bluuebunny/crossref_metadata_2025_split huggingface dataset:
Echocardiographic features of acute-phase microscopic polyangiitis in Japanese patients: A single-centre retrospective study
Authors: Nawata Takashi , Kinoshita Natsu , Okuda Shinichi , Kubo Makoto , Wada Yasuaki , Kobayashi Shigeki , Tanaka Nobuaki , Yano Masafumi 
Published: December 2021

ABSTRACT

Objectives
Microscopic polyangiitis (MPA) affects various organs. However, echocardiographic findings of MPA are unclear. We aimed to evaluate the echocardiographic features of acute-phase MPA in Japanese patients.

Methods
This single-centre retrospective study included 15 patients with MPA who underwent echocardiography within 2 weeks of commencing steroid therapy for induction or reinduction. The echocardiography parameters of thetients were compared with those of 30 age- and sex-matched controls.

Results
No significant differences in left ventricular (LV) diameter, LV ejection fraction, or e’ were observed between the two groups. However, the MPA group showed a significantly higher left atrial (LA) diameter and LA volume index, as well as higher early diastolic filling velocity, diastolic pulmonary venous flow velocity, and trans-tricuspid pressure gradient, and a shorter deceleration time (DCT). Serum C-reactive protein levels were positively correlated with E wave, E/A, and DCT. These results may indicate that increased LV stiffness, rather than impairment of LV relaxation, contributed to LV diastolic function, resulting in LA enlargement.

Conclusions
Patients with acute-phase MPA had LA dilatation associated with LV diastolic dysfunction. This finding indicates the importance of cardiac assessment in patients with MPA, especially in patients with a strong inflammatory reaction.
Ultrasound assessment of sarcopenia in patients with rheumatoid arthritis
Authors: Yoshida Takeshi , Kumon Yoshitaka , Takamatsu Naoko , Nozaki Taiki , Inoue Masataka , Nodera Hiroyuki , Albayda Jemima , Izumi Yuishin 
Published: December 2021

ABSTRACT

Objectives
To evaluate the efficacy of ultrasound (US) as a diagnostic tool for sarcopenia in patients with rheumatoid arthritis (RA).

Methods
Female RA patients aged &gt;50 years and matched controls were cross-sectionally assessed. Sarcopenia was diagnosed based on the 2019-updated Asian Working Group for Sarcopenia definition. The cross-sectional area (CSA) and echo intensity (EI) of the biceps brachii, rectus femoris, and EI of the vastus lateralis were examined bilaterally. Correction for subcutaneous fat and calculation of the recorrected EI (rcEI) were performed. We performed logistic regression using both muscle rcEI and CSA with receiver operating curve analysis to evaluate the discriminative performance per muscle group.

Results
Seventy-eight consecutive RA patients and 15 age-and sex-matched controls were assessed. Sarcopenia was diagnosed in 34 RA patients (43.6%). The rcEI of examined muscles were significantly higher, whereas CSA were significantly lower in sarcopenic RA patients than in non-sarcopenic patients and matched controls. The combined discriminative performance of rcEI and CSA was superior to those of rcEI or CSA alone.

Conclusions
This study suggests the use of US for the diagnosis of sarcopenia in RA patients. The diagnostic performance increases when both echogenicity and CSA are considered together rather than individually.
Mechanics of CRISPR-Cas12a and engineered variants on λ-DNA
Authors: Paul Bijoya , Chaubet Loïc , Verver Dideke Emma , Montoya Guillermo 
Published: December 2021

Abstract
Cas12a is an RNA-guided endonuclease that is emerging as a powerful genome-editing tool. Here, we selected a target site on bacteriophage λ-DNA and used optical tweezers combined with fluorescence to provide mechanistic insight into wild type Cas12a and three engineered variants, where the specific dsDNA and the unspecific ssDNA cleavage are dissociated (M1 and M2) and a third one which nicks the target DNA (M3). At low forces wtCas12a and the variants display two main off-target binding sites, while on stretched dsDNA at higher forces numerous binding events appear driven by the mechanical distortion of the DNA and partial matches to the crRNA. The multiple binding events onto dsDNA at high tension do not lead to cleavage, which is observed on the target site at low forces when the DNA is flexible. In addition, activity assays also show that the preferential off-target sites for this crRNA are not cleaved by wtCas12a, indicating that λ-DNA is only severed at the target site. Our single molecule data indicate that the Cas12a scaffold presents singular mechanical properties, which could be used to generate new endonucleases with biomedical and biotechnological applications.
Direct observation of nodeless superconductivity and phonon modes in electron-doped copper oxide Sr1−xNdxCuO2
Authors: Fan Jia-Qi , Yu Xue-Qing , Cheng Fang-Jun , Wang Heng , Wang Ruifeng , Ma Xiaobing , Hu Xiao-Peng , Zhang Ding , Ma Xu-Cun , Xue Qi-Kun , Song Can-Li 
Published: December 2021

Abstract
The microscopic understanding of high-temperature superconductivity in cuprates has been hindered by the apparent complexity of crystal structures in these materials. We used scanning tunneling microscopy and spectroscopy to study the electron-doped copper oxide compound Sr1−xNdxCuO2, which has only bare cations separating the CuO2 planes and thus the simplest infinite-layer structure of all cuprate superconductors. Tunneling conductance spectra of the major CuO2 planes in the superconducting state revealed direct evidence for a nodeless pairing gap, regardless of variation of its magnitude with the local doping of trivalent neodymium. Furthermore, three distinct bosonic modes are observed as multiple peak-dip-hump features outside the superconducting gaps and their respective energies depend little on the spatially varying gaps. As well as the bosonic modes, with energies identical to those of the external, bending and stretching phonons of copper oxides, our findings reveal the origin of the bosonic modes in lattice vibrations rather than spin excitations.
Multicenter, Prospective Validation of a Phenotypic Algorithm to Guide Carbapenemase Testing in Carbapenem-ResistantPseudomonas aeruginosaUsing the ERACE-PA Global Surveillance Program
Authors: Gill Christian M , Aktaþ Elif , Alfouzan Wadha , Bourassa Lori , Brink Adrian , Burnham Carey-Ann D , Canton Rafael , Carmeli Yehuda , Falcone Marco , Kiffer Carlos , Marchese Anna , Martinez Octavio , Pournaras Spyros , Satlin Michael J , Seifert Harald , Thabit Abrar K , Thomson Kenneth S , Villegas Maria Virginia , Nicolau David P 
Published: December 2021

AbstractBackgroundCarbapenemase-producing, carbapenem-resistant Pseudomonas aeruginosa (CP-CRPA) is a global challenge. However, detection efforts can be laborious because numerous mechanisms produce carbapenem resistance. A minimum inhibitory concentration–based algorithm (imipenem- or meropenem-resistant plus ceftazidime-nonsusceptible plus cefepime-nonsusceptible) was proposed to identify the isolates most likely to harbor a carbapenemase; however, prospective validation in geographies displaying genotypic diversity and varied carbapenemase prevalence is warranted.MethodsCRPA isolates were collected during the Enhancing Rational Antimicrobials for P. aeruginosa (ERACE-PA) global surveillance program from 17 sites in 12 countries. Isolates underwent susceptibility testing following local standards to ceftazidime, cefepime, and ceftolozane/tazobactam. Isolates underwent initial phenotypic carbapenemase screening followed by molecular testing if positive. The primary algorithm criteria were applied, and results were compared with phenotypic carbapenemase results to assess the performance of the algorithm. A secondary criterion, the algorithm criterion or imipenem- or meropenem-resistant plus ceftolozane/tazobactam-nonsusceptible, was assessed.ResultsA total of 807 CRPA were assessed, and 464 isolates met the algorithm criteria described above. Overall, testing was reduced by 43% compared with testing all CRPA. Carbapenemase-positive isolates missed by the algorithm were largely driven by Guiana extended spectrum (GES). Addition of the criterion of imipenem- or meropenem-resistant plus ceftolozane/tazobactam-nonsusceptible decreased the number of CP-CRPA missed by the algorithm (21 vs 40 isolates, respectively), reducing number of isolates tested by 39%.ConclusionsApplication of the initial algorithm (imipenem- or meropenem-resistant plus ceftazidime-nonsusceptible plus cefepime-nonsusceptible) performed well in a global cohort, with 33% phenotypically carbapenemase-positive isolates. The addition of imipenem- or meropenem-resistant plus ceftolozane/tazobactam-nonsusceptible reduced the number of phenotypically carbapenemase-positive isolates missed and may be useful in areas with a prominence of GES.
Investigation of the upper atmosphere in ultra-hot Jupiter WASP-76 b with high-resolution spectroscopy
Authors: Kawauchi Kiyoe , Narita Norio , Sato Bun’ei , Kawashima Yui 
Published: December 2021

Abstract
Alkali metal lines are one of the most important key opacity sources for understanding exoplanetary atmospheres because the Na i resonance doublets are thought to be the cause of low albedo, as the alkali metal’s wide line wings absorb almost all of the incoming stellar irradiation. High-resolution transmission spectroscopy of Na absorption lines can be used to investigate the temperature of the thermosphere of hot Jupiters, which is increased by stellar X-ray and extreme-ultraviolet irradiation. We applied high-resolution transmission spectroscopy to the ultra-hot Jupiter WASP-76 b with the High Dispersion Spectrograph (HDS) on the Subaru 8.2 m telescope. We report the detection of strong Na D excess absorption with line contrasts of $0.42 \pm 0.03\%$ (D1 at 5895.92 Å) and $0.38\pm 0.04\%$ (D2 at 5889.95 Å), full width at half maximum values of 1.63 ± 0.13 Å (D1) and 1.87 ± 0.22 Å (D2), and equivalent widths of (7.29 ± 1.43) × 10−3 Å (D1) and (7.56 ± 2.38) × 10−3 Å (D2). These results show that the Na D absorption lines are shallower and broader than those in previous work, whereas the absorption signals over the same passband are consistent with those in previous work. We derive the best-fitting isothermal temperature of 3700 K (without rotation) and 4200 K (with rotation). These results suggest the possibility of the existence of a thermosphere because the derived atmospheric temperature is higher than the equilibrium temperature (∼2160 K).
The radio dichotomy of active galactic nuclei
Authors: Xiao Hubing , Zhu Jingtian , Fu Liping , Zhang Shaohua , Fan Junhui 
Published: December 2021

Abstract
The question of radio dichotomy in active galactic nuclei (AGNs) is still in debate, even though it has been discussed for more than 40 years. In order to solve this old riddle, we collect a sample of AGNs with optical B band and radio 6 cm wavelength data to analyze the radio loudness log R. Our results indicate a separation of log R = 〈1.37 ± 0.02〉 between radio-loud (RL) AGNs and radio-quiet (RQ) AGNs, suggesting the existence of an RL/RQ dichotomy. For the first time, we suggest combining radio luminosity and radio loudness as a double criterion to divide AGNs into RLs and RQs to avoid misclassification problems that may happen in the single-criterion scenario; we propose the double-criterion dividing line log L6 cm = −2.7log R + 44.3 by using a machine-learning method. In addition, the key point of the RL/RQ dichotomy is the origin of radio emission for the two classes, and we suggest the radio emission from RLs and RQs share the same origin, e.g., jets and mini-jets (aborted-jet or outflow), through a correlation study between radio 6 cm luminosity and optical B-band luminosity.
The structural connectome in ADHD
Authors: Bu Xuan , Cao Miao , Huang Xiaoqi , He Yong 
Published: December 2021

Abstract
Attention-deficit/hyperactivity disorder (ADHD) has been conceptualized as a brain dysconnectivity disorder. In the past decade, noninvasive diffusion magnetic resonance imaging (dMRI) studies have demonstrated that individuals with ADHD have alterations in the white matter structural connectome, and that these alterations are associated with core symptoms and cognitive deficits in patients. This review aims to summarize recent dMRI-based structural connectome studies in ADHD from voxel-, tractography-, and network-based perspectives. Voxel- and tractography-based studies have demonstrated disrupted microstructural properties predominantly located in the frontostriatal tracts, the corpus callosum, the corticospinal tracts, and the cingulum bundle in patients with ADHD. Network-based studies have suggested abnormal global and local efficiency as well as nodal properties in the prefrontal and parietal regions in the ADHD structural connectomes. The altered structural connectomes in those with ADHD provide significant signatures for prediction of symptoms and diagnostic classification. These studies suggest that abnormalities in the structural connectome may be one of the neural underpinnings of ADHD psychopathology and show potential for establishing imaging biomarkers in clinical evaluation. However, given that there are inconsistent findings across studies due to sample heterogeneity and analysis method variations, these ADHD-related white matter alterations are still far from informing clinical practice. Future studies with larger and more homogeneous samples are needed to validate the consistency of current results; advanced dMRI techniques can help to generate much more precise estimation of white matter pathways and assure specific fiber configurations; and finally, dimensional analysis frameworks can deepen our understanding of the neurobiology underlying ADHD.
Evaluating the physicochemical effects of conjugating peptides into thermogelling hydrogels for regenerative biomaterials applications
Authors: Pearce Hannah A , Jiang Emily Y , Swain Joseph W R , Navara Adam M , Guo Jason L , Kim Yu Seon , Woehr Andrew , Hartgerink Jeffrey D , Mikos Antonios G 
Published: December 2021

Abstract
Thermogelling hydrogels, such as poly(N-isopropylacrylamide) [P(NiPAAm)], provide tunable constructs leveraged in many regenerative biomaterial applications. Recently, our lab developed the crosslinker poly(glycolic acid)-poly(ethylene glycol)-poly(glycolic acid)-di(but-2-yne-1,4-dithiol), which crosslinks P(NiPAAm-co-glycidyl methacrylate) via thiol-epoxy reaction and can be functionalized with azide-terminated peptides via alkyne-azide click chemistry. This study’s aim was to evaluate the impact of peptides on the physicochemical properties of the hydrogels. The physicochemical properties of the hydrogels including the lower critical solution temperature, crosslinking times, swelling, degradation, peptide release and cytocompatibility were evaluated. The gels bearing peptides increased equilibrium swelling indicating hydrophilicity of the hydrogel components. Comparable sol fractions were found for all groups, indicating that inclusion of peptides does not impact crosslinking. Moreover, the inclusion of a matrix metalloproteinase-sensitive peptide allowed elucidation of whether release of peptides from the network was driven by hydrolysis or enzymatic cleavage. The hydrophilicity of the network determined by the swelling behavior was demonstrated to be the most important factor in dictating hydrogel behavior over time. This study demonstrates the importance of characterizing the impact of additives on the physicochemical properties of hydrogels. These characteristics are key in determining design considerations for future in vitro and in vivo studies for tissue regeneration.
Two Factors, Five Factors, or Both? External Validation Studies of Negative Symptom Dimensions in Schizophrenia
Authors: Ahmed Anthony O , Kirkpatrick Brian , Granholm Eric , Rowland Laura M , Barker Peter B , Gold James M , Buchanan Robert W , Outram Tacina , Bernardo Miguel , Paz García-Portilla María , Mane Anna , Fernandez-Egea Emilio , Strauss Gregory P 
Published: December 2021

Abstract

Objectives
Negative symptom studies frequently use single composite scores as indicators of symptom severity and as primary endpoints in clinical trials. Factor analytic and external validation studies do not support this practice but rather suggest a multidimensional construct. The current study used structural equation modeling (SEM) to compare competing dimensional models of negative symptoms to determine the number of latent dimensions that best capture variance in biological, psychological, and clinical variables known to have associations with negative symptoms.

Methods
Three independent studies (total n = 632) compared unidimensional, two-factor, five-factor, and hierarchical conceptualizations of negative symptoms in relation to cognition, psychopathology, and community functioning (Study 1); trait emotional experience and defeatist performance beliefs (Study 2); and glutamate and gamma-aminobutyric acid levels in the anterior cingulate cortex quantified using proton magnetic resonance spectroscopy (Study 3).

Results
SEM favored the five-factor and hierarchical models over the unidimensional and two-factor models regardless of the negative symptom measure or external validator. The five dimensions—anhedonia, asociality, avolition, blunted affect, and alogia—proved vital either as stand-alone domains or as first-order domains influenced by second-order dimensions—motivation and pleasure and emotional expression. The two broader dimensions sometimes masked important associations unique to the five narrower domains. Avolition, anhedonia, and blunted affect showed the most domain-specific associations with external variables across study samples.

Conclusions
Five domains and a hierarchical model reflect the optimal conceptualization of negative symptoms in relation to external variables. Clinical trials should consider using the two dimensions as primary endpoints and the five domains as secondary endpoints.
Physical Activity and Sleep in 11-Year Old Children With a Familial High Risk of Schizophrenia or Bipolar Disorder. The Danish High Risk and Resilience Study—VIA 11
Authors: Søndergaard Anne , Wilms Martin , Gregersen Maja , Brandt Julie Marie , Krantz Mette Falkenberg , Rohd Sinnika Birkehøj , Johnsen Line Korsgaard , Hemager Nicoline , Hjorthøj Carsten , Ohland Jessica , Andreassen Anna Krogh , Knudsen Christina Bruun , Veddum Lotte , Greve Aja , Bliksted Vibeke , Mors Ole , Krustrup Peter , Thorsteinsson Troels , Schmidt-Andersen Peter , Kjærgaard Morten , Lykkegaard Kasper , Thorup Anne Amalie Elgaard , Nordentoft Merete 
Published: December 2021

Abstract

Objective
People with schizophrenia and bipolar disorder are at increased risk of having comorbid somatic illness. This is partly due to lack of physical activity, which may originate from childhood. Sleep disturbances are associated with schizophrenia and bipolar disorder. We aimed to assess physical activity and sleep in children at familial high risk of schizophrenia or bipolar disorder and population-based controls

Methods
This study is part of The Danish High Risk and Resilience Study—VIA 11. Children aged 11 born to parents with schizophrenia (FHR-SZ) (N = 133), bipolar disorder (FHR-BP) (N = 84), or controls (C) (N = 150) were assessed by accelerometry for an average of 6.9 days.

Results
High-intensity physical activity was significantly lower in children at FHR-SZ and FHR-BP compared to controls, (mean hours per day for FHR-SZ: 0.29, SD 0.19, for FHR-BP: 0.27, SD 0.24, and for controls 0.38, SD 0.22, P = &lt;.001). Sleep did not differ between the groups.

Conclusion
Children at FHR-SZ or FHR-BP had less physical activity compared to controls. Our study highlights a research area that reveals a hitherto unexplored disadvantage of being born to parents with schizophrenia or bipolar disorder. Further research is needed to enhance better understanding of causal pathways and consequences of reduced physical activity in children with FHR-SZ and FHR-BP.
PARP Inhibitors in Pancreatic Cancer
Authors: Brown Timothy J. , Reiss Kim A. 
Published: December 2021

Abstract
Despite representing only 5% of all annual cancer diagnoses in the United States, pancreatic cancer is projected to become the second leading cause of cancer-related death within the next 10 years. Progress in the treatment of advanced pancreatic cancer has been slow. Systemic therapies rely on combination cytotoxic agents, with limited options at progression. Recently, poly(ADP-ribose) polymerase inhibitors have demonstrated clinical activity in patients with advanced pancreatic cancer and pathogenic variants in BRCA1, BRCA2, and PALB2. In this review, we discuss the development of poly(ADP-ribose) polymerase inhibitors in pancreatic cancer, relevant clinical trials, and future directions.
Poly(ADP-Ribose) Polymerase Inhibitor Inhibition in Ovarian Cancer
Authors: Moore Kathleen N. , Pothuri Bhavana 
Published: December 2021

Abstract
The emergence of clinical trial data for poly(ADP-ribose) polymerase inhibitors (PARPi), in BRCA-associated ovarian cancer (epithelial ovarian cancer [EOC]) in 2009 (Lancet 2010;376:245–251) unleashed a rapid series of additional asset development and clinical trial activation across all lines of EOC treatment, ultimately leading to 8 new approvals of 3 different PARPi in EOC since 2014. Monotherapy iPARPi were approved as frontline maintenance treatment for all patients with EOC who respond to platinum-based chemotherapy irrespective of biomarker (niraparib) and for BRCA-associated cancers (olaparib) (https://www.azpicentral.com/lynparza_tb/lynparza_tb.pdf#page=1; https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208447s015s017lbledt.pdf). Combination of olaparib and bevacizumab was approved as maintenance for patients in response to platinum-based and bevacizumab containing frontline therapy whose tumor is characterized as homologous recombination deficient and as approved test by the Food and Drug Administration, inclusive of BRCA-associated cancers (N Engl J Med 2019;381:2416–2428). Niraparib, olaparib, and rucaparib were also approved as maintenance treatment following response to platinum-based therapy in the recurrent setting irrespective of biomarker (https://www.azpicentral.com/lynparza_tb/lynparza_tb.pdf#page=1; https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208447s015s017lbledt.pdf; https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209115s003lbl.pdf). All 3 PARPi were also approved as treatment in lieu of chemotherapy for patients with BRCA-associated cancers in third line and beyond (https://www.azpicentral.com/lynparza_tb/lynparza_tb.pdf#page=1;https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209115s003lbl.pdf) and platinum-sensitive homologous recombination deficient in the fourth line and beyond (https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208447s015s017lbledt.pdf), as well as the National Comprehensive Cancer Network listed in combination with bevacizumab for treatment of patients with platinum-sensitive recurrent disease (https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf). Ongoing clinical trials in all lines of treatment are evaluating combinations of therapies to improve efficacy among biomarker negative tumors as well as overcome acquired PARPi resistance due to prior use.