bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Catchment Population to Estimate Sporadic Creutzfeldt–Jakob Disease Incidence
Authors: Neeley Brandon C , Niazi Faraze A , Ebbert Michael A , Forman Alex G , Hobbs Gerald R , Riggs Jack E 
Published: December 2021

ABSTRACT

Introduction
Catchment populations have several uses. A method using catchment population to estimate the incidence of sporadic Creutzfeldt–Jakob disease (sCJD) is described.

Materials and Methods
A cohort of nine consecutive patients diagnosed with sCJD, symptom onset spanning 26 months, were observed at a rural tertiary university medical center that has approximately 40,000 hospital discharges annually. An effective catchment population was determined using surrounding county utilization frequency that captured all nine sCJD patients and accounted for over 87% of discharges.

Results
The effective sCJD hospital catchment population was 1.266 million, implying an annual sCJD incidence rate of 3.39 per million (95% CIs, 1.55-6.43), assuming a Poisson distribution for sCJD occurrence.

Conclusions
This annual incidence rate suggests that many sCJD patients are unrecognized and unreported. An advantage of this catchment population method is independence from death certificate accuracy, important in rare diseases that are both rapidly and invariably fatal. The relative absence of significant healthcare systems competition in this rural population enhances the reliability of this finding. The most likely explanation for the high sCJD incidence rate suggested by this study is enhanced clinical suspicion and improved diagnostic accuracy.
An Analysis of Ketamine Doses Administrated to Nonintubated Casualties Prehospital
Authors: Bebarta Grace E , Bebarta Vikhyat S , Fisher Andrew D , April Michael D , Atkinson Andrew J , McGhee Laura L , Schauer Steven G 
Published: December 2021

ABSTRACT

Introduction
Previous studies demonstrate that a significant proportion of casualties do not receive pain medication prehospital after traumatic injuries. To address possible reasons, the U.S. Military has sought to develop novel delivery methods to aid in administration of pain medications prehospital. We sought to describe the dose and route of ketamine administered prehospital to help inform materiel solutions.

Materials and Methods
This is a secondary analysis of a previously described dataset focused on prehospital data within the Department of Defense Trauma Registry from 2007 to 2020. We isolated encounters in which ketamine was administered along with the amount dosed and the route of administration in nonintubated patients.

Results
Within our dataset, 862 casualties met inclusion for this analysis. The median age was 28 and nearly all (98%) were male. Most were battle injuries (88%) caused by explosives (54%). The median injury severity score was 10 with the extremities accounting to the most frequent seriously injured body region (38%). The mean dose via intravenous route was 50.4 mg (n = 743, 95% CI 46.5-54.3), intramuscular was 66.7 mg (n = 234, 95% CI 60.3-73.1), intranasal was 56.5 mg (n = 10, 39.1-73.8), and intraosseous was 83.3 mg (n = 34, 66.3-100.4). Most had a medic or CLS in their chain of care (87%) with air evacuation as the primary mechanism of evacuation (86%).

Conclusions
The average doses administered were generally larger than the doses recommended by Tactical Combat Casualty Care guidelines. Currently, guidelines may underdose analgesia. Our data will help inform materiel solutions based on end-user requirements.
Kagoshima galactic object survey with the Nobeyama 45-metre telescope by mapping in ammonia lines (KAGONMA): star formation feedback on dense molecular gas in the W33 complex
Authors: Murase Takeru , Handa Toshihiro , Hirata Yushi , Omodaka Toshihiro , Nakano Makoto , Sunada Kazuyoshi , Shimajiri Yoshito , Nishi Junya 
Published: December 2021

ABSTRACT
We present the results of NH3 (1,1), (2,2), and (3,3) and H2O maser simultaneous mapping observations toward the high-mass star-forming region W33 with the Nobeyama 45-m radio telescope. W33 has six dust clumps, one of which, W33 Main, is associated with a compact H ii region. To investigate star-forming activity feedback on its surroundings, the spatial distribution of the physical parameters was established. The distribution of the rotational temperature shows a systematic change from west to east in our observed region. The high-temperature region obtained in the region near W33 Main is consistent with interaction between the compact H ii region and the peripheral molecular gas. The size of the interaction area is estimated to be approximately 1.25 pc. NH3 absorption features are detected toward the centre of the H ii region. Interestingly, the absorption features were detected only in the NH3 (1,1) and (2,2) transitions, with no absorption feature seen in the (3,3) transition. These complex profiles in NH3 are difficult to explain by a simple model and may suggest that the gas distribution around the H ii region is highly complicated.
The peculiar behaviour of burst oscillations in the accreting millisecond X-ray pulsar XTE J1814−338
Authors: Cavecchi Yuri , Patruno Alessandro 
Published: December 2021

ABSTRACT
Accreting millisecond X-ray pulsars (AMXPs) show burst oscillations during thermonuclear explosions of the accreted plasma that are markedly different from those observed in non-pulsating low-mass X-ray binaries. The AMXP XTE J1814−338 is known for having burst oscillations that are phase locked (constant phase difference) and coincident with the accretion-powered pulsations during all its thermonuclear bursts but the last one. In this work, we use a coherent timing analysis to investigate this phenomenon in more detail and with higher time resolution than was done in the past. We confirm that the burst oscillation phases are, on average, phase locked to the accretion-powered pulsations. However, they also display moderate (≲0.1 cycles) drifts during each individual burst, showing a repeating pattern that is consistently observed according to the thermonuclear burst phase (rise, peak, tail). Despite the existence of these drifting patterns, the burst oscillation phases somehow are able to average out at almost the exact position of the accretion-powered pulsations. We provide a kinematic description of the phenomenon and review the existing models in the literature. The phenomenon remains without a clear explanation, but we can place important constraints on the thermonuclear burst mechanism. In particular, the observations imply that the ignition point of the thermonuclear burst occurs close to the foot of the accretion column. We speculate that the burning fluid expands in a backward tilted accretion column trapped by the magnetic field, while at the same time the burning flame covers the surface.
Rheumatoid arthritis is a risk factor for refracture in patients with fragility fractures
Authors: Ishizu Hotaka , Shimizu Hirokazu , Shimizu Tomohiro , Ebata Taku , Ogawa Yuki , Miyano Masahiro , Arita Kosuke , Ohashi Yusuke , Iwasaki Norimasa 
Published: December 2021

ABSTRACT

Objectives
To determine whether patients with rheumatoid arthritis (RA) who have had fragility fractures are at an increased risk of refractures.

Methods
Patients with fragility fractures who were treated surgically at 10 hospitals from 2008 to 2017 and who underwent follow-up for &gt;24 months were either categorized into a group comprising patients with RA or a group comprising patients without RA (controls). The groups were matched 1:1 by propensity score matching. Accordingly, 240 matched participants were included in this study. The primary outcome was the refracture rate in patients with RA as compared to in the controls. Multivariable analyses were also conducted on patients with RA to evaluate the odds ratios (ORs) for the refracture rates.

Results
Patients with RA were significantly associated with increased rates of refractures during the first 24 months (OR: 2.714, 95% confidence interval [95% CI]: 1.015–7.255; p = 0.040). Multivariable analyses revealed a significant association between increased refracture rates and long-term RA (OR: 6.308, 95% CI: 1.195–33.292; p = 0.030).

Conclusions
Patients with RA who have experienced fragility fractures are at an increased risk of refractures. Long-term RA is a substantial risk factor for refractures.
Central sensitization in axial spondyloarthritis: An explorative study with quantitative sensory testing and clinical scales
Authors: Yücel Feyza Nur , Duruöz Mehmet Tuncay 
Published: December 2021

ABSTRACTObjectivesTo evaluate the central sensitization (CS) and the related parameters in patients with axial spondyloarthritis (axSpA).MethodsQuantitative sensory testing (QST) which consists of pressure pain threshold (PPT), temporal summation (TS), and conditioned pain modulation (CPM) were applied to the participants. Disease activity, functional status, sleep quality, pain, depression, and fatigue were assessed. Patients were divided as the ones with and without CS according to the central sensitization inventory (CSI) and the results were compared.ResultsOne hundred patients and 50 controls were recruited. Sixty axSpA patients had CS. When QST results were compared between the patient and control groups, all PPT scores were found lower (p &lt; 0.05) in patients. Regarding the comparison of the patients with and without CS, sacroiliac, and trapezius PPT scores were found lower in the patients with CS (p &lt; 0.05). There was no significant difference between groups in TS values (p &gt; 0.05). All investigated comorbidities were found to be significantly more frequent (p &lt; 0.001) in the patients with CS.ConclusionsCS and related comorbidities were found to be increased in axSpA patients. This increase should be taken into consideration in the management of these patients.
Efficacy of local oxygen–ozone therapy for the treatment of digital ulcer refractory to medical therapy in systemic sclerosis: A randomized controlled study
Authors: Kaymaz Serdar , Karasu Uğur , Alkan Hakan , Ulutaş Firdevs , Albayrak Yaşar Canan , Dündar Ök Zeynep , Çobankara Veli , Yiğit Murat , Yıldız Necmettin , Ardıç Füsun 
Published: December 2021

ABSTRACT

Background
This study aimed to investigate the efficacy of local oxygen–ozone therapy in systemic sclerosis (SSc) patients with digital ulcers (DUs) who were resistant to medical therapy and had impairment in activities of daily living.

Methods
Participants’ demographic data, and clinical parameters were recorded. Twenty-five SSc patients with DUs were randomized to the ozone group (I) (n = 13) to receive medical treatment plus local oxygen–ozone therapy and the control group (II) (n = 12) to receive medical treatment only. Hand functions were assessed using the Health Assessment Questionnaire (HAQ) and the Modified Hand Mobility in Scleroderma (HAMISm) test. Clinical parameters, HAQ, and mHAMIS scores were re-evaluated in participants 4 weeks after the initiation of treatment.

Results
Demographic and clinical characteristics of the two groups showed no significant differences. At 4 weeks after the initial treatment, the efficacy rate was significantly higher in the ozone group than that in the control group (92% versus 42% P = 0.010). Clinical parameters, HAQ, and HAMISm scores were significantly improved in the treatment group compared to those in the control group (P &lt; 0.05).

Conclusion
Local oxygen–ozone therapy was effective in the treatment of SSc patients with resistant DUs and improved clinical parameters and functional disability.
Periodontitis severity affects the clinical response to biological disease-modifying antirheumatic drugs in rheumatoid arthritis: A 1-year follow-up study
Authors: Kobayashi Tetsuo , Ito Satoshi , Murasawa Akira , Ishikawa Hajime , Tabeta Koichi 
Published: December 2021

ABSTRACT

Objectives
To assess whether periodontitis severity affects the clinical response to biological disease-modifying antirheumatic drugs (bDMARDs) for 1 year in rheumatoid arthritis (RA) patients.

Methods
Data were collected from 50 RA patients who had received corticosteroids, conventional synthetic DMARDs, or non-steroidal anti-inflammatory drugs before (baseline) and after 1 year of bDMARD therapy in a retrospective study. Rheumatologic conditions were compared between the two periodontitis severity groups according to the periodontal inflamed surface area (PISA) or Centers for Disease Control and Prevention (CDC)/American Academy of Periodontology (AAP) case definitions

Results
Twenty-eight patients with no or mild periodontitis showed significantly greater decreases in changes in Clinical Disease Activity Index (CDAI) and tender and swollen joint count in comparison to 22 patients with moderate and severe periodontitis (p = .02, p = .01, and p = .03). Both bivariate and multivariate analyses revealed a significantly positive association between the baseline CDC/AAP definitions and CDAI changes (p = .005 and p = .0038). However, rheumatologic conditions were comparable between 25 patients each in the low and high PISA groups.

Conclusions
Baseline periodontitis severity according to the CDC/AAP definitions is associated with the clinical response to bDMARDs for 1 year in RA patients.
Targeting genomic SARS-CoV-2 RNA with siRNAs allows efficient inhibition of viral replication and spread
Authors: Ambike Shubhankar , Cheng Cho-Chin , Feuerherd Martin , Velkov Stoyan , Baldassi Domizia , Afridi Suliman Qadir , Porras-Gonzalez Diana , Wei Xin , Hagen Philipp , Kneidinger Nikolaus , Stoleriu Mircea Gabriel , Grass Vincent , Burgstaller Gerald , Pichlmair Andreas , Merkel Olivia M , Ko Chunkyu , Michler Thomas 
Published: December 2021

Abstract
A promising approach to tackle the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) could be small interfering (si)RNAs. So far it is unclear, which viral replication steps can be efficiently inhibited with siRNAs. Here, we report that siRNAs can target genomic RNA (gRNA) of SARS-CoV-2 after cell entry, and thereby terminate replication before start of transcription and prevent virus-induced cell death. Coronaviruses replicate via negative sense RNA intermediates using a unique discontinuous transcription process. As a result, each viral RNA contains identical sequences at the 5′ and 3′ end. Surprisingly, siRNAs were not active against intermediate negative sense transcripts. Targeting common sequences shared by all viral transcripts allowed simultaneous suppression of gRNA and subgenomic (sg)RNAs by a single siRNA. The most effective suppression of viral replication and spread, however, was achieved by siRNAs that targeted open reading frame 1 (ORF1) which only exists in gRNA. In contrast, siRNAs that targeted the common regions of transcripts were outcompeted by the highly abundant sgRNAs leading to an impaired antiviral efficacy. Verifying the translational relevance of these findings, we show that a chemically modified siRNA that targets a highly conserved region of ORF1, inhibited SARS-CoV-2 replication ex vivo in explants of the human lung. Our work encourages the development of siRNA-based therapies for COVID-19 and suggests that early therapy start, or prophylactic application, together with specifically targeting gRNA, might be key for high antiviral efficacy.
Phase I study using crenolanib to target PDGFR kinase in children and young adults with newly diagnosed DIPG or recurrent high-grade glioma, including DIPG
Authors: Tinkle Christopher L , Broniscer Alberto , Chiang Jason , Campagne Olivia , Huang Jie , Orr Brent A , Li Xiaoyu , Patay Zoltan , Zhang Jinghui , Baker Suzanne J , Merchant Thomas E , Jain Vinay , Onar-Thomas Arzu , Stewart Clinton F , Wetmore Cynthia , Gajjar Amar 
Published: December 2021

AbstractBackgroundPlatelet-derived growth factor receptor (PDGFR) signaling has been directly implicated in pediatric high-grade gliomagenesis. This study evaluated the safety and tolerability of crenolanib, a potent, selective inhibitor of PDGFR-mediated phosphorylation, in pediatric patients with high-grade glioma (HGG).MethodsWe used a rolling-6 design to study the maximum tolerated dose (MTD) of once-daily crenolanib administered during and after focal radiation therapy in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) (stratum A) or with recurrent/progressive HGG (stratum B). Pharmacokinetics were studied during the first cycle at the first dose and at steady state (day 28). Alterations in PDGFRA were assessed by Sanger or exome sequencing and interphase fluorescence in situ hybridization or single nucleotide polymorphism arrays.ResultsFifty evaluable patients were enrolled in the 2 strata, and an MTD of 170 mg/m2 was established for both. Dose-limiting toxicities were primarily liver enzyme elevations and hematologic count suppression in both strata. Crenolanib AUC0–48h and CMAX did not differ significantly for crushed versus whole-tablet administration. Overall, PDGFRA alterations were observed in 25% and 30% of patients in stratum A and B, respectively. Neither crenolanib therapy duration nor survival outcomes differed significantly by PDGFRA status, and overall survival of stratum A was similar to that of historical controls.ConclusionsChildren tolerate crenolanib well at doses slightly higher than the established MTD in adults, with a toxicity spectrum generally similar to that in adults. Studies evaluating intratumoral PDGFR pathway inhibition in biomarker-enriched patients are needed to evaluate further the clinical utility of crenolanib in this population.
Quantitative cerebrospinal fluid circulating tumor cells are a potential biomarker of response for proton craniospinal irradiation for leptomeningeal metastasis
Authors: Wijetunga N Ari , Boire Adrienne , Young Robert J , Yamada Yoshiya , Wolden Suzanne , Yu Helena , Kris Mark , Seidman Andrew , Betof-Warner Allison , Diaz Maria , Reiner Anne , Malani Rachna , Pentsova Elena , Yang Jonathan T 
Published: December 2021

AbstractBackgroundLeptomeningeal metastasis (LM) involves cerebrospinal fluid (CSF) seeding of tumor cells. Proton craniospinal irradiation (pCSI) is potentially effective for solid tumor LM. We evaluated whether circulating tumor cells (CTCs) in the CSF (CTCCSF), blood (CTCblood), and neuroimaging correlate with outcomes after pCSI for LM.MethodsWe describe a single-institution consecutive case series of 58 patients treated with pCSI for LM. Pre-pCSI CTCs, the change in CTC post-pCSI (Δ CTC), and MRIs were examined. Central nervous system progression-free survival (CNS-PFS) and overall survival (OS) from pCSI were determined using Kaplan Meier analysis, Cox proportional-hazards regression, time-dependent ROC analysis, and joint modeling of time-varying effects and survival outcomes.ResultsThe median CNS-PFS and OS were 6 months (IQR: 4–9) and 8 months (IQR: 5–13), respectively. Pre-pCSI CTCCSF &lt; 53/3mL was associated with improved CNS-PFS (12.0 vs 6.0 months, P &lt; .01). Parenchymal brain metastases (n = 34, 59%) on pre-pCSI MRI showed worse OS (7.0 vs 13 months, P = .01). Through joint modeling, CTCCSF was significantly prognostic of CNS-PFS (P &lt; .01) and OS (P &lt; .01). A Δ CTC-CSF≥37 cells/3mL, the median Δ CTC-CSF at nadir, showed improved CNS-PFS (8.0 vs 5.0 months, P = .02) and further stratified patients into favorable and unfavorable subgroups (CNS-PFS 8.0 vs 4.0 months, P &lt; .01). No associations with CTCblood were found.ConclusionWe found the best survival observed in patients with low pre-pCSI CTCCSF and intermediate outcomes for patients with high pre-pCSI CTCCSF but large Δ CTC-CSF. These results favor additional studies incorporating pCSI and CTCCSF measurement earlier in the LM treatment paradigm.
1. The Relationship Between Chlorhexidine Skin Concentration and Multidrug-Resistant Organism (MDRO) Colonization in ICU Patients
Authors: Miller Loren G , Richter Stefan , Flores Evelyn A , Ceja Sandra , Torres Crystal , Tran Donna Phan , Salcido Samantha , Tchakalian Gregory , Bloomfield Leah , Gomez Angela , Pham Tuyen , Tong Oanh K , Nutkiewicz Max , Bolaris Michael , McKinnell James A 
Published: December 2021

Abstract

Background
Daily bathing of ICU patients with chlorhexidine gluconate (CHG) is an important method for healthcare-associated infection prevention. We set out to understand the relationship between CHG concentrations and MDRO colonization

Methods
In our trauma/surgical ICU at a large urban medical center, we performed CHG concentrations 2 days/week at 4 times points relative to CHG bathing (Medline, Northfiled, IL) application: 30 min. prior, and 30 min., 6 hrs., and 12 hrs. after application. CHG testing was done at 4 body sites: lateral neck, anterior chest, arm, and inguinal fold. On the contralateral side we tested the presence of the following 4 MDROs: methicillin resistant S. aureus (MRSA), and 3 enteric bacteria--extended spectrum beta-lactamase (ESBL)+ gram-negative rods, vancomycin resistant enterococcus (VRE), and carbapenem resistant enterobacteriaceae (CRE).

Results
We performed testing for 256 patient-days total, of which 42 were swabbed 1 time, 38 swabbed twice, 79 swabbed 3 times, and 97 swabbed 4 times (patient movement for tests, ICU transfer were limitations). Mean CHG skin concentrations were above the MICs of pathogens at all post-CHG application time points at all body sites at all times points (Figure) and decreased during the time points after bathing. In a logistic regression model controlling for patient characteristics, MRSA detection was inversely associated with CHG concentration with an 18% increase in odds of recovery for each 2-fold decrease in CHG concentration, as well as presence of a GI device and lack of ability to sit and roll. In a logistic regression model controlling for patient characteristics, resistant enteric bacteria detection was inversely associated with CHG concentration with an 11% increase in odds of recovery for each 2-fold decrease in CHG concentration, as well as mechanical ventilation, GI device, central line, and ICU duration.

Conclusion
In our large study of CHG use and its association with MDRO detection, CHG concentrations decreased during the 24 hours after application, but were typically above concentrations considered adequate to kill MDROs. CHG concentration were inversely associated with the presence of MRSA and resistant enterics, suggesting that CHG application quality is a key component of the CHG bathing process.

Disclosures
Loren G. Miller, MD, MPH, Medline (Grant/Research Support, Other Financial or Material Support, Contributed product) Stryker (Other Financial or Material Support, Contributed product) Xttrium (Other Financial or Material Support, Contributed product) James A. McKinnell, MD, Medline (Grant/Research Support)