bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unpublished clinical trials of common rheumatic diseases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

Abstract

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Randomized controlled trials (RCTs) provide high-quality evidence for treatment efficacy, but many RCTs remain unpublished. The objective of this study was to describe the proportion of unpublished RCTs in five rheumatic diseases and to identify factors associated with publication.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 The results of unpublished studies were identified in abstracts and press releases; reasons for non-publication were assessed by surveying corresponding authors.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Out of 203 studies that met eligibility criteria, 17.2% remained unpublished, representing data from 4281 trial participants. Higher proportions of published trials were phase 3 RCTs (57.1% vs 28.6% unpublished, P &lt; 0.05) or had a positive primary outcome measure (64.9% vs 25.7% unpublished, P &lt; 0.001).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 Corresponding authors of 10 unpublished trials cited ongoing preparation of the manuscript (50.0%), sponsor/funder issues (40.0%) and unimportant/negative result (20.0%) as reasons for lack of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Nearly one in five RCTs in rheumatology remain unpublished 2 years after trial completion, and publication is associated with positive primary outcome measures. Efforts to encourage universal publication of rheumatology RCTs and reanalysis of previously unpublished trials should be undertaken.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

Abstract
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.
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.
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.
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

AbstractBACKGROUNDA 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.OBJECTIVEPrompted 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.METHODSLongitudinal 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.RESULTSThe 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).CONCLUSIONSThere 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.FundingLSD Training Fellowship from Sanofi to MB.