bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of an algorithm to identify incident interstitial lung disease in patients with rheumatoid arthritis
Authors: Meehan M. , Shah A. , Lobo J. , Oates J. , Clinton C. , Annapureddy N. , Xie F. , Zhuo J. , Danila M. I. , England B. R. , Curtis J. R. 
Published: January 2022

Abstract
Background/purpose
Interstitial lung disease (ILD) is an important problem for patients with rheumatoid arthritis (RA). However, current approaches to ILD case finding in real-world data have been evaluated only in limited settings and identify only prevalent ILD and not new-onset disease. Our objective was to develop, refine, and validate a claims-based algorithm to identify both prevalent and incident ILD in RA patients compared to the gold standard of medical record review.

Methods
We used administrative claims data 2006–2015 from Medicare to derive a cohort of RA patients. We then identified suspected ILD using variations of ILD algorithms to classify both prevalent and incident ILD based on features of the data that included hospitalization vs. outpatient setting, physician specialty, pulmonary-related diagnosis codes, and exclusions for potentially mimicking pulmonary conditions. Positive predictive values (PPV) of several ILD algorithm variants for both prevalent and incident ILD were evaluated.

Results
We identified 234 linkable RA patients with sufficient data to evaluate for ILD. Overall, 108 (46.2%) of suspected cases were confirmed as ILD. Most cases (64%) were diagnosed in the outpatient setting. The best performing algorithm for prevalent ILD had a PPV of 77% (95% CI 67–84%) and for incident ILD was 96% (95% CI 85–100%).

Conclusion
Case finding in administrative data for both prevalent and incident interstitial lung disease in RA patients is feasible and has reasonable accuracy to support population-based research and real-world evidence generation.
Preterm birth is strongly affected by the glucocorticoid dose during pregnancy in women complicated by systemic lupus erythematosus
Authors: Shimada Hiromi , Wakiya Risa , Kanenishi Kenji , Miyatake Nobuyuki , Nakashima Shusaku , Mansour Mai Mahmoud Fahmy , Kato Mikiya , Miyagi Taichi , Sugihara Koichi , Ushio Yusuke , Mino Rina , Mizusaki Mao , Kameda Tomohiro , Kadowaki Norimitsu , Dobashi Hiroaki 
Published: January 2022

Abstract
Background
This study aimed to investigate the effect of glucocorticoid doses on adverse pregnancy outcomes (APOs) in women complicated by systemic lupus erythematosus (SLE).

Methods
We investigated 74 pregnancies complicated by SLE or SLE-dominant mixed connective tissue disease. The pregnancies were managed from conception to delivery in our institution. We retrospectively evaluated whether the mean glucocorticoid dose during pregnancy is associated with APOs, including preterm birth (PB), low birth weight (LBW), and light-for-date (LFD). We also calculated the cut-off dose of glucocorticoid that affected APOs.

Results
All APOs occurred in 35 (50.7%) patients, with 14 cases of PB, 23 cases of LBW, and 10 cases of LFD. Patients with all APOs or PB had a higher dose of glucocorticoid during pregnancy than patients without all APOs or with full-term birth (P = 0.03, P <  0.01, respectively). Logistic regression analysis for all APOs and PB showed that the cut-off values of the mean glucocorticoid dose were 6.5 and 10.0 mg/day, respectively. Patients who delivered LBW or LFD newborns showed no significant difference in the glucocorticoid dose used during pregnancy than patients without LBW or LFD newborns. Patients who delivered LBW newborns were more likely to have used glucocorticoids during pregnancy (P <  0.01).

Conclusions
In pregnancies complicated by SLE, a relatively lower dose of glucocorticoid than previously reported is significantly related to APOs, especially PB. Therefore, the disease activity of patients with SLE should be managed with the appropriate lower dose of glucocorticoid during pregnancy.
Comment on “the IS6 family, a clinically important group of insertion sequences including IS26” by Varani and co-authors
Authors: Hall Ruth M. 
Published: January 2022

AbstractThe insertion sequence IS26 has long been known to play a major role in the recruitment of antibiotic resistance genes into the mobile resistance gene pool of Gram-negative bacteria and IS26 also plays a major role in their subsequent broad dissemination. Related IS, IS431/257 and IS1216 are important in the same roles in Gram positive bacteria. However, until recently the properties of IS26 movement that could potentially explain this ability had not been explored. A much needed insight has come from our recent demonstration that IS26 uses a novel targeted mechanism that is conservative. The targeted conservative mechanism is much more efficient than the known replicative mechanism, which is now more accurately called copy-in. A recent review “The IS6 family, a clinically important group of insertion sequences including IS26” by Varani, He, Siguier, Ross and Chandler published in Mobile DNA has substantially misrepresented the recent studies on the targeted conservative mechanism and at the same time incorrectly implied that any mechanism established for IS26 can be assumed to apply to a range of IS that are at best very distantly related. A few of the most important issues are examined in this comment. Readers are advised to consult the original literature to check facts before drawing firm conclusions.
Epigenetic biomarkers of ageing are predictive of mortality risk in a longitudinal clinical cohort of individuals diagnosed with oropharyngeal cancer
Authors: Beynon Rhona A. , Ingle Suzanne M. , Langdon Ryan , May Margaret , Ness Andy , Martin Richard M. , Suderman Matthew , Ingarfield Kate , Marioni Riccardo E. , McCartney Daniel L. , Waterboer Tim , Pawlita Michael , Relton Caroline , Smith George Davey , Richmond Rebecca C. 
Published: January 2022

AbstractBackgroundEpigenetic clocks are biomarkers of ageing derived from DNA methylation levels at a subset of CpG sites. The difference between age predicted by these clocks and chronological age, termed “epigenetic age acceleration”, has been shown to predict age-related disease and mortality. We aimed to assess the prognostic value of epigenetic age acceleration and a DNA methylation-based mortality risk score with all-cause mortality in a prospective clinical cohort of individuals with head and neck cancer: Head and Neck 5000. We investigated two markers of intrinsic epigenetic age acceleration (IEAAHorvathandIEAAHannum), one marker of extrinsic epigenetic age acceleration (EEAA), one optimised to predict physiological dysregulation (AgeAccelPheno), one optimised to predict lifespan (AgeAccelGrim) and a DNA methylation-based predictor of mortality (ZhangScore). Cox regression models were first used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations of epigenetic age acceleration with all-cause mortality in people with oropharyngeal cancer (n = 408; 105 deaths). The added prognostic value of epigenetic markers compared to a clinical model including age, sex, TNM stage and HPV status was then evaluated.ResultsIEAAHannumandAgeAccelGrimwere associated with mortality risk after adjustment for clinical and lifestyle factors (HRs per standard deviation [SD] increase in age acceleration = 1.30 [95% CI 1.07, 1.57;p = 0.007] and 1.40 [95% CI 1.06, 1.83;p = 0.016], respectively). There was weak evidence that the addition ofAgeAccelGrimto the clinical model improved 3-year mortality prediction (area under the receiver operating characteristic curve: 0.80 vs. 0.77;pvalue for difference = 0.069).ConclusionIn the setting of a large, clinical cohort of individuals with head and neck cancer, our study demonstrates the potential of epigenetic markers of ageing to enhance survival prediction in people with oropharyngeal cancer, beyond established prognostic factors. Our findings have potential uses in both clinical and non-clinical contexts: to aid treatment planning and improve patient stratification.
Apolipoprotein E and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline
Authors: González-Domínguez Raúl , Castellano-Escuder Pol , Lefèvre-Arbogast Sophie , Low Dorrain Y. , Du Preez Andrea , Ruigrok Silvie R. , Lee Hyunah , Helmer Catherine , Pallàs Mercè , Urpi-Sarda Mireia , Sánchez-Pla Alex , Korosi Aniko , Lucassen Paul J. , Aigner Ludwig , Manach Claudine , Thuret Sandrine , Samieri Cécilia , Andres-Lacueva Cristina 
Published: January 2022

AbstractBackgroundFatty acids play prominent roles in brain function as they participate in structural, metabolic and signaling processes. The homeostasis of fatty acids and related pathways is known to be impaired in cognitive decline and dementia, but the relationship between these metabolic disturbances and common risk factors, namely the ɛ4 allele of the apolipoprotein E (ApoE-ɛ4) gene and sex, remains elusive.MethodsIn order to investigate early alterations associated with cognitive decline in the fatty acid-related serum metabolome, we here applied targeted metabolomics analysis on a nested case-control study (N=368), part of a prospective population cohort on dementia.ResultsWhen considering the entire study population, circulating levels of free fatty acids, acyl-carnitines and pantothenic acid were found to be increased among those participants who had greater odds of cognitive decline over a 12-year follow-up. Interestingly, stratified analyses indicated that these metabolomic alterations were specific for ApoE-ɛ4 non-carriers and women.ConclusionsAltogether, our results highlight that the regulation of fatty acids and related metabolic pathways during ageing and cognitive decline depends on complex inter-relationships between the ApoE-ε4 genotype and sex. A better understanding of the ApoE-ɛ4 and sex dependent modulation of metabolism is essential to elucidate the individual variability in the onset of cognitive decline, which would help develop personalized therapeutic approaches.
Autism screening at 18 months of age: a comparison of the Q-CHAT-10 and M-CHAT screeners
Authors: Sturner Raymond , Howard Barbara , Bergmann Paul , Attar Shana , Stewart-Artz Lydia , Bet Kerry , Allison Carrie , Baron-Cohen Simon 
Published: January 2022

Abstract
Background
Autism screening is recommended at 18- and 24-month pediatric well visits. The Modified Checklist for Autism in Toddlers—Revised (M-CHAT-R) authors recommend a follow-up interview (M-CHAT-R/F) when positive. M-CHAT-R/F may be less accurate for 18-month-olds than 24-month-olds and accuracy for identification prior to two years is not known in samples that include children screening negative. Since autism symptoms may emerge gradually, ordinally scoring items based on the full range of response options, such as in the 10-item version of the Quantitative Checklist for Autism in Toddlers (Q-CHAT-10), might better capture autism signs than the dichotomous (i.e., yes/no) items in M-CHAT-R or the pass/fail scoring of Q-CHAT-10 items. The aims of this study were to determine and compare the accuracy of the M-CHAT-R/F and the Q-CHAT-10 and to describe the accuracy of the ordinally scored Q-CHAT-10 (Q-CHAT-10-O) for predicting autism in a sample of children who were screened at 18 months.

Methods
This is a community pediatrics validation study with screen positive (n = 167) and age- and practice-matched screen negative children (n = 241) recruited for diagnostic evaluations completed prior to 2 years old.
Clinical diagnosis of autism was based on results of in-person diagnostic autism evaluations by research reliable testers blind to screening results and using the Autism Diagnostic Observation Schedule—Second Edition (ADOS-2) Toddler Module and Mullen Scales of Early Learning (MSEL) per standard guidelines.

Results
While the M-CHAT-R/F had higher specificity and PPV compared to M-CHAT-R, Q-CHAT-10-O showed higher sensitivity than M-CHAT-R/F and Q-CHAT-10.

Limitations
Many parents declined participation and the sample is over-represented by higher educated parents. Results cannot be extended to older ages.

Conclusions
Limitations of the currently recommended two-stage M-CHAT-R/F at the 18-month visit include low sensitivity with minimal balancing benefit of improved PPV from the follow-up interview. Ordinal, rather than dichotomous, scoring of autism screening items appears to be beneficial at this age. The Q-CHAT-10-O with ordinal scoring shows advantages to M-CHAT-R/F with half the number of items, no requirement for a follow-up interview, and improved sensitivity. Yet, Q-CHAT-10-O sensitivity is less than M-CHAT-R (without follow-up) and specificity is less than the two-stage procedure. Such limitations are consistent with recognition that screening needs to recur beyond this age.
Rescuing epileptic and behavioral alterations in a Dravet syndrome mouse model by inhibiting eukaryotic elongation factor 2 kinase (eEF2K)
Authors: Beretta Stefania , Gritti Laura , Ponzoni Luisa , Scalmani Paolo , Mantegazza Massimo , Sala Mariaelvina , Verpelli Chiara , Sala Carlo 
Published: January 2022

Abstract
Background
Dravet Syndrome is a severe childhood pharmaco-resistant epileptic disorder mainly caused by mutations in the SCN1A gene, which encodes for the α1 subunit of the type I voltage-gated sodium channel (NaV1.1), that causes imbalance between excitation and inhibition in the brain. We recently found that eEF2K knock out mice displayed enhanced GABAergic transmission and tonic inhibition and were less susceptible to epileptic seizures. Thus, we investigated the effect of inhibition of eEF2K on the epileptic and behavioral phenotype of Scn1a ± mice, a murine model of Dravet Syndrome.

Methods
To elucidate the role of eEF2K pathway in the etiopathology of Dravet syndrome we generated a new mouse model deleting the eEF2K gene in Scn1a ± mice. By crossing Scn1a ± mice with eEF2K−/− mice we obtained the three main genotypes needed for our studies, Scn1a+/+ eEF2K+/+ (WT mice), Scn1a ± eEF2K+/+ mice (Scn1a ± mice) and Scn1a ± eEF2K−/− mice, that were fully characterized for EEG and behavioral phenotype. Furthermore, we tested the ability of a pharmacological inhibitor of eEF2K in rescuing EEG alterations of the Scn1a ± mice.

Results
We showed that the activity of eEF2K/eEF2 pathway was enhanced in Scn1a ± mice. Then, we demonstrated that both genetic deletion and pharmacological inhibition of eEF2K were sufficient to ameliorate the epileptic phenotype of Scn1a ± mice. Interestingly we also found that motor coordination defect, memory impairments, and stereotyped behavior of the Scn1a ± mice were reverted by eEF2K deletion. The analysis of spontaneous inhibitory postsynaptic currents (sIPSCs) suggested that the rescue of the pathological phenotype was driven by the potentiation of GABAergic synapses.

Limitations
Even if we found that eEF2K deletion was able to increase inhibitory synapses function, the molecular mechanism underlining the inhibition of eEF2K/eEF2 pathway in rescuing epileptic and behavioral alterations in the Scn1a ± needs further investigations.

Conclusions
Our data indicate that pharmacological inhibition of eEF2K could represent a novel therapeutic intervention for treating epilepsy and related comorbidities in the Dravet syndrome.
Postoperative dysphagia caused by a delay in mandibular fracture treatment in a patient with severe intellectual disability: a case report
Authors: Yamamoto Shinsuke , Nashi Masanori , Maeda Keigo , Taniike Naoki , Takenobu Toshihiko 
Published: January 2022

Abstract
Background
The postoperative complications of mandibular fracture include malocclusion, infection, nonunion, osteomyelitis, and sensorial mental nerve dysfunction. However, there are no reports regarding postoperative dysphagia as a complication of mandibular fracture. Herein, we report a rare case of postoperative dysphagia caused by delayed mandibular fracture treatment in a patient with severe intellectual disability.

Case presentation
A 46-year-old Japanese male patient with severe intellectual disability fell down and struck his chin. The patient was referred to our department 10 days after the accident. Upon examination, he could not close his mouth because of severe left mandibular body fracture. Open reduction and internal fixation was performed under general anesthesia 16 days after sustaining the injury, and normal occlusion was eventually achieved. However, the patient could not swallow well a day after surgery. He was then diagnosed with postoperative dysphagia caused by disuse atrophy of muscles for swallowing based on videoendoscopic examination findings. Adequate dysphagia rehabilitation could not be facilitated because of the patient’s mental status. Postoperative dysphagia did not improve 21 days after surgery. Therefore, percutaneous endoscopic gastrostomy was required.

Conclusions
The treatment course of the patient had two important implications. First, postoperative dysphagia caused by disuse atrophy may occur if treatment is delayed in severe mandibular body fracture. Second, in particular, if a patient with severe intellectual disability develops postoperative dysphagia caused by disuse atrophy, adequate dysphagia rehabilitation cannot be facilitated, and percutaneous endoscopic gastrostomy may be required. Therefore, early open reduction and internal fixation is required for mandibular fracture in a patient with severe intellectual disability.
Sex and age interaction in fundamental circulatory volumetric variables at peak working capacity
Authors: Diaz-Canestro Candela , Montero David 
Published: January 2022

Abstract
Background
Whether the fundamental hematological and cardiac variables determining cardiorespiratory fitness and their intrinsic relationships are modulated by major constitutional factors, such as sex and age remains unresolved.

Methods
Transthoracic echocardiography, central hemodynamics and pulmonary oxygen (O2) uptake were assessed in controlled conditions during submaximal and peak exercise (cycle ergometry) in 85 healthy young (20–44 year) and older (50–77) women and men matched by age-status and moderate-to-vigorous physical activity (MVPA) levels. Main outcomes such as peak left ventricular end-diastolic volume (LVEDVpeak), stroke volume (SVpeak), cardiac output (Qpeak) and O2 uptake (VO2peak), as well as blood volume (BV), BV–LVEDVpeak and LVEDVpeak–SVpeak relationships were determined with established methods.

Results
All individuals were non-smokers and non-obese, and MVPA levels were similar between sex and age groups (P ≥ 0.140). BV per kg of body weight did not differ between sexes (P ≥ 0.118), but was reduced with older age in men (P = 0.018). Key cardiac parameters normalized by body size (LVEDVpeak, SVpeak, Qpeak) were decreased in women compared with men irrespective of age (P ≤ 0.046). Older age per se curtailed Qpeak (P ≤ 0.022) due to lower heart rate (P < 0.001). In parallel, VO2peak was reduced with older age in both sexes (P < 0.001). The analysis of fundamental circulatory relationships revealed that older women require a higher BV for a given LVEDVpeak than older men (P = 0.024).

Conclusions
Sex and age interact on the crucial circulatory relationship between total circulating BV and peak cardiac filling, with older women necessitating more BV to fill the exercising heart than age- and physical activity-matched men.
Sex differences in coronary angiographic findings in patients with stable chest pain: analysis of data from the KoRean wOmen’S chest pain rEgistry (KoROSE)
Authors: Kim Hack-Lyoung , Kim Hyun-Jin , Kim Mina , Park Sang Min , Yoon Hyun Ju , Byun Young Sup , Park Seong Mi , Shin Mi Seung , Hong Kyung-Soon , Kim Myung-A 
Published: January 2022

AbstractBackgroundFocused evaluations on potential sex differences in the angiographic findings of the coronary arteries are scarce. This study was performed to compare the angiographic extent and localization of coronary stenosis between men and women.MethodsA total of 2348 patients (mean age 62.5 years and 60% women) with stable chest pain undergoing invasive coronary angiography (CAG) were recruited from the database of the nation-wide chest pain registry. Obstructive coronary artery disease (CAD) was defined as ≥ 50% stenosis of the left main coronary artery and/or ≥ 70% stenosis of any other epicardial coronary arteries.ResultsAlthough women were older than men (64.4 ± 10.3 vs. 59.5 ± 11.4 years,P < 0.001), men had worse risk profiles including high blood pressure, more frequent smoking and elevated triglyceride and C-reactive protein. The prevalence of obstructive CAD was significantly higher in men than in women (37.0% vs. 28.4%,P < 0.001). Men had a higher prevalence of LM disease (10.3% vs. 3.5%,P < 0.001) and three-vessel disease (16.1% vs. 9.5%,P = 0.007) compared to women. In multiple binary logistic regression analysis, the risk of men having LM disease or three-vessel disease was 7.4 (95% confidence interval 3.48–15.97;P < 0.001) and 2.7 (95% confidence interval 1.57–4.64;P < 0.001) times that of women, respectively, even after controlling for potential confounders.ConclusionsIn patients with chest pain undergoing invasive CAG, men had higher obstructive CAD prevalence and more high-risk angiographic findings such as LM disease or three-vessel disease.
A technique for non-intrusive greedy piecewise-rational model reduction of frequency response problems over wide frequency bands
Authors: Pradovera Davide , Nobile Fabio 
Published: January 2022

AbstractIn the field of model order reduction for frequency response problems, the minimal rational interpolation (MRI) method has been shown to be quite effective. However, in some cases, numerical instabilities may arise when applying MRI to build a surrogate model over a large frequency range, spanning several orders of magnitude. We propose a strategy to overcome these instabilities, replacing an unstable global MRI surrogate with a union of stable local rational models. The partitioning of the frequency range into local frequency sub-ranges is performed automatically and adaptively, and is complemented by a (greedy) adaptive selection of the sampled frequencies over each sub-range. We verify the effectiveness of our proposed method with two numerical examples.
Enhancing energy efficiency for cellular-assisted vehicular networks by online learning-based mmWave beam selection
Authors: Gui Jinsong , Liu Yao 
Published: January 2022

AbstractMillimeter Wave (mmWave) technology has been regarded as a feasible approach for future vehicular communications. Nevertheless, high path loss and penetration loss raise severe questions on mmWave communications. These problems can be mitigated by directional communication, which is not easy to achieve in highly dynamic vehicular communications. The existing works addressed the beam alignment problem by designing online learning-based mmWave beam selection schemes, which can be well adapted to high dynamic vehicular scenarios. However, this kind of work focuses on network throughput rather than network energy efficiency, which ignores the consideration of energy consumption. Therefore, we propose an Energy efficiency-based FML (EFML) scheme to compensate for this shortfall. In EFML, the energy consumption is reduced as far as possible under the premise of meeting the basic data rate requirements of vehicle users, and the users requesting the same content in close proximity can be organized into the same receiving group to share the same mmWave beam. The simulation results demonstrate that, compare with the comparison method with best energy efficiency, the proposed EFML improves energy efficiency by 17–41% in different scenarios.