bluuebunny/crossref_metadata_2025 huggingface dataset:
RADIOLOGIST PERFORMANCE AND RELIABILITY OF MR SCORING SYSTEMS IN PERIANAL FISTULIZING CROHN’S DISEASE: RETROSPECTIVE ANALYSIS IN A REAL-WORLD CLINICAL PRACTICE
Authors: Devi Jalpa , Abushamma Suha , Arora Jyoti , Deepak Parakkal , Ballard David H , Ravella Balakrishna , George Alvin , Hickman John , Zulfiqar Maria , Ludwig Daniel R , Shetty Anup , Ganapathy Aravinda , Miller Philip , Elumalai Anusha , Bishop Grace
Published: January 2024

BACKGROUND

Perianal fistulizing Crohn’s disease (CD-PAF) is difficult to treat, and several MR scoring systems have been developed to assess treatment response.

OBJECTIVE

To assess the relationship between CD-PAF MR scoring systems and radiologists’ subjective assessment of CD-PAF severity and treatment response on baseline and follow-up pelvic MR.

METHODS

Retrospective single-institution study of consecutive symptomatic CD-PAF patients who underwent pelvic MR before and ≥3 months after initiating biologic therapy during a 10-year period (December 2011 to December 2021). One of four radiologists interpreted baseline and follow-up MRs. Scoring systems included variables in the modified Van Assche index (mVAI), magnetic resonance novel index for fistula imaging in CD (MAGNIFI-CD), and pediatric MR-based perianal Crohn’s disease (PEMPAC) index. For initial and follow-up MR, a 5-point Likert scale assessed severity (1=mild, 3=moderate, 5=marked). On follow-up MR, radiologists evaluated fistula response as 1-improved, 3-stable, or 5-worsened CD-PAF severity. All four study radiologists scored the baseline MR in 20 patients to calculate inter-reader agreement statistics. Interrater reliability was assessed with the Krippendorff α coefficient for categorical variables and intraclass correlation coefficient (ICC) for continuous variables.

RESULTS

The cohort included 96 CD-PAF patients (50 men; mean age=33.0 years) with 192 baseline and follow-up MRs. Agreement between radiologists was moderate to substantial for the MAGNIFI-CD, mVAI, PEMPAC, and Likert scores, with ICC values of 0.716, 0.756, 0.535, and 0.679, respectively. Individual components of MR scoring systems had fair to substantial agreement (Alpha: 0.195 to 0.730). Significant univariate associations were found between MR scoring systems and radiologists’ Likert severity assessments (p<.001, Pearson correlation coefficients ≥.820). In patients meeting criteria for change in disease severity (n=17), all scoring systems demonstrated AUC values ≥.93.

CONCLUSION

The MR scoring systems for CD-PAF (MAGNIFI-CD, mVAI, and PEMPAC) demonstrated strong associations with radiologists’ subjective assessments of severity and treatment response on baseline and follow-up pelvic MR. These scoring systems demonstrated better inter-reader agreement compared to individual MR factors.

CLINICAL IMPACT

The introduction of new medical therapies for CD-PAF and the growing utilization of MR fistula response in CD-PAF highlight the importance of a standardized approach in defining changes in CD-PAF severity on MR.

Table 1 Inter-reader reliability perianal Crohn’s disease MR scoring systems and length of fistula tract
MORTALITY IN INFLAMMATORY BOWEL DISEASE: A LONGITUDINAL POPULATION-BASED STUDY IN THE UNITED STATES
Authors: Maas Laura , Weber Andrew , Sauk Jenny , Parian Alyssa , Limketkai Berkeley
Published: January 2024

INTRODUCTION

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract. Data are limited regarding how longevity in IBD compares to the general population. The aim of this study was to compare the mean age of death and causes of mortality between patients with IBD and the general population in a nationally representative cohort.

METHODS

A retrospective study using 2010-2019 data from the National Readmissions Database (NRD) was performed. We identified hospitalized patients with CD and UC using International Classification of Diseases (ICD) codes. We compared the mean age of death and most common causes of mortality in CD, UC, and non-IBD patients.

RESULTS

The mean age of in-hospital death was significantly lower in the CD group (64.60 years) compared to the UC and non-IBD groups (67.43 and 67.07 years, respectively, p<0.01). Among all age groups, the highest death rates were among those ages 71 through 80 years of age (p<0.01). The UC group had significantly higher rates of death associated with cardiovascular causes, including myocardial infarction, congestive heart failure and cardiovascular disease, and infectious causes, including Clostridioides difficile infection and sepsis. Death rates did not significantly differ among the groups for those with diagnoses of leukemia and lymphoma (p=0.20 and p=0.19, respectively). UC patients had the highest in-hospital rate of death per year from 2010-2019, followed by the CD and non-IBD groups. Common diagnoses associated with death across all ages in the CD, UC, and non-IBD groups included fluid/electrolyte imbalance, respiratory failure, anoxic brain injury, sepsis, and renal failure.

CONCLUSION

While those with UC had higher in-hospital death dates, those with CD were more likely to die younger compared to the general population. UC patients were more likely to die if diagnosed with cardiovascular disorders or infections. Investigation of factors that drive premature mortality in CD patients and higher rates of mortality in UC patients is crucial to guide practice improvements and for management of co-morbid conditions.

Table 1 Patient demographics and hospital characteristics.

Figure 1 Death rates comparing non-IBD, CD and UC groups with specific inpatient diagnoses. * p < 0.05.
RISING INCIDENCE, MORTALITY, AND DISABILITY-ADJUSTED LIFE YEARS OF INFLAMMATORY BOWEL DISEASE IN THE UNITED STATES: A SYSTEMIC ANALYSIS OF THE GLOBAL BURDEN OF DISEASE STUDY
Authors: Pan Chun-Wei , Attar Bashar , Nieto-Dominguez Alejandro
Published: January 2024

INTRODUCTION: In North America, Inflammatory Bowel Disease (IBD) poses a significant burden, yet detailed data on its incidence, mortality, and disability-adjusted life years (DALYs) within the United States is scarce. Our study aims to systematically analyze these aspects of IBD while considering gender, age, and state-level variations. Methods: Utilizing the Global Burden of Disease database, we systematically analyzed IBD incidence, mortality, and DALYs in the United States from 1999 to 2019. We further stratified these metrics by gender and age groups (25-49 years, 50-75 years, and 75+ years) and calculated annual percentage changes (APC) using linear regression. Results: Between 1999 and 2019, IBD incidence cases increased from 65,555 to 85,388. The incidence rate per 100,000 person-years rose from 23.5 (95% UI: 21.4-26.2) to 26.0 (95% UI: 23.8-28.9), with APC of 1.0. Females consistently had higher incidence rates, increasing from 34,236 (95% UI: 31,052-38,351) in 1999 to 43,882 (95% UI: 39,953-48,871) in 2019. Incidence rates also rose, with males at 0.6% APC and females at 0.4%. In 2019, the 24-49 years age group had the highest incidence rate at 35.1 (95% UI: 30.3-40.1) per 100,000, with a 0.5% APC increase from 1999 to 2019.Mortality increased, with 5,910 IBD-related deaths in 2019. The mortality rate per 100,000 population rose from 1.1 (95% UI: 1.0-1.3) to 1.8 (95% UI: 1.4-2.0), reflecting a 2.4% APC. Although females had a higher mortality rate in 2019 (2.2 per 100,000), males had a 2.7% APC increase from 1999 to 2019. Geographically, notable differences in APC for incidence rates across states were observed. The highest increases were seen in Ohio (1.06%), North Dakota (1.04%), and Maine (0.96%), while Nevada had a slight decrease in APC (-0.02%). Mortality rate changes also varied by state, with substantial increases in Alaska (3.75%), Vermont (3.19%), and Tennessee (3.13%). Regarding DALYs, significant APC rate changes were observed in New Mexico (1.53%), Vermont (1.38%), and Mississippi (1.37%), while the lowest changes were seen in the District of Columbia (0.24%). Conclusions: This comprehensive analysis of IBD in the US from 1999 to 2019 reveals trends and disparities. IBD incidence steadily increased during this period, with notable rises in cases and rates. Gender-wise, females had higher incidence rates, while males displayed a slightly steeper increase. Geographic disparities were evident, with varying trends in incidence and mortality rates across states. Ohio, North Dakota, and Maine had the highest incidence increases, while Alaska, Vermont, and Tennessee saw significant mortality rate increases. Our study highlights the changing epidemiology of IBD and the need for targeted intervention to address changes in incidence and disease burden.

Fig 1. * Denotes P
THE IMPORTANCE OF PATIENT ENGAGEMENT IN THE MANAGEMENT OF INFLAMMATORY BOWEL DISEASE (IBD)
Authors: Kosinski Lawrence , Singh Sachin , Shahab Omer , Henderson Richard , Athmer Leslie
Published: January 2024

BACKGROUND

IBD constitutes a diverse and progressive spectrum of chronic illnesses, presenting formidable management challenges for both patients and healthcare providers. Due to the inherent unpredictability of disease progression, proactive monitoring strategies are crucial for optimal IBD management.

The linchpin of proactive monitoring in IBD is patient engagement, which is necessary for continuous monitoring of disease activity. GI practices using SonarMD, a technology-driven care coordination company specializing in IBD, have consistently maintained an enrollment and engagement rate exceeding 80%. This study demonstrates the disparity in clinical outcomes between an engaged patient population utilizing SonarMD’s platform and an unengaged cohort within a single large gastrointestinal (GI) practice under a value-based agreement with a major health plan.

METHODS

The study cohort was composed of a population of 1173 patients attributed by the heallth plan on the basis of ICD-10 Codes who had a diagnosis of Crohn's Disease (K50) or ulcerative colitis (K51). 939 (80%) enrolled in the program and 234 (20%) remaining unenrolled. Demographic and clinical characteristics of the patient groups are detailed in Table 1. The enrolled and unenrolled groups exhibited similar metrics with regard to: age, gender, average risk score (AVG), disease type, stricturing/fistulizing disease, and history of behavioral health diagnoses. The enrolled group did demonstrate a 10% higher utilization of biologics. The SonarMD platform was only deployed into the enrolled group.

Claims data (including pharma claims) from a single health plan, which insured all cohort patients, was the source for the utilization data analysis. The study period was the calendar year 2022 with a claim runoff period of 3 additional months.

RESULTS

The IBD specific Inpatient hospitalization rate and ED Visit rate for each group is shown in table 2. There is a 10X statistically significant difference in both hospital inpatient admission rate and ED visit rate between the engaged and unengaged populations. (p = 0.02). Two thirds of the INPT/ED admissions for the entire attributed population were driven by the unenrolled group.

CONCLUSIONS

This study highlights the influential role of proactive patient engagement in the management of IBD, exemplified by the utilization difference for inpatient care and ED usage and its potential to optimize clinical outcomes. Proactive patient engagement is critical in population management of symptomatic chronic disease. An unengaged population represents a significant risk for unnecessary morbidity and healthcare cost. Provider-payer-industry partnerships can help build the infrastructure necessary to accomplish high rates of engagement. You can’t manage the patient you don’t engage.
UNRAVELING THE CONNECTION: RACIAL INFLUENCE ON THE DEVELOPMENT OF ULCERATIVE COLITIS AFTER BARIATRIC SURGERY
Authors: Mohan Raj Mohan Ram , Joy Melvin , Magam Sai Greeshma , Magam Sai Reshma , Natt Dilman , Desai Jiten , Mustacchia Paul
Published: January 2024

INTRODUCTION

Bariatric surgery is an effective treatment for obesity and aids in enhancing metabolic health. However, it has been observed that there's a heightened occurrence of Ulcerative Colitis (UC), especially following Roux-en-Y gastric bypass surgery. This study aims to ascertain whether racial differences influence the risk of developing Ulcerative Colitis in patients who have undergone bariatric surgery. Illuminating this relationship is key to improving patient outcomes and refining care following surgery.

METHODS

Our retrospective analysis reviewed patients who underwent bariatric surgery at our facility between 2009 and 2022. We collected data concerning comorbidities, insurance statuses, types of surgical procedures, colonoscopy, pathology reports, and baseline characteristics, employing ICD and CPT codes. We monitored patients who manifested Ulcerative colitis (UC) after surgery until 2023, categorizing them by gender, race, and the time elapsed. To balance baseline characteristics, we used propensity score matching. Patients with a history of UC before surgery were omitted from the study. We utilized Kaplan-Meier survival analysis and Cox proportional hazards models to determine the timing of UC onset across different racial groups. We applied odds ratios to discern independent factors impacting the study's outcomes.

RESULTS

Between 2009 and 2022, our facility performed 960 bariatric surgeries. Of these procedures, 24 patients (or 0.02%) were diagnosed with UC, typically identified around 80±14.2 months post-surgery. The mean age of the participants was approximately 46±11.8 years, and females constituted 54.2% of the cohort. When examining racial breakdowns, 38.39% were African Americans, 24.4% were whites, 21% were Asians, and 16.21% were Hispanics. Notably, Hispanic patients manifested UC within a considerably shorter duration than other racial groups (Breslow: 11.836, p=0.022). Additionally, a heightened risk of UC was observed among individuals from the lowest income bracket (OR: 3.15, P=0.041), emphasizing the influence of socioeconomic status on health outcomes.

DISCUSSION

This research contributes to bridging the knowledge deficit regarding the influence of race on the occurrence of UC following bariatric surgery. Our retrospective examination of 960 surgeries from 2009 to 2022 indicated a 0.02% incidence of UC, usually identified approximately 45 months after surgery. Importantly, Hispanic patients experienced the onset of UC in a notably shorter period compared to other racial groups, with those in lower income brackets encountering elevated risk levels. Continued studies in this domain can facilitate the development of interventions to diminish these risks, thereby improving health outcomes for a broad spectrum of patient demographics.
PROTEOLYSIS TARGETING CHIMERAS (PROTACS) AS ATTRACTIVE THERAPEUTICS IN IBD THROUGH THE REGULATION OF HYPOXIA-INDUCIBLE FACTORS
Authors: Ornelas Alfredo , Countess Jacob , Welch Nichole , Cartwright Ian , Colgan Sean
Published: January 2024

Inflammatory bowel disease (IBD) represents a group of chronic mucosal inflammatory disorders, including Crohn’s disease (CD) and ulcerative colitis (UC). Many IBD patients have limited therapeutic options. Accumulating literature has implicated a prominent role for O2 metabolism and hypoxia in innate immunity of healthy intestinal tissue (“physiologic hypoxia”) and shifts associated with active inflammation (“inflammatory hypoxia”). Reduction of oxygen levels triggers the temporal stabilization of the transcription factors hypoxia-inducible factors HIF1a and HIF2a, which are essential in intestinal homeostasis. HIF-1/2α are regulated by a family of prolyl hydroxylases (PHDs). Inhibition of PHDs results in transient stabilization of HIF-1/2α, and thus, PHD inhibitors (PHDi) have become attractive targets for the therapeutic treatment of IBD and are reported as protective in mouse models of colitis. We have pursued the development of PHDi using proteolysis targeting chimeras (PROTACs), heterobifunctional compounds that contain a protein of interest ligand, a linker, and a E3 ubiquitin ligase ligand. PROTACs hold advantages over small-molecule inhibitors, including enhanced specificity, higher potency, and sustained pathway inhibition. In ongoing studies, we have synthesized and tested a panel of PHD targeting PROTACs. In cultured intestinal epithelial cells, we have observed PROTAC activity at the nanomolar concentrations in vitro, representing a 2-3 log increase in potency compared to PHDi small molecules. For these purposes, we monitor PHD protein degradation and HIF1/2α stabilization through immunoblotting. We have confirmed HIF transcriptional activity in intestinal epithelial cells exposed to these PROTACs through the induction of various HIF target genes. In parallel, we have established a stably transduced GFP-PHD cell line as a high-throughput assay to monitor PHD degradation in real time. Thus, PHD-targeted PROTACs hold promise as viable alternatives to small molecules for the stabilization of HIF in intestinal epithelial cells.
ZINC RESTRICTION BY INTESTINAL E. COLI - PRODUCED YERSINIABACTIN ACTIVATES HIF-1α IN MACROPHAGES TO PROMOTE CD-ASSOCIATED FIBROSIS
Authors: Ahn Ju-Hyun , Lopez Lacey , Tibbs Taylor , Yu Yen-Rei , Tighe Robert , Denson Lee , Arthur Janelle
Published: January 2024

Intestinal fibrosis is a significant complication in Crohn’s disease (CD) patients, causing severe intestinal strictures and obstructions that are ultimately relieved by surgical bowel resection. Mechanisms driving CD-associated fibrosis are poorly understood but implicate the microbiome, especially adherent-invasive E. coli (AIEC). Previously, our work demonstrated that AIEC production of the metallophore yersiniabactin (Ybt) promotes fibrosis in the well-established gnotobiotic Il10-/- CD mouse model. These pro-fibrotic effects do not require bacterial uptake/utilization of Ybt, suggesting Ybt directly targets the host. Here we show that CD11b+ F4/80+ MHCIIlow macrophages are abundant in the submucosa and muscularis of fibrotic lesions in our mouse model. Similarly, CD68+ macrophages are abundant in strictures, not adjacent margins, of ileocolonic CD patients. We hypothesized that Ybt targets host macrophages to drive fibrosis. A critical metal-dependent pathway for immune cell function during inflammation is HIF-1α. We demonstrate that AIEC infection activates HIF-1α in macrophages, which is dependent upon Ybt production. Importantly, in fibrotic lesions of CD mouse models and resected strictures of ileocolonic CD patients, HIF-1α is activated and localized in nuclei of F4/80+ or CD68+ macrophages. We identified that zinc sequestration by Ybt is responsible for HIF-1α activation, a novel mechanism of HIF-1α stabilization. Furthermore, Ybt-producing AIEC induce potent pro-fibrotic gene expression in macrophage:fibroblast co-cultures, a process dependent on macrophage HIF-1α. This implies that Ybt induces pro-fibrotic macrophages, activating adjacent fibroblasts and fostering intestinal fibrosis. In summary, our findings suggest that as intestinal macrophages encounter AIEC, Ybt sequesters zinc, causes an accumulation of nuclear HIF-1α, and this imbalance of metal homeostasis drives pro-fibrotic macrophage and fibroblast activation. Ultimately, effective fibrotic remodeling fails and leads to intestinal fibrosis in CD patients.
PHYSICAL ACTIVITY AND SOCIAL COGNITIVE THEORY CORRELATES AMONG POSTOPERATIVE PERSONS WITH CROHN'S DISEASE: PRELIMINARY RESULTS FROM A CROSS-SECTIONAL ANALYSIS
Authors: Neal Whitney , Chu Daniel , Motl Robert , Pekmezi Dori
Published: January 2024

INTRODUCTION

There is increasing research and clinical interest in physical activity (PA) behavior among persons with Crohn's disease (CD), but little is known regarding PA and its correlates among postoperative persons with CD. This is important as most patients with CD will require surgery within 10 years of diagnosis which may drastically alter PA levels and its benefits for CD. As found in past studies with other patient populations (e.g., colorectal cancer survivors), understanding the cognitive and behavioral factors associated with PA engagement among postoperative adults with CD is useful for informing the development of PA behavior change interventions for this population. This cross-sectional study examined self-reported PA levels and its associations with social cognitive theory (SCT) variables among postoperative persons with CD.

METHODS

Participants included 30 persons with CD who completed an online survey between November 2022 and June 2023. Of those participants, 18 reported a history of CD-related surgery. The survey assessed demographic and clinical characteristics, disease activity (Harvey-Bradshaw Index), leisure time exercise (Godin Leisure-Time Exercise Questionnaire and International Physical Activity Questionnaire), and related SCT variables (exercise self-efficacy, social support, outcome expectations, goal setting, and planning). Analyses included independent sample t-tests and non-parametric bivariate correlations (rs) for comparing PA levels and SCT survey scores among participants with and without a history of surgery.

RESULTS

There were differences in PA and SCT variables based on surgical history. Postoperative participants engaged in significantly more PA (t = 2.17, p = 0.04) and reported greater outcome expectations (t = 2.45, p = 0.02) and goal setting (t = 2.22, p = 0.04) scores compared with CD participants without a history of surgery. Among postoperative participants, only exercise goal setting was significantly correlated with PA (rs = .53, p = 0.03) such that postoperative participants with greater exercise goal setting behaviors reported higher levels of PA. None of the SCT variables were significantly associated with PA in the sample of participants without a history of surgery.

CONCLUSIONS

This study yielded novel findings regarding PA behavior and its SCT correlates in a small sample of postoperative persons with CD. The results suggest the need for further research into exercise goal setting as a potential target of behavior change interventions for increasing PA among postoperative persons with CD.
Full operator preconditioning and the accuracy of solving linear systems
Authors: Mohr Stephan , Nakatsukasa Yuji , Urzúa-Torres Carolina
Published: January 2024

Unless special conditions apply, the attempt to solve ill-conditioned systems of linear equations with standard numerical methods leads to uncontrollably high numerical error and often slow convergence of an iterative solver. In many cases, such systems arise from the discretization of operator equations with a large number of discrete variables and the ill-conditioning is tackled by means of preconditioning. A key observation in this paper is the sometimes overlooked fact that while traditional preconditioning effectively accelerates convergence of iterative methods, it generally does not improve the accuracy of the solution. Nonetheless, it is sometimes possible to overcome this barrier: accuracy can be improved significantly if the equation is transformed before discretization, a process we refer to as full operator preconditioning (FOP). We highlight that this principle is already used in various areas, including second kind integral equations and Olver–Townsend’s spectral method. We formulate a sufficient condition under which high accuracy can be obtained by FOP. We illustrate this for a fourth order differential equation which is discretized using finite elements.
A Genome-Wide Association Study of Respiratory Syncytial Virus Infection Severity in Infants
Authors: Johnson Mari , Chelysheva Irina , Öner Deniz , McGinley Joseph , Lin Gu-Lung , O’Connor Daniel , Robinson Hannah , Drysdale Simon B , Gammin Emma , Vernon Sophie , Muller Jill , Wolfenden Helen , Westcar Sharon , Anguvaa Lazarus , Thwaites Ryan S , Bont Louis , Wildenbeest Joanne , Martinón-Torres Federico , Aerssens Jeroen , Openshaw Peter J M , Pollard Andrew J
Published: January 2024

Background

Respiratory syncytial virus (RSV) is a significant cause of infant morbidity and mortality worldwide. Most children experience at least one 1 RSV infection by the age of two 2 years, but not all develop severe disease. However, the understanding of genetic risk factors for severe RSV is incomplete. Consequently, we conducted a genome-wide association study of RSV severity.

Methods

Disease severity was assessed by the ReSVinet scale, in a cohort of 251 infants aged 1 week to 1 year. Genotyping data were collected from multiple European study sites as part of the RESCEU Consortium. Linear regression models were used to assess the impact of genotype on RSV severity and gene expression as measured by microarray.

Results

While no SNPs reached the genome-wide statistical significance threshold (P < 5 × 10−8), we identified 816 candidate SNPs with a P-value of <1 × 10−4. Functional annotation of candidate SNPs highlighted genes relevant to neutrophil trafficking and cytoskeletal functions, including LSP1 and RAB27A. Moreover, SNPs within the RAB27A locus significantly altered gene expression (false discovery rate, FDR P < .05).

Conclusions

These findings may provide insights into genetic mechanisms driving severe RSV infection, offering biologically relevant information for future investigations.
Identification of CCL20 as a Prognostic Predictor for Severe Fever With Thrombocytopenia Syndrome Based on Plasma Proteomics
Authors: Zhang Yue , Li Lan , Liu Yuanni , Zhang Wei , Peng Wenjuan , Zhang Shuai , Qu Renliang , Ma Yuan , Liu Zishuai , Ge Ziruo , Zhou Yanxi , Tian Wen , Shen Yi , Liu Li , Duan Jianping , Chen Zhihai , Zhu Liuluan
Published: January 2024

Background

Severe fever with thrombocytopenia syndrome (SFTS), a lethal tick-borne hemorrhagic fever, prompted our investigation into prognostic predictors and potential drug targets using plasma Olink Proteomics.

Methods

Employing the Olink assay, we analyzed 184 plasma proteins in 30 survivors and 8 nonsurvivors of SFTS. Validation was performed in a cohort of 154 patients with SFTS via enzyme-linked immunosorbent assay. We utilized the Drug-Gene Interaction Database to identify protein-drug interactions.

Results

Nonsurvivors exhibited 110 differentially expressed proteins as compared with survivors, with functional enrichment in the cell chemotaxis–related pathway. Thirteen differentially expressed proteins—including C-C motif chemokine 20 (CCL20), calcitonin gene–related peptide alpha, and pleiotrophin—were associated with multiple-organ dysfunction syndrome. CCL20 emerged as the top predictor of death, demonstrating an area under the curve of 1 (P = .0004) and 0.9033 (P < .0001) in the discovery and validation cohorts, respectively. Patients with CCL20 levels exceeding 45.74 pg/mL exhibited a fatality rate of 45.65%, while no deaths occurred in those with lower CCL20 levels. Furthermore, we identified 202 Food and Drug Administration–approved drugs targeting 37 death-related plasma proteins.

Conclusions

Distinct plasma proteomic profiles characterize SFTS cases with different outcomes, with CCL20 emerging as a novel, sensitive, accurate, and specific biomarker for predicting SFTS prognosis.
Enrichment Reveals Extensive Integration of Hepatitis B Virus DNA in Hepatitis Delta Virus-Infected Patients
Authors: Ringlander Johan , Strömberg Lucia Gonzales , Stenbäck Joakim B , Andersson Maria E , Abrahamsson Sanna , Skoglund Catarina , Castedal Maria , Larsson Simon B , Rydell Gustaf E , Lindh Magnus
Published: January 2024

Background

Hepatitis B virus (HBV) DNA may become integrated into the human genome of infected human hepatocytes. Expression of integrations can produce the surface antigen (HBsAg) that is required for synthesis of hepatitis D virus (HDV) particles and the abundant subviral particles in the blood of HBV- and HDV-infected subjects. Knowledge about the extent and variation of HBV integrations and impact on chronic HDV is still limited.

Methods

We investigated 50 pieces of liver explant tissue from 5 patients with hepatitis D-induced cirrhosis, using a deep-sequencing strategy targeting HBV RNA.

Results

We found that integrations were abundant and highly expressed, with large variation in the number of integration-derived (HBV/human chimeric) reads, both between and within patients. The median number of unique integrations for each patient correlated with serum levels of HBsAg. However, most of the HBV reads represented a few predominant integrations.

Conclusions

The results suggest that HBV DNA integrates in a large proportion of hepatocytes, and that the HBsAg output from these integrations vary >100-fold depending on clone size and expression rate. A small proportion of the integrations seems to determine the serum levels of HBsAg and HDV RNA in HBV/HDV coinfected patients with liver cirrhosis.
Real-life data of immune recovery using bictegravir/emtricitabine/tenofovir alafenamide in virologically suppressed people living with HIV. Results at 48–96 weeks of RETROBIC Study
Authors: Troya Jesús , Pousada Guillermo , Micán Rafael , Galera Carlos , Sanz José , de los Santos Ignacio , Dueñas Carlos , Cabello Noemí , Martín Cristina , Galindo María Josefa , Garcinuño María Ángeles , Pedrero-Tomé Roberto , Buzón Luis
Published: January 2024

Background

Switching strategy with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) has become a gold standard for people living with HIV (PLWH), achieving high efficacy and safety rates. However, data regarding immune status in long-term real-life cohorts of pretreated patients are needed.

Methods

We performed a multicentre, non-controlled, retrospective study in virologically suppressed PLWH switching to B/F/TAF. We evaluated CD4+, CD8+ and CD4+/CD8+ ratio, efficacy and safety at weeks 48 and 96.

Results

The study comprised 1966 PLWH from 12 hospitals in Spain, of whom 80% were men, and the median age was 51.0 [42.0–57.0] years. The median time of HIV infection was 18.0 [10.0–27.0] years. No significant changes in CD4+, CD8+ T cells, or CD4+/CD8+ were observed after 96 weeks. Nevertheless, in women at weeks 48 and 96, we found a significant increase of CD4+ T cells and a significant decrease in CD8+ T cells. In patients ≥60 years at week 96, CD4 T cells significantly increased and CD8+ T cells significantly decreased at week 48. The on-treatment analysis revealed HIV-RNA <50 copies/mL in 95.6% (1700/1779) and 96.7% (1312/1356) of patients at weeks 48 and 96, respectively. The rates increased to 99.2% (1765/1779) and 99.7% (1352/1356) when considering HIV-RNA <200 copies/mL. No resistance mutations were detected in virologic failures. B/F/TAF discontinuations accounted for 10.2% (200). Simplification was the most common reason for discontinuation in 3.8% (74) of patients.

Conclusion

In long-term virologically controlled PLWH, B/F/TAF achieved high efficacy rates and slightly improved immune status in women and individuals aged 60 and over after 48 and 96 of switching.
The combined effect of systemic antibiotics and proton pump inhibitors on Clostridioides difficile infection and recurrence
Authors: Moreels Nele , Boven Annelies , Gressani Oswaldo , Andersson Fredrik L , Vlieghe Erika , Callens Steven , Engstrand Lars , Simin Johanna , Brusselaers Nele
Published: January 2024

Background

Antibiotics and proton pump inhibitors (PPI) are recognized risk factors for acquisition and recurrence of Clostridioides difficile infection (CDI), yet combined effects remain unclear.

Objectives

To assess the short- and long-term effects of antibiotics and PPIs on CDI risk and recurrence.

Methods

Population-based study including all 43 152 patients diagnosed with CDI in Sweden (2006–2019), and 355 172 matched population controls without CDI. The impact of antibiotics and PPIs on CDI risk and recurrence was explored for recent (0–30 days) and preceding (31–180 days) use prior to their first CDI diagnosis, using multivariable conditional logistic regression presented as odds ratios (ORs) and 95% confidence interval, adjusted for demographics, comorbidities and other drugs.

Results

Compared to controls, the combined effect of recent PPIs and antibiotics [ORAB+PPI = 17.51 (17.48–17.53)] on CDI risk was stronger than the individual effects [ORAB = 15.37 (14.83–15.93); ORPPI = 2.65 (2.54–2.76)]. Results were less pronounced for exposure during the preceding months. Dose–response analyses showed increasing exposure correlated with CDI risk [recent use: ORAB = 6.32 (6.15–6.49); ORPPI = 1.65 (1.62–1.68) per prescription increase].

Compared to individuals without recurrence (rCDI), recent [ORAB = 1.30 (1.23–1.38)] and preceding [ORAB = 1.23 (1.16–1.31); ORPPI = 1.12 (1.03–1.21)] use also affected the risk of recurrence yet without significant interaction between both. Recent macrolides/lincosamides/streptogramins; other antibacterials including nitroimidazole derivates; non-penicillin beta lactams and quinolones showed the strongest association with CDI risk and recurrence, particularly for recent use. PPI use, both recent and preceding, further increased the CDI risk associated with almost all antibiotic classes.

Conclusion

Recent and less recent use of PPIs and systemic antibiotics was associated with an increased risk of CDI, particularly in combination.
Whole blood transcriptome analysis for age- and gender-specific gene expression profiling in Japanese individuals
Authors: Aoki Yu-ichi , Taguchi Keiko , Anzawa Hayato , Kawashima Junko , Ishida Noriko , Otsuki Akihito , Hasegawa Atsushi , Baird Liam , Suzuki Takafumi , Motoike Ikuko N , Ohneda Kinuko , Kumada Kazuki , Katsuoka Fumiki , Kinoshita Kengo , Yamamoto Masayuki
Published: January 2024

Whole blood transcriptome analysis is a valuable approachin medical research, primarily due to the ease of sample collection and the richness of the information obtained. Since the expression profile of individual genes in the analysis is influenced by medical traits and demographic attributes such as age and gender, there has been a growing demand for a comprehensive database for blood transcriptome analysis. Here, we performed whole blood RNA sequencing (RNA-seq) analysis on 576 participants stratified by age (20–30s and 60–70s) and gender from cohorts of the Tohoku Medical Megabank (TMM). A part of female segment included pregnant women. We did not exclude the globin gene family in our RNA-seq study, which enabled us to identify instances of hereditary persistence of fetal hemoglobin based on the HBG1 and HBG2 expression information. Comparing stratified populations allowed us to identify groups of genes associated with age-related changes and gender differences. We also found that the immune response status, particularly measured by neutrophil-to-lymphocyte ratio (NLR), strongly influences the diversity of individual gene expression profiles in whole blood transcriptome analysis. This stratification has resulted in a data set that will be highly beneficial for future whole blood transcriptome analysis in the Japanese population.
Sphingosine-1-phosphate promotes osteogenesis by stimulating osteoblast growth and neovascularization in a vascular endothelial growth factor–dependent manner
Authors: Wille Annalena , Weske Sarah , von Wnuck Lipinski Karin , Wollnitzke Philipp , Schröder Nathalie H , Thomas Nadine , Nowak Melissa K , Deister-Jonas Jennifer , Behr Björn , Keul Petra , Levkau Bodo
Published: January 2024

Sphingosine-1-phosphate (S1P) plays multiple roles in bone metabolism and regeneration. Here, we have identified a novel S1P-regulated osteoanabolic mechanism functionally connecting osteoblasts (OBs) to the highly specialized bone vasculature. We demonstrate that S1P/S1PR3 signaling in OBs stimulates vascular endothelial growth factor a (VEGFa) expression and secretion to promote bone growth in an autocrine and boost osteogenic H-type differentiation of bone marrow endothelial cells in a paracrine manner. VEGFa-neutralizing antibodies and VEGF receptor inhibition by axitinib abrogated OB growth in vitro and bone formation in male C57BL/6J in vivo following S1P stimulation and S1P lyase inhibition, respectively. Pharmacological S1PR3 inhibition and genetic S1PR3 deficiency suppressed VEGFa production, OB growth in vitro, and inhibited H-type angiogenesis and bone growth in male mice in vivo. Together with previous work on the osteoanabolic functions of S1PR2 and S1PR3, our data suggest that S1P-dependent bone regeneration employs several nonredundant positive feedback loops between OBs and the bone vasculature. The identification of this yet unappreciated aspect of osteoanabolic S1P signaling may have implications for regular bone homeostasis as well as diseases where the bone microvasculature is affected such as age-related osteopenia and posttraumatic bone regeneration.
A novel fluid identification method based on a high-precision spectral decomposition method
Authors: Miao Fawei , He Yanxiao , Wang Shangxu , Huang Handong
Published: January 2024

Time-frequency decomposition technology is an effective tool for analyzing non-stationary signals. Improving resolution of spectral decomposition techniques is important to extract more useful information from the received signal. The Wigner-Ville distribution (WVD) has been widely applied in seismic signal analysis, it can better analyze seismic signals due to many excellent mathematical properties, but this method has a drawback that cross terms interference exists in the analyzing of multicomponent signals, which severely limits its application. The combination of the complex-domain matching pursuit (CDMP) with this approach effectively solves this problem. However, the conventional CDMP-WVD does not take the influence of the scale parameter on the Morlet wavelet waveform into account, which reduces the time-frequency resolution of CDMP-WVD. Therefore, to correct the defect that the atomic waveforms change only with the frequency parameter, we propose an improved spectral decomposition method ICDMP-WVD that considers the scale parameter. In this study, we first analyze influences of the scale parameter on Morlet wavelet waveform and make the scale parameter a search parameter that improves the computational efficiency and time-frequency resolution of the traditional CDMP-WVD method. Accordingly, the seismic dispersion-dependent attributes are calculated via combing the improved CDMP-WVD algorithm and the frequency-dependent AVO inversion. We adopt a two-step frequency-dependent AVO inversion method to improve the stability of the conventional frequency-dependent AVO inversion. Theoretical data and real data application show that the approach in this study can identify gas reservoirs efficiently and accurately.
Fine characterization of interbedding sand-mudstone based on waveform indication inversion
Authors: Shi Suzhen , Gao Weixu , Long Teng , Xie Dongshan , Li Li , Pei Jinbo , Cai Jianchao
Published: January 2024

Owing to the increasing challenges associated with coal mine exploration and development, extremely precise surveys with high-resolution images are required to support production. Conventional inversion methods cannot provide sufficiently precise images of the complex lithologies in coal measure strata. Accordingly, this study performed research in Qiyuan mining area, Shanxi Province, China, and predicted the complex lithology on the basis of facies control using waveform indication inversion and waveform indication simulation. Horizontal changes in seismic waveforms were used to reflect lithologic assemblage characteristics for facies-controlled constraints, and the vertical mapping the connection between seismic waveform and logging curves was shown. Moreover, high-resolution inversions of wave impedance and natural gamma parameters were conducted. Combined with lithologic shielding and accurate time–depth conversion, the inversions enabled the precise characterization of the lithological assemblage distribution in the study area. Our results showed that waveform indication inversion could distinguish between coal seams and limestone, whereas waveform indication simulation based on natural gamma could effectively distinguish between sandstone and mudstone. Furthermore, the horizontal resolution was improved and the vertical resolution extended to a thickness of 2–3 m. In addition, the inversion results were highly consistent with drilling results, with an error <0.1 m. Therefore, waveform indication inversion and simulation could be applied to coal mines for safe and efficient production.
Noninvasive EEG measurement of sleep in the family cat and comparison with the dog
Authors: Bálint Anna , Reicher Vivien , Csibra Barbara , Gácsi Márta
Published: January 2024

We have successfully measured the sleep electroencephalogram (EEG) of 12 family cats during an afternoon nap using a completely noninvasive methodology originally developed and validated for family dogs. Extracting both macrostructural and spectral sleep variables from the acquired data, we: (1) provided a descriptive analysis of sleep structure in cats and the power spectral density (PSD) distribution considering 3 sleep stages—drowsiness, non-rapid eye movement (NREM), and rapid eye movement (REM) sleep; and (2) compared the results to those obtained in family dogs measured under the same conditions and using the same methodology. Importantly, our description of sleep structure and PSD distribution in cats proved to be comparable to those of earlier invasive studies, highlighting that appropriate noninvasive methodologies may provide a viable alternative to those that are invasive in some cases. While no macrostructural differences were found between the sleep of cats and dogs, and the characteristic PSDs were mostly similar across sleep stages within the 2 species, the high-frequency resolution comparison of PSD distributions revealed differences between the 2 species in all sleep stages (concerning the delta, theta, alpha, sigma, and beta bands in drowsiness and NREM sleep; and the delta, alpha, and sigma bands in REM sleep). Potential factors underlying these differences are discussed, including differences in circadian rhythms, sleep homeostatic regulation, experienced stress, or even differential attitudes toward owners—highlighting important links between sleep characteristics and often more complex neural and behavioral features.
Three new shrews (Soricidae: Crocidura) from West Sumatra, Indonesia: elevational and morphological divergence in syntopic sister taxa
Authors: Nations Jonathan A , Handika Heru , Mursyid Ahmad , Darma Busta Ryski , Apandi  , Achmadi Anang S , Esselstyn Jacob A
Published: January 2024

We describe 3 new species of shrews (Eulipotyphla, Soricidae, Crocidura) from West Sumatra, Indonesia. Two of these taxa were found above 1,800 m on Mt. Singgalang. The third taxon was found above 1,660 m on Mt. Talamau, 65 km northwest of Mt. Singgalang. We also resurrect Crocidura aequicauda based on 2 specimens from Mts. Tujuh and Kerinci, which lie near the border between West Sumatra and Jambi provinces. Several methodological approaches support our findings: linear cranial morphometrics, landmark-based 2D geometric morphometrics, and molecular phylogenetics using both mtDNA and 6 nuclear exons. A multilocus species-tree analysis places the 3 new species and C. aequicauda in a clade with the Javan endemics C. monticola and C. umbra. Although the 2 taxa from Mt. Singgalang are recovered as sister species, 1 is nearly twice the size of the other, and they are divergent in several other morphological characters, such as tail length, cranium size, and pelage color and texture. Recently diverged yet morphologically disparate sister taxa living syntopically in an isolated habitat “island,” like the montane forests of Mt. Singgalang, is unusual in mammals but documented in other Crocidura on neighboring Java and Borneo; these 2 new taxa represent the first known case of this phenomenon on Sumatra. Our results bring the number of Sumatran Crocidura to 10, 9 of which are endemic to the island. All 3 of the new species appear to be endemic to a single mountain and were not detected in similar surveys of nearby mountains. If this local endemism pattern is common, it would indicate that Sumatra’s mammal diversity may be severely underestimated, largely due to the paucity of small-mammal surveys and museum specimens.
Changes in smoking use and subsequent lung cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study
Authors: Gutiérrez-Torres Daniela S , Kim Sungduk , Albanes Demetrius , Weinstein Stephanie J , Inoue-Choi Maki , Albert Paul S , Freedman Neal D
Published: January 2024

Background

Reducing cigarettes per day may lower the risk of lung cancer compared with continuing to smoke at the same intensity. Other changes in smoking behaviors, such as increasing cigarette consumption or quitting for a period and relapsing, may also affect lung cancer risk.

Methods

We examined changes in smoking status and cigarettes per day among 24 613 Finnish male smokers aged 50-69 years who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Longitudinal data on smoking were collected during study follow-up visits 3 times a year (approximately every 4 months) between 1985 and 1993. Incident lung cancer patients through 2012 were identified by the Finnish Cancer Registry. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression.

Results

Compared with smoking 20 cigarettes per day continuously across the intervention period, reducing an average of 5 cigarettes per day per year while smoking was associated with a 20% lower risk of lung cancer (95% CI = 0.71 to 0.90). A substantially lower risk of lung cancer was also observed when participants smoked at 50% (RR = 0.72, 95% CI = 0.57 to 0.90) and 10% (RR = 0.55, 95% CI = 0.36 to 0.83) of study visits, relative to smoked at 100% of study visits.

Conclusions

Smokers may lower their risk of lung cancer by reducing smoking intensity (cigarettes per day while smoking) and the time they smoke. However, quitting smoking completely is the most effective way for smokers to reduce their risk of lung cancer.
Shifts in local governments’ corporatization intensity: evidence from German cities
Authors: Rackwitz Maike , Raffer Christian
Published: January 2024

Why do local governments create and reform public service companies, given their uncertain economic benefits and potential damage to accountability and service transparency? Taking an extended transaction cost perspective, we argue that corporatization—the provision of public services by publicly owned companies—is a function of fiscal hardship, the decision maker’s economic orientation and the level of operator transparency. Using a two-way fixed effects regression, we test this expectation on 680 investment reports of 34 German cities from 1998 to 2017, representing 11,062 year-corporatized entity combinations. We show that the drivers of corporatization are sensitive to the depth of local ownership analyzed. In doing so, we highlight the theoretical need and potential for conceptual differentiation between ownership levels along a corporation’s lineage. Exploiting the data’s panel structure, we also find that the intensity of corporatization has heightened since the late 1990s, largely due to increasingly complex corporate structures of indirect ownership.