bluuebunny/crossref_metadata_2025 huggingface dataset:
Tentative detection of titanium oxide in the atmosphere of WASP-69 b with a 4m ground-based telescope
Authors: Ouyang Qinglin , Wang Wei , Zhai Meng , Chen Guo , Rojo Patricio , Liu Yujuan , Zhao Fei , Huang Jia-Sheng , Zhao Gang
Published: March 2023

Transiting planets provide unique opportunities for the atmospheric characterization of exoplanets as they can reveal composition and the temperature structures at the day–night terminator regions in planetary atmospheres, and help understand the atmospheric process and formation environments of exoplanets. Here, we present the optical transmission spectroscopic study of an inflated Saturn-mass planet WASP-69 b, obtained by the 4m ground-based telescope Southern Astrophysical Research Telescope (SOAR). We obtain spectroscopic transit light curves in 20 passbands from 502 to 890 nm, and fit them using Gaussian processes and an analytical transit model to obtain independent transit depths for each. The derived transmission spectrum of WASP-69 b shows a slope with absorption depth increasing towards blue wavelengths, indicating a Rayleigh scattering in the atmosphere consistent with previous works. The retrieval analysis yields a tentative detection of TiO absorption feature in the transmission spectrum. We present the first results from the SOAR telescope to characterize exoplanetary atmospheres proving its capability and precision for hot Jupiters around bright stars in an area dominated by results from large ground-based telescopes or space telescopes.
A sub-Neptune transiting the young field star HD 18599  at 40 pc
Authors: de Leon J P , Livingston J H , Jenkins J S , Vines J I , Wittenmyer R A , Clark J T , Winn J I M , Addison B , Ballard S , Bayliss D , Beichman C , Benneke B , Berardo D A , Bowler B P , Brown T , Bryant E M , Christiansen J , Ciardi D , Collins K A , Collins K I , Crossfield I , Deming D , Dragomir D , Dressing C D , Fukui A , Gan T , Giacalone S , Gill S , Gorjian V , González Alvarez E , Hesse K , Horner J , Howell S B , Jenkins J M , Kane S R , Kendall A , Kielkopf J F , Kreidberg L , Latham D W , Liu H , Lund M B , Matson R , Matthews E , Mengel M W , Morales F , Mori M , Narita N , Nishiumi T , Okumura J , Plavchan P , Quinn S , Rabus M , Ricker G , Rudat A , Schlieder J , Schwarz R P , Seager S , Shporer A , Smith A M S , Stassun K , Tamura M , Tan T G , Tinney C , Vanderspek R , Werner M W , West R G , Wright D , Zhang H , Zhou G
Published: March 2023

Transiting exoplanets orbiting young nearby stars are ideal laboratories for testing theories of planet formation and evolution. However, to date only a handful of stars with age <1 Gyr have been found to host transiting exoplanets. Here we present the discovery and validation of a sub-Neptune around HD 18599 , a young (300 Myr), nearby (d = 40 pc) K star. We validate the transiting planet candidate as a bona fide planet using data from the TESS , Spitzer , and Gaia  missions, ground-based photometry from IRSF , LCO , PEST , and NGTS , speckle imaging from Gemini, and spectroscopy from CHIRON , NRES , FEROS , and Minerva-Australis . The planet has an orbital period of 4.13 d , and a radius of 2.7 R⊕ . The RV data yields a 3-σ mass upper limit of 30.5 M⊕  which is explained by either a massive companion or the large observed jitter typical for a young star. The brightness of the host star (V∼9 mag) makes it conducive to detailed characterization via Doppler mass measurement which will provide a rare view into the interior structure of young planets.
A dual-purpose polymerase engineered for direct sequencing of pseudouridine and queuosine
Authors: Huber Luisa B , Kaur Navpreet , Henkel Melanie , Marchand Virginie , Motorin Yuri , Ehrenhofer-Murray Ann E , Marx Andreas
Published: March 2023

More than 170 posttranscriptional RNA modifications are so far known on both coding and noncoding RNA species. Within this group, pseudouridine (Ψ) and queuosine (Q) represent conserved RNA modifications with fundamental functional roles in regulating translation. Current detection methods of these modifications, which both are reverse transcription (RT)-silent, are mostly based on the chemical treatment of RNA prior to analysis. To overcome the drawbacks associated with indirect detection strategies, we have engineered an RT-active DNA polymerase variant called RT-KTq I614Y that produces error RT signatures specific for Ψ or Q without prior chemical treatment of the RNA samples. Combining this polymerase with next-generation sequencing techniques allows the direct identification of Ψ and Q sites of untreated RNA samples using a single enzymatic tool.
Rolling circle extension-assisted loop-mediated isothermal amplification (Rol-LAMP) method for locus-specific and visible detection of RNA N6-methyladenosine
Authors: Li Jiexin , Zhou Jiawang , Xia Yan , Rui Yalan , Yang Xianyuan , Xie Guoyou , Jiang Guanmin , Wang Hongsheng
Published: March 2023

N6-methyladenosine (m6A) is the most prevalent RNA modification in eukaryotic mRNAs. Currently available detection methods for locus-specific m6A marks rely on RT-qPCR, radioactive methods, or high-throughput sequencing. Here, we develop a non-qPCR, ultrasensitive, isothermal, and naked-eye visible method for m6A detection based on rolling circle amplification (RCA) and loop-mediated isothermal amplification (LAMP), named m6A-Rol-LAMP, to verify putative m6A sites in transcripts obtained from the high-throughput data. When padlock probes hybridize to the potential m6A sites on targets, they are converted to circular form by DNA ligase in the absence of m6A modification, while m6A modification hinders the sealing of padlock probes. Subsequently, Bst DNA polymerase-mediated RCA and LAMP allow the amplification of the circular padlock probe to achieve the locus-specific detection of m6A. Following optimization and validation, m6A-Rol-LAMP can ultra-sensitively and quantitatively determine the existence of m6A modification on a specific target site as low as 100 amol under isothermal conditions. Detections of m6A can be performed on rRNA, mRNA, lincRNA, lncRNA and pre-miRNA from biological samples with naked-eye observations after dye incubation. Together, we provide a powerful tool for locus-specific detection of m6A, which can simply, quickly, sensitively, specifically, and visually determine putative m6A modification on RNA.
ATXN3 controls DNA replication and transcription by regulating chromatin structure
Authors: Hernández-Carralero Esperanza , Cabrera Elisa , Rodríguez-Torres Gara , Hernández-Reyes Yeray , Singh Abhay N , Santa-María Cristina , Fernández-Justel José Miguel , Janssens Roel C , Marteijn Jurgen A , Evert Bernd O , Mailand Niels , Gómez María , Ramadan Kristijan , Smits Veronique A J , Freire Raimundo
Published: March 2023

The deubiquitinating enzyme Ataxin-3 (ATXN3) contains a polyglutamine (PolyQ) region, the expansion of which causes spinocerebellar ataxia type-3 (SCA3). ATXN3 has multiple functions, such as regulating transcription or controlling genomic stability after DNA damage. Here we report the role of ATXN3 in chromatin organization during unperturbed conditions, in a catalytic-independent manner. The lack of ATXN3 leads to abnormalities in nuclear and nucleolar morphology, alters DNA replication timing and increases transcription. Additionally, indicators of more open chromatin, such as increased mobility of histone H1, changes in epigenetic marks and higher sensitivity to micrococcal nuclease digestion were detected in the absence of ATXN3. Interestingly, the effects observed in cells lacking ATXN3 are epistatic to the inhibition or lack of the histone deacetylase 3 (HDAC3), an interaction partner of ATXN3. The absence of ATXN3 decreases the recruitment of endogenous HDAC3 to the chromatin, as well as the HDAC3 nuclear/cytoplasm ratio after HDAC3 overexpression, suggesting that ATXN3 controls the subcellular localization of HDAC3. Importantly, the overexpression of a PolyQ-expanded version of ATXN3 behaves as a null mutant, altering DNA replication parameters, epigenetic marks and the subcellular distribution of HDAC3, giving new insights into the molecular basis of the disease.
Locating, tracing and sequencing multiple expanded genetic letters in complex DNA context via a bridge-base approach
Authors: Wang Honglei , Zhu Wuyuan , Wang Chao , Li Xiaohuan , Wang Luying , Huo Bianbian , Mei Hui , Zhu Anlian , Zhang Guisheng , Li Lingjun
Published: March 2023

A panel of unnatural base pairs is developed to expand genetic alphabets. One or more unnatural base pairs (UBPs) can be inserted to enlarge the capacity, diversity, and functionality of canonical DNA, so monitoring the multiple-UBPs-containing DNA by simple and convenient approaches is essential. Herein, we report a bridge-base approach to repurpose the capability of determining TPT3-NaM UBPs. The success of this approach depends on the design of isoTAT that can simultaneously pair with NaM and G as a bridge base, as well as the discovering of the transformation of NaM to A in absence of its complementary base. TPT3-NaM can be transferred to C–G or A–T by simple PCR assays with high read-through ratios and low sequence-dependent properties, permitting for the first time to dually locate the multiple sites of TPT3-NaM pairs. Then we show the unprecedented capacity of this approach to trace accurate changes and retention ratios of multiple TPT3-NaM UPBs during in vivo replications. In addition, the method can also be applied to identify multiple-site DNA lesions, transferring TPT3-NaM makers to different natural bases. Taken together, our work presents the first general and convenient approach capable of locating, tracing, and sequencing site- and number-unlimited TPT3-NaM pairs.
Influence of Tobacco Variety and Curing on Free Radical Production in Cigarette Smoke
Authors: Bitzer Zachary T , Mocniak Leanne E , Trushin Neil , Smith Michael , Richie John P
Published: March 2023

Introduction

Cigarette smoke contains highly reactive free radicals thought to play an important role in tobacco smoke-induced harm. Previously, large variations in free radical and toxicant output have been observed in commercial cigarettes. These variations are likely because of cigarette design features (paper, filter, and additives), tobacco variety (burley, bright, oriental, etc.), and tobacco curing methods (air, sun, flue, and fire). Previous reports show that tobacco varieties and curing methods influence the production of tobacco smoke constituents like the tobacco-specific carcinogen nicotine-derived nitrosamine ketone (NNK).

Aims and Methods

We evaluated free radical, nicotine, and NNK production in cigarette smoke from cigarettes produced with 15 different types of tobacco. Gas-phase free radicals were captured by spin trapping with N-tert-butyl-α-phenylnitrone and particulate-phase radicals were captured on a Cambridge Filter pad (CFP). Both types of radicals were analyzed using electron paramagnetic resonance spectroscopy. Nicotine and NNK were extracted from the CFP and analyzed by gas chromatography flame ionization detection and liquid chromatography-mass spectrometry, respectively.

Results

Gas-phase radicals varied nearly 8-fold among tobacco types with Saint James Perique tobacco producing the highest levels (42 ± 7 nmol/g) and Canadian Virginia tobacco-producing the lowest levels (5 ± 2 nmol/g). Nicotine and NNK levels in smoke varied 14-fold and 192-fold, respectively, by type. Gas-phase free radicals were highly correlated with NNK levels (r = 0.92, p < .0001) and appeared to be most impacted by tobacco curing method.

Conclusions

Altogether, these data suggest that tobacco types used in cigarette production may serve as a target for regulation to reduce harm from cigarette smoking.

Implications

Variations in cigarette free radical and NNK levels vary based on the tobacco variety and curing method. Reducing the ratio of high-producing free radical and NNK tobacco types offer a potential tool for regulators and producers looking to reduce toxicant output from cigarettes.
Unpublished clinical trials of common rheumatic diseases
Authors: Pedersen Connor , Tai Shannon , Valley Erin , Henry Kathryn , Duarte-García Alí , Singla Shikha , Putman Michael
Published: March 2023

Objectives

Randomized controlled trials (RCTs) provide high-quality evidence for treatment efficacy, but many RCTs remain unpublished. The objective of this study was to describe the proportion of unpublished RCTs in five rheumatic diseases and to identify factors associated with publication.

Methods

Registered RCTs for five rheumatic diseases (SLE, vasculitis, spondyloarthritis, SS and PsA) with over 30 months since study completion were identified using ClinicalTrials.gov. Index publications were identified by NCT ID numbers and structured text searches of publication databases. The results of unpublished studies were identified in abstracts and press releases; reasons for non-publication were assessed by surveying corresponding authors.

Results

Out of 203 studies that met eligibility criteria, 17.2% remained unpublished, representing data from 4281 trial participants. Higher proportions of published trials were phase 3 RCTs (57.1% vs 28.6% unpublished, P < 0.05) or had a positive primary outcome measure (64.9% vs 25.7% unpublished, P < 0.001). In a multivariable Cox proportional hazards model, a positive outcome was independently associated with publication (hazard ratio 1.55; 95% CI: 1.09, 2.22). Corresponding authors of 10 unpublished trials cited ongoing preparation of the manuscript (50.0%), sponsor/funder issues (40.0%) and unimportant/negative result (20.0%) as reasons for lack of publication.

Conclusions

Nearly one in five RCTs in rheumatology remain unpublished 2 years after trial completion, and publication is associated with positive primary outcome measures. Efforts to encourage universal publication of rheumatology RCTs and reanalysis of previously unpublished trials should be undertaken.
Discovery of a new species and host record of Holophryxus Richardson, 1905 (Isopoda: Dajidae) from the central Arctic: a model of enhanced descriptive standards for epicaridean isopods
Authors: Huys Rony , Savchenko Alexandra S , Kosobokova Ksenia N
Published: March 2023

Adult isopods of the family Dajidae are exclusively ectoparasitic, typically infecting pelagic malacostracan crustaceans. It is assumed that their life cycle involves free-living and parasitic phases, with planktonic copepods acting as intermediate hosts. Most generic diagnoses proposed in the family have traditionally been incomplete, containing imperfect or misleading information, and characters whose states were wrongly assessed. In an attempt to analyse this state of affairs comprehensively, a taxonomic review and updated diagnosis of the species-rich genus Holophryxus are presented. Both traditional and novel morphological characters are critically assessed, forming the basis for updated differential diagnoses of all currently valid species. The presence of previously ignored sensory structures on the body and pereopods is highlighted and its significance discussed. Holophryxus citriformis sp. nov. is recorded on the common shrimp, Hymenodora glacialis, at 4300 m depth in the central Arctic Ocean. Its description, based on light microscopy and confocal laser scanning microscopy analysis of the female holotype, containing a dwarf male inside its marsupium, is proposed as a model of enhanced descriptive standards required in future morphological research on epicaridean isopods. Definitive host records and geographical distributions of all Holophryxus species are summarized as well as records of larval epicaridean stages associated with copepod hosts.
Competency-Based Medical Education in a Norm-Referenced World: A Root Cause Analysis of Challenges to the Competency-Based Paradigm in Medical School
Authors: Ryan Michael S. , Lomis Kimberly D. , Deiorio Nicole M. , Cutrer William B. , Pusic Martin V. , Caretta-Weyer Holly A.
Published: March 2023

Competency-based medical education (CBME) requires a criterion-referenced approach to assessment. However, despite best efforts to advance CBME, there remains an implicit, and at times, explicit, demand for norm-referencing, particularly at the junction of undergraduate medical education (UME) and graduate medical education (GME). In this manuscript, the authors perform a root cause analysis to determine the underlying reasons for continued norm-referencing in the context of the movement toward CBME. The root cause analysis consisted of 2 processes: (1) identification of potential causes and effects organized into a fishbone diagram and (2) identification of the 5 whys. The fishbone diagram identified 2 primary drivers: the false notion that measures such as grades are truly objective and the importance of different incentives for different key constituents. From these drivers, the importance of norm-referencing for residency selection was identified as a critical component. Exploration of the 5 whys further detailed the reasons for continuation of norm-referenced grading to facilitate selection, including the need for efficient screening in residency selection, dependence upon rank-order lists, perception that there is a best outcome to the match, lack of trust between residency programs and medical schools, and inadequate resources to support progression of trainees. Based on these findings, the authors argue that the implied purpose of assessment in UME is primarily stratification for residency selection. Because stratification requires comparison, a norm-referenced approach is needed. To advance CBME, the authors recommend reconsideration of the approach to assessment in UME to maintain the purpose of selection while also advancing the purpose of rendering a competency decision. Changing the approach will require a collaboration between national organizations, accrediting bodies, GME programs, UME programs, students, and patients/societies. Details are provided regarding the specific approaches required of each key constituent group.
A Regional Analysis of Low Back Pain Treatments in the Military Health System
Authors: Lurie Jon D. , Leggett Christopher G. , Skinner Jonathan , Carragee Eugene , Austin Andrea M. , Luan William Patrick
Published: March 2023

Study Design.

Claims-based analysis of cohorts of TRICARE Prime beneficiaries.

Objective.

To compare rates of utilization of 5 LBP treatments (physical therapy, manual therapy, behavioral therapies, opioid and benzodiazepine prescription) across catchment areas and assess their association with resolution of LBP.

Summary of Background.

Guidelines support focusing on nonpharmacologic management for LBP and reducing opioid use. Little is known about patterns of care for LBP across the Military Health System.

Methods.

Incident LBP diagnoses were identified data using International Classification of Diseases Ninth Revision before October 2015 and Tenth Revision after October 2015; beneficiaries with “red flag” diagnoses and those stationed overseas, eligible for Medicare, or having other health insurance were excluded. After exclusions, there were 159,027 patients remained in the final analytic cohort across 73 catchment areas. Treatment was defined by catchment level rates of treatment to avoid confounding by indication at the individual level; the primary outcome was resolution of LBP defined as absence of administrative claims for LBP during the 6-12 month period following the index diagnosis.

Results.

Adjusted rates of opioid prescribing across catchment areas ranged from 15% to 28%, physical therapy from 17% to 39%, and manual therapy from 5% to 26%. Multivariate logistic regression models showed a negative and marginally significant association between opioid prescriptions and LBP resolution (odds ratio 0.97, 95% C.I. 0.93 to 1.00; P=0.051) but no significant association with physical therapy, manual therapy, benzodiazepine prescription, or behavioral therapies. When the analysis was restricted to the subset of only active-duty beneficiaries, there was a stronger negative association between opioid prescription and LBP resolution (odds ratio 0.93, 95% C.I. 0.89 to 0.97).

Conclusion.

We found substantial variability across catchment areas within TRICARE for the treatment of LBP. Higher rates of opioid prescription were associated with worse outcomes.
Quantifying the Contribution of Lower Limb Compensation to Upright Posture
Authors: Lafage Renaud , Duvvuri Priya , Elysee Jonathan , Diebo Bassel , Bess Shay , Burton Douglas , Daniels Alan , Gupta Munish , Hostin Richard , Kebaish Khaled , Kelly Michael , Kim Han Jo , Klineberg Eric , Lenke Lawrence , Lewis Stephen , Ames Christopher , Passias Peter , Protopsaltis Themistocles , Shaffrey Christopher , Smith Justin S. , Schwab Frank , Lafage Virginie ,   On behalf of the International Spine Study Group
Published: March 2023

Study Design.

This is a multicenter, prospective cohort study.

Objective.

This study tests the hypothesis that the elimination of lower limb compensation in patients with adult spinal deformity (ASD) will significantly increase the magnitude of sagittal malalignment.

Summary of Background Data.

ASD affects a significant proportion of the elderly population, impairing functional sagittal alignment and inhibiting the overall quality of life. To counteract these effects, patients with ASD use their spine, pelvis, and lower limbs to create a compensatory posture that allows for standing and mobility. However, the degree to which each of the hips, knees, and ankles contributes to these compensatory mechanisms has yet to be determined.

Methods.

Patients undergoing corrective surgery for ASD were included if they met at least one of the following criteria: complex surgical procedure, geriatric deformity surgery, or severe radiographic deformity. Preoperative full-body x-rays were evaluated, and age and pelvic incidence -adjusted normative values were used to model spine alignment based upon three positions: compensated (all lower extremity compensatory mechanisms maintained), partially compensated (removal of ankle dorsiflexion and knee flexion, with maintained hip extension), and uncompensated (ankle, knee, and hip compensation set to the age and pelvic incidence norms).

Results.

A total of 288 patients were included (mean age 60 yr, 70.5% females). As the model transitioned from the compensated to uncompensated position, the initial posterior translation of the pelvis decreased significantly to an anterior translation versus the ankle (P.Shift: 30 to −7.6 mm). This was associated with a decrease in pelvic retroversion (pelvic tilt: 24.1–16.1), hip extension (SFA: 203–200), knee flexion (knee angle: 5.5–0.4), and ankle dorsiflexion (ankle angle: 5.3–3.7). As a result, the anterior malalignment of the trunk significantly increased: sagittal vertical axis (65–120 mm) and G-SVA (C7-ankle from 36 to 127 mm).

Conclusions.

Removal of lower limbs compensation revealed an unsustainable truncal malalignment with two-fold greater SVA.
Can Pelvic Incidence Change After Lumbo-Pelvic Fixation for Adult Spine Deformity, and Would the Change be Affected by the Type of Pelvic Fixation?
Authors: Rizkallah Maroun , Shen Jesse , Phan Philippe , Al-Shakfa Fidaa , Kamel Yousef , Liu Jia , Shedid Daniel , Yuh Sung Joo , Boubez Ghassan , Wang Zhi
Published: March 2023

Study design.

Retrospective review.

Objective.

To assess the change in pelvic incidence (PI) after lumbo-pelvic fixation and the differential impact of the type of pelvic fixation: S2-alar-iliac screws (S2AI) versus Iliac screws (IS) on postoperative PI.

Summary of background data.

Recent studies suggest that changes occur to the previously assumed fixed PI after spino-pelvic fixation.

Methods.

Adult spine deformity (ASD) patients who underwent spino-pelvic fixation with≥4 levels of fusion were included. Preoperative and postoperative PI, lumbar lordosis (LL), thoracic kyphosis, pelvic tilt, sacral slope, PI-LL mismatch, and the Sagittal Vertical Axis (SVA) were analyzed on EOS imaging. A significant PI change was established at≥6°. Patients were categorized based on the type of pelvic fixation (S2AI vs. IS).

Results.

One-hundred-forty-nine patients were included. Of these, 77(52%) had a>6° change in their PI postoperatively. In patients with high preoperative PI (>60°), 62% had a significant PI change compared with 33% of patients with normal PI (40°–60°) and 53% in patients with low PI (<40°; P=0.01). PI was likely to decrease in patients with high baseline PI (>60°) and to increase in patients with low baseline PI (<40°). Patients with a significant PI change had a higher PI-LL. Patients in the S2AI group (n=99) and those in the IS group (n=50) were comparable at baseline. In the S2AI group, 50 (51%) patients had>6° change in their PI compared with 27(54%) patients in the IS group(P=0.65). In both groups, patients with high preoperative PI were more prone to significant postoperative changes (P=0.02 in IS, P=0.01 in S2AI).

Conclusion.

PI changed significantly in 50% of patients postoperatively, especially in those with high/low preoperative PI and those with severe baseline sagittal imbalance. This occurs similarly in patients with S2AI and those with IS screws. Surgeons should keep in mind these anticipated changes while planning ideal LL, as this impacts postoperative PI-LL mismatch.

Level of Evidence.

4.
Novel magnetic resonance KTRANS measurement of blood-brain barrier permeability correlated with covert HE
Authors: Chaganti Joga , Zeng Georgia , Tun Nway , Lockart Ian , Abdelshaheed Christina , Cysique Lucette , Montagnese Sara , Brew Bruce J , Danta Mark
Published: March 2023

Background:

Using dynamic contrast-enhanced (DCE) MR perfusion and MR spectroscopy this study aimed to characterize the blood-brain barrier permeability and metabolite changes in patients with cirrhosis and without covert HE.

Methods:

Covert HE was defined using psychometric HE score (PHES). The participants were stratified into 3 groups: cirrhosis with covert HE (CHE) (PHES<-4); cirrhosis without HE (NHE) (PHES≥-4); and healthy controls (HC). Dynamic contrast-enhanced MRI and MRS were performed to assess KTRANS, a metric derivative of blood-brain barrier disruption, and metabolite parameters. Statistical analysis was performed using IBM SPSS (v25).

Results:

A total of 40 participants (mean age 63 y; male 71%) were recruited as follows: CHE (n=17); NHE (n=13); and HC (n=10). The KTRANS measurement in the frontoparietal cortex demonstrated increased blood-brain barrier permeability, where KTRANS was 0.01±0.02 versus 0.005±0.005 versus 0.004±0.002 in CHE, NHE, and HC patients, respectively (p = 0.032 comparing all 3 groups). Relative to HC with a value of 0.28, the parietal glutamine/creatine (Gln/Cr) ratio was significantly higher in both CHE 1.12 mmoL (p < 0.001); and NHE 0.49 (p = 0.04). Lower PHES scores correlated with higher glutamine/Cr (Gln/Cr) (r=-0.6; p < 0.001) and lower myo-inositol/Cr (mI/Cr) (r=0.6; p < 0.001) and lower choline/Cr (Cho/Cr) (r=0.47; p = 0.004).

Conclusion:

The dynamic contrast-enhanced MRI KTRANS measurement revealed increased blood-brain barrier permeability in the frontoparietal cortex. The MRS identified a specific metabolite signature with increased glutamine, reduced myo-inositol, and choline, which correlated with CHE in this region. The MRS changes were identifiable in the NHE cohort.
Early paracentesis is associated with better prognosis compared with late or no-paracentesis in hospitalized veterans with cirrhosis and ascites
Authors: Patel Nilang , Silvey Scott , O’Leary Jacqueline G. , Morgan Timothy , Patton Heather , Rogal Shari S. , Bajaj Jasmohan S.
Published: March 2023

Guidelines recommend that all hospitalized patients with cirrhosis and ascites receive an early (<24 h from admission) paracentesis. However, national data are not available regarding compliance with and the consequences of this quality metric. We used the national Veterans Administration Corporate Data Warehouse and validated International Classification of Disease codes to evaluate the rate and subsequent outcomes of early, late, and no paracentesis for patients with cirrhosis and ascites during their first inpatient admission between 2016 and 2019. Of 10,237 patients admitted with a diagnosis of cirrhosis with ascites, 14.3% received an early paracentesis, 7.3% received a late paracentesis, and 78.4% never received a paracentesis. In multivariable modeling, compared with an early paracentesis: both late paracentesis and no-paracentesis were significantly associated with increased odds of acute kidney injury (AKI) development [OR: 2.16 (95% CI, 1.59–2.94) and 1.34 (1.09–1.66), respectively]; intensive care unit (ICU) transfer [OR: 2.43 (1.71–3.47) and 2.01 (1.53–2.69), respectively] and inpatient death [OR: 1.54 (1.03–2.29) and 1.42 (1.05–1.93), respectively]. Nationally, only 14.3% of admitted veterans with cirrhosis and ascites received the American Association for the Study of Liver Diseases (AASLD) guideline-recommended diagnostic paracentesis within 24 hours of admission. Failure to complete early paracentesis was associated with higher odds of AKI, ICU transfer, and inpatient mortality. Universal and site-specific barriers to this quality metric should be evaluated and addressed to improve patient outcomes.
Favorable changes in the survival of patients with cancers of digestive organs – Poland, 2000–2019
Authors: Caetano dos Santos Florentino Luciano , Michalek Irmina Maria , Wojciechowska Urszula , Didkowska Joanna
Published: March 2023

Objective

This study aimed to estimate cancer survival in Poland in 2000–2019 for malignant neoplasms of digestive organs, namely for cancer of the esophagus, stomach, small intestine, colorectum, anus, liver and intrahepatic bile ducts, gallbladder, other and unspecified parts of the biliary tract and pancreas.

Methods

Data were obtained from the Polish National Cancer Registry and age-standardized 5- and 10-year net survival was estimated.

Results

Overall, 534 872 cases were included in the study, reflecting a total of 3 178 934 years of life lost within the 2 decades of observation. Colorectal cancer represented both the highest 5-year and 10-year age-standardized net survival (5-year net survival: 53.0%, 95% confidence interval, 52.8–53.3%; 10-year net survival: 48.6%, 48.2–48.9%). Between 2000–2004 and 2015–2019, the highest statistically significant increase in age-standardized 5-year survival was noted for the small intestine at +18.3 percentual points (P < 0.001). The male-female incidence ratio disparity was the highest for esophageal (4:1) and anus and gallbladder cancer (1:2). The highest standardized mortality ratios were observed in esophageal and pancreatic cancer (23.9, 23.5–24.2 and 26.4, 26.2–26.6, respectively). Overall, death hazard ratios were lower for women (hazard ratio = 0.89, 0.88–0.89, P < 0.001).

Conclusion

In most cancers, there were statistically significant differences between sexes for all studied metrics. In the last 2 decades, survival for digestive organ cancers has increased considerably. Special attention should be given to liver, esophagus, pancreatic cancer survival and the disparities between sexes.
A Comparison of Clinical and Cost Outcomes After Pancreatectomies at a Safety-net Hospital using a National Registry
Authors: Pather Keouna , Mobley Erin M. , Guerrier Christina , Esma Rhemar , Awad Ziad T.
Published: March 2023

Background:

Our institution (UFHJ) meets the criteria of both a large, specialized medical center (LSCMC) and a safety-net hospital (AEH). Our aim is to compare pancreatectomy outcomes at UFHJ against other LSCMCs, AEHs, and against institutions that meet criteria for both LSCMC and AEH. In addition, we sought to evaluate differences between LSCMCs and AEHs.

Materials and Methods:

Pancreatectomies for pancreatic cancer were queried from the Vizient Clinical Data Base (2018 to 2020). Clinical and cost outcomes were compared between UFHJ and LSCMCs, AEHs, and a combined group, respectively. Indices >1 indicated the observed value was greater than the expected national benchmark value.

Results:

The mean number of pancreatectomy cases performed per institution in the LSCMC group was 12.15, 11.73, and 14.31 in 2018, 2019, and 2020, respectively. At AEHs, 25.33, 24.56, and 26.37 mean cases per institution per year, respectively. In the combined group of both LSCMCs and AEHs, 8.10, 7.60, and 7.22 mean cases, respectively. At UFHJ, 17, 34, and 39 cases were performed each year, respectively. Length of stay index decreased below national benchmarks at UFHJ (1.08 to 0.82), LSCMCs (0.91 to 0.85), and AEHs (0.94 to 0.93), with an increasing case mix index at UFHJ (3.33 to 4.20) from 2018 to 2020. In contrast, length of stay index increased in the combined group (1.14 to 1.18) and overall was the lowest at LSCMCs (0.89). Mortality index declined at UFHJ (5.07 to 0.00) below national benchmarks compared with LSCMCs (1.23 to 1.29), AEHs (1.19 to 1.45), and the combined group (1.92 to 1.99), and was significantly different between all groups (P<0.001). Thirty-day re-admissions were lower at UFHJ (6.25% to 10.26%) compared with LSCMCs (17.62% to 16.83%) and AEHs (18.93% to 15.51%), and significantly lower at AEHs compared with LSCMCs (P<0.001). Notably, 30-day re-admissions were lower at AEHs compared with LSCMCs (P<0.001) and declined over time and were the lowest in the combined group in 2020 (17.72% to 9.52%). Direct cost index at UFHJ declined (1.00 to 0.67) below the benchmark compared with LSCMCs (0.90 to 0.93), AEHs (1.02 to 1.04), and the combined group (1.02 to 1.10). When comparing LSCMCs and AEHs, there were no significant differences between direct cost percentages (P=0.56); however, the direct cost index was significantly lower at LSCMCs.

Conclusion:

Pancreatectomy outcomes at our institution have improved over time exceeding national benchmarks and often were significant to LSCMCs, AEHs, and a combined comparator group. In addition, AEHs were able to maintain good quality care when compared with LSCMCs. This study highlights the role that safety-net hospitals can provide high-quality care to a medically vulnerable patient population in the presence of high-case volume.
Comparison of motor function recovery and brain changes in intracerebral hemorrhagic and ischemic rats with similar brain damage
Authors: Tamakoshi Keigo , Meguro Kota , Takahashi Yuri , Oshimi Ryu , Iwasaki Natsuka
Published: March 2023

In this study, we compared the mechanisms of brain recovery in intracerebral hemorrhage and ischemia, focusing on synapses, glial cells, and dopamine expression, which are considered fundamental for neural recovery after stroke. Male Wistar rats were divided into intracerebral hemorrhage, ischemia, and sham surgery (SHAM) groups. The intracerebral hemorrhage group was injected with a collagenase solution, the ischemia group was injected with an endothelin-1 solution, and the SHAM group was injected with physiological saline. The motor function of these rats was evaluated using a rotarod test on days 7, 14, 21, and 28 post-surgery. On postoperative day 29, lesion volume was analyzed using Nissl staining. In addition, the protein expression levels of NeuN, GFAP, tyrosine hydroxylase, and PSD95 were analyzed in the striatum and motor cortex. There was no significant difference between the ischemia and intracerebral hemorrhage groups in terms of lesion volume in the striatum; however, the motor recovery of the intracerebral hemorrhage group occurred more rapidly than that of the ischemia group, and the intracerebral hemorrhage group exhibited higher GFAP protein expression in the motor cortex. The rapid motor recovery in intracerebral hemorrhage rats relative to that in ischemia rats may be associated with changes in astrocytes in brain regions remote from the injury site.
Disparity in Breast Cancer Care: Current State of Access to Screening, Genetic Testing, Oncofertility, and Reconstruction
Authors: Crown Angelena , Fazeli Soudabeh , Kurian Allison W , Ochoa Daniela A , Joseph Kathie-Ann
Published: March 2023

Breast cancer is the most common cancer diagnosed in women, accounting for an estimated 30% of all new women cancer diagnoses in 2022. Advances in breast cancer treatment have reduced the mortality rates over the past 25 years by up to 34% but not all groups have benefitted equally from these improvements. These disparities span the continuum of care from screening to the receipt of guideline-concordant therapy and survivorship. At the 2022 American College of Surgeons Clinical Congress, a panel session was dedicated to educating and discussing methods of addressing these disparities in a coordinated manner. While there are multilevel solutions to address these disparities, this paper focuses on screening, genetic testing, reconstruction, and oncofertility.
Prediction-based uncertainty quantification for exchangeable sequences
Authors: Fortini Sandra , Petrone Sonia
Published: March 2023

Prediction has a central role in the foundations of Bayesian statistics and is now the main focus in many areas of machine learning, in contrast to the more classical focus on inference. We discuss that, in the basic setting of random sampling—that is, in the Bayesian approach, exchangeability—uncertainty expressed by the posterior distribution and credible intervals can indeed be understood in terms of prediction. The posterior law on the unknown distribution is centred on the predictive distribution and we prove that it is marginally asymptotically Gaussian with variance depending on thepredictive updates, i.e. on how the predictive rule incorporates information as new observations become available. This allows to obtain asymptotic credible intervals only based on the predictive rule (without having to specify the model and the prior law), sheds light on frequentist coverage as related to the predictive learning rule, and, we believe, opens a new perspective towards a notion ofpredictive efficiencythat seems to call for further research.

This article is part of the theme issue ‘Bayesian inference: challenges, perspectives, and prospects’.
The Bayesian lens and Bayesian blinkers
Authors: Stephens Matthew
Published: March 2023

I discuss the benefits of looking through the ‘Bayesian lens’ (seeking a Bayesian interpretation of ostensibly non-Bayesian methods), and the dangers of wearing ‘Bayesian blinkers’ (eschewing non-Bayesian methods as a matter of philosophical principle). I hope that the ideas may be useful to scientists trying to understand widely used statistical methods (including confidence intervals andp-values), as well as teachers of statistics and practitioners who wish to avoid the mistake of overemphasizing philosophy at the expense of practical matters.

This article is part of the theme issue ‘Bayesian inference: challenges, perspectives, and prospects’.
Differentiable samplers for deep latent variable models
Authors: Doucet Arnaud , Moulines Eric , Thin Achille
Published: March 2023

Latent variable models are a popular class of models in statistics. Combined with neural networks to improve their expressivity, the resulting deep latent variable models have also found numerous applications in machine learning. A drawback of these models is that their likelihood function is intractable so approximations have to be carried out to perform inference. A standard approach consists of maximizing instead an evidence lower bound (ELBO) obtained based on a variational approximation of the posterior distribution of the latent variables. The standard ELBO can, however, be a very loose bound if the variational family is not rich enough. A generic strategy to tighten such bounds is to rely on an unbiased low-variance Monte Carlo estimate of the evidence. We review here some recent importance sampling, Markov chain Monte Carlo and sequential Monte Carlo strategies that have been proposed to achieve this.

This article is part of the theme issue ‘Bayesian inference: challenges, perspectives, and prospects’.
Osteonecrosis in Gaucher Disease in the era of multiple therapies: biomarker set for risk stratification from a tertiary referral center
Authors: Basiri Mohsen , Ghaffari Mohammad E. , Ruan Jiapeng , Murugesan Vagishwari , Kleytman Nathaniel , Belinsky Glenn , Akhavan Amir , Lischuk Andrew , Guo Lilu , Klinger Katherine , Mistry Pramod K.
Published: March 2023

BACKGROUND

A salutary effect of treatments for Gaucher disease (GD) has been reduction in the incidence of avascular osteonecrosis (AVN). However, there are reports of AVN in patients receiving enzyme replacement therapy (ERT), and it is not known whether it is related to individual treatments,GBAgenotypes, phenotypes, biomarkers of residual disease activity or anti-drug antibodies.

OBJECTIVE

Prompted by development of AVN in several patients receiving ERT, we aimed to delineate the determinants of AVN in patients receiving ERT or eliglustat substrate reduction therapy (SRT) during 20 years in a tertiary referral center.

METHODS

Longitudinal follow-ups of 155 GD patients between 2001 and 2021, were analyzed for episodes of AVN on therapy, type of therapy,GBA1genotype, spleen status, biomarkers, and other disease indicators. We applied mixed-effects logistic model to delineate the independent correlates of AVN while receiving treatment.

RESULTS

The patients received cumulative 1382 years of treatment. There were 16 episodes of AVN in 14 patients, with two episodes, each occurring in two patients. Heteroallelic p.Asn409Ser GD1 patients were 10 times (95% CI,1.5 - 67.2) more likely than p.Asn409Ser homozygous patients to develop osteonecrosis during treatment. History of AVN prior to treatment initiation was associated with 4.8-fold increased risk of AVN on treatment (95% CI, 1.5-15.2). The risk of AVN among patients receiving velaglucerase ERT was 4.68 times higher compared to patients receiving imiglucerase ERT (95% CI,1.67-13). No patient receiving eliglustat SRT suffered AVN. There was a significant correlation between GlcSph levels and AVN. Together, these biomarkers reliably predicted risk of AVN during therapy (ROC AUC 0.894, p<0.001).

CONCLUSIONS

There is a low, but significant risk of AVN in GD in the era of ERT/SRT. We found increased risk of AVN was related toGBAgenotype, history of AVN prior to treatment initiation, residual serum GlcSph level, and the type of ERT. No patient receiving SRT developed AVN. These findings exemplify a new approach to biomarker applications in a rare inborn error of metabolism to evaluate clinical outcomes in comprehensively followed patients and will aid identification of GD patients at higher risk of AVN who will benefit from closer monitoring and treatment optimization.

Funding

LSD Training Fellowship from Sanofi to MB.
Dysbiosis of Gut microbiota in patients with Large-Artery Atherosclerotic Stroke: a pilot study
Authors: Samuthpongtorn Chatpol , Saraya Abhinbhen W. , Joyjinda Yutthana , Rodpan Apaporn , Suwanwela Nijasri C.
Published: March 2023

Introduction

Increasing data demonstrate an association between gut microbiome in brain diseases via the gut-brain axis. However, few studies have evaluated the association between gut microbiome and large-artery atherosclerotic ischemic stroke patients.

Method

A cross-sectional pilot study was conducted among 15 patients with large-artery atherosclerotic ischemic stroke and 15 asymptomatic persons. Large-artery atherosclerotic stroke were diagnosed using TOAST classification. The control group was selected based on age- and sex-match with the patient group. Participants provided a stool sample profiled by 16S-ribosomal gene-specific methods Next-generation sequencing. The Mann-Whitney U test was used to compare the differences in gut microbiota profile between stroke and control groups. Alpha (Shannon diversity index) and beta diversity (Bray-Curtis dissimilarity) were used to evaluate gut microbial diversity. Generalized linear mixed effects models were used to relate gut microbial genus and stroke which were adjusted for age, BMI, underlying disease (diabetes, hypertension and dyslipidemia), and alcohol use.

Result

The average age of stroke patients was 61.1±7.1 and 59.2±8.2 in the control group. Beta-diversity (Bray-Curtis dissimilarity) of the gut microbiome was statistically significant in order, family and genus level (P-value=0.017, 0.011 and 0.003, respectively) between stroke and control groups; however, there was no statistically significant difference in alpha-diversity (Shannon diversity index; P-value=0.852). The relative abundance ofClass Bacteriodiaincreased in stroke group. Using generalized linear mix effect model, we found 6 genera was significantly associated with stroke after multivariate adjustment.Ruminococcus spp.(P-value=0.017),Streptococcus spp.(P-value=0.019),Actinomyces spp.(P-value=0.02) andDorea spp.(P-value=0.021) showed positive association whileBifidobacterium spp.(P-value=0.04) andFaecalibacterium spp.(P-value=0.041) showed negatively association with stroke.

Conclusion

Patients with large-artery atherosclerotic stroke had a decreased microbiome beta-diversity and certain gut microbiota genera may be related to large-artery atherosclerotic stroke. Future implications of this study could include the development of targeted interventions to modulate gut microbiota in order to improve outcomes for patients with large-artery atherosclerotic stroke.
CESCProg: A COMPACT PROGNOSTIC MODEL AND NOMOGRAM FOR CERVICAL CANCER BASED ON miRNA BIOMARKERS
Authors: Muthamilselvan Sangeetha , Palaniappan Ashok
Published: March 2023

Cervical squamous cell carcinoma, more commonly cervical cancer, is the fourth common cancer among women worldwide with substantial burden of disease, and less-invasive, reliable and effective methods for its prognosis are necessary today. Micro-RNAs are increasingly recognized as viable alternative biomarkers for direct diagnosis and prognosis of disease conditions, including various cancers. In this work, we addressed the problem of systematically developing an miRNA-based nomogram for the reliable prognosis of cervical cancer. Towards this, we preprocessed public-domain miRNA -omics data from cervical cancer patients, and applied a cascade of filters in the following sequence: (i) differential expression criteria with respect to controls; (ii) significance with univariate survival analysis; (iii) passage through dimensionality reduction algorithms; and (iv) stepwise backward selection with multivariate Cox modeling. This workflow yielded a compact prognostic DEmiR signature of three miRNAs, namely hsa-miR-625-5p, hs-miR-95-3p, and hsa-miR-330-3p, which were used to construct a risk-score model for the classification of cervical cancer patients into high-risk and low-risk groups. The risk-score model was subjected to blind validation on an unseen test dataset, yielding a one-year AUROC of 0.84 and five-year AUROC of 0.71. The model was validated with an out-of-domain, external dataset yielding significantly worse prognosis for high-risk patients. The risk-score was combined with significant features of the clinical profile to establish a validated predictive prognostic nomogram. Both the miRNA-based risk score model and the integrated nomogram are freely available for academic and not-for-profit use at CESCProg, a web-app (https://apalania.shinyapps.io/cescprog).