Primary Type Research Articles

Surgical treatment of stage IV gastroenteropancreatic neuroendocrine carcinoma: Experience and outcomes in the United States.

Surgery for metastatic gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) has not been well-studied. This retrospective cohort study describes patients in the United States with stage IV GEP-NEC and their survival outcomes segregated by surgery. Patients diagnosed with stage IV GEP-NEC from 2004 to 2017 in the National Cancer Database were categorized into three groups: no surgery, primary site or metastatic site ("single-site") surgery, and primary site and metastatic site ("multisite") surgery. Factors associated with surgical treatment were identified, and risk-adjusted overall survival of each group was compared. Of 4171 patients included, 958 (23.0%) underwent single-site surgery and 374 (9.0%) underwent multisite surgery. The strongest predictor of surgery was primary tumor type. Compared with no surgery, the risk-adjusted mortality reduction associated with single-site surgery ranged from 63% for small bowel (HR = 0.37, 0.23-0.58, p < 0.001) NEC to 30% for colon and appendix NEC (HR = 0.70, 0.61-0.80, p < 0.001), while the mortality reduction associated with multisite surgery ranged from 77% for pancreas NEC (HR = 0.23, 0.17-0.33, p < 0.001) to 48% for colon and appendix NEC (HR = 0.52, 0.44-0.63, p < 0.001). We observed an association between extent of surgical intervention and overall survival for patients with stage IV GEP-NEC. Surgical resection should be further investigated as a treatment option for highly-selected patients with this aggressive disease.

Type catalogue of Oedipodinae (Orthoptera: Acrididae) present in Naturalis Biodiversity Center Leiden (Netherlands).

A type catalogue of Oedipodinae in the collection of Naturalis Biodiversity Center is presented altogether 82 type specimens including 13 primary types and 5 junior synonyms: holotypes (4 species), neotype (1 species), lectotypes (2 species, 1 subspecies), and syntypes (5 species). Furthermore 50 additional secondary type specimens were recorded. Here, we present the full type material catalogue including a locality map of all species and pictures of the 15 primary type species.

Tuning lattice defects and photocurrent response of ZnO thin films by Mg doping and Ar-H2 atmospheric plasma treatment

The effects of Mg doping and Ar-H2 atmospheric pressure plasma jet (APPJ) treatment on zinc oxide (ZnO) thin films were investigated. Mg doping has been demonstrated to facilitate the incorporation of atomic hydrogen in the ZnO lattice via Ar-H2 APPJ. The co-doping of Mg and H changed ZnO’s primary oxygen defect type from vacancy (VO) to interstitial (Oi), which reduced photocorrosion significantly. The dominance of interstitial defects (i.e., Zni and Oi) in the H-doped Zn0.9Mg0.1O thin film was confirmed by photoluminescence spectroscopy. Zni shallow donors improved light absorption at wavelengths > 650 nm, increasing the film’s photocurrent density. Without Mg, doping H via Ar-H2 APPJ was ineffective for pure ZnO thin film. The dominance of VO in pure ZnO thin film after APPJ, though enhanced light absorbance, gave rise to an erratic photocurrent response due to the instability of VO. The lack of acceptor states also led to severe photocorrosion.

Functional interrogation of lymphocyte subsets in alopecia areata using single-cell RNA sequencing

Alopecia areata (AA) is among the most prevalent autoimmune diseases, but the development of innovative therapeutic strategies has lagged due to an incomplete understanding of the immunological underpinnings of disease. Here, we performed single-cell RNA sequencing (scRNAseq) of skin-infiltrating immune cells from the graft-induced C3H/HeJ mouse model of AA, coupled with antibody-based depletion to interrogate the functional role of specific cell types in AA in vivo. Since AA is predominantly T cell-mediated, we focused on dissecting lymphocyte function in AA. Both our scRNAseq and functional studies established CD8+ T cells as the primary disease-driving cell type in AA. Only the depletion of CD8+ T cells, but not CD4+ T cells, NK, B, or γδ T cells, was sufficient to prevent and reverse AA. Selective depletion of regulatory T cells (Treg) showed that Treg are protective against AA in C3H/HeJ mice, suggesting that failure of Treg-mediated immunosuppression is not a major disease mechanism in AA. Focused analyses of CD8+ T cells revealed five subsets, whose heterogeneity is defined by an "effectorness gradient" of interrelated transcriptional states that culminate in increased effector function and tissue residency. scRNAseq of human AA skin showed that CD8+ T cells in human AA follow a similar trajectory, underscoring that shared mechanisms drive disease in both murine and human AA. Our study represents a comprehensive, systematic interrogation of lymphocyte heterogeneity in AA and uncovers a novel framework for AA-associated CD8+ T cells with implications for the design of future therapeutics.

Smoke and Spike: Benzo[a]pyrene Enhances SARS-CoV-2 Infection by Boosting NR4A2-Induced ACE2 and TMPRSS2 Expression.

Cigarette smoke aggravates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the underlying mechanisms remain unclear. Here, they show that benzo[a]pyrene in cigarette smoke extract facilitates SARS-CoV-2 infection via upregulating angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Benzo[a]pyrene trans-activates the promoters of ACE2 and TMPRSS2 by upregulating nuclear receptor subfamily 4 A number 2 (NR4A2) and promoting its binding of NR4A2 to their promoters, which is independent of functional genetic polymorphisms in ACE2 and TMPRSS2. Benzo[a]pyrene increases the susceptibility of lung epithelial cells to SARS-CoV-2 pseudoviruses and facilitates the infection of authentic Omicron BA.5 in primary human alveolar type II cells, lung organoids, and lung and testis of hamsters. Increased expression of Nr4a2, Ace2, and Tmprss2, as well as decreased methylation of CpG islands at the Nr4a2 promoter are observed in aged mice compared to their younger counterparts. NR4A2 knockdown orinterferon-λ2/λ3 stimulationdownregulates the expression of NR4A2, ACE2, and TMPRSS2, thereby inhibiting the infection. In conclusion, benzo[a]pyrene enhances SARS-CoV-2 infection by boosting NR4A2-induced ACE2 and TMPRSS2 expression. This study elucidates the mechanisms underlying the detrimental effects of cigarette smoking on SARS-CoV-2 infection and provides prophylactic options for coronavirus disease 2019, particularly for the elderly population.

Broiler breast muscle myopathies: association with satellite cells

Heavy weight fast-growing meat-type broiler chickens have largely been selected for growth rate, muscle mass yield especially for the breast muscle, and feed conversion. Substantial improvements have been made, but in recent years breast meat quality issues resulting in product downgrades or condemnation have occurred especially from necrotic and fibrotic myopathies like Wooden Breast. In general, the morphological structure of the broiler breast muscle has changed in the modern commercial broiler with muscle fiber diameters increased, circulatory supply decreased, and connective spacing between individual fibers and fiber bundles decreased. Satellite cells are the primary cell type responsible for all posthatch muscle growth, and the repair and regeneration of muscle fibers. Recent evidence is suggestive of changes in the broiler satellite cell populations which will limit the ability of the satellite cells to regenerate damaged muscle fibers back to their original. These changes in the cellular biology of broiler satellite cells are likely associated with the necrosis and fibrosis observed in myopathies like Wooden Breast.

High-grade non-intestinal type sinonasal adenocarcinoma with ETV6::NTRK3 fusion, distinct from secretory carcinoma by immunoprofile and morphology

We report 2 cases of high-grade sinonasal adenocarcinoma with a distinct morphological and immunohistochemical phenotype. Albeit histologically different from secretory carcinoma of the salivary glands, both tumors presented here share an ETV6::NTRK3 fusion. The highly cellular tumors were composed of solid and dense cribriform nests, often with comedo-like necroses in the center, and minor areas with papillary, microcystic, and trabecular formations without secretions, mostly located at the periphery of the lesion. The cells displayed high-grade features, with enlarged, crowded, and often vesicular nuclei with conspicuous nucleoli and brisk mitotic activity. The tumor cells were immunonegative for mammaglobin while showing immunopositivity for p40/p63, S100, SOX10, and GATA3, as well as for cytokeratins 7, 18, and 19. For the first time, we describe 2 cases of primary high-grade non-intestinal type adenocarcinomas of the nasal cavity, distinct from secretory carcinoma by morphology and immunoprofile, harboring the ETV6::NTRK3 fusion.

Bile Acids and Short-Chain Fatty Acids Are Modulated after Onion and Apple Consumption in Obese Zucker Rats.

Gut microorganisms are involved in the development and severity of different cardiovascular diseases, and increasing evidence has indicated that dietary fibre and polyphenols can interact with the intestinal microbiota. The study objective was to investigate the effect of onion and apple intake on the major types of microbial-derived molecules, such as short-chain fatty acids (SCFAs) and bile acids (BAs). Obese Zucker rats were randomly assigned (n = eight rats/group) to a standard diet (OC), a standard diet/10% onion (OO), or a standard diet/10% apple (OA). Lean Zucker rats fed a standard diet served as a lean control (LC) group. Faecal samples were collected at baseline, and 8 weeks later, the composition of the microbial community was measured, and BA and SCFA levels were determined using high-performance liquid chromatography-mass spectrometry (HPLC-MS) and gas chromatography-mass spectrometry (GC-MS), respectively. Rats fed onion- and apple-enriched diets had increased abundance of beneficial bacteria, such as Bifidobacterium spp. and Lactobacillus spp., enhanced SCFAs (acetic, propionic, isobutyric, and valeric acids), decreased excretion of some BAs, mainly of the primary (CA, α-MCA, and β-MCA) and secondary type (ω-MCA, HDCA, NCA, DCA, and LCA), and increased amount of taurine- and glycine-conjugated BAs compared to the OC group. The contribution of specific bioactive compounds and their metabolites in the regulation of the microbiome and the pathways linked to SCFA and BA formation and their relationship with some diseases needs further research.

End stage renal disease due to primary hyperoxaluria in a 7-month infant; a case report

Primary hyperoxaluria (PH) is a rare genetic metabolic disease presented severely in infants with end-stage renal disease (ESRD). Promoting diagnosis with aggressive management is essential in these patients. Here we presented a rare case of primary hyperoxaluria type 1 (PH1) in a seven-month infant girl who underwent dialysis with prospective kidney transplantation in the future.

Downregulation of a potential therapeutic target NPAS2, regulated by p53, alleviates pulmonary fibrosis by inhibiting epithelial-mesenchymal transition via suppressing HES1

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease and a severe form of pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) of alveolar epithelial cells is induced in response to epithelial injury, which leads to the accumulation of extracellular matrix in the lung parenchyma and contributes to pulmonary fibrosis. NPAS2 (neuronal PAS domain protein 2) is significantly increased in the lung tissues of IPF patients according to microarray dataset GSE10667 and NPAS2 is downregulated in differentiated human pulmonary type 2 epithelial cells in vitro based on microarray dataset GSE3306 from Gene Expression Omnibus (GEO). In this study, we demonstrated that NPAS2 was increased in bleomycin (BLM)- induced fibrotic lungs in mice. Knockdown of NPAS2 inhibited EMT in primary mouse lung alveolar type 2 epithelial (pmATII) cells and human lung alveolar type 2 epithelial cell line A549 cells under BLM challenge in vitro. Moreover, the silence of NPAS2 alleviated the BLM-induced pulmonary fibrosis in a murine model. Mechanistically, NPAS2 promotes EMT through positively regulating hairy and enhancer of split 1 (HES1) expression. In this study, we present novel findings that have not been previously reported, emphasizing that p53 transcriptionally activates NPAS2 in ATII cells and overexpression of NPAS2 weakens the effects of TP53 knockdown on EMT of pmATII and A549 cells. Our results suggest NPAS2 is a novel target gene of p53 in regulating BLM-mediated EMT in ATII cells and pulmonary fibrosis.

Chemotherapy-associated liver morphological changes in hepatic metastases (CALMCHeM).

To review imaging findings in chemotherapy-associated liver morphological changes in hepatic metastases (CALMCHeM) on computed tomography (CT)/magnetic resonance imaging (MRI) and its association with tumor burden. We performed a retrospective chart review to identify patients with hepatic metastases who received chemotherapy and subsequent follow-up imaging where CT or MRI showed morphological changes in the liver. The morphological changes searched for were nodularity, capsular retraction, hypodense fibrotic bands, lobulated outline, atrophy or hypertrophy of segments or lobes, widened fissures, and one or more features of portal hypertension (splenomegaly/venous collaterals/ascites). The inclusion criteria were as follows: a) no known chronic liver disease; b) availability of CT or MRI images before chemotherapy that showed no morphological signs of chronic liver disease; c) at least one follow-up CT or MRI image demonstrating CALMCHeM after chemotherapy. Two radiologists in consensus graded the initial hepatic metastases tumor burden according to number (≤10 and >10), lobe distribution (single or both lobes), and liver parenchyma volume affected (<50%, or ≥50%). Imaging features after treatment were graded according to a pre-defined qualitative assessment scale of "normal," "mild," "moderate," or "severe." Descriptive statistics were performed with binary groups based on the number, lobar distribution, type, and volume of the liver affected. Chi-square and t-tests were used for comparative statistics. The Cox proportional hazard model was used to determine the association between severe CALMCHeM changes and age, sex, tumor burden, and primary carcinoma type. A total of 219 patients met the inclusion criteria. The most common primaries were from breast (58.4%), colorectal (14.2%), and neuroendocrine (11.0%) carcinomas. Hepatic metastases were discrete in 54.8% of cases, confluent in 38.8%, and diffuse in 6.4%. The number of metastases was >10 in 64.4% of patients. The volume of liver involved was <50% in 79.8% and ≥50% in 20.2% of cases. The severity of CALMCHeM at the first imaging follow-up was associated with a larger number of metastases (P = 0.002) and volume of the liver affected (P = 0.015). The severity of CALMCHeM had progressed to moderate to severe changes in 85.9% of patients, and 72.5% of patients had one or more features of portal hypertension at the last follow-up. The most common features at the final follow-up were nodularity (95.0%), capsular retraction (93.4%), atrophy (66.2%), and ascites (65.7%). The Cox proportional hazard model showed metastases affected ≥50% of the liver (P = 0.033), and the female gender (P = 0.004) was independently associated with severe CALMCHeM. CALMCHeM can be observed with a wide variety of malignancies, is progressive in severity, and the severity correlates with the initial metastatic liver disease burden.

Mineral forms of tungsten at the Porokhovskoe and Yugo-Konevskoe deposits (South Urals)

The ore hand specimens and technological ore samples from the Porokhovskoe and Yugo-Konevskoe W greisen deposits in the South Urals are studied. The major W minerals of primary ores at both deposits include hubnerite and scheelite. The secondary and accessory minerals are pyrite, chalcopyrite and molybdenite, rare minerals include sphalerite, galena, bismuthinite, aikinite, unidentifed chalcogenides and sulfosalts, magnetite, rutile, ilmenite, titanite and columbite. The veins are mainly composed of quartz and muscovite with subordinate calcite, dolomite and fuorite, rare chlorite and amphibole and accessory zircon, apatite and uraninite. No zonation in the distribution of wolframite with various Fe content is identifed relative to the Yugo-Konevsky granite pluton, however, wolframite of the Northern area of the Porokhovskoe deposit is enriched in Fe compared to that of the Central area and Yugo-Konevskoe deposit. In addition to veined wolframite and scheelite, the oxidized ores also contain Fe and Mn oxyhydroxides, malachite, pyromorphite and bromargyrite. Tungsten is part of Mn and Fe oxyhydroxides, which replace wolframite and less often sulfdes. The WO3 content of pseudomorphic Mn and Fe oxyhydroxides after hubnerite reaches 18 wt. %. Single grains of stolzite and russellite are found. According to the results of phase chemical analysis of technological samples, the amount of tungstite in oxidized ores is minor, therefore all ores of both deposits were ascribed to primary type. Keywords: South Urals, Porokhovskoe deposit, Yugo-Konevskoe deposit, tungsten, hubnerite, scheelite, stolzite, trace elements.

Grandparents with different health statuses as primary caregivers: Are they bad for children's health?

AbstractThe prevalence and intensity of grandparenting have continued to increase in the era of rapid aging. However, little is known about grandparents with different health statuses as primary caregivers and their implications for children's health. A nationally representative cohort of over 8990 Chinese children interviewed from 2010 to 2018 was used. Random effects logit models were constructed to assess the association of the primary caregiver type (grandparents vs. parents) and caregiver health with child health. Subsequently, additive interactions between the primary caregiver type and caregiver health were estimated to determine whether children cared for by grandparents with poor health were the most vulnerable children in terms of health. Deterioration of health status was found among children cared for mainly by grandparents, manifested as a higher likelihood of illness, depressive symptoms and unmet health care needs. However, children looked after by healthy grandparents tended to exhibit better health than their counterparts who were cared for by unhealthy parents. Grandparents as primary caregivers might not have a universally detrimental effect on child health. Thus, interventions to prompt child health could consider grandparents as caregivers, especially healthy grandparents.

Seroprvalence of Transforming Growth Factor-β1 and some hormones on Male Infertility in Nasiriya City, Iraq

Male infertility is a problem that affects 10–15% of males in reproductive age. The current study aimed to detect the role of Transforming Growth Factor-β1 (TGF-β1) cytokine and some hormones in infertility outpatients males at Al-Nasiriya Teaching Hospital/ Infertility Unit/Thi-Qar Governorate, Iraq. During the period from September 2022 to March 2023, 88 Serum samples from (76 infertility males and 12 control) were collected to assay the levels of TGF-β1, Testosterone, follicle Stimulating and Prolactin hormones by Sandwich-ELISA technique. Infertility patients were distributed to primary and secondary infertility type with a 66(86.84%) and 10 (13.016%) patient, respectively (P≤0.01). All infertility patients showed an elevated mean sera levels of TGF-β1 with (0.734±0.45 ng/ml), as compared with controls (0.670±0.393 ng/ml). No statistical differences were presented between the two groups included in present study regarding this cytokine (P&gt;0.05). The levels of Testosterone, follicle Stimulating Hormone and Prolactin were (3.12 ± 0.76, 7.69 ± 3.67, 15.65 ± 2.75), (3.69 ±1.15, 5.77 ± 0.89, 13.23 ± 0.57) in primary and secondary infertility types compared to control was (6.08 ± 1.42, 7.08 ± 0.73, 11.37 ± 1.15). The present study results may shed light the role of TGF-β1 and some hormones as a serological and diagnosis tool in male infertility. This finding may be contributes as a useful tool in disease classification and assessment.

Service Strategy on Tourism Business Development: Empirical Study on Purbalingga Panyatan Waterfall Tourism Spot

Purpose: The aim of this study is to examine the impact of service strategy rural tourism on tourism business development in Panyatan Waterfall in Purbalingga, Central Java, Indonesia&#x0D; &#x0D; Theoretical framework: Previous study showed that service strategy has positive impact on tourism business development, especially in fomous and well-managed tourism site. However, there is still much to investigate if the situation is occurred in rural destination that not categorized tourism site, like Panyatan Waterfall.&#x0D; &#x0D; Design/methodology/approach: This research is a primary research type. The authors conducted field research on April-June 2022 to interview and distribute questionnaire to visistors. There are 543 visitors who respond and answer our questionnaire. The respondents were selected using an accidental sampling technique with the Lemeshow formula. The data were analyzed using validity, reliability, and descriptive analyses, as well as simple linear regression.&#x0D; &#x0D; Findings: The results showed that service strategy in rural tourism has significant effect to tourism business development in this area.&#x0D; &#x0D; Research, Practical &amp; Social implications: The study revealed that service strategy that conducted by local people surrounding tourist site in Panyatan Waterfall lead positively impact to the economy of community in Panyatan Waterfall.&#x0D; &#x0D; Originality/value: The result of study indicated that the friendliness of the resident surrounding the tourist site become part of the external service of community, and it attract tourists to visit Panyatan Waterfall.

Association of Primary Kidney Disease Type and Donor Relatedness With Live Donor Kidney Transplant Outcomes: An Analysis of ANZDATA

There is limited information about the association between primary kidney disease and donor relatedness with transplant outcomes. This study addresses this gap by evaluating clinical outcomes after kidney transplantation in recipients of living donor kidneys as a function of primary kidney disease type and donor relatedness in Australia and New Zealand. Retrospective observational study. Kidney transplant recipients who received allografts from living donors between January 1, 1998, and December 31, 2018, as recorded in the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA). Primary kidney disease type categorized as majority monogenic, minority monogenic, or other primary kidney disease based on disease heritability as well as donor relatedness. Primary kidney disease recurrence, graft failure. Kaplan-Meier analysis and Cox proportion hazards regression to generate hazard ratios for primary kidney disease recurrence, allograft failure, and mortality. Partial likelihood ratio test was used to examine possible interactions between primary kidney disease type and donor relatedness for both study outcomes. Among 5,500 live donor kidney transplant recipients, majority monogenic (adjusted HR, 0.58, P<0.001) and minority monogenic primary kidney diseases (adjusted HR, 0.64, P<0.001) were associated with reduced primary kidney disease recurrence compared with other primary kidney diseases. Majority monogenic primary kidney disease was also associated with reduced allograft failure (adjusted HR, 0.86, P=0.04) compared with other primary kidney diseases. Donor relatedness was not associated with primary kidney disease recurrence nor graft failure. No interaction was detected between primary kidney disease type and donor relatedness for either study outcome. Potential misclassification of primary kidney disease type, incomplete ascertainment of primary kidney disease recurrence, unmeasured confounding. Monogenic primary kidney disease is associated with lower rates of primary kidney disease recurrence and allograft failure. Donor relatedness was not associated with allograft outcomes. These results may inform pretransplant counseling and live donor selection. There are theoretical concerns that live-donor kidney transplants may be associated with increased risks of kidney disease recurrence and transplant failure due to unmeasurable shared genetic factors between the donor and the recipient. This study analyzed data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry and showed that, although disease type was associated with the risk of disease recurrence and transplant failure, donor relatedness did not impact transplant outcomes. These findings may inform pretransplant counseling and live donor selection.

Low let-7d microRNA levels in chick embryos enhance innate immunity against Mycoplasma gallisepticum by suppressing the mitogen-activated protein kinase pathway

Chick embryos are a valuable model for studying immunity and vaccines. Therefore, it is crucial to investigate the molecular mechanism of the Mycoplasma gallisepticum (MG)-induced immune response in chick embryos for the prevention and control of MG. In this study, we screened for downregulated let-7d microRNA in MG-infected chicken embryonic lungs to explore its involvement in the innate immune mechanism against MG. Here, we demonstrated that low levels of let-7d are a protective mechanism for chicken embryo primary type II pneumocytes (CP-II) in the presence of MG. Specifically, we found that depressed levels of let-7 in CP-II cells reduced the adhesion capacity of MG. This suppressive effect was achieved through the activated mitogen-activated protein kinase phosphatase 1 (MKP1) target gene and the inactivated mitogen-activated protein kinase (MAPK) pathway. Furthermore, MG-induced hyperinflammation and cell death were both alleviated by downregulation of let-7d. In conclusion, chick embryos protect themselves against MG infection through the innate immune molecule let-7d, which may result from its function as an inhibitor of the MAPK pathway to effectively mitigate MG adhesion, the inflammatory response and cell apoptosis. This study may provide new insight into the development of vaccines against MG.

HOGA1 variants in Chinese patients with primary hyperoxaluria type 3: genetic features and genotype-phenotype relationships.

The aim of our study is to describe the genetic features and correlation between the genotype and phenotype of Chinese patients with primary hyperoxaluria type 3 (PH3). The genetic and clinical data of PH3 patients in our cohort were collected and analyzed retrospectively. All published studies of Chinese PH3 populations between January 2010 and November 2022 were searched and enrolled based on inclusive standards. A total of 60 Chinese PH3 patients (21 cases from our cohort and 39 cases from previous studies) were included. The mean age of onset was 1.62 ± 1.35 (range 0.4-7) years. A total of 29 different variants in the HOGA1 gene were found. The mutations were most commonly clustered in exons 1, 6, and 7. Among the genotypes, exon 6 skipping (c.834G > A and c.834_834 + 1GG > TT mutations) was the most common, followed by c.769T > G; the allele frequencies (AFs) were 48.76% and 12.40%, respectively. Patients homozygous for exon 6 skipping exhibited a median age of onset of 0.67 (0.58-1) years, which was significantly lower than that observed among heterozygotes and nonexon 6 skipping patients (p = 0.021). A total of 22.5% (9/40) of PH3 patients had a decreased estimated glomerular filtration rate, and one patient with homozygous exon 6 skipping developed end-stage renal disease. A hotspot mutation, potential hotspot mutation and genotype-phenotype correlation were found in Chinese PH3 patients. This study expands the mutational spectrum and contributes to the understanding of genotypic profiles of PH3, which may provide a potential diagnostic and therapeutic target.

Social justice implications of&amp;nbsp;smart urban technologies:&amp;nbsp;an intersectional approach

Techno-optimistic visions around smart buildings, homes, cities, grids, healthcare, etc. have become ubiquitous over the past decade. Using variations of machine learning and artificial intelligence, smart urbanism (SU) envisions an efficient, digital society. However, research shows that smart technologies reinscribe inequalities by prioritising the interests of the free market, technology-centric governance and data monetisation. Although there has been a growing concern over the injustices SU perpetuates, there is a lack of systematic engagement with power systems such as capitalism or heterosexism that underpin SU visions. A novel framework is presented that situates intersectional justice at the heart of SU. A mapping of 70 cases of ‘trouble’ with the promises of SU is used to address three core research questions: What are the ‘troubles’ with SU? To what extent are they intersectional? What can intersectionality add to the development of a just SU? The analysis shows how SU politics play out in relation to how users are understood and engaged, how different actors institutionalise SU and how dominant power systems are challenged. The presented strategy contributes to understanding not just the data politics in urban spaces, but also how they can be renegotiated and re-evaluated to solve multiple and interconnected urban crises without compromising on social justice. Practice relevance Citizen-led initiatives against SU should commit to intersectionality’s radical core to dismantle power structures to ensure local smart urban projects do not entrench global business-as-usual neoliberal agendas. Intersectional thinking can create spaces for deliberative dialogues between civil society groups and build alliances across groups that seek to challenge the hegemony of exclusionary urban policies. Urban planners and local governments, which are at the forefront of SU applications, should decentre technologies and rather focus efforts on working out how smart technologies can work in conjunction with other kinds of urban interventions, such as social, economic and environmental policy changes, collaborative planning, community development, etc. to herald more just urban futures. Designers of smart urban technologies should apply intersectional approaches to further challenge ‘Homo economicus’ (rational, White, technophilic, able-bodied) as the primary user type and to replace it with diverse user archetypes that express humanity, justice and generosity.

#5635 SYSTEMIC OXALOSIS: AN OVERVIEW OF THE FINDINGS AND PREVALENCE IN PRIMARY HYPEROXALURIA

Abstract Background and Aims Systemic oxalosis is a severe co-morbidity that may arise in patients with primary hyperoxaluria type 1 (PH1). It is caused by precipitation of calcium oxalate crystals in organs besides the kidneys, as a result of high endogenous oxalate production. In this study, we aimed to provide an overview of the prevalence, features, screening modalities and factors that play a role in developing systemic oxalosis as cohort studies are currently lacking. Method A retrospective registry study was conducted using data from the OxalEurope registry, one of the largest registries of patients with PH1. All patients with primary hyperoxaluria and data on systemic oxalosis were identified. Data was analyzed using descriptive statistics, Chi-square tests, Mann-Whitney U tests and Kaplan Meier analyses. Results A total of 159 out of 291 (55%) screened PH1 patients were diagnosed with systemic oxalosis. In addition, 110 patients were recorded having no signs of systemic oxalosis at follow-up, however screening was not performed. Sixty-two patients had already developed systemic oxalosis at moment of diagnosis and systemic oxalosis was most often found in patients with ESKD (95%). The eyes, bones and heart are most frequently affected, nevertheless deposits occurred in many organs, as shown by obduction. Fundus photography (n = 16), X-ray (n = 43), and echocardiography (n = 59) are the modalities used most often to screen respectively the eyes, bones and heart. Patients who developed systemic oxalosis had significantly higher upper plasma oxalate levels (median 22 versus 175 umol/L, p&amp;lt;0.001). Furthermore, patients with systemic oxalosis had a significant higher mortality rate compared to patients without systemic oxalosis (48 out of 142 versus 10 out of 212, p&amp;lt;0.001), which difference persisted after correcting for ESKD (p&amp;lt;0.001). Kaplan Meier analysis (Figure 1) showed that pediatric patients with ESKD tended to developed systemic oxalosis more frequently than adults (p&amp;lt;0.001). Conclusion This is the first research to systematically study and report systemic oxalosis in patients with primary hyperoxaluria type 1. Systemic oxalosis is prevalent among PH1 patients, especially when ESKD is present, and may lead to significant morbidity and mortality. Patients with systemic oxalosis have a higher mortality rate and pediatric patients may develop systemic oxalosis more frequently than adults. Given the high incidence and possible implications, we would like to make an appeal on screening all patients with systemic oxalosis. Future research should focus on reliable screening modalities for early signs of systemic oxalosis.