bluuebunny/crossref_metadata_2025 huggingface dataset:
Milliarcsecond localization of the hyperactive repeating FRB 20220912A
Authors: Hewitt Danté M , Bhandari Shivani , Marcote Benito , Hessels Jason W T , Nimmo Kenzie , Kirsten Franz , Bach Uwe , Bezrukovs Vladislavs , Bhardwaj Mohit , Blaauw Richard , Bray Justin D , Buttaccio Salvatore , Corongiu Alessandro , Gawroński Marcin P , Giroletti Marcello , Keimpema Aard , Maccaferri Giuseppe M , Paragi Zsolt , Trudu Matteo , Snelders Mark P , Venturi Tiziana , Wang Na , Williams-Baldwin David R A , Wrigley Nicholas H , Yang Jun , Yuan Jianping P
Published: March 2024

We present very long-baseline interferometry (VLBI) observations of the hyperactive repeating FRB 20220912A using the European VLBI Network (EVN) outside of regular observing sessions (EVN-Lite). We detected 150 bursts from FRB 20220912A over two observing epochs in 2022 October. Combining the burst data allows us to localize FRB 20220912A to a precision of a few milliarcseconds, corresponding to a transverse scale of less than 10 pc at the distance of the source. This precise localization shows that FRB 20220912A lies closer to the centre of its host galaxy than previously found, although still significantly offset from the host galaxy’s nucleus. On arcsecond scales, FRB 20220912A is coincident with a persistent continuum radio source known from archival observations; however, we find no compact persistent emission on milliarcsecond scales. The 5σ upper limit on the presence of such a compact persistent radio source is 120 μJy, corresponding to a luminosity limit of (D/362.4 Mpc)$^2\, 1.8\times 10^{28}$erg s−1 Hz−1. The persistent radio emission is thus likely to be from star formation in the host galaxy. This is in contrast to some other active FRBs, such as FRB 20121102A and FRB 20190520B.
Comparing emission- and absorption-based gas-phase metallicities in GRB host galaxies at z = 2−4 using JWST
Authors: Schady P , Yates R M , Christensen L , De Cia A , Rossi A , D’Elia V , Heintz K E , Jakobsson P , Laskar T , Levan A , Salvaterra R , Starling R L C , Tanvir N R , Thöne C C , Vergani S , Wiersema K , Arabsalmani M , Chen H -W , De Pasquale M , Fruchter A , Fynbo J P U , García-Benito R , Gompertz B , Hartmann D , Kouveliotou C , Milvang-Jensen B , Palazzi E , Perley D A , Piranomonte S , Pugliese G , Savaglio S , Sbarufatti B , Schulze S , Tagliaferri G , Postigo A de Ugarte , Watson D , Wiseman P
Published: March 2024

Much of what is known of the chemical composition of the universe is based on emission line spectra from star-forming galaxies. Emission-based inferences are, nevertheless, model-dependent and they are dominated by light from luminous star-forming regions. An alternative and sensitive probe of the metallicity of galaxies is through absorption lines imprinted on the luminous afterglow spectra of long gamma ray bursts (GRBs) from neutral material within their host galaxy. We present results from a JWST/NIRSpec programme to investigate for the first time the relation between the metallicity of neutral gas probed in absorption by GRB afterglows and the metallicity of the star-forming regions for the same host galaxy sample. Using an initial sample of eight GRB host galaxies at z = 2.1–4.7, we find a tight relation between absorption and emission line metallicities when using the recently proposed $\hat{R}$ metallicity diagnostic (±0.2 dex). This agreement implies a relatively chemically homogeneous multiphase interstellar medium and indicates that absorption and emission line probes can be directly compared. However, the relation is less clear when using other diagnostics, such as R23 and R3. We also find possible evidence of an elevated N/O ratio in the host galaxy of GRB 090323 at z = 4.7, consistent with what has been seen in other z > 4 galaxies. Ultimate confirmation of an enhanced N/O ratio and of the relation between absorption and emission line metallicities will require a more direct determination of the emission line metallicity via the detection of temperature-sensitive auroral lines in our GRB host galaxy sample.
Cigarette Prices and Smoking Experimentation Among Zimbabwean Children: A Survival Analysis of the 2014 Global Youth Tobacco Survey
Authors: Dare Chengetai , Boachie Micheal Kofi , van Walbeek Corné
Published: March 2024

Introduction

Zimbabwe has a smoking prevalence of 11.7% among the adult population (15 years and older). Thus, in the absence of effective tobacco control measures, the economic burden of tobacco use will be aggravated, especially considering the increasing tobacco industry activity in the country. Increasing cigarette prices is one possible strategy to reduce tobacco consumption. This study seeks to examine the relationship between cigarette prices and smoking experimentation among children in Zimbabwe, thereby expanding the evidence base for the likely impact of excise taxes on cigarette demand in low- and middle-income countries.

Aims and Methods

A survival analysis using the Zimbabwe 2014 Global Youth Tobacco Survey data.

Results

A 10% increase in the price of cigarettes reduces the probability of experimenting with smoking by 9%. Also, children are more likely to experiment with smoking if they have a smoking brother or father who smokes, or see teachers who smoke. The likelihood of experimenting with smoking is higher among boys than girls and is positively associated with age.

Conclusions

There is strong evidence that increasing excise taxes can play an effective role in discouraging children from experimenting with cigarette smoking. Considering the relatively low excise tax burden in Zimbabwe, the government should consider substantially increasing the excise tax burden.

Implications

With the number of smokers in low- and middle-income countries expected to increase as the industry intensively expands its market by targeting the youth, increasing excise taxes will play a significant role in preventing children from initiating smoking and help those who are already using tobacco to quit. An increase in the excise tax increases the retail price of tobacco products, making them less affordable, and reduces the demand for them.
Genetic Susceptibility to Astrovirus Diarrhea in Bangladeshi Infants
Authors: Chen Laura , Munday Rebecca M , Haque Rashidul , Duchen Dylan , Nayak Uma , Korpe Poonum , Mentzer Alexander J , Kirkpatrick Beth D , Wojcik Genevieve L , Petri William A , Duggal Priya
Published: March 2024

Background

Astroviral infections commonly cause acute nonbacterial gastroenteritis in children globally. However, these infections often go undiagnosed outside of research settings. There is no treatment available for astrovirus, and Astroviridae strain diversity presents a challenge to potential vaccine development.

Methods

To address our hypothesis that host genetic risk factors are associated with astrovirus disease susceptibility, we performed a genome-wide association study of astrovirus infection in the first year of life from children enrolled in 2 Bangladeshi birth cohorts.

Results

We identified a novel region on chromosome 1 near the loricrin gene (LOR) associated with astrovirus diarrheal infection (rs75437404; meta-analysis P = 8.82 × 10−9; A allele odds ratio, 2.71) and on chromosome 10 near the prolactin releasing hormone receptor gene (PRLHR) (rs75935441; meta-analysis P = 1.33 × 10−8; C allele odds ratio, 4.17). The prolactin-releasing peptide has been shown to influence feeding patterns and energy balance in mice. In addition, several single-nucleotide polymorphisms in the chromosome 1 locus have previously been associated with expression of innate immune system genes PGLYRP4, S100A9, and S100A12.

Conclusions

This study identified 2 significant host genetic regions that may influence astrovirus diarrhea susceptibility and should be considered in further studies.
The World Health Organization as an engine of ideational robustness
Authors: Denis Jean-Louis , Foucault Gaëlle , Larouche Pierre , Régis Catherine , Cohen Miriam , Girard Marie-Andrée
Published: March 2024

The paper focuses on the role of the World Health Organization (WHO) in promoting a healthy world population as a generative and robust idea within health policy. The WHO’s health credo transcends national boundaries to promote health globally. It is embedded in norms, values, and standards promulgated by the organization and contributes in shaping the health responses of national governments. Ideational robustness refers to the ability of the WHO to adapt its health credo to changing contexts and circumstances, thus promoting the legitimacy of an international health order. Disturbances, including the Covid-19 pandemic, test the credo’s robustness, forcing the WHO to constantly work at reframing ideas to adapt to political forces and competing logics that structure the field of international health. Empirically, the paper is based on an historical analysis of the evolution of the health credo of the WHO since its inception. Qualitative content analysis of secondary sources, such as policy documents, explores how ideational work performed by WHO leaders impacts on the organization’s position and legitimacy. Ideational robustness appears to be largely influenced by leadership vision, preexisting organizational structure, and the political economy of international health. Ideational robustness appears as a powerful yet insufficient ingredient of policy success.
Impact of a resilience-building energy management intervention for people with systemic sclerosis: a mixed methods study
Authors: Chen Yen T , Harper Alexandra E , Phanhdone Tiffany , Alore Mary , Hicks Sheri , Pape Adam , Jay Gina M , Bolde Shannen , Feldpausch Jennie , Guetterman Timothy C , Khanna Dinesh , Murphy Susan L
Published: March 2024

Objectives

People with SSc often experience fatigue, which significantly affects daily life functioning and quality of life. We aimed to explore participants’ experiences of a peer health–coached resilience-building energy management to enhance well-being (RENEW) intervention on symptoms and well-being and to use mixed methods to compare how SSc duration influenced the experiences of participants who had clinically significant fatigue improvement vs those who did not.

Methods

Semi-structured interviews were conducted with 21 participants from the parent clinical trial randomized to the RENEW intervention. Data were analysed using the rigorous and accelerated data reduction technique combined with thematic content analysis. A mixed methods approach used a joint display to identify themes related to the impact of SSc duration on fatigue improvement status. Participants were categorized into short/improvement, short/limited improvement, long/improvement, and long/limited improvement.

Results

Our team generated four themes: participant and peer health–coach relationship, physical and psychological well-being improvement, need for a tailored approach and easy program access through technology. Mixed methods analysis revealed that, regardless of SSc duration, participants with improved fatigue reported increasing self-awareness of SSc-related symptoms and learning coping strategies to manage fatigue. Participants in the short/improvement group reported preferences for slower pacing of the program and pairing with a coach with similar symptom severity. Participants in the long/limited improvement group sought SSc-specific symptom management information.

Conclusion

Incorporating peer health coaches and technology is beneficial for self-management interventions for people with SSc. Future tailoring of RENEW based on SSc duration and symptom severity is needed.

Clinical trial registration number

clinicatrials.gov, NCT04908943.
Methacrylated gelatin and platelet-rich plasma based hydrogels promote regeneration of critical-sized bone defects
Authors: Lian Shichao , Mu Zhiyu , Yuan Zhengchao , Shafiq Muhammad , Mo Xiumei , Mu Weidong
Published: March 2024

Physiological repair of large-sized bone defects requires instructive scaffolds with appropriate mechanical properties, biocompatibility, biodegradability, vasculogenic ability and osteo-inductivity. The objective of this study was to fabricate in situ injectable hydrogels using platelet-rich plasma (PRP)-loaded gelatin methacrylate (GM) and employ them for the regeneration of large-sized bone defects. We performed various biological assays as well as assessed the mechanical properties of GM@PRP hydrogels alongside evaluating the release kinetics of growth factors (GFs) from hydrogels. The GM@PRP hydrogels manifested sufficient mechanical properties to support the filling of the tissue defects. For biofunction assay, the GM@PRP hydrogels significantly improved cell migration and angiogenesis. Especially, transcriptome RNA sequencing of human umbilical vein endothelial cells and bone marrow-derived stem cells were performed to delineate vascularization and biomineralization abilities of GM@PRP hydrogels. The GM@PRP hydrogels were subcutaneously implanted in rats for up to 4 weeks for preliminary biocompatibility followed by their transplantation into a tibial defect model for up to 8 weeks in rats. Tibial defects treated with GM@PRP hydrogels manifested significant bone regeneration as well as angiogenesis, biomineralization, and collagen deposition. Based on the biocompatibility and biological function of GM@PRP hydrogels, a new strategy is provided for the regenerative repair of large-size bone defects.
A Dynamic Theory of Lending Standards
Authors: Fishman Michael J , Parker Jonathan A , Straub Ludwig
Published: March 2024

We analyze a dynamic credit market where banks choose lending standards, modeled as costly effort to screen out bad borrowers. Tighter standards worsen the borrower pool, increasing banks’ incentives to employ tight standards in the future. This dynamic complementarity in lending standards can amplify and prolong downturns, decreasing lending and increasing credit spreads. Because lending standards have negative externalities, the market can converge to a steady state with inefficiently tight lending standards. We discuss the role of optimal policy to avoid this outcome as well as the impact of balance sheet costs on lending standards.
Osteoporosis is associated with anti-topoisomerase I positivity and glucocorticoids use in patients with systemic sclerosis
Authors: Midol Charles , Wiebe Edgar , Siegert Elise , Huscher Dörte , Béhal Hélène , Launay David , Hachulla Eric , Matteson Eric L , Buttgereit Frank , Sobanski Vincent
Published: March 2024

Objectives

Patients with systemic sclerosis (SSc) are at increased risk for osteoporosis (OP) and associated fragility fractures. This study aimed to identify underlying risk factors for these conditions in patients with SSc.

Methods

This cross-sectional study was based on a large prospective cohort of patients with SSc using retrospectively collected bone health data. OP was defined as the presence of a T-score below -2.5 at the femoral neck or lumbar spine, a previous major osteoporotic fracture, or the prescription of anti-osteoporotic therapy.

Results

A total of 485 patients fulfilling the ACR/EULAR 2013 diagnostic criteria for SSc, followed in the Lille University Hospital, were included in the study. The prevalence of OP was 23%; fragility fractures occurred in 18% of patients. OP was associated with higher age, diffuse cutaneous subset, interstitial lung disease (ILD), anti-topoisomerase I positivity, treatment with glucocorticoids (GC) and DMARDs in univariable analysis. Multivariable analysis indicated that higher age (OR 1.06 [95%CI 1.04–1.08]), anti-topoisomerase I antibody positivity (OR 2.22 [1.18–4.16]) and treatment with GC (OR 4.48 [2.42–8.26]) were significantly and independently associated with OP.

Conclusion

Our study shows that OP risk in patients with SSc is determined by age, disease-related factors such as diffuse cutaneous subset, ILD and anti-topoisomerase I antibody positivity, but also treatment with GC independently of other factors.
Radioprotection issues in uraniferous minerals collections with reference to an actual case
Authors: Cupparo Ilaria , Fedeli Luca , Doria Sandra , Moggi Cecchi Vanni , Gori Cesare
Published: March 2024

Our work investigated the radioprotection implications associated with the possession of a collection of uraniferous minerals. Considering different scenarios, we developed (and applied to an actual collection) specific formulas for radiation doses evaluation. We discussed the shielding necessary to reduce the gamma irradiation down to the required values. A mathematical model was developed to estimate the minimum air flow rate to reduce the radon air concentration below the reference values. The radiation risks associated to the handling of single specimens was also addressed, including hand skin irradiation and shielding capabilities of surgical lead gloves. Finally, we discussed the radiation risks associated to the exhibition of a single specimen. The results, compared to the safety standards of the EU Directive 13/59, show that the exhibition of uraniferous samples with activity of a few MBq do not need specific radioprotection requirements nor for the involved personnel nor for visitors.
Compulsive sexual behavior disorder in an inpatient sample with substance use disorder
Authors: Golder Sarah , Walter Bertram , Bengesser Isabel , Kramer Dietmar , Muhl Christian , Tahmassebi Nadja , Storz Florian , Markert Charlotte , Stark Rudolf
Published: March 2024

Background

Several studies indicate that compulsive sexual behavior disorder (CSBD) shares core elements with substance use disorder (SUD). These findings support the assumption of common mechanisms in addiction, which may lead to a higher tendency in patients with SUD to have comorbid CSBD. Nevertheless, this relationship between CSBD and SUD is poorly understood to date.

Aim

This study aimed to compare the prevalence of CSBD and its subtype pornography use disorder (PUD) between a SUD group and a matched control group. Herein, we aimed to test whether patients with SUD are more likely to have a comorbid CSBD/PUD. We further hypothesized that a higher CSBD/PUD prevalence in patients with SUD is accompanied by more pronounced CSBD- and PUD-related personal characteristics.

Methods

We assessed CSBD, PUD, and related personal characteristics in an inpatient SUD sample (N = 92) and a healthy control sample matched by age, gender, and educational level.

Outcomes

Primary outcomes were the diagnoses of CSBD/PUD as assessed by questionnaires. CSBD/PUD-related personal characteristics were the early onset of problematic pornography consumption, relationship status as a single person, a high sexual motivation, a high level of time spent watching pornography, and a high degree of problematic pornography consumption (Problematic Pornography Consumption Scale, short version).

Results

There was no significant difference between groups regarding CSBD prevalence (SUD sample, 3.3%; control sample, 7.6%) and PUD prevalence (SUD sample, 2.2%; control sample, 6.5%). We found relationship status as a single person and the sexual motivation dimension of importance of sex to be the only CSBD-related personal characteristics that were more pronounced in the SUD sample than the matched control group.

Clinical Implications

Results indicate no higher tendency for patients with SUD to develop comorbid CSBD/PUD, yet important vulnerabilities (eg, emotional dysregulation) should be considered when treating addictive disorder to prevent possible symptom displacement.

Strengths and Limitations

A strength of the study is that we compared a sample of patients with SUD with a matched control sample and used an instrument based on ICD-11 criteria for CSBD. Possible limitations are significant differences between the groups because of the restrictions in an inpatient clinic that may have influenced responses (eg, roommates) and that the control group was not screened for SUD. Therefore, the results should be interpreted with some caution.

Conclusion

We found no evidence of an overcomorbidity of SUD and CSBD/PUD. However, a higher rate of vulnerability factors for CSBD/PUD in the SUD sample might suggest some similarities between SUD and CSBD/PUD.
Safety assessment of transgenic maize CC-2 by 90-day feeding study in Sprague-Dawley rats
Authors: Chen Chen , Shi Lili , Mao Hongmei , Han Chao , Zhao Jinpeng , Zhuo Qin , Li Yan
Published: March 2024

Objective

The purpose of this study was to assess the safety of transgenic maize CC-2 through a 90-day feeding study in Sprague-Dawley rats.

Methods

Transgenic maize CC-2 and its parental counterpart maize Zhengdan 958 were respectively incorporated into diets at levels of 70%, 35% or 17.5% (w/w) and were administrated to rats (n = 10/sex/group) for 90 days. An additional control group of rats (n = 10/sex/group) were fed with the AIN93 breeding diet. All formulated diets were nutritionally balanced.

Results

There was no death and obvious toxic symptom in all rats. Food consumption, body weight, total food consumption rate, hematology, urinalysis, organ weight and organ coefficient were comparable between transgenic groups and the corresponding dose parental groups. There were significant differences of food consumption rate on some timepoint between high dose transgenic group and high dose parental group; male rats in high dose transgenic group showed significantly higher ALT/AST than high dose parental group on the middle or end of the experiment; but the differences showed no biological significance. There were no significant differences of other serum biochemistry parameters and pathological changes.

Conclusion

The results in this study demonstrated that the transgenic maize CC-2 didn't cause any related toxicity in rats.
Metformin switches cell death modes to soothe the apical periodontitis via ZBP1
Authors: Liu Hui , Liu Yu‐Xuan , Fan Wei , Fan Bing
Published: March 2024

Apical periodontitis (AP) is a disease caused by pathogenic microorganisms and featured with the degradation of periapical hard tissue. Our recent research showed the crucial role of Z‐DNA binding protein 1 (ZBP1)‐mediated necroptosis and apoptosis in the pathogenesis of AP. However, the specific regulatory mechanisms of ZBP1 in AP are not fully elucidated. It was found that metformin has a regulatory role in cell necroptosis and apoptosis. But whether and how metformin regulates necroptosis and apoptosis through the ZBP1 in the context of AP remains unknown. This study provided evidence that lipopolysaccharide (LPS) promotes the synthesis of left‐handed Z‐nucleic acids (Z‐NA), which in turn activates ZBP1. Knockout of Zbp1 by CRISPR/Cas9 technology significantly reduced LPS‐induced necroptosis and apoptosis in vitro. By using Zbp1‐knockout mice, periapical bone destruction was alleviated. Moreover, type I interferon induced the expression of interferon‐stimulated genes (ISGs), which serve as a major source of Z‐NA. In addition, the RNA‐editing enzyme Adenosine Deaminase RNA specific 1 (ADAR1) prevented the accumulation of endogenous Z‐NA. Meanwhile, metformin suppressed the ZBP1‐mediated necroptosis by inhibiting the expression of ZBP1 and the accumulation of ISGs. Metformin also promoted mitochondrial apoptosis, which is critical for the elimination of intracellular bacterial infection. The enhanced apoptosis further promoted the healing of infected apical bone tissues. In summary, these results demonstrated that the recognition of Z‐NA by ZBP1 plays an important role in AP pathogenesis. Metformin suppressed ZBP1‐mediated necroptosis and promoted apoptosis, thereby contributing to the soothing of inflammation and bone healing in AP.
Does Epidural Corticosteroid Application During Spinal Surgery Reduce Postoperative Pain?: An Adjunct to Multimodal Analgesia
Authors: Song Hyun , Edwards Charles , Curto Ryan , Perez Alejandro , Cruess Cailin , Schell Adam , Park Justin
Published: March 2024

Study Design:

A prospective, randomized, placebo-controlled, double-blinded study.

Objective:

To examine the effect of intraoperative epidural administration of Depo-Medrol on postoperative back pain and radiculitis symptoms in patients undergoing Transforaminal Lumbar Interbody Fusion (TLIF).

Summary of Background Data:

Postoperative pain is commonly experienced by patients undergoing spinal fusion surgery. Adequate management of intense pain is necessary to encourage early ambulation, increase patient satisfaction, and limit opioid consumption. Intraoperative steroid application has been shown to improve postoperative pain in patients undergoing lumbar decompression surgeries. There have been no studies examining the effect of epidural steroids on both back pain and radicular pain in patients undergoing TLIF.

Method:

In all, 151 patients underwent TLIF surgery using rh-BMP2 with 3 surgeons at a single institution. Of those, 116 remained in the study and were included in the final analysis. Based on a 1:1 randomization, a collagen sponge saturated with either Saline (1 cc) or Depo-Medrol (40 mg/1 cc) was placed at the annulotomy site on the TLIF level. Follow-up occurred on postoperative days 1, 2, 3, 7, and postoperative months 1, 2, and 3. Lumbar radiculopathy was measured by a modified symptom- and laterality-specific Visual Analog Scale (VAS) regarding the severity of back pain and common radiculopathy symptoms.

Results:

The patients who received Depo-Medrol, compared with those who received saline, experienced significantly less back pain on postoperative days 1, 2, 3, and 7 (P<0.05). There was no significant difference in back pain beyond day 7. Radiculopathy-related symptoms such as leg pain, numbness, tingling, stiffness, and weakness tended to be reduced in the steroid group at most time points.

Conclusion:

This study provides Level 1 evidence that intraoperative application of Depo-Medrol during a TLIF surgery with rh-BMP2 significantly reduces back pain for the first week after TLIF surgery. The use of epidural Depo-Medrol may be a useful adjunct to multimodal analgesia for pain relief in the postoperative period.
Simple blood tests to diagnose compensated advanced chronic liver disease and stratify the risk of clinically significant portal hypertension
Authors: Semmler Georg , Hartl Lukas , Mendoza Yuly Paulin , Simbrunner Benedikt , Jachs Mathias , Balcar Lorenz , Schwarz Michael , Hofer Benedikt Silvester , Fritz Laurenz , Schedlbauer Anna , Stopfer Katharina , Neumayer Daniela , Maurer Jurij , Szymanski Robin , Meyer Elias Laurin , Scheiner Bernhard , Quehenberger Peter , Trauner Michael , Aigner Elmar , Berzigotti Annalisa , Reiberger Thomas , Mandorfer Mattias
Published: March 2024

Background and Aims:

Compensated advanced chronic liver disease (cACLD) identifies patients at risk for clinically significant portal hypertension (CSPH), and thus, for liver-related complications. The limited availability of liver stiffness measurements (LSM) impedes the identification of patients at risk for cACLD/CSPH outside of specialized clinics. We aimed to develop a blood-based algorithm to identify cACLD by fibrosis-4 (FIB-4) and CSPH by von Willebrand factor/platelet count ratio (VITRO).

Approach and Results:

Patients with (suspected) compensated chronic liver disease undergoing FIB-4+LSM were included in the LSM/FIB-4 cohorts from Vienna and Salzburg. The HVPG/VITRO cohorts included patients undergoing HVPG-measurement + VITRO from Vienna and Bern.

LSM/FIB-4–derivation-cohort: We included 6143 patients, of whom 211 (3.4%) developed hepatic decompensation. In all, 1724 (28.1%) had LSM ≥ 10 kPa, which corresponded to FIB-4 ≥ 1.75. Importantly, both LSM (AUROC:0.897 [95% CI:0.865–0.929]) and FIB-4 (AUROC:0.914 [95% CI:0.885–0.944]) were similarly accurate in predicting hepatic decompensation within 3 years. FIB-4 ≥ 1.75 identified patients at risk for first hepatic decompensation (5 y-cumulative incidence:7.6%), while in those <1.75, the risk was negligible (0.3%).

HVPG/VITRO–derivation cohort: 247 patients of whom 202 had cACLD/FIB-4 ≥ 1.75 were included. VITRO exhibited an excellent diagnostic performance for CSPH (AUROC:0.889 [95% CI:0.844–0.934]), similar to LSM (AUROC:0.856 [95% CI:0.801–0.910], p = 0.351) and the ANTICIPATE model (AUROC:0.910 [95% CI:0.869–0.952], p = 0.498). VITRO < 1.0/ ≥ 2.5 ruled-out (sensitivity:100.0%)/ruled-in (specificity:92.4%) CSPH. The diagnostic performance was comparable to the Baveno-VII criteria.

LSM/FIB-4–derivation cohort findings were externally validated in n = 1560 patients, while HVPG/VITRO–derivation-cohort findings were internally (n = 133) and externally (n = 55) validated.

Conclusions:

Simple, broadly available laboratory tests (FIB-4/VITRO) facilitate cACLD detection and CSPH risk stratification in patients with (suspected) liver disease. This blood-based approach is applicable outside of specialized clinics and may promote early intervention.
Boucher-Neuhauser Syndrome: Chorioretinal Changes in a Single Case Over Time
Authors: Adeghate Jennifer O. , Sherman Jerome , Bass Sherry , Liu James , Hufnagel Robert B. , Yannuzzi Lawrence A.
Published: March 2024

Purpose:

To describe chorioretinal changes in a single case of Boucher-Neuhauser Syndrome (BNHS) over 45 years of follow-up. Methods: Retrospective chart review was performed. Color fundus photography from 1977 to 2003 was obtained and digitized. Current fundus photography was obtained with widefield imaging. High-resolution spectral-domain optical coherence tomography (OCT) was performed. Genetic analysis was performed using an inherited retinal disorders panel. Results: Fundus examination demonstrated central chorioretinal atrophy with sclerotic choroidal vessels. Short posterior ciliary arteries became more prominent and tortuous over time. Mid-peripheral atrophy extends to the equator and demonstrates a scalloped pattern with islands of atrophy intervening with areas of normal retina. The far periphery remained minimally affected. High-resolution OCT demonstrated outer retinal atrophy and choriocapillaris loss. Genetic testing showed a homozygous variant for PNPLA6 and a heterozygous variant for TYRP1. Conclusion: Chorioretinal changes in BNHS vary in onset and severity. It is important to diagnose this condition in order to begin timely management of visual and systemic sequelae.
Prevalence of Burn Pit Associated Symptoms Among US Veterans Who Utilize Non-Veteran’s Affairs Private Healthcare
Authors: Conti Michael A. , Bardes James M. , Oury Jeffrey , Goodboy Alan K. , Shin Matt , Wilson Alison
Published: March 2024

Objective

Do the 3.5 million US veterans, who primarily utilize private healthcare, have similar burn pit exposure and disease compared to the VA Burn Pit registry?

Methods

This is an online volunteer survey of Gulf War and Post-9/11 veterans.

Results

Burn pit exposure had significantly higher odds of extremity numbness, aching pain and burning, asthma, chronic obstructive pulmonary disease, interstitial lung disease, constrictive bronchiolitis, pleuritis, and pulmonary fibrosis. Chi-square did not reveal a difference in burn pit exposure and cancer diagnoses.

Conclusions

These data demonstrate increased risk of neurological symptoms associated with burn pit exposure, which are not covered in the 2022 federal Promise to Address Comprehensive Toxics Act. Additional data will allow for the continued review and consideration for future medical benefits.
Personalized circulating tumor DNA monitoring improves recurrence surveillance and management after curative resection of colorectal liver metastases: A prospective cohort study
Authors: Li Yaqi , Xu Jing , Hu Xiang , Chen Yikuan , Liu Fangqi , Chen Yun , Ma Xiaoji , Dong Qiduo , Sun Lei , Mo Shaobo , Zhang Long , He Xingfeng , Tong Shanyou , Wu Huizi , Li Wenhua , Cai Sanjun , Zhu Shida , Pan Qi , Peng Junjie
Published: March 2024

Background:

Approximately 60% of patients with CRLM experience relapse within 2 years after radical resection, previous studies have proven that repeat local treatment (LT) could prolong survival, however, it is difficult to seize the window for LT due to the lack of a high-sensitive surveillance method. In this study, we aim to examine the value of longitudinal circulating tumor DNA (ctDNA) in guiding adjuvant chemotherapy (ACT), optimizing clinical surveillance strategy, and thereby improving CRLM outcomes.

Materials and Methods:

We conducted a prospective clinical trial using a personalized, tumor-informed ctDNA assay to monitor 60 CRLM patients undergoing resection with curative intent. Formalin-fixed paraffin-embedded (FFPE) tumor samples were collected after surgery. Blood samples were collected before surgery, 30 days after surgery (post-OP), and every third month until relapse or up to 2 years.

Results:

A total of 394 plasma samples from 60 eligible patients were analyzed, with a median follow-up time of 31.3 months. Landmark analyses revealed that detectable ctDNA at post-OP (HR, 4.8), post-ACT (HR, 6.0), and end-of-treatment (EOT) (HR, 5.6) were associated with higher recurrence risk (P < 0.001). Post-OP ctDNA positivity served as the only independent prognostic marker in the multivariant analysis (HR, 5.1; P < 0.001). Longitudinal ctDNA analysis identified relapsed patients at both sensitivity and specificity of 100%. Most (75%) patients were found with radiological relapse within 6 months after the first detectable ctDNA with a median lead time of 3.5 months. In relapsed patients, 73.2% had oligometastatic disease and 61% were liver-restricted, of which 72.0% received repeat LTs, and 60.0% achieved a secondary no evidence of disease (NED) status.

Conclusions:

Longitudinal ctDNA monitoring assists in early prediction of relapse, and thereby improves survival of CRLM patients by increased secondary resection rate and secondary NED rate.
Development of interpretable machine learning models for prediction of acute kidney injury after noncardiac surgery: a retrospective cohort study
Authors: Sun Rao , Li Shiyong , Wei Yuna , Hu Liu , Xu Qiaoqiao , Zhan Gaofeng , Yan Xu , He Yuqin , Wang Yao , Li Xinhua , Luo Ailin , Zhou Zhiqiang
Published: March 2024

Background:

Early identification of patients at high risk of postoperative acute kidney injury (AKI) can facilitate the development of preventive approaches. This study aimed to develop prediction models for postoperative AKI in noncardiac surgery using machine learning algorithms. We also evaluated the predictive performance of models that included only preoperative variables or only important predictors.

Materials and methods:

Adult patients undergoing noncardiac surgery were retrospectively included in the study (76,457 patients in the discovery cohort and 11,910 patients in the validation cohort). AKI was determined using the KDIGO criteria. The prediction model was developed using 87 variables (56 preoperative variables and 31 intraoperative variables). A variety of machine learning algorithms were employed to develop the model, including logistic regression, random forest, extreme gradient boosting, and gradient boosting decision trees (GBDT). The performance of different models was compared using the area under the receiver operating characteristic curve (AUROC). Shapley Additive Explanations (SHAP) analysis was employed for model interpretation.

Results:

The patients in the discovery cohort had a median age of 52 years (IQR: 42-61 y), and 1179 patients (1.5%) developed AKI after surgery. The GBDT algorithm showed the best predictive performance using all available variables, or only preoperative variables. The AUROCs were 0.849 (95% CI, 0.835-0.863) and 0.828 (95% CI, 0.813-0.843), respectively. The SHAP analysis showed that age, surgical duration, preoperative serum creatinine and gamma-glutamyltransferase, as well as American Society of Anesthesiologists physical status III were the most important five features. When gradually reducing the features, the AUROCs decreased from 0.852 (including the top 40 features) to 0.839 (including the top 10 features). In the validation cohort, we observed a similar pattern regarding the models’ predictive performance.

Conclusions:

The machine learning models we developed had satisfactory predictive performance for identifying high-risk postoperative AKI patients. Further, we found that model performance was only slightly affected when only preoperative variables or only the most important predictive features were included.
Prognostic implication of residual inflammatory trajectories in acute type I aortic dissection: dual-center prospective cohort study
Authors: Liu Hong , Diao Yi-fei , Shao Yong feng , Qian Si-chong , Zeng Zhi-hua , Fan Guo-liang , Ma Lu-yao , Zhang Hong-jia ,   on the behalf of the Additive Anti-inflammatory Action for Aortopathy & Arteriopathy (5A) Investigators
Published: March 2024

Background:

Peripheral platelet-white blood cell ratio (PWR) integrating systemic inflammatory and coagulopathic pathways is a key residual inflammatory measurement in the management of acute DeBakey type I aortic dissection (AAD); however, trajectories of PWR in AAD is poorly defined.

Methods:

Two AAD cohorts were included in two cardiovascular centers (2020–2022) if patients underwent emergency total arch replacement with frozen elephant trunk implantation. PWR data were collected over time at baseline and five consecutive days after surgery. Trajectory patterns of PWR were determined using the latent class mixed modelling (LCMM). Cox regression was used to determine independent risk factors. By adding PWR Trajectory, a user-friendly nomogram was developed for predicting mortality after surgery.

Results:

Two hundred forty-six patients with AAD were included with a median follow-up of 26 (IRQ 20–37) months. Three trajectories of PWR were identified [cluster α 45(18.3%), β105 (42.7%), and γ 96 (39.0%)]. Cluster γ was associated with higher risk of mortality at follow-up (crude HR, 3.763; 95% CI: 1.126–12.574; P=0.031) than cluster α. By the addition of PWR trajectories, an inflammatory nomogram, composed of age, hemoglobin, estimated glomerular filtration rate, and cardiopulmonary time was developed and internally validated, with adequate discrimination [the area under the receiver-operating characteristic curve 0.765, 95% CI: 0.660–0.869)], calibration, and clinical utility.

Conclusion:

Based on PWR trajectories, three distinct clusters were identified with short-term outcomes, and longitudinal residual inflammatory shed some light to individualize treatment strategies for AAD.
The Impact of Market Factors on Meaningful Use of Electronic Health Records Among Primary Care Providers
Authors: Alexandre Pierre K. , Monestime Judith P. , Alexandre Kessie
Published: March 2024

Background:

Using federal funds from the 2009 Health Information Technology for Economic and Clinical Health Act, the Centers for Medicare and Medicaid Services funded the 2011–2021 Medicaid electronic health record (EHR) incentive programs throughout the country.

Objective:

Identify the market factors associated with Meaningful Use (MU) of EHRs after primary care providers (PCPs) enrolled in the Florida—EHR incentives program through Adopting, Improving, or Upgrading (AIU) an EHR technology.

Research Design:

Retrospective cohort study using 2011–2018 program records for 8464 Medicaid providers.

Main Outcome:

MU achievement after first-year incentives.

Independent Variables:

The resource dependence theory and the information uncertainty perspective were used to generate key-independent variables, including the county’s rurality, educational attainment, poverty, health maintenance organization penetration, and number of PCPs per capita.

Analytical Approach:

All the county rates were converted into 3 dichotomous measures corresponding to high, medium, and low terciles. Descriptive and bivariate statistics were calculated. A generalized hierarchical linear model was used because MU data were clustered at the county level (level 2) and measured at the practice level (level 1).

Results:

Overall, 41.9% of Florida Medicaid providers achieved MU after receiving first-year incentives. Rurality was positively associated with MU (P<0.001). Significant differences in MU achievements were obtained when we compared the “high” terciles with the “low” terciles for poverty rates (P=0.002), health maintenance organization penetration rates (P=0.02), and number of PCPs per capita (P=0.01). These relationships were negative.

Conclusions:

Policy makers and health care managers should not ignore the contribution of market factors in EHR adoption.
Optimal systemic therapy in men with low-volume prostate cancer
Authors: Saxena Akshat , Andrews Jack , Bryce Alan Haruo , Riaz Irbaz Bin
Published: March 2024

Purpose of review

Low-volume prostate cancer is an established prognostic category of metastatic hormone-sensitive prostate cancer. However, the term is often loosely used to reflect the low burden of disease across different prostate cancer states. This review explores the definitions of low-volume prostate cancer, biology, and current evidence for treatment. We also explore future directions, including the impact of advanced imaging modalities, particularly prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scans, on refining patient subgroups and treatment strategies for patients with low-volume prostate cancer.

Recent findings

Recent investigations have attempted to redefine low-volume disease, incorporating factors beyond metastatic burden. Advanced imaging, especially PSMA PET, offers enhanced accuracy in detecting metastases, potentially challenging the conventional definition of low volume. The prognosis and treatment of low-volume prostate cancer may vary by the timing of metastatic presentation. Biomarker-directed consolidative therapy, metastases-directed therapy, and de-escalation of systemic therapies will be increasingly important, especially in patients with metachronous low-volume disease.

In the absence of validated biomarkers, the management of low-volume prostate cancer as defined by CHAARTED criteria may be guided by the timing of metastatic presentation. For metachronous low-volume disease, we recommend novel hormonal therapy (NHT) doublets with or without consolidative metastasis-directed therapy (MDT), and for synchronous low-volume disease, NHT doublets with or without consolidative MDT and prostate-directed radiation. Docetaxel triplets may be a reasonable alternative in some patients with synchronous presentation. There is no clear role of docetaxel doublets in patients with low-volume disease. In the future, a small subset of low-volume diseases with oligometastases selected by genomics and advanced imaging like PSMA PET may achieve long-term remission with MDT with no systemic therapy.
Prevention, diagnosis, and treatment of urolithiasis in geriatric patients - differences, similarities and caveats in comparison to the general population
Authors: Schrag Tarek A. , Diarra Danielle , Veser Julian
Published: March 2024

Purpose of review

Purpose of the review is to address management and prevention of urolithiasis in elderly patients examining the dynamic interplay between general measures, dietary adjustments, lifestyle modifications, and targeted pharmacological and/ or surgical interventions. The goal is to provide understanding of the evolving strategies required for effective urolithiasis prevention in the geriatric population.

Recent findings

Age-specific diagnostic considerations are necessary because urolithiasis in the elderly population is characterized by bigger stones, greater peri-operative risks, and heightened symptom severity. When comorbidities are present, conservative treatments – especially analgesia – provide difficulties. Surgical procedures prove to be safe and effective, with complication rates and practical application comparable to younger cohorts. Prevention approaches that include lifestyle changes and the investigation of novel pharmaceutical options such as sodium-dependent glucose co-transporter 2 (SGLT-2)-inhibitors are promising in the management of urolithiasis in the elderly population.

Our review offers a thorough investigation of urolithiasis in the elderly population, elucidating distinct clinical manifestations, complex diagnostic issues, and treatment implications. The safety and effectiveness of ureteroscopy in older patients, as well as the possible prophylactic function of SGLT-2-I, offer crucial insights for clinicians. Subsequent studies are necessary to enhance age-specific therapies, addressing the distinct obstacles presented by urolithiasis in the elderly population within this rapidly growing demographic.
Delayed Rewarming Thrombocytopenia: A Suggested Preventable and Treatable Cause of Rewarming Deaths
Authors: Cohen Ian J.
Published: March 2024

The lack of a consensus of accepted prognostic factors in hypothermia suggests an additional factor has been overlooked. Delayed rewarming thrombocytopenia (DRT) is a novel candidate for such a role. At body temperature, platelets undergoing a first stage of aggregation are capable of progression to a second irreversible stage of aggregation. However, we have shown that the second stage of aggregation does not occur below 32°C and that this causes the first stage to become augmented (first-stage platelet hyperaggregation). In aggregometer studies performed below 32°C, the use of quantities of ADP that cause a marked first-stage hyperaggregation can cause an augmented second-stage activation of the platelets during rewarming (second-stage platelet hyperaggregation). In vivo, after 24 hours of hypothermia, platelets on rewarming seem to undergo second-stage hyperaggregation, from ADP released from erythrocytes, leading to life-threatening thrombocytopenia. This hyperaggregation is avoidable if heparin is given before the hypothermia or if aspirin, alcohol or platelet transfusion is given during the hypothermia before reaching 32°C on rewarming. Many of the open questions existing in this field are explained by DRT. Prevention and treatment of DRT could be of significant value in preventing rewarming deaths and some cases of rescue collapse. Performing platelet counts during rewarming will demonstrate potentially fatal thrombocytopenia and enable treatment with platelet infusions aspirin or alcohol.
Acute Myeloid Leukemia and Next-Generation Sequencing Panels for Diagnosis: A Comprehensive Review
Authors: Chaudhary Spandan , Chaudhary Pooja , Ahmad Firoz , Arora Neeraj
Published: March 2024

Acute myeloid leukemia (AML) is a genetically heterogeneous clonal disorder characterized by the accumulation of acquired somatic genetic alterations in hematopoietic progenitor cells, which alter the normal mechanisms of self-renewal, proliferation, and differentiation. Due to significant technological advancements in sequencing technologies in the last 2 decades, classification and prognostic scoring of AML has been refined, and multiple guidelines are now available for the same. The authors have tried to summarize, latest guidelines for AML diagnosis, important markers associated, epigenetics markers, various AML fusions and their importance, etc. Review of literature suggests lack of study or comprehensive information about current NGS panels for AML diagnosis, genes and fusions covered, their technical know-how, etc. To solve this issue, the authors have tried to present detailed review about currently in use next-generation sequencing myeloid panels and their offerings.