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The prevalence, clinical features, and long-term outcome of patients with primary Sjögren’s syndrome with renal involvement

Uterine organoids reveal insights into epithelial specification and plasticity in development and disease

Understanding how epithelial cells in the female reproductive tract (FRT) differentiate is crucial for reproductive health, yet the underlying mechanisms remain poorly defined. At birth, FRT epithelium is highly malleable, allowing differentiation into various epithelial types, but the regulatory pathways guiding these early cell fate decisions are unclear. Here, we use neonatal mouse endometrial organoids and assembloid coculture models to investigate how innate cellular plasticity and external mesenchymal signals influence epithelial differentiation. Our findings demonstrate that uterine epithelium undergoes marked age-dependent changes, transitioning from a highly plastic state capable of forming both monolayered and multilayered structures to a more restricted fate as development progresses. Interestingly, parallels emerge between the developmental plasticity of neonatal uterine epithelium and pathological conditions such as endometrial cancer, where similar regulatory mechanisms may reactivate, driving abnormal epithelial differentiation and tumorigenesis. These results not only deepen our understanding of early uterine development but also offer a valuable model for studying the progression of reproductive diseases and cancers.

An investigation of hydraulic fracturing initiation and location of hydraulic fracture in preforated oil shale formations

Activation of the conserved Hippo kinases by inflammasome-triggered proteolytic cleavage controls programmed cell death in macrophages

The mammalian Hippo kinases, MST1 and MST2, regulate organ development and suppress tumor formation by balancing cell proliferation and death. In macrophages, inflammasomes detect molecular patterns from invading pathogens or damaged host cells and trigger programmed cell death. In addition to lytic pyroptosis, the signatures associated with apoptosis are induced by inflammasome activation, but how the inflammasomes coordinate different cell death processes remains unclear. Here, we identify the crucial role of MST1/2 in inflammasome-triggered cell death. Macrophages proteolytically convert full-length MST1/2 into the MST1/2 N-terminal fragments (MST1/2-NT) when the NLRC4 inflammasome detects flagellin from the pathogenic bacterium, Legionella pneumophila . Activation of the NLRP3 inflammasome by the damage-associated molecular pattern, extracellular ATP, also produces MST1/2-NT. Caspase-1, the protease activated by these inflammasomes, directly cleaves MST1/2, and blockage of caspase-1 inhibits MST1/2-NT production in macrophages challenged with L. pneumophila . Importantly, MST1/2-NT production is critical for macrophages to trigger a set of death processes associated with apoptosis upon inflammasome activation and knocking out Mst1/2 causes dysregulated gasdermin protein cleavage for pyroptotic death. Furthermore, macrophages lacking MST1/2 have increased susceptibility to virulent L. pneumophila, revealing that the Hippo kinases are important restriction factors against the pathogen. These findings demonstrate that proteolytic cleavage of MST1/2 induced by inflammatory stimuli is an immune pathway to regulate programmed cell death in macrophages and uncover a unique link between the tumor-suppressive Hippo kinases and the inflammasomes in innate immunity.

Validated HPLC method for simultaneous determination of azelastine hydrochloride fluticasone propionate and oxymetazoline in nasal mucosa and nasopharyngeal swabs from real human samples

Abstract A combination of three co-administrated drugs, such as azelastine hydrochloride (AZT), fluticasone propionate (FP), and oxymetazoline (OXY), is more effective than single therapy for the treatment of seasonal allergy and COVID-19. We established an efficient methodology for the determination of those analytes in spiked nasal mucosa and nasopharyngeal swabs from real human samples. A simple and quick protein precipitation method was used for sample extraction, using acetonitrile. RP-HPLC/DAD method was performed using an Exsil 100 ODS C18 (250 × 4.6 mm, 5 μm) column with an acetonitrile: water (70:30 v/v) solvent system at a flow rate of 0.7 mL/min. A photodiode array detector was applied at 240 nm. A good separation of the three proposed analytes with a short run time of 10 min was noted. Our method was validated according to FDA guidelines for bioanalytical validation methods. Calibration curves were linear in nasal mucosa samples at concentration ranges of 8–125, 10–100, and 10–125 µg/mL, with average recoveries ± SD of 101.56%±0.39, 102.45%±0.86, and 104.61%±4.52 for AZT, FP, and OXY; respectively. The results of precision and accuracy are within acceptable limits. According to stability assays, the three analytes under investigation were stable throughout sample preparation, storage, and injection. Our method was applied to real nasopharyngeal swabs. It shows that the results of the swabs were not affected by gender or age. Good recoveries with low % RSD were observed: 99.03% ± 0.75, 100.02% ± 0.94, and 100.94% ± 1.98 for both genders, and 100.45% ± 0.96, 100.69% ± 1.08, and 100.32% ± 1.53 for different ages for AZT, FP, and OXY; respectively. Moreover, the amount of those drugs in the nasal mucosa was observed for seven hours, and a constant concentration with a low% RSD was noted for the first four hours. Therefore, this method can be applied to monitor the therapeutic dose in the nasal mucosa for the determination of those analytes.

Institutional distance, trade agreements, and intellectual property trade networks: Evidence from cross-border data

Based on the Temporal Exponential Random Graph Models (TERGM), this paper applies global intellectual property trade data between countries to investigate the impact and mechanism of institutional distance on the intellectual property trade network. The study finds that the smaller the institutional distance between countries, the more conducive it is to build an intellectual property trade network. This conclusion remains valid after controlling for geographical adjacency, use of a common language, existence of colonial relationships, and characteristics of the intellectual property trade network. Moreover, through regression by year, it is found that this impact increases year by year. Further, after regressing on sub-indicators of institutional distance, it is found that the smaller the distance in political stability, government efficiency, and regulatory quality, the greater the probability of generating an intellectual property trade relationship. Mechanism analysis reveals that economies with smaller institutional distances are more likely to sign trade agreements, thereby generating trade relationships and promoting the establishment of intellectual property trade networks. In order to deeply participate in the intellectual property trade network, countries should actively align with international institutional norms and sign bilateral or multilateral trade agreements with countries with similar institutional levels to enhance the production level and export of intellectual property.

4-Hydroxy-2-nonenal causes nuclear accumulation of p62 by inhibiting Xpo1 and promoting the proteolytic pathway in the nucleus

p62, an adapter protein involved in selective autophagy, is mainly found in the cytoplasm under normal conditions. Because p62 has nuclear localization signal (NLS) and a nuclear export signal, it has been suggested that p62 shuttles between the nucleus and cytoplasm. We studied the effect of 4-hydroxy-nonenal (4-HNE), an endogenous lipid peroxidation product, on intracellular p62 distribution in mouse embryonic fibroblasts. We found that treatment of 4-HNE causes p62 translocation from the cytoplasm to the nucleus. Further analysis revealed that 4-HNE directly binds to exportin-1 (Xpo1), essential protein for nuclear export of various proteins. Further analysis 4-HNE enhanced intranuclear EGFP-NLS-CL1 degradation in a p62-dependent manner. Our results suggest that 4-HNE changes p62 localization to the nucleus by inhibiting Xpo1 and might affect intranuclear protein quality control.

The evolution of food security in Japan—Based on an indicator evaluation system including climate change indicators

As climate change intensifies, food security has received widespread attention. This study examines the development of Japan’s food security index and its relationship with climate change. From these findings, a food security indicator system for Japan was established. The food security system has six dimensions: availability, nutrition, climate change, society, economics, and fertilizer. The factors affecting food security are complex and variable, and this paper adds the Fertilizer Security Index (FSI) to the previous studies. The overuse of fertilizers directly contributes to soil and atmospheric pollution, which can indirectly lead to issues of food quality insecurity. Including this factor within the food security system is fully justified. This enhances the precision of the food security index system to some degree. The results showed that Japan’s overall food security index exhibited a slight downward trend from 0.113 in 1980 to 0.099 in 2022. Food security reached its lowest point of about 0.067 in 1993. In addition, all five indicators, except the fertilizer index, put pressure on the food security index. Due to the uncertainty inherent in climate change, specifically its ambiguous positive and negative impacts on food security, the Climate Change Security Index provides detailed evidence in this paper supporting whether climate change contributes to or undermines food security. Finally, the study put forward recommendations to ensure food security.

Surgical informed consent practice and associated factors among adult postoperative patients in public hospitals of Mekelle, Tigray, Ethiopia 2023/2024. Cross sectional

Background Substantial weaknesses and omissions of surgical informed consent are evident and the current elements of the surgical informed consent process are largely neglected in daily practice. This study aimed to assess surgical informed consent practice and associated factors among adult postoperative patients in public hospitals of Mekelle, Tigray, Ethiopia. Methods Institution based cross-sectional study was conducted among 314 adult postoperative patients in public hospitals of Mekelle, Tigray, Ethiopia. Participants were selected using systematic random sampling. A pretested interviewer-administered questionnaire was used to collect data. Descriptive, Descriptive, bivariate and multivariable logistic regression analyses were performed using statistical package for social science version 27. Result Only 35.8% (CI 95%, 30.6, 41) of the respondents were identified to have received the recommended (6 or more) components of surgical informed consent. Educational level [AOR 5.76 (1.02, 32.6)], timing of surgical informed consent delivery [AOR 3.27 (1.5, 7.11)], qualification of counselor who took surgical informed consent them [AOR3.185 (1.21, 8.38)], hospital type [AOR 2.85 (1.26, 6.46)], and duration of counseling [AOR 6.9 (3.33, 14.3)] were statistically significant at P<0.05. Conclusion Majority of participants did not receive comprehensive information during the surgical informed consent process in the study hospitals. To improve the delivery it is suggested that health professionals; create rapport with patient, spend more time during counseling.

Utilizing MV-FLOW™ and multidimensional ultrasound characteristics for prognosticating FET outcomes in RIF patients: Study Protocol for a cross-sectional study

Recurrent implantation failure (RIF) is a common issue in frozen-thawed embryo transfer (FET). Prior to transfer, uterine endometrial receptivity of FET patients can be assessed using multimodal transvaginal ultrasound indicators to predict the success rate of the current FET cycle. Endometrial blood flow is a crucial element in evaluating endometrial receptivity. MV-FLOW™ is an advanced two-dimensional superb microvascular imaging technology that can detect and display blood flow in micro-vessels. The data for this study were obtained from an ongoing cross-sectional study comprising 323 RIF patients and 323 first implantation (FI) patients, who underwent transvaginal ultrasound before FET. We collected basic clinical data and multimodal ultrasound data from these patients as predictive features, with clinical pregnancy as the predictive label, for model training. Based on the above, this study aims to establish and validate a clinical prediction model for FET outcomes using support vector classification (SVC) algorithms, based on MV-FLOW™ and multidimensional transvaginal ultrasound imaging features. The objective is to determine the predictive role of multimodal transvaginal ultrasound in embryo transfer outcomes and provide evidence for the clinical application of MV-FLOW™. Trial registration: Trial Registration: ChiCTR2400086401.

Unsupervised monocular depth estimation with omnidirectional camera for 3D reconstruction of grape berries in the wild

Japanese table grapes are quite expensive because their production is highly labor-intensive. In particular, grape berry pruning is a labor-intensive task performed to produce grapes with desirable characteristics. Because it is considered difficult to master, it is desirable to assist new entrants by using information technology to show the recommended berries to cut. In this research, we aim to build a system that identifies which grape berries should be removed during the pruning process. To realize this, the 3D positions of individual grape berries need to be estimated. Our environmental restriction is that bunches hang from trellises at a height of about 1.6 meters in the grape orchards outside. It is hard to use depth sensors in such circumstances, and using an omnidirectional camera with a wide field of view is desired for the convenience of shooting videos. Obtaining 3D information of grape berries from videos is challenging because they have textureless surfaces, highly symmetric shapes, and crowded arrangements. For these reasons, it is hard to use conventional 3D reconstruction methods, which rely on matching local unique features. To satisfy the practical constraints of this task, we extend a deep learning-based unsupervised monocular depth estimation method to an omnidirectional camera and propose using it. Our experiments demonstrate the effectiveness of the proposed method for estimating the 3D positions of grape berries in the wild.

Unique North American isolates of severe metastatic hypervirulent Klebsiella pneumoniae strain infections with hepatic abscesses seen in young patients within Texas

Rationale Hypervirulent Klebsiella pneumoniae (hvKp) infections have principally been identified in Asia. Within a two-month period, two patients between the ages of 30 to 50 years old presented to a tertiary referral hospital in Texas with septic shock, hepatic abscess, and septic thrombophlebitis. Blood cultures were positive for Klebsiella pneumoniae (isolates 2020CK-00441 and 2021CK-00720 respectively). The first patient survived after a prolonged hospital course while the second patient expired. Objectives Describe the clinical presentation of these two patients. Perform whole genome sequencing and bioinformatic analysis to evaluate potential outbreak of specific hvKp bacteria isolates. Methods Whole genome sequencing was performed using both paired-end Illumina MiSeq and nanopore sequencing to obtain a Completed genome for both isolates. Main results 2020CK-00441 belonged to ST23 type while 2021CK-00720 was a ST65 type isolate. Kleborate analyses predicted with high confidence both isolates were hvKp. Phylogenetic analyses showed the two strains are not closely related to each other nor to any known hvKp isolates reported. Both isolates had yersiniabactin, colibactin, aerobactin and salmochelin producing loci which likely confer these isolates hvKp phenotype. 2020CK-00441 and 2021CK-00720 had a unique pK2044 like plasmid. Conclusions HvKp strains capable of causing devastating metastatic septic infections have emerged in Texas. These isolates are unique compared to other hvKp strains globally. Country-wide surveillance and whole genome sequencing of these strains is essential to prevent a major public health emergency in the USA.

Study on disaster-causing probability evaluation of gas pipeline in karst area

In this paper, a disaster-causing probability evaluation method of gas pipelines in karst areas based on disaster system theory and vulnerability theory is proposed. The hazard evaluation index system of gas pipeline disaster events in karst areas is established from three aspects: the activity of disaster-prone environment, the risk of disaster factors and the vulnerability of disaster-bearing bodies. Combined with the advantages of information transmission and updating of the Bayesian network model, the hazard probability of disaster events is gradually calculated from a multi-level perspective. Based on the structural reliability theory, the vulnerability evaluation function of gas pipelines in karst areas is established by considering the interaction between disaster hazard intensity and disaster resistance ability. Meanwhile, the design checkpoint method and finite element simulation are used to calculate the vulnerability probability. Finally, a new disaster-causing probability evaluation approach for gas pipelines in karst areas is formed, which comprehensively considers the event hazard and the pipeline vulnerability. The work presented in this paper can provide a reference for the safety management and accident prevention of gas pipelines crossing the karst areas.

A CACTA-like transposon in the Anthocyanidin synthase 1 (Ans-1) gene is responsible for apricot fruit colour in the raspberry (Rubus idaeus) cultivar ‘Varnes’

Cultivated raspberries (Rubus idaeus L.) most commonly bear small, red, highly aromatic fruits. Their colour is derived predominantly from anthocyanins, water soluble polyphenolic pigments, but as well as red forms, there exist cultivars that display yellow- and apricot-coloured fruits. In this investigation, we used a multi-omics approach to elucidate the genetic basis of the apricot fruit colour in raspberry. Using metabolomics, we quantified anthocyanins in red and apricot raspberry fruits and demonstrated that, in contrast to red-fruited raspberries, fruits of the apricot cultivar ‘Varnes’ contain low concentrations of only a small number of anthocyanin compounds. By performing RNASeq, we revealed differential expression patterns in the apricot-fruited ‘Varnes’ for genes in the anthocyanin biosynthesis pathway and following whole genome sequencing using long-read Oxford Nanopore Technologies sequencing, we identified a CACTA-like transposable element (TE) in the second exon of the Anthocyanidin synthase (Ans) gene that caused a truncated predicted ANS protein. PCR confirmed the presence in heterozygous form of the transposon in an unrelated, red-fruited cultivar ‘Veten’, indicating apricot fruit colour is recessive to red and that it may be widespread in raspberry germplasm, potentially explaining why apricot forms appear at regular intervals in modern raspberry breeding populations.

Cerebrovascular accidents association between serum trace elements and toxic metals level, a case-control study

Background Cerebrovascular accidents (CVAs) are among the most common complications of patients today. As the prevalence of ischemic CVAs rises, detecting related risk factors is crucial. Metal concentration has previously been considered a major risk factor in several neural complications, and in this study, we will investigate this. Methods In this case-control study, 70 CVA (clinically approved ischemic stroke cases by imaging and NIH Stroke Scale (NIHSS)) and 70 individuals with no history of CVA controls were enrolled as the control group. The serum level of several metals, including Fe (Iron), Co (Cobalt), Ni (Nickel), Cu (copper), Zn (Zinc), Mn (Manganese), Pb (lead), Hg (Mercury), has been assessed using Inductively coupled plasma mass spectrometry (ICP-MS) method. Logistic regression (LR) has also been used to determine the association between metals’ levels and CVA occurrence. Results As the mean age of the CVA group was 48.68  ±  15.25 years and for the non-CVA group was 47.89 ± 9.65 years, the result indicated that the serum level of Cu and Pb has been statically higher in the CVA group (respectively; P  <  0.001 and P  =  0.002) and Ni level was significantly lower (P  =  0.003). Other measured metals’ levels (Fe, Co, Ni, Mn, Hg) were not significantly different between CVA and non-CVA groups. In the LR model, all Cu, Pb, and Zn metals had a P value of 0.03 and an odd ratio (OR) and confidence interval (CI) of 1.34 (1.02–1.75), 1.19 (1.01–1.39) and 1.01 (1.001–1.02) respectively. Conclusion Given that some metals are associated with a higher risk of CVA, researchers and physicians must better understand the risk factors and causes of the burden of CVA. However, further studies with a larger population and investigation of the exact pathogenesis of these metals are needed.

The Interfaces Twitter Elections Dataset: Construction process and characteristics of big social data during the 2022 presidential elections in Brazil

The main objective of this study is to describe the process of collecting data extracted from Twitter (X) during the Brazilian presidential elections in 2022, encompassing the post-election period and the event of the attack on the buildings of the executive, legislative, and judiciary branches in January 2023. The work of collecting data took one year. Additionally, the study provides an overview of the general characteristics of the dataset created from 282 million tweets, named “The Interfaces Twitter Elections Dataset” (ITED-Br), the third most extensive dataset of tweets with political purposes. The process of collecting and creating the database for this study went through three major stages, subdivided into several processes: (1) A preliminary analysis of the platform and its operation; (2) Contextual analysis, creation of the conceptual model, and definition of Keywords and (3) Implementation of the Data Collection Strategy. Python algorithms were developed to model each primary collection type. The “token farm” algorithm, was employed to iterate over available API keys. While Twitter is generally a “public” access platform and fits into big data standards, extracting valuable information is not trivial due to the volume, speed, and heterogeneity of data. This study concludes that acquiring informational value requires expertise not only in sociopolitical areas but also in computational and informational studies, highlighting the interdisciplinary nature of such research.

Do health professionals know about overdiagnosis in screening, and how are they dealing with it? A mixed-methods systematic scoping review

Introduction Medical screening is a major driver of overdiagnosis, which should be considered when making an informed screening decision. Health professionals (HPs) often initiate screening and are therefore responsible for informing eligible screening participants about the benefits and harms of screening. However, little is known about HPs’ knowledge of overdiagnosis and whether they are prepared to inform screening candidates about this risk and enable people to make an informed screening decision. Methods This is a systematic review of studies examining HPs’ knowledge and perception of overdiagnosis, whether it affects their position on offering screening, and their willingness to inform screening candidates about overdiagnosis. We conducted systematic searches in MEDLINE, Embase, Web of Science, Scopus, CINAHL, and PsycArticles without language restrictions. Two authors analysed the qualitative and quantitative data separately. Confidence in the findings of the qualitative data was assessed using the GRADE-CERQual approach. Results We included 23 publications after screening 9786 records. No studies directly examined HPs’ knowledge of overdiagnosis. HPs’ perceptions of overdiagnosis varied widely, from considering it a significant harm to seeing it as negligible. This seems linked to their overall beliefs about the benefits and harms of screening and to their position on offering screening, which varies from discouraging to actively promoting it. HPs also hold diverging approaches to informing screening candidates about overdiagnosis, from providing detailed explanations to limited or no information. Conclusion There is a lack of research on HPs’ knowledge of overdiagnosis, however, HPs who do know about overdiagnosis attribute substantially different levels of harm to it. This seems intertwined with their overall beliefs about the benefits of screening, their position towards offering screening, and their willingness to inform screening candidates about overdiagnosis. This has important implications for the public’s right to evidence-based information and compromises an individual’s right to make an informed screening decision.

A meta-analysis of the impact of TOE adoption on smart agriculture SMEs performance

Background Agricultural SMEs face distinct challenges due to factors such as weather, climate change, and commodity price changes. Technology has become essential in helping SMEs overcome these challenges and grow their businesses. The relationship between technology and SMEs in the agriculture sector covers various aspects, such as using hardware and software, digital applications, sensors, and e-commerce strategies to be examined in further depth through literature study. Problem statement The implementation of the TOE (technology, organization, and environment) framework in smart agriculture faces several challenges. To overcome these challenges, an integrated approach is needed that involves technological capacity building, organizational management changes, and adequate policy and infrastructure support to help SMEs in the agricultural sector develop their businesses. Objectives This research aims to demonstrate and identify how TOE plays an important role in the performance of SMEs, particularly with regard to agriculture in order to improve agricultural productivity, efficiency, and sustainability while enabling access to broader markets in several countries. This study employs a meta-analysis method using a quantitative approach taken by each publication, which typically used SEM. Methods PRISMA technique was used to examine evidence from clinical trials, and clinical significance was determined using the GRADE approach. Statistical analysis was performed using the Fisher test to combine the results of several studies and Cohen’s approach to interpreting effect sizes. Findings The results of this study are in line with the findings of 27 previous studies which showed a direct positive relationship between TOE construction and the performance of agricultural SMEs, with variables including technological factors, organizational factors, environmental factors, and SME performance. The synergy between technology adoption by agricultural SMEs and Industry 4.0 can increase connectivity and automation in the agricultural sector. However, it is important to remember that adopting TOE to realize the smart agriculture concept has its own challenges and risks, such as resource management (technology), good organizational management (organization), and internal and external organizational environments (environments), including intense competition Research implication TOE adoption improves access to information about competitors and customers, providing practitioners and decision-makers with a clearer understanding. It enables focus on factors with a significant impact on TOE adoption, so that they are more independent in developing effective business concepts that are adaptive to the era of agricultural technology 4.0.

Development of an expectation management intervention for patients with Long COVID: A focus group study with affected patients

Background A significant number of individuals who have contracted SARS-CoV-2 report persistent somatic symptoms after the infection has resolved. Evidence-based treatment options for Long COVID are lacking to date. To ensure that an expectation management intervention, designed for the research project SOMA.COV, addresses relevant patient needs as well as to promote treatment acceptance and adherence, a participatory approach was chosen. Objective The aim of the present study was to explore needs and wishes of patients with Long COVID regarding the preliminary version of an expectation management intervention and to thereby inform the further development of the treatment manual. Methods Twenty-two patients affected by Long COVID participated in one of four focus groups in June and July 2023. Participants were presented with the draft content of a four-session expectation management intervention. Feedback was audio-recorded, transcribed, and analyzed using thematic analysis. Results Thirteen themes relating to the main components of the intervention manual were developed. Large parts of the manual received overall positive feedback, including psychoeducation on the biopsychosocial etiology of the condition, elements of cognitive restructuring, and an imagination exercise. Patients’ response to the presented vicious circle of fear and a behavior change exercise was mixed. Modifications to the manual were made in response to patients’ feedback. Conclusion Patients with Long COVID provided positive feedback on an expectation management intervention while also highlighting important adaptations necessary for this patient group. The study results informed the finalization of the treatment manual within the SOMA.COV project, which investigates the effectiveness of this intervention for patients with Long COVID in a three-armed randomized controlled trial.

Hypergamy reconsidered: Marriage in England, 1837–2021

It is widely believed that women value social status in marital partners more than men, leading to female marital hypergamy (“marrying up”), and more female intergenerational social mobility. Using evidence from more than 33 million marriages and 67 million births in England 1837–2021 we show that within this era there was never significant hypergamous marriage by women. The average status of women’s fathers equaled that of their husbands’ fathers. For marriages 1912–2007 the average social status of female surnames equaled that of male. This was true also for parent surnames of children. Consistent with this, there was no differential tendency in England of men and women to marry by family status. There is also ancillary evidence that physical attraction cannot have been the significant determinant of matching in marriages in any period 1837–2021, based on the very strong correlation observed in underlying social status for marital partners throughout these years.