bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comorbidities, healthcare resource utilization & treatment pattern among patients with prurigo nodularis, compared to a benchmark in Germany: A real‐world evidence claims data study
Authors: Ständer Sonja , Ketz Miriam , Akumo Divine , Kossack Nils , Pignot Marc , Chavda Rajeev , Gabriel Sylvie 
Published: December 2023

AbstractBackgroundPrurigo nodularis (PN) is a rare chronic inflammatory skin disease with a high disease burden, but data on clinical and economic burden are still scarce.ObjectiveTo describe the real‐world epidemiologic, clinical and therapeutic characteristics and related economic burden of patients with PN compared to a benchmark population in Germany.MethodsThis retrospective study was based on an excerpt of German Statutory Health Insurance data of patients with an initial PN diagnosis between 2012 and 2016. PN cohort contained no record of PN in eight quarters before the index quarter and was followed up for eight quarters (unless deceased). Benchmark cohort without PN was calculated using direct standardization and 1:1 matching to PN cohort.ResultsOut of 4,536,002 insured patients, 2309 incident patients with PN were identified and matched to the benchmark cohort out of 3,018,382 patients without PN. Patients were mostly between 45 and 80 years when diagnosed with PN. Higher comorbidity rates were reported for PN than benchmark, with a rising disease burden at follow‐up. Most patients with PN (91.3%) were diagnosed outpatient and had >50% more outpatient visits than the benchmark cohort. Hospitalization rates were higher in PN (53.9%) versus benchmark (35.1%), yielding twice longer mean hospital stays for PN (12 days) compared to benchmark (6 days) (p < 0.001). The most common initial therapy for patients with PN was topical corticosteroids (47.6%); ≥10% of patients were treated with antidepressants, antihistamines or systemic corticosteroids. Therapy rates were higher for PN compared to benchmark (p < 0.001). Mean initial costs were twofold higher in PN versus benchmark for outpatient, inpatient and drugs. During follow‐up, an increase of >70% in mean PN costs compared to benchmark was identified for outpatient, inpatient and concomitant treatments (p < 0.001).ConclusionThis study highlights the significantly higher clinical and economic burden incurred by PN compared to benchmark patients in Germany, reflecting the unmet medical need for PN.
Confirmatory test of active IHHNV infection in shrimp by immunohistochemistry and IHHNV‐LongAmp PCR
Authors: Imsonpang Supapong , Pudgerd Arnon , Chotwiwatthanakun Charoonroj , Srisala Jiraporn , Sanguanrut Piyachat , Kasamechotchung Chanadda , Sritunyalucksana Kallaya , Taengchaiyaphum Suparat , Vanichviriyakit Rapeepun 
Published: December 2023

AbstractThe presence of endogenous viral elements (EVE) in the penaeid shrimp genome has been recently reported and suggested to be involved in the host recognition of viral invaders. Our previous report of a search for EVE of infectious hypodermal and haematopoietic necrosis virus (IHHNV‐EVE) in the Thai Penaeus monodon whole genome sequence project (GenBank accession no. JABERT000000000) confirmed the presence of three clusters of EVE derived from IHHNV in the shrimp genome. This study aimed to compare an immunohistochemistry method (IHC) and a PCR method to detect infectious IHHNV infection in shrimp. First, specimens collected from farms were checked for IHHNV using three PCR methods; two methods were recommended by WOAH (309 and 389 methods), and a newly established long‐range PCR for IHHNV (IHHNV‐LA PCR) targeting almost the whole genome (>90%) of IHHNV. Among 29 specimens tested, 24 specimens were positive for WOAH methods (at least one method). Among 24 WOAH‐positive specimens (WOAH+), there were 18 specimens with positive IHHNV‐LA PCR method (WOAH+/LA+), six specimens with negative IHHNV‐LA PCR method (WOAH+/LA−). Six specimens were negative for all methods (WOAH−/LA−). The positive signals detected by IHC method were found only in the specimens with WOAH+/LA+. The results suggest that the WOAH+/LA− specimens were not infected with IHHNV, and the positive WOAH method might result from the EVE‐IHHNV. The study recommends combining the IHHNV‐LA PCR method and IHC with positive PCR results from WOAH's recommended methods to confirm IHHNV infection.
Legal Risk and Insider Trading
Authors: KACPERCZYK MARCIN , PAGNOTTA EMILIANO S. 
Published: December 2023

ABSTRACTDo illegal insiders internalize legal risk? We address this question with hand‐collected data from 530 SEC (the U.S. Securities and Exchange Commission) investigations. Using two plausibly exogenous shocks to expected penalties, we show that insiders trade less aggressively and earlier and concentrate on tips of greater value when facing a higher risk. The results match the predictions of a model where an insider internalizes the impact of trades on prices and the likelihood of prosecution and anticipates penalties in proportion to trade profits. Our findings lend support to the effectiveness of U.S. regulations' deterrence and the long‐standing hypothesis that insider trading enforcement can hamper price informativeness.
Increased risk of placenta previa and preterm birth in pregnant women with endometriosis/adenomyosis: A propensity‐score matching analysis of a nationwide perinatal database in Japan
Authors: Kato Kosuke , Iriyama Takayuki , Hara Konan , Suzuki Kensuke , Hashimoto Ayako , Sayama Seisuke , Ichinose Mari , Toshimitsu Masatake , Seyama Takahiro , Sone Kenbun , Kumasawa Keiichi , Nagamatsu Takeshi , Hirota Yasushi , Koga Kaori , Osuga Yutaka 
Published: December 2023

AbstractAimWe aimed to investigate the associations of endometriosis and adenomyosis with pregnancy complications by using a large‐scale Japanese database.MethodsWe retrospectively analyzed 145 590 singleton pregnancies from the Japan Perinatal Registry Network Database. Pregnant women registered as having endometriosis or adenomyosis were designated as the case group (EA), whereas the control group (non‐EA) was selected using propensity‐score matching adjusted for variables such as age, parity, BMI, smoking history, and the use of assisted reproductive technology. The main outcomes included placental malposition, preterm birth, and hypertensive disorders of pregnancy (HDP).ResultsIn total, 1203 patients from both the EA and non‐EA groups were matched and evaluated. The EA group showed significantly higher rates of placenta previa (odds ratio [OR], 3.01; 95% confidence interval [CI], 1.84–4.92), low‐lying placenta (OR, 2.02; 95% CI, 1.06–3.86), and preterm birth (OR, 1.44; 95% CI, 1.13–1.84) than the non‐EA group. However, no significant difference was observed in the incidence of HDP (OR, 1.22; 95% CI, 0.90–1.66).ConclusionThe use of propensity‐score matching to analyze a nationwide perinatal database in Japan clarified that EA was associated with increased pregnancy complications, specifically placental malposition, including placenta previa and low‐lying placenta, and preterm birth, but not with HDP.
Food deserts and dental care utilization in the United States
Authors: Testa Alexander , Mungia Rahma , van den Berg Alexandra , C. Hernandez Daphne 
Published: December 2023

AbstractObjectivesAlthough food deserts are known to impact health and healthcare utilization, no research has investigated the relationship between food deserts and dental care utilization. This study aimed to fill this gap by assessing the relationship between living in a food desert and self‐reported dental care utilization in the past year.MethodsData are from the National Longitudinal Study of Adolescent to Adult Health (N = 10,495). The association between food deserts and dental care utilization was assessed using covariate‐adjusted multiple logistic regression.ResultsLiving in a food desert was associated with higher odds of not utilizing dental care in the past year. This association was concentrated among high‐poverty areas (≥20% poverty rate).ConclusionsThe current study is the first to assess the relationship between living in a food desert and dental care utilization. The findings demonstrate that individuals living in low‐income urban food deserts may be at increased risk for not utilizing dental care.
Herbarium specimens reveal that mycorrhizal type does not mediate declining temperate tree nitrogen status over a century of environmental change
Authors: Michaud Talia J. , Cline Lauren C. , Hobbie Erik A. , Gutknecht Jessica L. M. , Kennedy Peter G. 
Published: December 2023

Summary

Rising atmospheric carbon dioxide concentrations (CO2) and atmospheric nitrogen (N) deposition have contrasting effects on ectomycorrhizal (EM) and arbuscular mycorrhizal (AM) symbioses, potentially mediating forest responses to environmental change.

In this study, we evaluated the cumulative effects of historical environmental change on N concentrations and δ15N values in AM plants, EM plants, EM fungi, and saprotrophic fungi using herbarium specimens collected in Minnesota, USA from 1871 to 2016. To better understand mycorrhizal mediation of foliar δ15N, we also analyzed a subset of previously published foliar δ15N values from across the United States to parse the effects of N deposition and CO2 rise.

Over the last century in Minnesota, N concentrations declined among all groups except saprotrophic fungi. δ15N also declined among all groups of plants and fungi; however, foliar δ15N declined less in EM plants than in AM plants. In the analysis of previously published foliar δ15N values, this slope difference between EM and AM plants was better explained by nitrogen deposition than by CO2 rise.

Mycorrhizal type did not explain trajectories of plant N concentrations. Instead, plants and EM fungi exhibited similar declines in N concentrations, consistent with declining forest N status despite moderate levels of N deposition.
ldi‐miR396‐LdPMaT1 enhances reactive oxygen species scavenging capacity and promotes drought tolerance in Lilium distichum Nakai autotetraploids
Authors: Fu Linlan , Zhang Jing , Li Min , Wang Chunxia , Chen Yang , Fan Xinyue , Sun Hongmei 
Published: December 2023

AbstractDrought is a key environmental stress that inhibits plant growth, development, yield and quality. Whole‐genome replication is an effective method for breeding drought resistant cultivars. Here, we evaluated the tolerance of Lilium distichum Nakai diploids (2n = 2× = 24) and artificially induced autotetraploids (2n = 4× = 48) to drought simulated by polyethylene glycol (PEG) stress. Autotetraploids showed stronger drought tolerance than diploids, and high‐throughput sequencing during PEG stress identified five differentially expressed miRNAs. Transcriptome analysis revealed significantly different reactive oxygen species (ROS)‐scavenger expression levels between diploids and autotetraploids, which increased the drought tolerance of autotetraploids. Specifically, we identified ldi‐miR396b and its only target gene (LdPMaT1) for further study based on its expression level and ROS‐scavenging ability in response to drought stress (DS). Autotetraploids showed higher expression of LdPMaT1 and significantly downregulated expression of ldi‐miR396b under DS compared with diploids. Through a short tandem target mimic (STTM) in transgenic lilies, functional studies revealed that miR396b silencing promotes LdPMaT1 expression and the DS response. Under PEG stress, STTM393 transgenic lines showed improved drought resistance mediated by lowered MDA content but exhibited high antioxidant enzyme activity, consistent with the autotetraploid results. Collectively, these findings suggest that ldi‐miR396b‐LdPMaT1 potentially enhances ROS‐scavenging ability, which contributes to improved stress adaptation in autotetraploid lilies.
Unveiling the intricacies of COVID‐19: Autoimmunity, multi‐organ manifestations and the role of autoantibodies
Authors: Ding Zetao , Wei Xingyi , Pan Haoyu , Shi Hui , Shi Yue 
Published: December 2023

AbstractCOVID‐19 is a severe infectious disease caused by a SARS‐CoV‐2 infection. It has caused a global pandemic and can lead to acute respiratory distress syndrome (ARDS). Beyond the respiratory system, the disease manifests in multiple organs, producing a spectrum of clinical symptoms. A pivotal factor in the disease's progression is autoimmunity, which intensifies its severity and contributes to multi‐organ injuries. The intricate interaction between the virus' spike protein and human proteins may engender the generation of autoreactive antibodies through molecular mimicry. This can further convolute the immune response, with the potential to escalate into overt autoimmunity. There is also emerging evidence to suggest that COVID‐19 vaccinations might elicit analogous autoimmune responses. Advanced technologies have pinpointed self‐reactive antibodies that target diverse organs or immune‐modulatory proteins. The interplay between autoantibody levels and multi‐organ manifestations underscores the importance of regular monitoring of serum antibodies and proinflammatory markers. A combination of immunosuppressive treatments and antiviral therapy is crucial for managing COVID‐19‐associated autoimmune diseases. The review will focus on the generation of autoantibodies in the context of COVID‐19 and their impact on organ health.
Intravenous albumin utilization audit at a large community hospital
Authors: Jug Rachel , Callum Jeannie , Ruijs Theodora , Liu Yang , Barty Rebecca , Thompson Troy 
Published: December 2023

AbstractBackgroundThere is a literature gap in terms of albumin utilization practices.Methods/MaterialsWe conducted a single‐center retrospective observational electronic audit of adult admitted patients who received one or more vials of albumin (5% or 25%) between September 1, 2019 and August 31, 2020 at a large community hospital. The Research Ethics Board approval was obtained. Utilization data identified through the laboratory information system were independently adjudicated by two reviewers and resolved by consensus as appropriate‐acceptable, appropriate‐may be acceptable, or inappropriate. The primary objective of this audit is to determine the proportion of 5% and 25% intravenous albumin infusions meeting a priori appropriateness criteria for indication. Secondary outcomes include determining the patterns of practice surrounding intravenous albumin use: patient demographics, most responsible diagnosis, location at time of order, clinical outcomes of albumin recipients, and types, volumes, and cost of albumin infused.ResultsThe mean total albumin administered was 569.2 mL across 456 total recipients (58% male) with a 29% appropriateness rate. This cohort had an in‐hospital mortality rate of 38%, with an average of 6 days from first dose of albumin to death. The mean length of stay was 14 days, with a mean intensive care length of stay of 8 days. The purchase cost of inappropriately transfused albumin was CAD $65,538.ConclusionBased on a lack of or an unacceptable indication provided, 71% of patients were inappropriately transfused. Albumin use deviating from guideline recommendations may be contributing to increased healthcare costs, pressure on limited supply, and potential patient harm.
Simultaneous pharmacokinetic modeling of unbound and total darunavir with ritonavir in adolescents: a substudy of the SMILE trial
Authors: Abdalla Seef , Compagnucci Alexandra , Riault Yoann , Chan Man K. , Bamford Alasdair , Nolan Aoife , Ramos José T. , Constant Valentin , Nguyen Thao-Nguyen , Zheng Yi , Tréluyer Jean-Marc , Froelicher-Bournaud Léo , Neveux Nathalie , Saidi Yacine , Cressey Tim R. , Hirt Déborah ,   on behalf of the SMILE study group
Published: December 2023

ABSTRACT

Darunavir (DRV) is an HIV protease inhibitor commonly used as part of antiretroviral treatment regimens globally for children and adolescents. It requires a pharmacological booster, such as ritonavir (RTV) or cobicistat. To better understand the pharmacokinetics (PK) of DRV in this younger population and the importance of the RTV boosting effect, a population PK substudy was conducted within SMILE trial, where the maintenance of HIV suppression with once daily integrate inhibitor + darunavir/ritonavir in children and adolescents is evaluated. A joint population PK model that simultaneously used total DRV, unbound DRV, and total RTV concentrations was developed. Competitive and non-competitive models were examined to define RTV’s influence on DRV pharmacokinetics. Linear and non-linear equations were tested to assess DRV protein binding. A total of 443 plasma samples from 152 adolescents were included in this analysis. Darunavir PK was best described by a one-compartment model first-order absorption and elimination. The influence of RTV on DRV pharmacokinetics was best characterized by ritonavir area under the curve on DRV clearance using a power function. The association of non-linear and linear equations was used to describe DRV protein binding to alpha-1 glycoprotein and albumin, respectively. In our population, simulations indicate that 86.8% of total and unbound DRV trough concentrations were above 0.55 mg/L [10 times protein binding-adjusted EC
50
for wild-type (WT) HIV-1] and 0.0243 mg/L (10 times EC
90
for WT HIV-1) targets, respectively. Predictions were also in agreement with observed outcomes from adults receiving 800/100 mg DRV/r once a day. Administration of 800/100 mg of DRV/r once daily provides satisfactory concentrations and exposures for adolescents aged 12 years and older.
The
Mycobacterium tuberculosis
MmpL3 inhibitor MSU-43085 is active in a mouse model of infection
Authors: Williams John T. , Giletto Matthew , Haiderer Elizabeth R. , Aleiwi Bilal , Krieger-Burke Teresa , Ellsworth Edmund , Abramovitch Robert B. 
Published: December 2023

ABSTRACT

Addressing drug resistance in
Mycobacterium tuberculosis
(Mtb) requires the development of new drugs with new targets. We previously identified 13 MmpL3 inhibitors from a screen of a small library of Mtb growth inhibitors. In this report, we describe the biological activities of a set of HC2099 analogs active against Mtb
in vitro
, intracellular Mtb, as well as
M. abscessus
and
M. avium
. Pharmacokinetic (PK) studies identified MSU-43085 as orally bioavailable with a short half-life. High dosing (100 mg/kg) saturates clearance processes, enabling efficacy studies. The results of an
in vivo
efficacy study found that MSU-43085 was active against Mtb in an acute murine TB infection model but lacked activity in a chronic murine TB infection model. The results of this study serve as a proof of concept for this series and support further optimizations of the HC2099 series of MmpL3 inhibitors.

IMPORTANCE

MmpL3 is a protein that is required for the survival of bacteria that cause tuberculosis (TB) and nontuberculous mycobacterial (NTM) infections. This report describes the discovery and characterization of a new small molecule, MSU-43085, that targets MmpL3 and is a potent inhibitor of
Mycobacterium tuberculosis
(Mtb) and
M. abscessus
survival. MSU-43085 is shown to be orally bioavailable and efficacious in an acute model of Mtb infection. However, the analog is inactive against Mtb in chronically infected mice. Pharmacokinetic and metabolite identification studies identified
in vivo
metabolism of MSU-43085, leading to a short half-life in treated mice. These proof-of-concept studies will guide further development of the MSU-43085 series for the treatment of TB or NTM infections.
Exploring disease-related and treatment-related issues and concerns experienced by adults with spondyloarthritis, inflammatory bowel disease and psoriasis to identify unmet needs: a qualitative clinical concept mapping study
Authors: Stisen Zara R , Skougaard Marie , Christensen Katrine Risager , Ainsworth Mark Andrew , Hansen Rebekka Lund , Thomsen Simon Francis , Mogensen Mette , Dreyer Lene , Kristensen Lars Erik , Jørgensen Tanja Schjødt 
Published: December 2023

ObjectivesExploring patients’ perspectives for significant factors of relevance in living with a chronic disease is important to discover unmet needs and challenges. The primary objective of this study was to explore disease-related and treatment-related issues and concerns experienced by adults with spondyloarthropathies (SpA) and associated diseases. As a secondary objective, we wanted to explore whether these factors were generic or disease dependent.DesignWe used group concept mapping (GCM), a validated qualitative method, to identify disease-related and treatment-related issues and concerns. Participants generated statements in the GCM workshops and organised them into clusters to develop concepts. Furthermore, participants rated each statement for importance from 1: ‘not important at all’ to 5: ‘of great importance’.SettingParticipants were recruited during routine care at the outpatient clinic at the hospitals in the period from May 2018 to July 2022.ParticipantsEligible participants were adults ≥18 years and diagnosed with axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), psoriasis (PsO) or inflammatory bowel disease —split into Crohn’s disease (CD) and ulcerative colitis (UC).Results52 patients participated in the 11 workshops divided into groups according to their diagnosis. They created a total of 1275 statements that generated 10 AxSpA concepts, 7 PsA concepts, 7 PsO concepts, 10 CD concepts and 11 UC concepts. The highest rated concepts within each disease group were: AxSpA, ‘lack of understanding/to be heard and seen by healthcare professionals’ (mean rating 4.0); PsA, ‘medication (effects and side effects)’ (mean rating 3.8); PsO, ‘social and psychological problems, the shame’ (mean rating 4.0); CD, ‘positive attitudes’ (mean rating 4.3) and UC; ‘take responsibility and control over your life’ (mean rating 4.0).ConclusionPeople with SpA and associated diseases largely agree on which concepts describe their disease-related and treatment-related issues and concerns with a few of them being more disease-specific.