 2014). The MHb-IPN pathway is enriched in nicotinic acetylcholine receptor (nAChR) and influences the brain response to nicotine (Antolin-Fontes et al., 2014). Theoretical work (Vadovičová, 2015) showed how the MHb→IPN→MRN circuit activates serotonin release and inhibits the theta states, arousal, alert wakefulness, awareness and REM sleep linked circuits. Study proposed that MHb activates IPN which activates MRN that promotes rest, slow wave sleep (SWS), slow wave oscillations, recovery, hippocampo-cortical replay of temporaly, spatialy and relationally bound memories, sharp wave ripples, cortical spindles, synaptogenesis and BDNF linked growth (Vadovičová, 2015). This paper will show how the stress, danger, worries and safety interact with the MHb-IPN circuit. It will show new neural mechanism for loss of awareness and memory replay, anesthesia, respiratory slowdown, opiates induced respiratory depression OIRD (circuit underneath the opiate crisis) and sudden infant death syndrome SIDS. This study will link claustrum and cortex to the hippocampus →posterior septum →MHb →IPN →MRN circuit.

Background: Biomarkers for metabolic dysfunction-associated steatohepatitis (MASH) have been considered based on proteomic and lipidomic data from plasma and liver tissue without clinical benefits. This study evaluated proteomics-based plasma and liver tissue biomarkers collected simultaneously from patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: Liver tissue samples and plasma samples were collected during liver biopsy for diagnosis. Untargeted proteomics was performed on 64 patients with MASLD. Results: Twenty plasma proteins were up or downregulated in patients with MASH compared with those without MASH. The biomarkers utilizing the best combinations of these plasma proteins had an area under the receiver operating curve (AUROC) of 0.671 for detecting those with MASH compared with those without it. However, none of the 20 plasma proteins were represented among the significantly regulated liver tissue proteins in patients with MASH. Ten of them displayed a trend and relevance in liver tissue with MASLD progression. These ten plasma proteins had an AUROC of 0.793 for MASH identification and higher positive and negative predictive values. Conclusion: The plasma and liver protein expressions of patients with MASH were not directly comparable. Plasma protein biomarkers that are also expressed in liver tissue can help improve MASH detection.

A rare case of Non-lupus full house nephropathy in a transplanted kidney, case report:Ahmad Matarneh(1), Omar Salameh(2), Sundus Sardar(1), Amanda Karasinski(1), Theja Channapragada(2), Muhammad Abdulbasit(1), Erik Washburn(3), , Nasrollah Ghahramani(1)Affiliations: 1. Department of nephrology, Penn state Milton S Hershey Medical Center, United States of America2. Department of Internal Medicine, Penn state Milton S Hershey Medical Center, United States of America3. Department of pathology, Penn state Milton S Hershey Medical Center, United States of AmericaCorresponding authorAhmad MatarnehAffiliation: Penn State health , Milton S.hershey medical centerContact: Email ahmadmatarneh99@gmail.comPhone # 717-708-6754Keywords:Autoimmune disorders, Systemic lupus erythematosus, Transplant rejection. Full house nephropathyAbstract:Non lupus full house nephropathy is a rare entity with an unclear incidence. It describes the kidney biopsy findings of positive deposits for IgG, IgA, IgM, C3, C1q on immunofluorescence in the absence of the classical diagnostic features of systemic lupus nephritis. This disease entity is becoming more recognised but further studies are still needed to evaluate the incidence, etiologies and management of this condition. Transplant glomerulopathy is a major cause for renal graft loss. It can present with a wide variety of manifestations; It can cause AKI, CKD or glomerular inflammations through an immune complex or autoimmune mediated damage.Introduction:Non lupus full house nephropathy is defined as having the classical findings of lupus nephritis which are positive deposits for IgG, IgA, IgM, C3, C1q on immunofluorescence but without the other extra-renal or seologic manifestations needed for SLE diagnosis i.e ACR criteria.(1) Systemic lupus erythematosus is a multi-system autoimmune disorder. It can involve several organs with variable presentations. The diagnosis of SLE is mainly based on establishing the presence of >= 4 points of the American College of Rheumatology criteria. (2) Lupus nephritis is the renal manifestation of SLE, it can have a wide range of manifestations which can include AKI, nephrotic or nephritic syndrome secondary to glomerulonephritis or it can ultimately lead to ESRD. Kidney biopsy remains the gold standard test to diagnose and to guide the treatment of lupus nephritis. Classical kidney involvement in SLE is based mainly on the pattern of histological involvement and it is divided into several classes according to the international society of nephrology. (3) Transplant rejection remains a huge challenge to both patients and treating physicians, it can result in variable degree of kidney dysfunction and ultimately it might lead to graft loss.(4) Several risk factors for transplant rejection have been described in literature and certainly, autoimmune diseases remain high on the list.(5) We hereby report a patient who presented with nephrotic syndrome and was found to have de-novo non lupus full house nephropathy in the transplanted kidney.Case presentation: Patient is a 57-year-old female with a past medical history of End-Stage Renal Disease that was managed with a living unrelated kidney transplant in 2016, Hypothyroidism, and Type 1 Diabetes Mellitus (T1DM) managed with an insulin pump. The patient underwent a living unrelated kidney transplant in 2016 with significant post-transplant complications with ureteral strictures. Initially, she was managed by nephrostomy followed by multiple indwelling stent exchanges. However, stents were repeatedly colonized with multiple bacterial and candida infections, requiring antibiotic and antifungal therapy. Due to recurrent acute infections mycophenolate mofetil was held and she had a stent removal in an attempt to decrease her risk of UTI’s.She presented to an outside hospital with a 1-week history of progressively worsening generalized headaches, nausea/vomiting, and elevated home blood pressures. Her blood pressure was noted to be 200/120. Initial labs were notable for hemoglobin of 8.5g/dl, blood urea nitrogen (BUN) of 82 mg/dL, and creatinine of 3.35mg/dL, with baseline creatinine 2.2-2.5mg/dL.Physical exam on presentation was significant for +1 lower extremity edema, with the remainder of the physical exam within normal limits, Patient was afebrile and BP was noted to be 171/81 mmHg.Investigations:Labs notable for potassium 6.1 mEq/L, chloride 116 mEq/L, bicarbonate 18 mmol/L, blood urea nitrogen (BUN) 82 mg/dL, creatinine 3.64 mg/dL, phosphorus 6.0 mg/dL, hemoglobin 8.7 g/dl, and platelets 148. VBG showed pH 7.240, PCO2 41, PO2 42, bicarbonate 17.6. Blood, urine, and fungal cultures were normal. A urine protein/creatinine (PCR) ratio was 12.74, consistent with nephrotic range proteinuria. (Table 1)Table 1. Laboratory investigations.Ultrasound retroperitoneal revealed hydronephrosis in the right lower quadrant, transplant kidney with urothelial and collecting system thickening, stable from the previous ultrasound one month prior. Given the patient’s history of prior urethral stricture, however, she had a right ureteral stent placed with the urology team. Following stent placement, however, the patient’s urine output was less than 200cc, and her creatinine rose to 3.9.An additional renal ultrasound with doppler was done to evaluate blood flow through the transplanted kidney, revealing increased renal artery resistive indices of 0.93 and associated high resistance arterial waveform, concerning for chronic rejection. While CMV/BK and donor-specific antibiotics were negative, Further immunological workup was done revealing positive Antinuclear Antibody (ANA) but negative anti-double stranded DNA (anti-dsDNA) and anti-smith antibody (Sm). C3 was borderline low and C4 was normal. Additional workup for membranoproliferative glomerulonephritis, including hepatitis B and C serologies, were negative. there were still concerns about rejection, and the patient underwent a renal biopsy with interventional radiology. The preliminary read from the biopsy was concerning T-cell kidney transplant rejection versus membranoproliferative glomerulonephritis versus lupus nephritis.The final read of the biopsy demonstrated membranoproliferative glomerulopathy, immune complex-mediated with rare cellular crescents, and foci of fibrinoid necrosis. The full-house immunofluorescence staining suggests lupus nephritis as a possible etiology. Mild tubulitis and interstitial mononuclear inflammation meet the criteria for borderline/suspicious for acute T-cell mediated rejection. (Figures 1-5)She was diagnosed as a case of chronic rejection with immune complex deposition disease. She was treated with 1 gram of intravenous methylprednisolone once and transitioned to 60 mg oral prednisone once daily throughout the remainder of the course and at discharge. Her BUN continued to rise in the setting of steroid use, as high as 178 mg/dL at discharge.. In addition, patient developed hypoalbuminemia with associated anasarca. Her anasarca was managed with a bumetanide drip that was transitioned to intermittent dosing of 2 mg bumetanide on discharge. The patient’s urine output increased to over 1L with diuretics, with creatinine levels down trending. On discharge, the patient’s creatinine was 2.98 mg/dL.Outcome:The patient was followed up in the transplant nephrology clinic two weeks after discharge. Creatinine improved to 2.63 mg/dL. Proteinuria decreased to 5.7 with a 50% reduction from hospital admission. Patient’s lower extremity swelling decreased significantly. She was maintained on tacrolimus 2 mg twice daily, MMF 500 mg twice daily. Given the biopsy findings and her improvement of her creatinine and proteinuria degree it was decided to continue treatment as an underlying chronic rejection.Discussion: Glomerulonephritis remains one of the leading causes of renal graft loss following kidney transplant.(6) The incidence is widely variable and differs between studies. Recurrent and de-novo glomerulonephritis following kidney transplant are not uncommon and have been described as a cause of renal graft loss and/or dysfunction. Recurrence of GN is typically more common than de-novo processes.(7) GN is one of the main causes of renal graft loss after kidney transplant, according to one of the studies it was noted that recurrence of GN was the third most common cause of renal graft loss. (8) De-novo disease is defined as any new disease process that occurs in the kidney graft unrelated to the primary kidney disease. De-novo disease can have a variable presentation as it can manifest as acute, subacute to chronic with manifestations usually arising from glomerulonephritis, tubulointerstitial nephritis or vascular disease. The incidence of de-novo GN is unclear and has been hypothesized to be occurring in 4-20% of transplant recipients.(9) Most common patterns of GN are FSGS, MGN, MPGN. (10) Transplant glomerulopathy remains one of the major debilitating conditions that transplant patients deal with. It can present with a chronic or acute rejection picture in the form of steady rise in creatinine and GN pattern of injury. (11) Systemic lupus nephritis is a chronic inflammatory autoimmune condition that can affect multiple organs with variable presentations. Diagnosis is usually based on the classical serologic and extra renal criteria. (12)Lupus nephritis is one of the serious manifestations of SLE, it is defined as the presence of significant proteinuria and classical findings on kidney biopsy. Classical kidney biopsy findings of lupus nephritis under light microscopy are I. minimal mesangial, II. Proliferative mesangial, III. Focal proliferative, IV. Diffuse proliferative, V. membranous and VI. Sclerosing. One of the relatively specific findings on direct immunofluorescence on kidney biopsy is finding deposits positive for IgG, IgA, IgM, C3 and C1q, a pattern that is usually referred to as the full house pattern. (13) This finding is relatively specific for lupus nephritis however, in order to establish the diagnosis of SLE, the ACR criteria must be met.(14) Non lupus nephritis describes the classical IF findings of LN but without the clinical or serological evidence of lupus. It is a newly developing entity and that means further studies are still needed to better understand the incidence and its exact pathophysiology and presentations. (15)Kidney transplant remains the gold standard treatment for ESRD. It has shown to improve both quality of life and survival in comparison to renal replacement therapies. (16) Transplant rejection occurs as a result of the body’s own immune system creating antibodies against the alloantigen from the transplanted kidney. (17) The response can be variable in intensity and onset, it ranges from hyperacute which can happen within minutes of transplant and is usually related to preformed antibodies or ABO mismatch. Acute rejection occurs any time following transplant and is subclassified depending on the underlying factor and immune mechanism to antibody mediated rejection (ABMR), which usually happens as a result of donor specific alloantibodies damaging the kidney causing peritubulitis/capillaritis. And acute T-cell mediated rejection (TCMR_ which is characterized by lymphocytic infiltrate into tubules, interstitium and arterial intima. Chronic rejection on the other hand usually occurs after 3 months and can be as a result of chronic T cell mediated or chronic antibody mediated. (18)Risk factors for transplant rejection include: HLA mismatch, Positive B cell crossmatchAdvanced age of the donor type of transplant and inadequate immunosuppression. (19) Patients with rejection present differently, any increase in creatinine more than 25% of the baseline or the presence / worsening of proteinuria should raise the suspicion for rejection. Kidney biopsy might be warranted if transplant rejection is suspected as it would guide the management and further prognosis. (20)There has been no cases in literature describing the presence of non-lupus-full house nephropathy in the setting of post kidney transplant, we hypothesize that it might be related to circulating immune complex mediated damage to the transplant kidney possibly in the setting of chronic rejection. The point of interest in this condition and in our case in particular is that the patient was treated mainly for the possible underlying rejection with resuming mycophenolate and optimizing tacrolimus with institution steroids which lead to improvement in her kidney parameters and more than 50% drop in the degree of proteinuria. This further suggests that the possible underlying mechanism is related to the rejection process causing the non lupus pattern and nephrotic syndrome.Conclusion: Non lupus full house nephropathy is rare and is poorly understood. It has been described in association to several conditions however, There has been no data describing the associated post kidney transplant and rejection. Non lupus full house nephropathy can occur in the setting of kidney transplant and it might be related to transplant rejection. We wanted to raise awareness about this condition and possible association in transplant recipients as it carried out a worse prognosis and can lead to loss of graft function, also, to describe the methods in the diagnosis and a proposed treatment regimen.References:• Silva MD, Oliveira PV, Vale PH, Cunha RD, Lages JS, Brito DJ, Salgado Filho N, Guedes FL, Silva GE, Santos RF. Non-lupus full-house nephropathy: a case series. Brazilian Journal of Nephrology. 2020 Nov 11;43:586-90. • Mok CC, Lau CS. Pathogenesis of systemic lupus erythematosus. Journal of clinical pathology. 2003 Jul;56(7):481. • Ayoub I, Cassol C, Almaani S, Rovin B, Parikh SV. The kidney biopsy in systemic lupus erythematosus: a view of the past and a vision of the future. Advances in chronic kidney disease. 2019 Sep 1;26(5):360-8. • Vaillant AA, Mohseni M. Chronic Transplantation Rejection. InStatPearls [Internet] 2023 Jan 1. StatPearls Publishing. • Neuberger J. Incidence, timing, and risk factors for acute and chronic rejection. Liver transplantation and surgery: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 1999 Jul 1;5(4 Suppl 1):S30-6. •Allen PJ, Chadban SJ, Craig JC, Lim WH, Allen RD, Clayton PA, Teixeira-Pinto A, Wong G. Recurrent glomerulonephritis after kidney transplantation: risk factors and allograft outcomes. Kidney international. 2017 Aug 1;92(2):461-9.• • Jafari R, Mehrazma M, Vahedi M, Ossareh S. Prevalence and Prognosis of Post-transplant Glomerulonephritis in Kidney Transplant Biopsies, A Single-Center Report. Iranian Journal of Kidney Diseases. 2023 Mar 1;17(2):92. • Briganti EM, Russ GR, McNeil JJ, Atkins RC, Chadban SJ. Risk of renal allograft loss from recurrent glomerulonephritis. New England Journal of Medicine. 2002 Jul 11;347(2):103-9. • Abbas F, El Kossi M, Jin JK, Sharma A, Halawa A. De novo glomerular diseases after renal transplantation: How is it different from recurrent glomerular diseases?. World Journal of Transplantation. 2017 Dec 12;7(6):285. • Hariharan S, Adams MB, Brennan DC, Davis CL, First MR, Johnson CP, Ouseph R, Peddi VR, Pelz CJ, Roza AM, Vincenti F. RECURRENT AND DE NOVO GLOMERULAR DISEASE AFTER RENAL TRANSPLANTATION: A Report from Renal Allograft Disease Registry (RADR): 1, 2. Transplantation. 1999 Sep 15;68(5):635-41. • Filippone EJ, McCue PA, Farber JL. Transplant glomerulopathy. Modern Pathology. 2018 Feb 1;31(2):235-52. • Gill JM, Quisel AM, Rocca PV, Walters DT. Diagnosis of systemic lupus erythematosus. American family physician. 2003 Dec 1;68(11):2179-87. • Musa R, Brent LH, Qurie A. Lupus nephritis. • Anders HJ, Saxena R, Zhao MH, Parodis I, Salmon JE, Mohan C. Lupus nephritis. Nature reviews Disease primers. 2020 Jan 23;6(1):7. • Wani AS, Zahir Z, Gupta A, Agrawal V. Clinicopathological pattern of non-lupus full house nephropathy. Indian Journal of Nephrology. 2020 Sep;30(5):301. • Braun MM, Khayat M. Kidney Disease: End-Stage Renal Disease. FP essentials. 2021 Oct 1;509:26-32. • Halloran PF, Einecke G, Sikosana ML, Madill-Thomsen K. The biology and molecular basis of organ transplant rejection. InPharmacology of Immunosuppression 2022 Jan 29 (pp. 1-26). Cham: Springer International Publishing. • Wood KJ, Goto R. Mechanisms of rejection: current perspectives. Transplantation. 2012 Jan 15;93(1):1-0. • Oweira H, Ramouz A, Ghamarnejad O, Khajeh E, Ali-Hasan-Al-Saegh S, Nikbakhsh R, Reißfelder C, Rahbari N, Mehrabi A, Sadeghi M. Risk factors of rejection in renal transplant recipients: a narrative review. Journal of Clinical Medicine. 2022 Mar 3;11(5):1392. • Williams WW, Taheri D, Tolkoff-Rubin N, Colvin RB. Clinical role of the renal transplant biopsy. Nature Reviews Nephrology. 2012 Feb;8(2):110-21.Acknowledgments: We thank the nephrology department at penn state health for giving us the opportunity and support to conduct this workAuthor contribution: Ahmad Matarneh: Manuscript writing, literature review, Clinical careOmar salameh Manuscript writing, literature review, Clinical careSundus sardar Manuscript writing, literature review, Clinical careTheja Channapragada Manuscript writing, literature review, Clinical careMohammad Abdulbasit Manuscript writing, literature review, Clinical careAmanda Karasinsk iManuscript writing, literature review, Clinical careErik Washburn HistopathologyNasrollah ghahramani: Clinical care, literature review, manuscript write up, MentorConsent: Verbal informed consent was obtained from the patient to publish this report in accordance with the journal’s patient consent policyConflict of interest The authors associated with the this case report have no actual or possible conflict of interest to declareDate availability statement: The data that support the findings of this study are available on request from the corresponding authorFunding: The funding process is solely done from the writing authors

The 4T1 tumor model closely approximates the characteristics of human breast cancer and is widely used in laboratory research. Knowledge of the optical parameters of the tumor is important for choosing the correct parameters for laser treatment. In this paper, optical properties and refraction indices of breast tissue in healthy mice and 4T1-model breast tumor have been measured. Using these measurements, absorption coefficient and reduced scattering coefficient have been reconstructed. A significant decrease in both the scattering and refractive index of tumor tissue has been observed. The change in tissue morphology has induced the change in the slope of the scattering spectrum. Thus, the light penetration depth into tumor has increased by almost 1.5-2 times in the NIR “optical windows.” Raman spectra have shown lower lipid content and higher protein content in tumor. The results may be useful for modeling the distribution of laser radiation in healthy tissues and cancers.

Activation-induced cytidine deaminase (AID) is an enzyme that plays a crucial role in mediating somatic hypermutation (SHM) and class-switch recombination (CSR). It has been found to be related to aberrant immunoglobulin CSR in activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL). In a previous study, we demonstrated that proteasome inhibitor MG132 had a significant anti-lymphoma effect on ABC-DLBCL, but the mechanism behind this remains unknown. In this study, we observed that MG132 induced significant cell death in ABC-DLBCL cells and inhibited the growth of ABC-DLBCL cell xenograft tumors. Our results also showed that MG132 impairs proteasome degradation of AID, leading to AID accumulation. Using AID-deficient C57/BL6 mice as a control, we found excessive endogenous AID accumulation in C57/BL6 wildtype mice treated with MG132, and apparent CSR of IgM to IgG1, IgG3 and IgE. In stimulation of cytokines such as LPS and/or IL4, ABC-DLBCL cells showed a noticeable increase in CSR of IgM to IgG1, IgG3 and IgE with decreased AID ubiquitination. This study demonstrates that MG132 can induce AID accumulation, which in turn restores dysfunctional CSR in ABC-DLBCL. The use of MG132 as a tool elucidates the anti-lymphoma effect of proteasome inhibitors on ABC-DLBCL by rescuing the abnormal AID-induced CSR.