Persistent Increase Research Articles

Inhalation Exposure to Cross-linked Polyacrylic Acid Induces Pulmonary Disorders.

Organic polymers, widely used in food, daily necessities, and medicines, include cross-linked polyacrylic acid (CL-PAA), which has been reported to induce severe lung disease. While previous studies mainly used intratracheal instillation, our research focused on inhalation exposure to corroborate these findings. We conducted 5-day (short-term) and 13-week (subchronic) inhalation exposure studies with CL-PAA. In the short-term study, male F344 rats inhaled CL-PAA at 0.2, 2.0, or 20mg/m³ for 6hours/day over 5 days. Rats were dissected 3 days and 1 month post-exposure. In the subchronic study, rats inhaled CL-PAA at 0.2 or 2.0mg/m³ for 6hours/day, 5 days/week for 13 weeks, with dissections from 3 days to 6 months post-exposure. To investigate the mechanism of pulmonary disorders, an additional short-term study with 20mg/m³ CL-PAA included intraperitoneal injections of the antioxidant N-acetylcysteine (NAC) (200mg/kg) with dissection the day after exposure. Short-term exposure led to concentration-dependent increases in neutrophil influx, cytokine-induced neutrophil chemoattractant (CINC), total protein, lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in lung tissue. Histopathology showed concentration-dependent neutrophil infiltration. Subchronic exposure caused persistent increases in BALF total protein and lung HO-1, with ongoing neutrophil infiltration and fibrosis. NAC administration reduced neutrophils, total protein, LDH, and CINC in BALF, and HO-1 in lung tissue, improving histopathological findings. Inhalation of CL-PAA caused concentration-dependent lung inflammation and persistent fibrosis. The no observed adverse effect level (NOAEL) for chronic pulmonary disorders was 0.2mg/m³. Oxidative stress linked to CL-PAA-induced inflammation was mitigated by NAC administration.

Acute intermittent hypoxia elicits sympathetic neuroplasticity independent of peripheral chemoreflex activation and spinal cord tissue hypoxia in a rodent model of high-thoracic spinal cord injury.

The loss of medullary control of spinal circuits controlling the heart and blood vessels is a unifying mechanism linking both hemodynamic instability and the risk for cardiovascular diseases (CVD) following spinal cord injury (SCI). As such, new avenues to regulate sympathetic activity are essential to mitigate CVD in this population. Acute intermittent hypoxia (AIH) induces a type of neuroplasticity known as long-term facilitation (LTF), a persistent increase in nerve activity post-AIH in spinal motor circuits. Whether LTF occurs within the sympathetic circuit following SCI is largely unknown. We aimed to test whether AIH elicits sympathetic LTF (i.e., sLTF) and attenuates hypoactivity in sub-lesional splanchnic sympathetic circuits in a male rat model of SCI. In 3 experimental series, we tested whether 1) high-thoracic contusion SCI induces hypoactivity in splanchnic sympathetic nerve activity, 2) AIH elicits sLTF following SCI, and 3) sLTF requires carotid chemoreflex or spinal cord tissue hypoxia. Our results indicate that a single-session of AIH therapy (10 × 1 min of FiO2 = 0.1, interspersed with 2 min of FiO2 = 1.0) delivered at 2 weeks following SCI attenuates SCI-induced sympathetic hypoactivity by eliciting sLTF 90 min post-treatment that is independent of peripheral chemoreflex activation and/or spinal cord hypoxia. These findings advance our mechanistic understanding of AIH in the field and yield new insights into factors underpinning AIH-induced sLTF following SCI in a rat model. Our findings also set the stage for the chronic application of AIH to alleviate secondary complications resulting from sympathetic hypoactivity following SCI.

Short- and Long-Term Effects of Inhaled Ultrafine Particles on Blood Pressure: A Systematic Review and Meta-Analysis

Background: Air pollution contributes to up to 60% of premature mortality worldwide by worsening cardiovascular conditions. Ultrafine particles (UFPs) may negatively affect cardiovascular outcomes, and epidemiological studies have linked them to short- and long-term blood pressure (BP) imbalance. Methods: We conducted a systematic review and meta-analysis of the short- and long-term effects of UFP exposure on systolic (SBP) and diastolic (DBP) blood pressure. Eligibility criteria were established using the Population, Exposure, Comparator, Outcome, and Study Design (PECOS) model, and literature searches were conducted in Web of Science, PubMed, Embase, and Scopus for studies published between 1 January 2013 and 9 October 2024. Risk of Bias (RoB) was assessed following World Health Organization (WHO) instructions. Separate meta-analyses were performed for the short- and long-term effects of UFP exposure on SBP and DBP. Additionally, we analyzed SBP and DBP imbalances across different timespans following short-term exposure. Results: The results showed an increase in BP during short-term UFP exposure, which returned to baseline values after a few hours. Changes in SBP were greater than in DBP following both short- and long-term exposure. Prolonged exposure to UFPs is associated with increased SBP and concurrently low DBP values. Chronic exposure to UFPs may lead to a persistent increase in SBP, even without a concurrent increase in DBP. Conclusions: The findings presented here highlight that UFPs may contribute to worsening cardiovascular outcomes in vulnerable populations living in air-polluted areas.

Abstract 4137845: A single-cell lung atlas of human pulmonary arterial hypertension

Introduction: Pulmonary arterial hypertension (PAH) is a disaster disease characterized by obliterative vascular remodeling and persistent increase of vascular resistance, leading to right heart failure and premature death. Understanding the cellular and molecular mechanisms will help develop novel therapeutic approaches for PAH patients. Hypothesis: We hypothesis that single-cell RNA sequencing analysis can help understand the cellular and molecular mechanisms that drive the disease initiation and progression. Methods: 10 healthy donors, 10 idiopathic PAH, 10 drug and toxin induced PAH, 10 systemic and pulmonary shunting induced PAH patients from both male and female, and different ethical groups and races, and ages were obtained from PHBI. Lung tissue specimens were processed for fixed scRNA-seq. The cell proportion change, gene expression, and pathway analysis were evaluated between different disease subclasses, sex, age on different cell types. Results: Our analysis reveals 317,414 cells, 33 clusters and 9 major cell types, including endothelial cells (ECs), alveolar cells, fibroblast, smooth muscle cells (SMCs), pericytes, myeloid cells, lymphocytes, airway epithelial cells, platelet. Cell proportion analysis demonstrated an increase in the proportions of venous ECs, adventitial fibroblasts and myofibroblasts, alveolar macrophages, B cells, plasma cells and a reduction in capillary ECs 2 and pericytes in PAH lungs. KEGG Pathway analysis showed that upregulated pathways related Herpes simplex virus 1 infection, ECM-receptor interaction, Complement and coagulation cascades, Hedgehog signaling, TGF-beta signaling pathway, and downregulated pathways related to IL-17 signaling, TNF signaling, MAPK signaling pathway were enriched in the PAH patients. Female PAH patients exhibit an increase of myofibroblasts and platelets proportion compared to male PAH patients. MsigDB Hallmark Pathway analysis showed that p53 pathway was upregulated, whereas Inflammatory Response, Hypoxia, Epithelial Mesenchymal Transition were downregulated in female PAH patients. PAH patients older than 21 years exhibit an increase in the cell proportion of Platelet, SMCs, Arterial ECs and Venous ECs, and alveolar macrophages and a reduction of B cells and plasma cells. Conclusions: Our integrated analysis of human PAH lung atlas dataset provides a comprehensive understanding of lung cell populations and molecular signature in PAH patients with different sex, age and subclasses

Pediatric Hospitalizations and Emergency Department Visits Related to Mental Health Conditions and Self-Harm

Mental disorders among the pediatric population are a major area of public health concern. Little is known regarding changes in pediatric hospital resource use related to mental health (MH) long after the onset of the COVID-19 pandemic in March 2020. To assess rates and trends of hospitalizations and emergency department (ED) visits related to MH and self-harm (SH) among children before and during the 3 years following the pandemic onset. This cross-sectional study used national hospital data. The study sample included all MH- and SH-related hospitalizations and ED visits among children aged 6 to 17 years in France between January 1, 2016, to May 31, 2023. Interrupted time-series analysis of monthly rates of MH- and SH-related hospitalizations and ED visits per 100 000 children was conducted to assess changes before and every year after the pandemic onset. Rate ratios (RRs) between estimated and expected rates were calculated. Overall, 583 244 hospitalizations (81.4% for MH and 18.6% for SH) and 432 725 ED visits (79.9% for MH and 20.1% for SH) were analyzed. The mean (SD) age of the children was 13.7 (2.9) and 14.8 (1.7) years for MH-related and SH-related hospitalizations, respectively, and 14.2 (2.6) and 14.6 (2.1) years for MH-related and SH-related ED visits, respectively. For MH-related hospitalizations, 52.6% were female and 47.4% were male; for SH-related hospitalizations, 83.1% were female and 16.9% were male. For MH-related ED visits, 62.8% were female and 37.2% were male; for SH-related ED visits, 77.4% were female and 22.6% were male. Before the pandemic, an increasing trend in all monthly rates, except that of MH-related hospitalizations, was observed. After an immediate decrease in hospitalization and ED visit rates during the initial pandemic period (March 1 to May 31, 2020), trends increased in the first 2 years following the pandemic onset and decreased thereafter. Overall, rates of MH-related hospitalizations and ED visits exceeded expected rates in only the second year after the pandemic onset, with increases of 6.0% (RR, 1.06 [95% CI, 1.05-1.06]) and 5.0% (RR, 1.05 [95% CI, 1.04-1.05]), respectively. However, rates of hospitalizations and ED visits for behavioral syndromes (mainly eating and sleeping disorders) persistently exceeded expected rates, with increases of 29.0% (RR, 1.29 [95% CI, 1.25-1.34]) and 26.0% (RR, 1.26 [95% CI, 1.21-1.31]) in the third year, respectively. Likewise, rates of SH-related hospitalizations and ED visits persistently rose above expected rates, with increases of 29.0% (RR, 1.29 [95% CI, 1.26-1.32]) and 43.0% (RR, 1.43 [95% CI, 1.40-1.47]) in the third year, respectively. In this cross-sectional study, persistent increases in the use of hospital resources to treat eating and sleeping disorders and intentional SH among pediatric patients were observed long after the onset of the COVID-19 pandemic. These findings warrant future research to identify persistent stress factors in children.

Elderly patients with decompensated heart failure: prospective analysis from the LECRA-HF registry

Abstract Background/Introduction Heart failure (HF) presents as a clinical syndrome associated with an adverse prognosis, increased mortality risk, and recurrent hospitalizations for HF (HHF). In Poland, there has been a persistent increase in the overall prevalence and hospitalizations of HF among patients. Each subsequent HHF is associated with progressively worsening prognosis. In Europe, HF is most prevalent in elderly individuals, rendering this patient group particularly susceptible to HF exacerbations. Purpose The aim of this study was to conduct a comprehensive analysis of the oldest patients (≥80 years) hospitalized due to HF decompensation, compared to the rest of the evaluated cohort, including overall mortality after median 46 months of observation. Methods The prospective registry of patients with HF decompensation (LECRA-HF) is an ongoing registry conducted at a tertiary cardiology center specializing in HF treatment. Patients enrolled in the registry (n=1394) were evaluated for the presence of cardiovascular risk factors, HF phenotype, laboratory, and echocardiographic findings, as well as overall mortality. Due to the frequent occurrence of HF in elderly patients, we arbitrarily chose to compare two cohorts of patients: those above (n=306) vs. below 80 years of age (n=1088). Results Median age of elderly patients was 84 [82-86] years, of which only 7.8% were >90 years of age. HFrEF was the most common HF phenotype, which, occurred less frequently in the elderly (54.4 vs 74.4%, P<0.001). In turn, HFpEF was more prevalent in elderly group (39.2 vs 17.7%, P<0.001). Elderly patients were more often female (45.1 vs 30.2%, P<0.001) and had more comorbidities: arterial hypertension (85.6 vs 78.6%, P=0.007), atrial fibrillation (61.1 vs 45.7%, P<0.001), renal failure (49.7 vs 28.5%, P<0.001) as well as peripheral arterial disease (17 vs 9.8%, P=0.005). Those patients had more frequently implanted cardiac pacemakers (28.6 vs 12.6%, P<0.001), but less often implantable cardioverter-defibrillators (7.9 vs 14.3%, P=0.003). During HHF they were less often qualified to elective coronary angiography (24.2 vs 31.5%, P=0.039). At discharge mineralocorticoid receptor antagonist were less often prescribed in that group (42.4 vs 50.3%, P=0.010). During long-term observation patients ≥80 years had a higher all-cause mortality (81 vs 67.4%, P<0.001, Panel A). Moreover, it was also higher elderly with NT-proBNP>4497 pg/mL (P<0.001) and LVEF<41% (P=0.014) (Panel B). Conclusion(s) Patients aged ≥80 years were characterized by a higher burden of comorbidities. They were more often qualified to cardiac pacemakers, but less often to implantable cardioverter-defibrillators and invasive coronary procedures. The most common HF phenotype was HFrEF, however with a significant increase in HFpEF. They exhibited significantly higher overall mortality compared to those <80 years old, which was associated with both LVEF and NT-proBNP levels.

Clinical implications of persistently increased blood urea nitrogen/serum creatinine ratio (PI-BUN/Cr) in severe COVID-19 patients

BackgroundPatients with COVID-19 may experience a persistent increase in the blood urea nitrogen over creatinine ratio (PI-BUN/Cr). Its elevation could reflect multiple underlying pathophysiological processes beyond prerenal injury but also warrants nuanced interpretation due to its complex interplay with various factors, underscoring the importance of investigating its effects on mortality and acute kidney injury in this population.MethodsWe analized a retrospective and longitudinal cohort of patients admitted to a single center in Mexico City for patients with severe COVID-19. Between March 5, 2020 and August 25, 2021, we included patients with confirmed positive diagnosis for SARS-CoV-2, age > 18 years, disease severity was defined by clinical data of respiratory distress syndrome and a ratio of partial oxygen pressure to inspired oxygen fraction < 300 mmHg on admission. We excluded patients with End Stage Kidney Disease. Data was obtained from electronic medical records. PI-BUN/Cr was defined as an increase in the BUN/Cr ratio > 30 in more than 60% of measurements in the hospital. The outcomes included: risk factors to mortality and AKI in-hospital.ResultsThe cohort included 3,007 patients with a median age of 54.6 ± 14.5 years. 35% of patients died; 44.6% developed PI-BUN/Cr ratio and 71.4% AKI. Mortality was associated with older age > 60 years [Hazard ratio (HR)] = 1.45, 95% CI: 1.28–1.65; p < 0.001); male (HR 1.25, 95% CI 1.09–1.44; p = 0.002) and AKI (HR 3.29, 95% CI 2.42–4.46; p < 0.001); PI-BUN/CR & Non-AKI (HR = 2.82, 95% CI: 1.61–4.93; p < 0.001); Non PI-BUN/CR & AKI (HR = 5.47, 95% CI: 3.54–8.44; p < 0.001); and PI-BUN/CR & AKI (HR = 4.26, 95% CI: 2.75–6.62, p < 0.001). Only hiperuricemia was a risk factor for AKI (HR = 1.71, 95% CI: 1.30–2.25, p < 0.001).ConclusionsWhile PI-BUN/Cr alone may not directly associate with mortality, its capacity to sub-phenotype patients according to their AKI status holds significant promise in offering valuable insights into patient prognosis and outcomes. Understanding the nuanced relationship between PI-BUN/Cr and AKI enhances our comprehension of renal function dynamics. It equips healthcare providers with a refined tool for risk stratification and personalized patient management strategies.

Анализ эффективности и безопасности применения CFTR-модулятора лумакафтор/ивакафтор у пациентов с муковисцидозом в разных возрастных группах

Russia’s first registered CFTR-modulator lumacaftor/ivacaftor was developed for patients with cystic fibrosis (CF) with the F508del/F508del genotype. The purpose of this research was to study the efficacy and safety of lumacaftor/ivacaftor therapy in different age groups. Materials and methods used: the data of homozygotes for F508del aged 2 to 18 y/o in the Russian CF Patient Registry who had been treated with lumacaftor/ivacaftor were analyzed. The effectiveness of therapy was evaluated in 3 age groups based on examination data, nutritional status, spirometry, sweat test at the start of therapy and after 12 months. In order to assess the safety, examination data, assessment of adverse events (AE), blood biochemical parameters, blood pressure and lens condition were taken into account in 334 pediatric patients in the first month of therapy and in 180 after 12 months. Results: decrease in sweat conductivity was noted in three age groups (p&lt;0.001), only in the 2 to 6 y/o age group were negative values obtained in 6.8%. An increase in BMI was observed in the 6 to 12 y/o and 12 to 18 y/o age groups (р&lt;0.001) whilst an improvement in FVC was observed only in the 12 to 18 y/o age group (p=0.015). Changes in biochemical parameters were statistically significant, both downward and upward, only in the age groups of 6 to 12 y/o and 12 to 18 y/o, changing not significantly. Withdrawal of the drug was required in only a single patient with a persistent increase in transaminase level. Fluctuations in blood pressure occurred within the normal age limits. Frequency of AE was comparable with the results of other studies, it was noted at the start in all groups and after 12 months more often in the age group of 12 to 18 y/o. The best tolerance was noted in the age group of 2 to 6 y/o. Conclusion: for the first time, the efficacy and tolerability of lumacaftor/ivacaftor in patients with CF in Russia was studied against the age aspect according to the 2022-2024 Registry. In the 2 to 6 y/o age group, the achievement of normal sweat test values and the lowest number of adverse reactions were noted, while in the 12 to 18 y/o age group, the positive dynamics were noted for a greater number of indicators, incl. an increase in FVC.

Effect and mechanism of allergen-specific immunotherapy on small airway dysfunction in children with asthma.

The purpose of this study was to investigate the effectiveness of allergen-specific immunotherapy (AIT) on small airway dysfunction (SAD) and the underlying mechanism with a special focus on basophils. Sixty-five children with mild to moderate asthma who were under regular inhaled corticosteroid (ICS) treatment for more than 1 year but whose FEF75 remained below 65% of the predicted value and had positive results for serum Der p or Der f were enrolled. Children with asthma underwent house dust mite (HDM) subcutaneous immunotherapy (SCIT) treatment for 1 year. Clinical symptoms and lung function were evaluated every 3 months during HDM SCIT treatment. Basophil activation test (BAT) was carried out before and after HDM SCIT treatment. RNA sequencing was performed in isolated basophils from peripheral blood after 6 months of HDM SCIT treatment, followed by GO term and KEGG pathway enrichment analysis between patients with and without HDM SCIT treatment. HDM AIT treatment ameliorated clinical symptoms while concurrently improved lung function parameters, such as FEV1/FVC, FEF75, FEF50 and MMEF (p < .05). It is worth noting that FEF75 values showed a highly significant, gradual and persistent increase (from 49.55 ± 1.27% at baseline to 71.89 ± 2.64% after 1 year of therapy) and 22 of 35 patients no longer had SAD after 1 year of treatment. BAT results revealed that AIT treatment significantly reduced basophil activity to the inhalant allergen mixtures containing HDM in vitro challenge from baseline. GO term and KEGG pathway enrichment analysis of basophils revealed that downregulated genes were mainly involved in immune cell activation, antigen presentation, and Th2 cell differentiation. Our study demonstrated that HDM AIT not only improved SAD related lung function parameters, but also reduced basophil activity. RNA sequencing revealed the inhibition of phagocytosis and the phagosome pathway in basophils which may affect the polarization of Th2 cell differentiation after HDM AIT.

Spatiotemporal Dynamics and Driving Factors of Vegetation Greenness in Typical Tourist Region: A Case Study of Hainan Island, China

Vegetation greenness has been one of the most widely utilized indicators to assess the vegetation growth status for the better ecological environment. However, in typical tourist regions, the impact of the geographical environment, socioeconomic development, and tourism development on vegetation greenness changes is still a challenge. To address this challenge, we used the Google Earth Engine (GEE) cloud platform combined with a series of Landsat remote sensing images to calculate the fractional vegetation cover (FVC) which can be used as an indicator to characterize the spatiotemporal evolution of vegetation greenness in Hainan Island from 2000 to 2020. Furthermore, we employed geographic detector and structural equation models to quantify the relative importance and explanatory power of the geographical environment, socioeconomic development, and tourism development on vegetation greenness changes and to clarify the interaction of mechanisms of various factors in Haikou and Sanya. The results show that the annual growth rate of the FVC in Hainan Island was 0.0025/a. In terms of spatial distribution, the trend of the FVC changes was mainly characterized by non-significant and extremely significant improvement, accounting for 35.34% and 29.38% of the study area. Future vegetation greenness was dominated by weak counter-persistent increase and weak persistent increase. The geographical environmental factors were the main factors affecting vegetation greenness in Haikou, followed by the socioeconomic and the tourism development factors, while the geographical environmental factors also dominate in Sanya, followed by the tourism development factors and finally the socioeconomic factors. Specifically, the spatial distribution of vegetation greenness was primarily influenced by land use types, elevation, slope, and travel services. Geographical environmental factors could indirectly affect changes in socioeconomic and tourism development, thereby indirectly affecting the spatial distribution of vegetation greenness. These findings can provide some significant implications to guide the ecological environmental protection for sustainable development in Hainan Island in China.

Heightened lateral habenula activity during stress produces brainwide and behavioral substrates of susceptibility.

Some individuals are susceptible to chronic stress, and others are more resilient. While many brain regions implicated in learning are dysregulated after stress, little is known about whether and how neural teaching signals during stress differ between susceptible and resilient individuals. Here, we seek to determine if activity in the lateral habenula (LHb), which encodes a negative teaching signal, differs between susceptible and resilient mice during stress to produce different outcomes. After (but not before) chronic social defeat stress, the LHb is active when susceptible mice are in proximity of the aggressor strain. During stress, activity is higher in susceptible mice during aggressor interactions, and activation biases mice toward susceptibility. This manipulation generates a persistent and widespread increase in the balance of subcortical vs. cortical activity in susceptible mice. Taken together, our results indicate that heightened activity in the LHb during stress produces lasting brainwide and behavioral substrates of susceptibility.

Persistent Increase in the Blood Urea Nitrogen/Creatinine Index (PI-BUN/Cr) Phenotypes the Clinical Course of Patients with Severe COVID-19

Persistent Increase in the Blood Urea Nitrogen/Creatinine Index (PI-BUN/Cr) Phenotypes the Clinical Course of Patients with Severe COVID-19

The application of the Fuzzy Analytical Hierarchy Process (FAHP) as a multi-criteria analysis tool for road risk assessment: Algeria as a case study

In response to the escalating road safety challenges and the persistent increase in traffic accidents, it is imperative to adopt an integrated approach to address this multifaceted issue effectively. The main objective of this research is to classify or identify high-risk areas by studying the impact of the most significant factors contributing to road accidents. The methodology is based on a hierarchical model of three levels, including the essential factors that increase road risk. Subsequently, a fuzzy hierarchy process (FAHP) is conducted using a fuzzy scale to evaluate and analyse the most influential factors to determine the risk level for each road segment. This approach has been applied to the motorway in Algeria, specifically in the Mascara region, where the road was divided into 83 sections of 100 metres. The study's results revealed that factors related to infrastructure and those associated with drivers had the most significant impact, while environmental factors had less influence on road safety. The studied area exhibited risk levels ranging from moderate to low. The current state analysis of the roads (open to traffic) allows for the evaluation of factors that heighten road risks, this comprehensive evaluation is instrumental in formulating sustainable road safety strategies to mitigate future traffic accidents.

The alpha beta gamma of the labor market

We access a long panel dataset of US workers to document the extent to which individuals are heterogeneous with respect to their pattern of transitions across employment states. We find that heterogeneity is well approximated by three latent types: αs, βs and γs. Workers of type α leave unemployment quickly and, once they find a job, they are likely to keep it for more than 2 years. Workers of type γ find employment slowly and, once they do find a job, they are likely to leave it within 1 year. We use our empirical findings to calibrate a search-theoretic model in which workers are heterogeneous with respect to the parameters governing their employment transitions. We find that αs move quickly out of unemployment to employment because they have large gains from trade, and they are likely to stay on a job for more than 2 years because their productivity is similar in different jobs. In contrast, γs exit unemployment slowly because their gains from trade are small, and they are likely to leave a job within 1 year because they are much more productive in a small fraction of jobs than in the majority of jobs. We find that a negative shock to aggregate productivity leads to a large and persistent increase in unemployment that is mainly driven by γ-workers. The predictions of the model align well with the unemployment dynamics observed during the Great Recession.

Chronic lymphoproliferative disorder of natural killer cells-related neurolymphomatosis with severe autonomic dysfunction: a case report

BackgroundChronic lymphoproliferative disorder of natural killer cells (CLPD-NK) is a rare disease characterized by a persistent increase in NK cells in peripheral blood and is generally asymptomatic. If present, symptoms may include fatigue, B symptoms (fever, night sweats, and unintentional weight loss), autoimmune-associated diseases, splenomegaly, and infection due to neutropenia. Peripheral neuropathy, however, is uncommon with an incidence of 3%. Neurolymphomatosis is a neurological manifestation of non-Hodgkin lymphoma and leukemia in which neurotropic neoplastic cells infiltrate the nerves. Moreover, neurolymphomatosis caused by CLPD-NK is extremely rare, with even fewer cases of autonomic dysfunction. We report a case of neurolymphomatosis associated with CLPD-NK and developed autonomic dysfunction, including orthostatic hypotension and gastrointestinal symptoms.Case presentationThe patient was a 61-year-old male who was referred to our hospital for leukocytosis. He was diagnosed with CLPD-NK; however, was untreated since he had no hepatosplenomegaly, and other systemic symptoms. He later developed numbness in his lower extremities. Cerebral spinal fluid examination revealed a markedly elevated protein level of 140 mg/dL, and contrast-enhanced magnetic resonance imaging showed bilateral L4 and 5 nerve roots with enlargement and contrast effect. An immune-mediated polyradiculoneuropathy was suspected, and he was treated with intravenous methylprednisolone and immunoglobulin followed by oral prednisolone and cyclosporine. Although his symptoms were relieved by the immunotherapy, significant autonomic dysfunction, including intractable diarrhea, decreased sweating, and orthostatic hypotension, appeared. Additionally, tests for onconeuronal antibodies, ganglionic nicotinic acetylcholine receptor (gAChR) antibody, NF155, CNTN1, Caspr1 antibody, and anti-ganglioside antibodies were all negative. A sural nerve biopsy revealed lymphocytic infiltration, and immunohistochemical staining of lymphocytes confirmed the infiltration of NK and T cells. Therefore, a diagnosis of neurolymphomatosis caused by CLPD-NK was made, and chemotherapy led to partial symptom improvement.ConclusionsWe experienced a case of pathologically diagnosed neurolymphomatosis with autonomic dysfunction associated with CLPD-NK. In cases of subacute to chronic autonomic dysfunction, paraneoplastic neuropathy, amyloidosis, and autoimmune autonomic ganglionopathy are considered; however neurolymphomatosis caused by CLPD-NK, an important cause of autonomic dysfunction, is not. In difficult to make diagnosis, aggressive nerve biopsy is required.

Using machine learning to investigate the determinants of loan default in P2P lending: Are there differences between before and during COVID-19?

The coronavirus disease (COVID-19) has led to a persistent increase in the volatility of the credit market and triggered a series of financial distress and bankruptcy. To investigate whether there are differences in loan default determinants before and during COVID-19 and to identify the most effective predictors of loan default during COVID-19, this study employs machine learning methods to establish a comprehensive loan default prediction model for Peer-to-peer (P2P) lending based on four perspectives: loan characteristics, credit transaction history, personal information, and macroeconomic environment. The results show that the EXtreme Gradient Boosting (XGBoost) outperforms the other models and that credit transaction history plays a vital role in forecasting loan default over the two periods. We also find discrepancies between the effects of consumer price index, purchasing manager’ index, and the number of bidders on loan default before and during the pandemic. Our study contributes to related research fields on loan default prediction by identifying loan default determinants that are more applicable to unstable periods and investigating the impact of COVID-19 on default predictions. Meanwhile, our findings can provide P2P lending investors, platforms, and policymakers with practical implications to reduce uncertainty and losses that result from similar black swan events.

A50-year-old patient with pancreatitis revealing pancreatitis, panniculitis, and polyarthritis syndrome-acase report and review of the literature.

The combination of pancreatitis, panniculitis, and polyarthritis (PPP) is arare systemic syndrome that occurs in patients with acute or chronic pancreatitis or pancreatic malignancies. A50-year-old male patient presented with polyarthritis increasing for 1week and consequent inability to walk unaided. In addition, the patient had several isolated nodules on the lower extremities without any tenderness to pressure. Laboratory tests showed elevated pancreatic enzymes indicative of pancreatitis, which was thereafter confirmed by abdominal CT scan, with signs of chronic pancreatitis and concrements in the pancreatic duct. The diagnosis of panniculitis was established by dermatological consultation. Considering all these clinical features, PPP syndrome was diagnosed. In accordance with the pre-existing literature, oral glucocorticoid therapy and nonsteroidal anti-inflammatory drugs (NSAIDs) were given but failed to improve pain and polyarthritis. In the further clinical course, due to the persistent increase in lipase and amylase, endoscopic retrograde cholangiopancreatography (ERCP) was performed, showing small concrements in the pancreatic duct. During the intervention, the pancreatic duct was widened, the small concrements were removed, and apancreatic duct stent was then implanted. Following ERCP, an instant decrease in pancreatic enzymes was observed, accompanied by aclear and sustained improvement of joint swellings and pain. With the typical triad of clinical findings in mind, one should consider PPP syndrome in the context of acute or chronic pancreatitis as well as in pancreatic malignancies. All involved disciplines (gastroenterology, dermatology, and rheumatology) should be familiar with this rare but severe condition. The prognosis depends on the extent of the functional deficit of the extremities and the progression of the underlying disease.

Early B lymphocyte subsets in blood predict prognosis in sepsis.

B lymphocytes play a key role in immunosuppression. This study investigated the prognostic value of B cell subsets in sepsis. Flow cytometry was used to assess peripheral B cell subsets from patients with sepsis on the first and seventh days following admission, as well as 111 healthy controls. The patients were divided into survivors and non-survivors, based on 28-day prognosis. The analysis showed abnormal distribution and selective depletion of B cells and its subsets in the early stages of sepsis. On day 1, compared with survivors, non-survivors showed significant decreases in the proportion and absolute count of transitional (Tr) B cells, reductions in the proportion of CD5+ B cells, and increases in the proportion of double-negative (DN) B cells. On day 7, the proportions and absolute counts of Tr and CD5+ B cells significantly decreased whereas the proportion of DN B cells significantly increased in non-survivors. Ninety-four survivors and 15 non-survivors were included in our paired-sample rank-sum test. Compared to day 1, only the survivors showed significant increases in absolute B, Tr B, and CD5+ B cell counts by day 7. Multivariate Cox regression analysis showed that the proportion of DN B cells on day 1 (hazard ratio = 1.092 [95% confidence interval: 1.035-1.152], P = 0.001) was a risk factor for mortality, and Kaplan-Meier survival curve analysis showed that patients with proportions of DN B cells > 11.81% on day 1 had poorer prognoses. Receiver operating characteristic curve analysis showed that B cell subset parameters could predict mortality (area under the receiver operating characteristic curve [AUC], 0.741) and enhanced the prognostic value of the Acute Physiology and Chronic Health Evaluation II score (AUC, 0.840). Our study revealed that deficiencies of B, Tr B, and CD5+ B cells, as well as a persistent increase in the proportion of DN B cells, were associated with poor prognosis-and that B cell subsets showed predictive value to mortality. These results provide new insights into the roles of B cell subsets in sepsis, as well as ways to better manage its progression and predict its course.

How to interpret consumer confidence shocks? State-level evidence

Using novel quarterly data of 29 U.S. states from 2005:I to 2015:IV, we revisit the link between consumer confidence and economic activity. We find that an innovation in consumer confidence is followed by a significant and persistent increase in consumption and output but a temporary decline in inflation. These findings suggest that the supply-side (news) interpretation of consumer confidence receives more empirical support than the demand-side (animal spirit) interpretation in our sample.

Patterns of incidence and characteristics of youth with new-onset diabetes mellitus during the COVID era

Objectives: The incidence of diabetes mellitus (DM) in children, adolescents, and young adults has been on the rise for many decades. The COVID-19 pandemic has been associated with a dramatic increase in new cases of pediatric DM and a shift in the seasonal pattern of incidence. We aimed to determine the incidence of DM and its subtypes during the COVID-19 pandemic (2020–2022) and pre-pandemic (2017–2019). We sought to assess for a difference in seasonality and temporal pattern of new-onset DM between the two periods and aimed to describe and compare the clinical characteristics of the patients diagnosed during this time. Material and Methods: In this retrospective chart review, data were collected from medical records for all patients aged 1–21 years diagnosed with DM at our center between January 1, 2017 and December 31, 2022. Results: The incidence of DM at our center increased 38% during the pandemic (incidence rate ratio [IRR] 1.38, 95% confidence interval; [CI] 1.20–1.58). The incidence of type 1 diabetes (T1D) increased 11% (IRR 1.11, 95% CI 1.01–1.23) and the median body mass index percentile increased for those diagnosed during the pandemic (P = 0.012). The incidence of type 2 diabetes (T2D) increased 238% (IRR 3.38, 95% CI 2.17–5.28) during the pandemic, with the highest rate of diagnosis in a younger age group (P = 0.015). The pattern of incidence of T1D shifted from lowest in the summer pre-pandemic to highest in the summer during the pandemic (IRR 1.82, 95% CI 1.22–2.72). The overall incidence trend for DM, T1D, and T2D, peaked in spring 2021 and then declined until it stabilized in summer 2022. Conclusion: Our study showed a persistent increase in the incidence of both T1D and T2D in the pediatric population during the pandemic. Those diagnosed with T2D during the pandemic were younger than those diagnosed in the pre-pandemic period. There was a shift in seasonal pattern of T1D incidence during the pandemic with the highest rates of incidence during the summer. Further studies are needed to evaluate the underlying mechanisms of the persistent increase in incidence.