bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of abdominal visceral fat on mortality risk in patients with severe acute pancreatitis
Authors: Higaki Yu , Nishida Tsutomu , Matsumoto Kengo , Yamaoka Sho , Osugi Naoto , Sugimoto Aya , Mukai Kaori , Nakamatsu Dai , Hayashi Shiro , Yamamoto Masashi , Nakajima Sachiko , Fukui Koji , Inada Masami
Published: November 2021

Background and Aim

Obesity is a well‐known risk factor for the development and severity of acute pancreatitis (AP), but the relationship between the abdominal visceral fat area (VFA) and mortality is unclear. We evaluated the effect of the VFA on mortality in severe AP (SAP).

Methods

This retrospective, single‐center cohort study examined 119 consecutive patients with SAP from April 2009 to March 2019. The VFA at the umbilical level was assessed using computed tomography. The primary endpoint was to evaluate whether visceral obesity affects mortality in SAP.

Results

The median age was 63 years, and 66% of participants were male. Nine patients (7.5%) died during their hospital stay. The median body mass index (BMI) was 22.2 kg/m2, and six obese patients had a BMI of over 30 kg/m2 (5%). The median waist circumference and VFA were 85.5 cm and 112 cm2, respectively. Sixty‐eight (57.1%) patients had a VFA over 100 cm2. The prognostic factor score based on the Japanese guidelines for AP management (cutoff value [COV], 4; area under the curve [AUC] = 0.869) and age [COV, 72; AUC = 0.780]) showed moderate accuracy for predicting mortality, followed by the VFA (COV, 167 cm2; AUC = 0.679). Univariate logistic analysis, but not multivariate analysis, showed that an increased VFA was associated with a significantly higher odds ratio (OR) for predicting mortality (OR: 4.38, P = 0.0406). The survival times of SAP patients with and without an increased VFA of 167 cm2 were not significantly different.

Conclusions

Visceral obesity did not have a significant impact on predicting mortality in patients with SAP.
Chimeric antigen receptor T‐cell therapy: Challenges and framework of outpatient administration
Authors: Gatwood Katie S. , Dholaria Bhagirathbhai R. , Lucena Mariana , Baer Brittney , Savani Bipin N. , Oluwole Olalekan O.
Published: November 2021

Adoptive cellular therapy has made a landmark change within the treatment paradigm of several hematologic malignancies, and novel cellular therapy products, such as chimeric antigen receptor T‐cell therapy (CART), have demonstrated impressive efficacy and produced durable responses. However, the CART treatment process is associated with significant toxicities, healthcare resource utilization, and financial burden. Most of these therapies have been administered in the inpatient setting due to their toxicity profile. Improved toxicity management strategies and a better understanding of cellular therapy processes are now established. Therefore, efforts to transition CART to the outpatient setting are warranted with the potential to translate into enhanced patient quality of life and cost savings. A successful launch of outpatient CART requires several components including a multidisciplinary cellular therapy team and an outpatient center with appropriate clinical space and personnel. Telemedicine should be incorporated for closer monitoring. Additionally, clear criteria for admission upon clinical decompensation, a pathway for prompt inpatient transition, and clear toxicity management guidelines should be implemented. Effective education about cellular therapy and toxicity management is imperative, especially for the Emergency Department and Intensive Care Unit teams. Here, we have outlined the various logistical and clinical considerations required for the care of CART patients, which will aid centers to establish an outpatient CART program.
Role of bridging therapy during chimeric antigen receptor T cell therapy
Authors: Bhaskar Shakthi T. , Dholaria Bhagirathbhai R. , Sengsayadeth Salyka M. , Savani Bipin N. , Oluwole Olalekan O.
Published: November 2021

Chimeric antigen receptor (CAR) T‐cell therapy has been approved for use in several relapsed/refractory hematologic malignancies and has significantly improved outcomes for these diseases. A number of different CAR T products are now being used in clinical practice and have demonstrated excellent outcomes to those in clinical trials. However, increased real‐world use of CAR T therapy has uncovered a number of barriers that can lead to significant delays in treatment. As a result, bridging therapy has become a widely used tool to stabilize or debulk disease between leukapheresis and CAR T cell administration. Here we review the available data regarding bridging therapy, with a focus on patient selection, choice of therapy, timing of therapy, and potential pitfalls.
Efficacy and safety of temperature‐controlled intraductal radiofrequency ablation in advanced malignant hilar biliary obstruction: A pilot multicenter randomized comparative trial
Authors: Kang Huapyong , Han Sung Yong , Cho Jae Hee , Kim Eui Joo , Kim Dong Uk , Yang Jae Kook , Jeon Soyoung , Park Goeun , Lee Tae Hoon
Published: November 2021

Purpose

We aimed to evaluate the efficacy and safety of temperature‐controlled intraductal radiofrequency ablation (ID‐RFA) for advanced malignant hilar biliary obstruction (MHBO).

Methods

Patients were randomly assigned to RFA group (ID‐RFA and bilateral plastic stent [PS]) or non‐RFA group (bilateral PS) at a 1:1 ratio. Exchange to self‐expanding metal stent (SEMS) was performed after 3 months or when premature PS occlusion occurred. Total event‐free stent patency, overall survival (OS), and adverse events (AEs) were analyzed.

Results

A total of 30 patients from three hospitals were enrolled. Stent patency and OS did not differ between the two groups (178 days vs 122 days, P = .154; 230 days vs 144 days, P = .643; respectively). In patients with each stricture length ≥11 mm on both sides, stent patency was longer in the RFA group than in the non‐RFA group (175 days vs 121 days, P = .028). More patients received elective exchange to SEMS without PS occlusion in the RFA group than in the non‐RFA group (69.2% vs 23.1%, P = .018). AE rates did not differ between the two groups.

Conclusions

Temperature‐controlled ID‐RFA for advanced MHBO was safe and feasible. It could prevent premature PS occlusion within 3 months.
Development of the temporomandibular joint in miniature pig embryos
Authors: Xiang Lei , Wang Xuewen , Li Yongfeng , Liu Hua Wei , Zhang Xianhua , Mu Xiaodan , Liu Changkui , Hu Min
Published: November 2021

The temporomandibular joint (TMJ) is a synovial joint involved in sliding and hinge movements of lower jaw in mammals. Studies on TMJ development in embryos have been mainly performed using rodents. However, the TMJ structure in rodents differs in several aspects from that in humans. There are few studies on the embryonic development of TMJ in large mammals. In the present study, we investigated the embryonic developmental characteristics of the TMJ in pigs histologically. Embryonic day 35 (E35), E45, E55, E75, E90, and postnatal day 1(P1) embryos/fetuses from the pigs were used for the study. The results showed condensation of mesenchymal cells on E35. The inferior articular cavity was formed on E45, together with a narrow crack in the superior articular cavity region. The superior and inferior articular cavities and articular disc of the TMJ were completely formed on E55. On E75, the condyle showed an obvious conical shape and the superior and inferior joint cavities were enlarged. Furthermore, the mandibular ramus and mandibular body under the neck of the condyle were ossified from E75 to P1 day. The chondrocyte layer of the condyle was significantly thinner from E75 to P1. It is speculated that the spatiotemporal development of the TMJ in miniature pig embryos is similar to that in humans. Embryonic development of the pig TMJ is an important bridge for translating the results of rodent research to medical applications.
Ex‐VivoMRI of the Normal Human Placenta: Structural–Functional Interplay and the Association With Birth Weight
Authors: Link‐Sourani Daphna , Avisdris Netanell , Harel Shaul , Ben‐Sira Liat , Ganot Tuvia , Gordon Zoya , Many Ariel , Ben Bashat Dafna
Published: November 2021

Background

Advanced magnetic resonance imaging (MRI) methods are increasingly being used to assess the human placenta. Yet, the structure–function interplay in normal placentas and their associations with pregnancy risks are not fully understood.

Purpose

To characterize the normal human placental structure (volume and umbilical cord centricity index (CI)) and function (perfusion) ex‐vivo using MRI, to assess their association with birth weight (BW), and identify imaging‐markers for placentas at risk for dysfunction.

Study Type

Prospective.

Population

Twenty normal term ex‐vivo placentas.

Field Strength/Sequence

3 T/ T1 and T2 weighted (T1W, T2W) turbo spin‐echo, three‐dimensional susceptibility‐weighted image, and time‐resolved angiography with interleaved stochastic trajectories (TWIST), during passage of a contrast agent using MRI compatible perfusion system that mimics placental flow.

Assessment

Placental volume and CI were manually extracted from the T1W images by a fetal‐placental MRI scientist (D.L., 7 years of experience). Perfusion maps including bolus arrival‐time and full‐width at half maximum were calculated from the TWIST data. Mean values, entropy, and asymmetries were calculated from each perfusion map, relating to both the whole placenta and volumes of interest (VOIs) within the umbilical cord and its daughter blood vessels.

Statistical Tests

Pearson correlations with correction for multiple comparisons using false discovery rate were performed between structural and functional parameters, and with BW, with P < 0.05 considered significant.

Results

All placentas were successfully perfused and scanned. Significant correlations were found between whole placenta and VOIs perfusion parameters (mean R = 0.76 ± 0.06, range = 0.67–0.89), which were also significantly correlated with CI (mean R = 0.72 ± 0.05, range = 0.65–0.79). BW was correlated with placental volume (R = 0.62), but not with CI (P = 0.40). BW was also correlated with local perfusion asymmetry (R = −0.71).

Data Conclusion

Results demonstrate a gradient of placental function, associated with CI and suggest several ex‐vivo imaging‐markers that might indicate an increased risk for placental dysfunction.

Level of Evidence

1

Technical Efficacy

Stage 1
Effects of uninterrupted dabigatran on the intensity of anticoagulation during atrial fibrillation ablation
Authors: Osawa Takumi , Mori Hitoshi , Kawai Akane , Kawano Daisuke , Tsutsui Kenta , Ikeda Yoshifumi , Yamaga Mitsuki , Sato Atsushi , Gatate Youdou , Hamabe Akira , Tabata Hirotsugu , Kato Ritsushi , Matsumoto Kazuo
Published: November 2021

Background

Uninterrupted dabigatran during atrial fibrillation (AF) ablation is now established as the standard therapy. However, there are few reports on the effects of uninterrupted dabigatran on the intensity of anticoagulation during AF ablation.

Methods

We retrospectively analyzed 247 consecutive patients who underwent AF ablation in our hospital from January 2017 to December 2018. Patients who took warfarin or uninterrupted direct oral anticoagulants (DOACs) except for dabigatran were excluded. 89 patients underwent ablation with uninterrupted dabigatran (uninterrupted group, male 71, mean age 59.6 ± 14.0) and 124 with interrupted DOACs (interrupted group, male 105, mean age 56.9 ± 12.9) during AF ablation. The initial ACT level, proportion of ACT levels of more than 300 s, and total amount of heparin were compared. Furthermore, the incidence of procedure complications was also evaluated.

Results

The initial ACT levels were significantly higher in the uninterrupted group, and the total number of ACTs of more than 300 s was significantly higher in the uninterrupted group (uninterrupted vs. interrupted; initial ACT level, 315.6 ± 59.8 vs. 264.5 ± 48.6, p < .001; total number of ACTs ≧300, n [%], 304/ 484 [62.8 %] vs. 372/745 [49.9%], p < .001). The total amount of heparin during procedure was significantly lower in the uninterrupted group (uninterrupted group vs. interrupted group; 12966 ± 4773 vs. 16371 ± 5212, p < .001). There was no significant difference in the incidence of complications between the two groups.

Conclusions

In the catheter ablation of AF, uninterrupted dabigatran would be useful to obtain a stable anticoagulation status during the entire procedure.
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

MicroRNAs (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

The 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

Black 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

Cognitive‐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

Due 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

To 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

Background and Aims

Biliary 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).

Methods

We 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.

Results

Although 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.

Conclusions

Although 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

Self‐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

The 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.
Kennedy Forum event calls for urgent school‐based MH support
Authors: Canady Valerie A.
Published: November 2021

In the weeks following a declaration by the American Academy of Child and Adolescent Psychiatry, American Academy of Pediatrics and Children's Hospital Association of a national emergency in children's mental health brought on by the pandemic and other existing challenges, The Kennedy Forum convened a panel discussion of education experts to discuss innovative approaches to engage youth and strategies for addressing common challenges.
Supercloseness in a balanced norm of finite element methods on Shishkin and Bakhvalov–Shishkin rectangular meshes for reaction–diffusion problems
Authors: Zhang Jin , Liu Xiaowei
Published: November 2021

We present a convergence analysis for finite element methods of any order, which are applied on Shishkin mesh and Bakhvalov–Shishkin mesh to a singularly perturbed reaction–diffusion problem. A new interpolant is introduced for analysis in the balanced norm. By means of this interpolant and some superconvergence estimations, we prove supercloseness results in the cases of Shishkin mesh and Bakhvalov–Shishkin mesh. Numerical experiments also support these theoretical results.
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

Purpose

Compared 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.

Methods

SDDRO 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.

Results

FLASH‐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.

Conclusions

Both 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

Purpose

To 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.

Methods

Data 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.

Results

In 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.

Conclusions

The 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

The 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

Motivated 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.
A duality‐based coupling of Cosserat crystal plasticity and phase field theories for modeling grain refinement
Authors: Baek Jonghyuk , Chen Jiun‐Shyan , Tupek Michael , Beckwith Frank , Fang H. Eliot
Published: November 2021

High‐rate deformation processes of metals entail intense grain refinement and special attention needs to be paid to capture the evolution of microstructure. In this article, a new formulation for coupling Cosserat crystal plasticity and phase field is developed. A common approach is to penalize kinematic incompatibility between lattice orientation and displacement‐based elastic rotation. However, this can lead to significant solution sensitivity to the penalty parameter, resulting in low accuracy and convergence rates. To address these issues, a duality‐based formulation is developed which directly imposes the rotational kinematic compatibility. A weak inf‐sup‐based skew‐symmetric stress projection is introduced to suppress instabilities present in the dual formulation. An additional least squares stabilization is introduced to suppress the spurious lattice rotation with a suitable parameter range derived analytically and validated numerically. The required high‐order continuity is attained by the reproducing kernel approximation. It is observed that equal order displacement‐rotation‐phase field approximations are stable, which allows efficient employment of the same set of shape functions for all independent variables. The proposed formulation is shown to yield superior accuracy and convergence with marginal parameter sensitivity compared to the penalty‐based approach and successfully captures the dominant rotational recrystallization mechanism including block dislocation structures and grain boundary migration.
An efficient 4‐node facet shell element for the modified couple stress elasticity
Authors: Shang Yan , Wu Huan‐Pu , Cen Song , Li Chen‐Feng
Published: November 2021

This work proposes a simple but robust 4‐node 24‐DOF facet shell element for static analysis of small‐scale thin shell structures. To accommodate the size effects, the modified couple stress theory is employed as the theoretical basis. The element is constructed via two main innovations. First, the trial functions that can a priori satisfy related governing differential equations are adopted as the basic functions for formulating the element interpolations. Second, the generalized conforming theory and the penalty function method are employed to meet the C1 continuity requirement in weak sense for ensuring the computation convergence property. Several benchmarks of shells with different geometries are tested to assess the new facet shell element's capability. The numerical results reveal that the element can effectively simulate the size‐dependent mechanical behaviors of small‐scale thin shells, exhibiting satisfactory numerical accuracy and low susceptibility to mesh distortion. Moreover, as the shell element uses only six degrees of freedom per node, it can be incorporated into the commonly available finite element programs very readily.
Spectral Galerkin method for state constrained optimal control of fractional advection‐diffusion‐reaction equations
Authors: Wang Fangyuan , Zhou Zhaojie
Published: November 2021

In this article a spectral Galerkin approximation of fractional advection diffusion optimal control problem with state constraint in norm is discussed. The continuous first order optimality condition is derived. Weighted Jacobi polynomials are used to approximate the state and adjoint state. A priori error estimates for state, adjoint state, and control variables in and weighted norms are derived. Numerical examples are presented to verify the theoretical findings.
Long‐term weight loss maintenance with obesity pharmacotherapy: A retrospective cohort study
Authors: Tchang Beverly G. , Aras Mohini , Wu Alan , Aronne Louis J. , Shukla Alpana P.
Published: November 2021

Objective

To determine the association of anti‐obesity medications (AOMs) with weight loss maintenance over 2 years.

Methods

This is a retrospective observational cohort study of adults treated for obesity between 1 April 2014 and 1 April 2016 at a tertiary academic weight management center and who completed 2 years of follow‐up. Main outcome measures were mean percent weight loss, percent of individuals who achieved clinically significant long‐term weight loss (≥5% weight loss over 2 years), and long‐term weight loss maintenance (achievement of ≥5% weight loss at 1 year and maintenance of the ≥5% reduction for the second year).

Results

Of the 1566 new patients, 421 completed 1‐ and 2‐year follow‐up appointments. Patients were mostly female and on average 51 years old; they weighed 100.1 kg and had a BMI of 35.8 kg/m2 at initial visit. Mean weight losses at 1 and 2 years were 10.1% and 10.2%, respectively. The proportion of patients who experienced ≥5% weight loss was 75.5% at 1 year and 72.9% at 2 years. Long‐term weight loss maintenance was achieved by 65.3% of patients. Almost all (96.2%) were on ≥1 AOM at 2 years, with metformin, phentermine, and topiramate among the most prescribed. AOM usage and older age demonstrated trends toward predicting weight loss maintenance over 2 years.

Conclusions

Long‐term weight loss maintenance was observed among adults with medically managed obesity who completed 2 years of follow‐up.
Development of temperature‐responsive polymeric gels with physical crosslinking due to intermolecular 𝜋–𝜋 interactions
Authors: Shah Rishabh A , Runge Tyler , Ostertag Thomas W , Tang Shuo , Dziubla Thomas D , Hilt J Zach
Published: November 2021

Poly(N‐isopropylacrylamide) was polymerized with comonomers containing a biphenyl moiety to create a unique thermoresponsive physically crosslinked system due to the presence of π–π interactions between the biphenyl moieties. The biphenyl monomers used were 2‐phenylphenol monoacrylate (2PPMA) and 4‐phenylphenol monoacrylate (4PPMA). These monomers were utilized to synthesize a set of polymers with biphenyl monomer (2PPMA/4PPMA) content from 2.5 to 7.5 mol% and with initiator concentrations of 0.1 and 1.0 wt%. The resulting polymers were characterized using various techniques, such as gel permeation chromatography (GPC), swelling studies and mechanical testing. A decrease in the average molecular weight of the polymers due to the increase in the concentration of initiator was confirmed from GPC results. Swelling studies confirmed the expected temperature‐dependent swelling properties and explored the impact of the biphenyl comonomers. These studies indicated that with an increase in biphenyl comonomer content, the physical crosslinking increases which leads to a decrease in the swelling ratio. The results from the mechanical tests also indicate the effect of the concentration of biphenyl comonomers. These physically crosslinked polymeric systems with their unique properties have potential applications spanning environmental remediation/sensing, biomedicine, etc. © 2021 Society of Industrial Chemistry.
Structure and impact properties of a thermoplastic elastomer/silly putty blend
Authors: Zhao Zhigang , Liu Fang , Yang Xue , Zhang Dan , Luan Shifang , Xu Donghua , Shi Tongfei
Published: November 2021

The structure and impact properties of a thermoplastic elastomer/silly putty blend are explored. The impact‐resistant materials are made with polyolefin‐based thermoplastic elastomer HYBRAR™ 5127 and silly putty DOWSIL™ 3179. The peak impact force decreases with the content of silly putty, as part of the impact energy might be dissipated by the dissociation of boron–oxygen dynamic dative bonds in silly putty. It is also observed that the crack behavior of samples under impact is related to the phase structure of silly putty in the samples. For the samples with high content of silly putty, a macroscopic crack is observed for these samples under impact, as a crack can spread in the continuous phase structure of silly putty. Different energy dissipation ratios in rheological, compression and impact experiments are also observed. It is concluded that the results of linear dynamic oscillatory shear and compression at a low strain rate cannot give a direct predication of energy dissipation ratios of samples under impact at a high strain rate. © 2021 Society of Industrial Chemistry.
Regio‐regular and cross‐conjugated poly(thienylene vinylene)s through acyclic diene metathesis
Authors: Bader Yousef M. Katba , Guan Chao , Qin Yang
Published: November 2021

Poly(thienylene vinylene)s (PTV's) are early examples of conjugated polymers but have not been extensively studied when compared with closely analogous polythiophenes. PTV's synthesized through previously reported techniques are similar in structures that contain various alkyl or alkoxy side‐chains that exert limited impact on the polymer electronic properties. Herein, we report the preparation of a series of regio‐regular PTV's (rr‐PTV's) bearing cross‐conjugated side‐chains through ADMET polymerization of a common brominated di(thienylene vinylene) (DTV) monomer followed by PPM reactions on the resulting brominated PTV. These new polymers contain a bulky silyloxy alkyl side‐chain and a functionalized thiophene moiety on every main‐chain thiophene unit, and their regio‐regular placement is confirmed by NMR spectroscopy. The thienyl based side‐groups broaden polymer absorption ranges and at the same time lead to uncommon emission properties that are results of light‐induced charge transfer events between the polymer main‐chains and side‐chains. Removal of the silyl groups on one of these rr‐PTV's led to insoluble materials and x‐ray diffraction experiments on the collected solids displayed distinct scattering peaks that are absent from similarly functionalized regio‐random PTV's reported previously, thus suggesting better crystallinity originated from regio‐regularity.
Crystal structure of Aedes aegypti trypsin inhibitor in complex with μ‐plasmin reveals role for scaffold stability in Kazal‐type serine protease inhibitor
Authors: Walvekar Varsha Ashok , Ramesh Karthik , Jobichen Chacko , Kannan Muthu , Sivaraman J. , Kini R. Manjunatha , Mok Yu Keung
Published: November 2021

Kazal‐type protease inhibitor specificity is believed to be determined by sequence of the reactive‐site loop that make most, if not all, contacts with the serine protease. Here, we determined the complex crystal structure of Aedes aegypti trypsin inhibitor (AaTI) with μ‐plasmin, and compared its reactivities with other Kazal‐type inhibitors, infestin‐1 and infestin‐4. We show that the shortened 99‐loop of plasmin creates an S2 pocket, which is filled by phenylalanine at the P2 position of the reactive‐site loop of infestin‐4. In contrast, AaTI and infestin‐1 retain a proline at P2, rendering the S2 pocket unfilled, which leads to lower plasmin inhibitions. Furthermore, the protein scaffold of AaTI is unstable, due to an elongated Cys‐V to Cys‐VI region leading to a less compact hydrophobic core. Chimeric study shows that the stability of the scaffold can be modified by swapping of this Cys‐V to Cys‐VI region between AaTI and infestin‐4. The scaffold instability causes steric clashing of the bulky P2 residue, leading to significantly reduced inhibition of plasmin by AaTI or infestin‐4 chimera. Our findings suggest that surface loops of protease and scaffold stability of Kazal‐type inhibitor are both necessary for specific protease inhibition, in addition to reactive site loop sequence. PDB ID code: 7E50.