bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating miRNAs associated with bone mineral density in healthy adult baboons
Authors: Quillen Ellen. E. , Foster Jaydee , Sheldrake Anne , Stainback Maggie , Glenn Jeremy , Cox Laura A. , Bredbenner Todd L. 
Published: November 2021

AbstractMicroRNAs (miRNAs) regulate gene expression post‐transcriptionally and circulate in the blood, making them attractive biomarkers of disease state for tissues like bone that are challenging to interrogate directly. Here, we report on five miRNAs—miR‐197‐3p, miR‐320a, miR‐320b, miR‐331‐5p, and miR‐423‐5p—associated with bone mineral density (BMD) in 147 healthy adult baboons. These baboons ranged in age from 15 to 25 years (45–75 human equivalent years) and 65% were female with a broad range of BMD values including a minority of osteopenic animals. miRNAs were generated via RNA sequencing from buffy coats collected at necropsy and areal BMD (aBMD) measured postmortem via dual‐energy X‐ray absorptiometry (DXA) of the lumbar vertebrae. Differential expression analysis controlled for the underlying pedigree structure of these animals to account for genetic variation which may drive miRNA abundance and aBMD values. While many of these miRNAs have been associated with the risk of osteoporosis in humans, this finding is of interest because the cohort represents a model of normal aging and bone metabolism rather than a disease cohort. The replication of miRNA associations with osteoporosis or other bone metabolic disorders in animals with healthy aBMD suggests an overlap in normal variation and disease states. We suggest that these miRNAs are involved in the regulation of cellular proliferation, apoptosis, and protein composition in the extracellular matrix throughout life; and age‐related dysregulation of these systems may lead to disease. These miRNAs may be early indicators of progression to disease in advance of clinically detectible osteoporosis.
Novel solid‐phase microextraction fiber coatings: A review
Authors: Peng Sheng , Huang Xiaoyu , Huang Yuyan , Huang Yiquan , Zheng Juan , Zhu Fang , Xu Jianqiao , Ouyang Gangfeng 
Published: November 2021

AbstractThe materials used for the fabrication of solid‐phase microextraction fiber coatings in the past five years are summarized in the current review, including carbon, metal‐organic frameworks, covalent organic frameworks, aerogel, polymer, ionic liquids/poly (ionic liquids), metal oxides, and natural materials. The preparation approaches of different coatings, such as sol‐gel technique, in‐situ growth, electrodeposition, and glue methods, are briefly reviewed together with the evolution of the supporting substrates. In addition, the limitations of the current coatings and the future development directions of solid‐phase microextraction are presented.
Development of a method to screen and isolate xanthine oxidase inhibitors from black bean in a single step: Hyphenation of semipreparative liquid chromatography and stepwise flow rate countercurrent chromatography
Authors: Niu Hua‐zhou , Liu Chun‐ming , Hou Wan‐chao , Li Sai‐nan , Zhang Yu‐chi , Liu Zhen , Yun Hao‐cheng 
Published: November 2021

AbstractBlack bean, in which isoflavones are the main active constituent, also contains saponins and monoterpenes. Soybean isoflavone is a secondary metabolite that is formed during the growth of soybean; it exhibits antioxidant and cardiovascular activities and traces estrogen‐like effects. In this study, black bean isoflavones were extracted with n‐butanol, and ultrafiltration–liquid chromatography–mass spectrometry was used to screen their activity. Subsequently, the inhibitors were isolated and purified using semipreparative liquid chromatography and stepwise flow rate countercurrent chromatography. Thereafter, five active compounds were identified using mass spectrometry and nuclear magnetic resonance experiments. Finally, the inhibition types of the xanthine oxidase inhibitors were determined using enzymatic kinetic studies. The IC50 values of daidzin, glycitein‐7‐O‐glucoside, genistin, daidzein, and genistein were determined to be 35.08, 56.22, 30.76, 68.79, and 95.37 μg/mL, respectively. Daidzin, genistin, and daidzein exhibited reversible inhibition, whereas glycitein‐7‐O‐glucoside and genistein presented irreversible inhibition. This novel approach, which was based on ultrafiltration–liquid chromatography–mass spectrometry and stepwise flow rate countercurrent chromatography, is a powerful method for screening and isolating xanthine oxidase inhibitors from complex matrices. The study of enzyme inhibition types is helpful for understanding the underlying inhibition mechanism. Therefore, a beneficial platform was developed for the large‐scale production of bioactive and nutraceutical ingredients.
Secondary individual outcomes following multicouple group therapy for posttraumatic stress disorder: An uncontrolled pilot study with military dyads
Authors: Macdonald Alexandra , Fredman Steffany J. , Taylor Daniel J. , Pruiksma Kristi E. , Blount Tabatha H. , Hall‐Clark Brittany N. , Fina Brooke A. , Dondanville Katherine A. , Mintz Jim , Litz Brett T. , Young‐McCaughan Stacey , Le Yunying , Jenkins August I. C. , Monson Candice M. , Yarvis Jeffrey S. , Keane Terence M. , Peterson Alan L. ,   for the Consortium to Alleviate PTSD
Published: November 2021

AbstractCognitive‐behavioral conjoint therapy (CBCT) for posttraumatic stress disorder (PTSD) has demonstrated efficacy for improving PTSD and comorbid symptoms and relationship adjustment. To enhance treatment efficiency and scalability, we developed a 2‐day, abbreviated, intensive, multicouple group version of CBCT for PTSD (AIM‐CBCT for PTSD). Prior work demonstrated that AIM‐CBCT for PTSD wasassociated with reductions in PTSD and comorbid symptoms in a sample of 24 post‐9/11 active duty military or veteran couples who received the treatment in a retreat format over a single weekend. The current study investigated secondary outcomes regarding trauma‐related cognitions, psychosocial impairment, and insomnia. For trauma‐related cognitions, reductions were nonsignificant and small at 1‐month follow‐up, ds = −0.14 to −0.32. However, by 3‐month follow‐up, there were significant, medium effect size reductions in total trauma‐related cognitions, d = −0.68, and negative views of self and others, ds = −0.64 and −0.57, respectively, relative to baseline. There was also a nonsignificant, small‐to‐medium effect‐size reduction in self‐blame, d = −0.43, p = .053, by 3‐month follow‐up. For psychosocial impairment, there were significant and medium‐to‐large and large effect size reductions by 1‐ and 3‐month follow‐ups, ds = −0.73 and −0.81, respectively. There were nonsignificant, small effect size reductions in insomnia at both 1‐ and 3‐month follow‐ups relative to baseline, ds = −0.30 and −0.34, respectively. These findings suggest that AIM‐CBCT for PTSD is associated with reductions in maladaptive posttraumatic cognitions and psychosocial impairment but that adjunctive interventions may be needed to address insomnia.
Cognitive behavioral treatments for children and adolescents exposed to traumatic events: A meta‐analysis examining variables moderating treatment outcomes
Authors: Yohannan Justina , Carlson John S. , Volker Martin A. 
Published: November 2021

AbstractDue to the negative impact of trauma exposure, effective treatments are necessary to prevent and improve negative trauma‐related outcomes. Cognitive behavioral therapy (CBT) is considered an efficacious treatment for children and adolescents exposed to traumatic events. Despite the various meta‐analyses that have examined trauma treatments, there is a paucity of research on the moderating variables that may impact treatment outcomes. This meta‐analytic CBT study addressed those limitations by examining the moderating effects of treatment components on outcomes. A search identified 94 CBT studies with 97 relevant effect sizes for children and adolescents exposed to traumatic events. Consistent with prior meta‐analytic studies, CBT was shown to be effective for trauma‐exposed youth. CBT subtreatments did not produce significantly different results from one another. Moderators shown to significantly impact CBT treatment outcomes for posttraumatic stress symptom were trauma type, Q = 24.09, p = .004, ds = −0.22 to −1.42, and gender, Q = 10.68, p = .005, ds = −0.53 to −1.36, whereas moderators shown to impact treatment outcomes for depression were study design, Q = 10.95, p = .004, ds = −0.26 to −0.50, and treatment setting, Q = 10.98, p = .004, ds = −0.31 to −0.56. The implications of these findings for research and practice are discussed.
Effect of patient characteristics on posttraumatic stress disorder treatment retention among veterans: A systematic review
Authors: Maglione Margaret A. , Chen Christine , Franco Meghan , Gizaw Mahlet , Shahidinia Nima , Baxi Sangita , Hempel Susanne 
Published: November 2021

AbstractTo identify baseline patient characteristics (i.e., demographic and psychological factors, military background) associated with better posttraumatic stress disorder (PTSD) treatment retention among veterans, we conducted a systematic review. After an electronic database search for studies of PTSD treatment in veterans, two reviewers independently screened the literature for eligibility, abstracted study‐level information, and assessed risk of bias. As most studies used multivariate models to assess multiple potential predictors of retention simultaneously, the results were described narratively. The GRADE approach, adapted for prognostic literature, was used to assess the overall quality of evidence (QoE). In total, 19 studies reported in 25 publications met the inclusion criteria (n = 6 good quality, n = 9 fair quality, n = 4 poor quality). Definitions of treatment completion and dropout varied, and some studies lumped different therapy approaches together. Older age and higher treatment expectations were associated with better retention (moderate QoE). In 5 of 6 studies, baseline PTSD severity was not associated with retention, and the remaining study reported an association between better retention and more severe PTSD symptoms; the presence of more co‐occurring psychiatric disorders was associated with better retention (moderate QoE). QoE was low or insufficient to support conclusions for any other characteristics due to inconsistent results, imprecision, potential publication bias, possible study population overlap, study limitations, or lack of studies. More research is needed regarding the associations between modifiable factors (e.g., motivation, barriers, expectations) and retention, and consistent definitions of treatment completion and minimally adequate treatment should be adopted throughout the field.
Current development and future perspective of IDH1 inhibitors in cholangiocarcinoma
Authors: Adeva Jorge 
Published: November 2021

AbstractBackground and AimsBiliary tract cancer (BTC) represents a major public health problem due to its increasing rates of incidence and mortality, especially the intrahepatic cholangiocarcinoma (IHCCA) subtype. First line palliative systemic treatment with cisplatin and gemcitabine has been the unique level IA evidence option until last few years when a deeper understanding of its molecular landscape has unveiled CCA as a very rich targetable disease. This has revolutionised the patient's scenario and has brought new targeted therapies guided by molecular aberrations. Isocitrate dehydrogenase (IDH)1 mutations are the most prevalent targetable alteration in CCA (13% of IHCCA). Ivosidenib has been very recently approved by FDA for IDH1 mutated CCA patients based on a randomised clinical trial (ClarIDHy).MethodsWe review evidences related to IDH1 mutations in general oncogenesis focusing on CCA and summarise the present and potential future clinical options for the diagnosis and treatment of IDH1m CCA patients.ResultsAlthough the knowledge of the pathogenesis of IDH mutation is still a work in progress, epigenetic and metabolic dysregulation due to the oncometabolite 2‐hydroxyglutarate (2HG) are key in this process. Blocking mIDH1 with ivosidenib has shown significant and clinical benefit for this subgroup of patients. Primary and secondary resistance mechanisms to IDH inhibitors are now being described leading to the investigation of novel treatments such as more potent IDH inhibitors or other drugs that indirectly targets mIDH, as well as looking for novel biomarkers.ConclusionsAlthough ivosidenib is already available for treating advanced refractory IDH1 mutated CCA, there is still much space to improve outcomes. Several new treatment and diagnostic options in development could hopefully do it for this important subgroup of patients.
Factors Affecting Secondary and Supramolecular Structures of Self‐Assembling Peptide Nanocarriers
Authors: Pitz Megan E. , Nukovic Alexandra M. , Elpers Margaret A. , Alexander‐Bryant Angela A. 
Published: November 2021

AbstractSelf‐assembling peptides are a popular vector for therapeutic cargo delivery due to their versatility, tunability, and biocompatibility. Accurately predicting secondary and supramolecular structures of self‐assembling peptides is essential for de novo peptide design. However, computational modeling of such assemblies is not yet able to accurately predict structure formation for many peptide sequences. This review identifies patterns in literature between secondary and supramolecular structures, primary sequences, and applications to provide a guide for informed peptide design. An overview of peptide structures, their applications as nanocarriers, and analytical methods for characterizing secondary and supramolecular structure is examined. A top‐down approach is then used to identify trends between peptide sequence and assembly structure from the current literature, including an analysis of the drivers at work, such as local and nonlocal sequence effects and solution conditions.
Normalizing notations in the Ershov hierarchy
Authors: Peng Cheng 
Published: November 2021

AbstractThe Turing degrees of infinite levels of the Ershov hierarchy were studied by Liu and Peng [8]. In this paper, we continue the study of Turing degrees of infinite levels and lift the study of density property to the levels beyond ω2. In doing so, we rely on notations with some nice properties. We introduce the concept of normalizing notations and generate normalizing notations for higher levels. The generalizations of the weak density theorem and the nondensity theorem are proved for higher levels in the Ershov hierarchy. Furthermore, we also investigate the minimal degrees in the infinite levels of the Ershov hierarchy.
Simultaneous dose and dose rate optimization (SDDRO) of the FLASH effect for pencil‐beam‐scanning proton therapy
Authors: Gao Hao , Liu Jiulong , Lin Yuting , Gan Gregory N , Pratx Guillem , Wang Fen , Langen Katja , Bradley Jeffrey D , Rotondo Ronny L , Li Harold H , Chen Ronald C 
Published: November 2021

AbstractPurposeCompared to CONV‐RT (with conventional dose rate), FLASH‐RT (with ultra‐high dose rate) can provide biological dose sparing for organs‐at‐risk (OARs) via the so‐called FLASH effect, in addition to physical dose sparing. However, the FLASH effect only occurs, when both dose and dose rate meet certain minimum thresholds. This work will develop a simultaneous dose and dose rate optimization (SDDRO) method accounting for both FLASH dose and dose rate constraints during treatment planning for pencil‐beam‐scanning proton therapy.MethodsSDDRO optimizes the FLASH effect (specific to FLASH‐RT) as well as the dose distribution (similar to CONV‐RT). The nonlinear dose rate constraint is linearized, and the reformulated optimization problem is efficiently solved via iterative convex relaxation powered by alternating direction method of multipliers. To resolve and quantify the generic tradeoff of FLASH‐RT between FLASH and dose optimization, we propose the use of FLASH effective dose based on dose modifying factor (DMF) owing to the FLASH effect.ResultsFLASH‐RT via transmission beams (TB) (IMPT‐TB or SDDRO) and CONV‐RT via Bragg peaks (BP) (IMPT‐BP) were evaluated for clinical prostate, lung, head‐and‐neck (HN), and brain cases. Despite the use of TB, which is generally suboptimal to BP for normal tissue sparing, FLASH‐RT via SDDRO considerably reduced FLASH effective dose for high‐dose OAR adjacent to the target. For example, in the lung SBRT case, the max esophageal dose constraint 27 Gy was only met by SDDRO (24.8 Gy), compared to IMPT‐BP (35.3 Gy) or IMPT‐TB (36.6 Gy); in the brain SRS case, the brain constraint V12Gy≤15cc was also only met by SDDRO (13.7cc), compared to IMPT‐BP (43.9cc) or IMPT‐TB (18.4cc). In addition, SDDRO substantially improved the FLASH coverage from IMPT‐TB, e.g., an increase from 37.2% to 67.1% for lung, from 39.1% to 58.3% for prostate, from 65.4% to 82.1% for HN, from 50.8% to 73.3% for the brain.ConclusionsBoth FLASH dose and dose rate constraints are incorporated into SDDRO for FLASH‐RT that jointly optimizes the FLASH effect and physical dose distribution. FLASH effective dose via FLASH DMF is introduced to reconcile the tradeoff between physical dose sparing and FLASH sparing, and quantify the net effective gain from CONV‐RT to FLASH‐RT.
Dosimetric predictors and Lyman normal tissue complication probability model of hematological toxicity in cervical cancer patients with treated with pelvic irradiation
Authors: Wang Dandan , Yin Yueju , Zhou Qichao , Li Zirong , Ma Xingmin , Yin Yong , Li Baosheng , Bai Tong , Li Dapeng , Zhu Jian 
Published: November 2021

AbstractPurposeTo identify dosimetric parameters associated with acute hematological toxicity (HT) and identify the corresponding normal tissue complication probability (NTCP) model in cervical cancer patients receiving helical tomotherapy (Tomo) or fixed‐field intensity‐modulated radiation therapy (ff‐IMRT) in combination with chemotherapy, that is, concurrent chemoradiotherapy (CCRT) using the Lyman–Kutcher–Burman normal tissue complication probability (LKB‐NTCP) model.MethodsData were collected from 232 cervical cancer patients who received Tomo or ff‐IMRT from 2015 to 2018. The pelvic bone marrow (PBM) (including the ilium, pubes, ischia, acetabula, proximal femora, and lumbosacral spine) was contoured from the superior boundary (usually the lumbar 5 vertebra) of the planning target volume (PTV) to the proximal end of the femoral head (the lower edge of the ischial tubercle). The parameters of the LKB model predicting ≥grade 2 hematological toxicity (Radiation Therapy Oncology Group [RTOG] grading criteria) (TD50(1), m, and n) were determined using maximum likelihood analyses. Univariate and multivariate logistic regression analyses were used to identify correlations between dose–volume parameters and the clinical factors of HT.ResultsIn total, 212 (91.37%) patients experienced ≥grade 2 hematological toxicity. The fitted normal tissue complication probability model parameters were TD50(1) = 38.90 Gy (95%CI, [36.94, 40.96]), m = 0.13 (95%CI [0.12, 0.16]), and n = 0.04 (95%CI [0.02, 0.05]). Per the univariate analysis, the NTCP (the use of LKB‐NTCP with the set of model parameters found, p = 0.023), maximal PBM dose (p = 0.01), mean PBM dose (p = 0.021), radiation dose (p = 0.001), and V16–53 (p < 0. 05) were associated with ≥grade 2 HT. The NTCP (the use of LKB‐NTCP with the set of model parameters found, p = 0.023; AUC = 0.87), V16, V17, and V18 ≥ 79.65%, 75.68%, and 72.65%, respectively (p < 0.01, AUC = 0.66∼0.68), V35 and V36 ≥ 30.35% and 28.56%, respectively (p < 0.05; AUC = 0.71), and V47 ≥ 13.43% (p = 0.045; AUC = 0.80) were significant predictors of ≥grade 2 hematological toxicity from the multivariate logistic regression analysis.ConclusionsThe volume of the PBM of patients treated with concurrent chemoradiotherapy and subjected to both low‐dose (V16–18) and high‐dose (V35,36 and V47) irradiation was associated with hematological toxicity, depending on the fractional volumes receiving the variable degree of dosage. The NTCP were stronger predictors of toxicity than V16–18, V35, 36, and V47. Hence, avoiding radiation hot spots on the PBM could reduce the incidence of severe HT.
Enhancement of a high‐cycle accumulation model by an adaptive strain amplitude and its application to monopile foundations
Authors: Staubach P. , Machaček J. , Tschirschky L. , Wichtmann T. 
Published: November 2021

AbstractThe high‐cycle accumulation (HCA) model by Niemunis et al. allows the prediction of the mechanical response of sand under millions of load cycles . It has originally been developed with focus on sand under drained high‐cyclic loading assuming a constant strain amplitude, which can be periodically updated. In order to apply it for partially drained or fully undrained conditions, an adaptive definition of the strain amplitude is proposed in this work. The proposed extension allows taking into account the influence of rapid changes in soil stiffness on the strain amplitude as encountered, for example, in case of large changes in effective stress during the high‐cyclic loading. Two approaches are presented for the update of the strain amplitude: a ‘private’ update in each integration point combined with a nonlocal smoothing algorithm and an update in a separate analysis performed parallel to the simulation using the HCA model. Both approaches are compared to the methodology used in previous work employing so‐called update cycles. The importance and advantages of the proposed modifications are demonstrated by the simulation of undrained cyclic triaxial tests and monopile foundations for offshore wind turbines (OWTs) under high‐cyclic lateral loading and partially drained conditions.
Sequential detection of common transient signals in high dimensional data stream
Authors: Wu Yanhong , Wu Wei Biao 
Published: November 2021

AbstractMotivated from sequential detection of transient signals in high dimensional data stream, we first study the performance of EWMA and MA charts for detecting a transient signal in a single sequence in terms of the power of detection under the constraint of false detecting probability in the stationary state. Satisfactory approximations are given for the false detection probability and the power of detection. Comparison of EWMA, MA, and CUSUM charts shows that both charts are quite competitive. A multivariate EWMA procedure is considered by using the squared sum of individual EWMA processes and a fairly accurate approximation for the false detection probability is also given. To increase the power of detection, we use the Min‐δ procedure by truncating the estimated weak signals. Dow Jones 30 industrial stock prices are used for illustration.