bluuebunny/crossref_metadata_2025 huggingface dataset:
Pandemic‐resilient target setting in colorectal cancer screening for vulnerable older population
Authors: Shibata Toshiaki , Shinjo Daisuke , Takahashi Junichi , Fushimi Kiyohide
Published: June 2022

Background

Colorectal cancer screening (CRCS) needs to be pandemic‐resilient to avoid long‐lasting shutdowns; however, realistic participation target remains unelucidated. This study aimed to identify the lowest acceptable participation rate in CRCS during a pandemic, focusing on vulnerable older populations who require urgent intervention.

Methods

This nationwide cross‐sectional study included 80,946 inpatients aged 70–85 years who were first diagnosed with colorectal cancer (CRC) after 70 years of age, between April 1, 2014 and March 31, 2019, in Japan. To evaluate the association between area‐level CRCS participation rate and individual early CRC detection, a multilevel logistic regression model was constructed. The mandatorily implemented screening rates were converted to the total screening rate equivalents (TSREs), which reflect the remaining contributions of voluntarily provided screenings.

Results

Early detections during stages 0–I were significantly observed when primary screening rate was ≥38% (TSRE) and combined follow‐up rate was ≥85%. For early detection during Tis–T1, primary screening rate ≥ 38% (TSRE) and combined follow‐up rate ≥ 90% were necessary. For follow‐up rates ≥70% or ≥75%, there were cases where missed detection of Tis–T1 were observed.

Conclusion

The results indicate that, even during pandemic, CRCS should achieve a primary screening rate of 38% and follow‐up rate of 85% for vulnerable older populations. These values, lower than the current desirable rates, suggest the maximum possible compromise in balancing the resources between cancer screening and pandemic measures. Moreover, they also indicate the minimum target for shifting to fecal immunochemical test‐focused program. Further explorations with varied CRCS settings are necessary for verification.
You have to give power to empower your team
Authors: Skipworth Stan
Published: June 2022

Although there's a good amount of truth to the familiar adage “you have to spend money to make money,” the reality is that some people have much simply given to them and yet they may not have the skills to augment their resources beyond that point.
Transcatheter aortic valve implantation in patients with uninterrupted vitamin K antagonists
Authors: Robert Pierre , Akodad Mariama , Lattuca Benoit , Gandet Thomas , Macia Jean‐Christophe , Schmutz Laurent , Delseny Delphine , Piot Christophe , Leclercq Florence , Cayla Guillaume
Published: June 2022

Background

Bridging of vitamin K antagonist (VKA) with heparin is usually not promoted during interventional or surgical procedures related to increased risk of bleeding and thrombotic events but this strategy has not been evaluated during transcatheter aortic valve implantation (TAVI).

Purpose

The aim of this study was to evaluate the rate of major bleeding and vascular complications after TAVI performed in patients with uninterrupted VKA.

Methods

From January 2016 to October 2017, consecutive patients who underwent TAVI with uninterrupted VKA (International Normalized Ratio [INR] between 1.5 and 3.5) were prospectively included in a monocentric registry. TAVI was performed according to current guidelines and a 50 U/kg bolus of heparin was injected at the beginning of the procedure for all patients. Vascular and bleeding complications were assessed using the Valve Academic Research Consortium 3 (VARC3) and the Bleeding Academic Research Consortium (BARC) definitions at a 30‐day follow‐up.

Results

A total of 88 patients were included with a median age of 84 years (81.8–87.0), 42% being female. The median society of thoracic surgeons score was 5.1 (4.1–7.5), the median CHADS2‐VASc was 5.5 (5–6) and 60.2% had a chronic kidney failure. Median INR at the time of implantation was 2.1 (1.8–2.6). The main VKA indication was atrial fibrillation. Transfemoral access was used in 88.6% of the patients. Major bleeding (BARC ≥ 3b) occurred in five patients (5.7%) and major vascular complications occurred in seven patients (8.0%). At 1 month follow‐up, major bleeding (BARC ≥ 3) or vascular complications occurred in 10 patients (11.4%). In patients with major bleeding peripheral arterial disease (RR = 10.95; 95% confidence interval (CI) 1.63–73.75; p = 0.014) and carotid access (RR = 8.56; 95% CI 1.19–1.51; p = 0.033) were more common. INR > 2.5 was significantly associated with vascular complications (RR = 7.14; 95% CI 1.29–39.63; p = 0.025). At 30 days, mortality and stroke rates were 2.3% and 4.5%, respectively.

Conclusion

TAVI with uninterrupted VKA treatment seems feasible and safe with a low risk of major bleeding and vascular complications in this first single‐center experience. Particular caution is advocated in high body mass index patients and to keep INR < 2.5.
Structural Engineering of Nitrogen‐Doped MoS2 Anchored on Nitrogen‐Doped Carbon Nanotubes towards Enhanced Hydrogen Evolution Reaction
Authors: Li He , Xie Fei , Snyders Rony , Bittencourt Carla , Li Wenjiang
Published: June 2022

Molybdenum disulfide (MoS2) has emerged as an attractive non‐noble‐metal electrocatalyst for hydrogen evolution reaction (HER), but its performance is limited by scarce active sites and poor conductivity. Herein, we construct a hetero‐structure of nitrogen‐doped MoS2 ultrathin nanosheets anchored on nitrogen‐doped multi‐walled carbon nanotubes (N−MoS2/N−CNTs) using urea as N‐doping reagent. It is demonstrated that the N species can expand the interlayer spacing of MoS2 and in‐situ substitute the S atoms in MoS2 lattices to create more structural defects, enabling highly exposed basal plane/edge sites. Simultaneously, N species in CNTs favor the interface coupling between N−MoS2 and N−CNTs, which can maintain structural stability and accelerate electron/proton reaction kinetics. Consequently, N−MoS2/N−CNTs exhibits the in‐depth enhancement of HER activity with a low onset potential (77 mV), small Tafel slope (40.5 mV dec−1) and excellent cycling stability. Furthermore, the essential relationship between the N‐doping concentration and HER activity of N−MoS2/N−CNTs was demonstrated.
Reconstitution of muscle cell microtubule organization in vitro
Authors: Nadkarni Ambika V. , Heald Rebecca
Published: June 2022

Skeletal muscle differentiation occurs as muscle precursor cells (myoblasts) elongate and fuse to form multinucleated syncytial myotubes in which the highly‐organized actomyosin sarcomeres of muscle fibers assemble. Although less well characterized, the microtubule cytoskeleton also undergoes dramatic rearrangement during myogenesis. The centrosome‐nucleated microtubule array found in myoblasts is lost as the nuclear membrane acquires microtubule nucleating activity and microtubules emerge from multiple sites in the cell, eventually rearranging into a grid‐like pattern in myotubes. In order to characterize perinuclear microtubule organization using a biochemically tractable system, we isolated nuclei from mouse C2C12 skeletal muscle cells during the course of differentiation and incubated them in cytoplasmic extracts prepared from eggs of the frog Xenopus laevis. Whereas centrosomes associated with myoblast nuclei gave rise to radial microtubule arrays in extracts, myotube nuclei produced a sun‐like pattern with microtubules transiently nucleating from the entire nuclear envelope. Perinuclear microtubule growth was suppressed by inhibition of Aurora A kinase or by degradation of RNA, treatments that also inhibited microtubule growth from sperm centrosomes. Myotube nuclei displayed microtubule motor‐based movements leading to their separation, as occurs in myotubes. This in vitro assay therefore recapitulates key features of microtubule organization and nuclear movement observed during muscle cell differentiation.
Efficacy of post‐induction therapy for high‐risk neuroblastoma patients with end‐induction residual disease
Authors: Desai Ami V. , Applebaum Mark A. , Karrison Theodore G. , Oppong Akosua , Yuan Cindy , Berg Katherine R. , MacQuarrie Kyle , Sokol Elizabeth , Hall Anurekha G. , Pinto Navin , Wolfe Ian , Mody Rajen , Shusterman Suzanne , Smith Valeria , Foster Jennifer H. , Nassin Michele , LaBelle James L. , Bagatell Rochelle , Cohn Susan L.
Published: June 2022

BACKGROUND

High‐risk neuroblastoma patients with end‐induction residual disease commonly receive post‐induction therapy in an effort to increase survival by improving the response before autologous stem cell transplantation (ASCT). The authors conducted a multicenter, retrospective study to investigate the efficacy of this approach.

METHODS

Patients diagnosed between 2008 and 2018 without progressive disease with a partial response or worse at end‐induction were stratified according to the post‐induction treatment: 1) no additional therapy before ASCT (cohort 1), 2) post‐induction “bridge” therapy before ASCT (cohort 2), and 3) post‐induction therapy without ASCT (cohort 3). χ2 tests were used to compare patient characteristics. Three‐year event‐free survival (EFS) and overall survival (OS) were estimated by the Kaplan‐Meier method and survival curves were compared by log‐rank test.

RESULTS

The study cohort consisted of 201 patients: cohort 1 (n = 123), cohort 2 (n = 51), and cohort 3 (n = 27). Although the end‐induction response was better for cohort 1 than cohorts 2 and 3, the outcomes for cohorts 1 and 2 were not significantly different (P = .77 for EFS and P = .85 for OS). Inferior outcomes were observed for cohort 3 (P < .001 for EFS and P = .06 for OS). Among patients with end‐induction stable metastatic disease, 3‐year EFS was significantly improved for cohort 2 versus cohort 1 (P = .04). Cohort 3 patients with a complete response at metastatic sites after post‐induction therapy had significantly better 3‐year EFS than those with residual metastatic disease (P = .01).

CONCLUSIONS

Prospective studies to confirm the benefits of bridge treatment and the prognostic significance of metastatic response observed in this study are warranted.
12(S)‐hydroxyeicosatetraenoic acid is significantly increased in diabetic kidney disease and associated with renal function decline
Authors: Xu Jie , Jin Li , Sun Yi , Zhang Rong , Chen Xianghui , Zhou Ranran , Gu Yunjuan , Hu Cheng
Published: June 2022

Aims

12(S)‐hydroxyeicosatetraenoic (12(S)‐HETE), an alternate arachidonic acid metabolite, has been recently examined in metabolic disease. However, the role of 12(S)‐HETE in diabetic kidney disease (DKD) remains unclear. We studied for the first time the relationship of serum 12(S)‐HETE and DKD and renal function parameters in a Chinese population.

Materials and Methods

We recruited 275 subjects who were diagnosed with type 2 diabetes (T2DM) for more than 10 years, including 149 DKD patients and 126 T2DM patients without DKD. Serum 12(S)‐HETE was measured using the enzyme‐linked immunosorbent assay.

Results

Serum 12(S)‐HETE was significantly higher in DKD patients than controls [384.69 (77.54, 1003.05) pg/ml and 17.77 (8.11, 75.13) pg/ml, respectively, p < 0.0001]. Compared to controls, 12(S)‐HETE was significantly increased in both macroalbuminuria and microalbuminuria groups (p < 0.0001). Further, the macroalbuminuria group also had a higher serum 12(S)‐HETE level compared to the microalbuminuria group (p = 0.0063). Moreover, serum 12(S)‐HETE was positively correlated with the albuminuria level (r = 0.5833, p < 0.0001), serum creatinine (r = 0.2725, p < 0.0001), and was negatively associated with the estimated glomerular filtration rate (r = −0.2085, p = 0.0005). Further, receiver operating characteristic analysis (ROC) revealed that 12(S)‐HETE had a good performance of distinguishing DKD from controls (AUC 0.828) with a sensitivity of 0.913 and a specificity of 0.711.

Conclusion

Our findings revealed that serum 12(S)‐HETE significantly associated with DKD and disease severity, suggesting that serum 12(S)‐HETE may be used as a potential biomarker for the early diagnosis of DKD.
Anomalous coloration in European pine marten Martes martes in Elba Island, Central Italy
Authors: Manzo Emiliano , Bartolommei Paola , Dell’Agnello Filippo , Cozzolino Roberto
Published: June 2022

Evidence of abnormal coloration in wild animals provides useful information to better understand its adaptive function and its impact on survival. For this reason, we need to know the frequency and distribution of these abnormal phenotypes in wild populations. Here, we report two records of hypopigmentation in European pine marten Martes martes, obtained during a camera‐trapping survey on Elba Island, Central Italy. We do not know what has caused anomalous coloration of pine marten on Elba Island, but it is possible that the inbreeding may have played a role in this isolated population. Although the light coloration certainly entails an increased visibility of pine martens, it is possible that the low predator pressure and the absence of other wild carnivore populations in our study could mitigate the mortality risk due to the light phenotype. The increased use of camera traps across the world can potentially facilitate the discovery of cases of anomalous colorations in wild populations, providing an unprecedented insight into the occurrence of this phenomenon in wild mammal species.
Towards the Synthesis of Highly Hindered Pyrrolidines by Intramolecular AAC Click Reactions: What Can Be Learned from DFT Calculations?**
Authors: Cicetti Soledad , Maestre Eugenia , Spanevello Rolando A. , Sarotti Ariel M.
Published: June 2022

A straightforward synthesis of a highly substituted biomass‐derived chiral pyrrolidine conveniently functionalized to obtain macrocycles through intramolecular “click” reactions is reported. The experimental difficulties encountered during the macrocyclization stage led us to conduct an extensive DFT study to understand the origins of the findings. The results suggest that the improper conformational landscape of the reactant precludes the pre‐organization required to connect the reactive moieties. We propose that the cumulative Boltzmann amplitudes of reactive conformations (CBAR) prove to be a simple and useful parameter to predict the success or failure of related transformations.
A splitting method for the numerical simulation of free surface flows with sediment deposition and resuspension
Authors: Mrad Arwa , Caboussat Alexandre , Picasso Marco
Published: June 2022

We present a numerical model for the simulation of 3D sediment transport in a Newtonian flow with free surfaces. The Navier–Stokes equations are coupled with the transport, deposition, and resuspension of the particle concentrations, and a volume‐of‐fluid approach to track the free surface between water and air. The numerical method relies on operator splitting to decouple advection and diffusion phenomena, and a two‐grid method. An appropriate combination of characteristics, finite volumes, and finite elements methods is advocated. The numerical model is validated through comparisons with numerical experiments, sediment flushing, shear flow erosion, and the formation of dunes.
Analysis of cost and outcomes in bony versus soft tissue midface free flap reconstruction
Authors: Alnemri Angela , Philips Ramez , Sussman Sarah , Xu Vivian , Givens Alyssa , Patel Anjali , Swendseid Brian , Agarwal Aarti , Keith Scott , Shimada Ayako , Selman Yamil , Cognetti David M. , Heffelfinger Ryan , Goldman Richard , Luginbuhl Adam J. , Wax Mark K. , Sweeny Larissa , Curry Joseph M.
Published: June 2022

Background

Outcomes and cost of soft tissue versus bony midface free flap reconstruction (MR) with and without virtual surgical planning (VSP) were evaluated.

Methods

Retrospective review of MR including ischemic time (IT), operative duration (OD), length of stay (LOS), and total cost (TC). Eighty‐one soft tissue and 76 bony MR (VSP = 23) were reviewed.

Results

Bony MR was used for higher complexity defects (p = 0.003) and was associated with higher IT (p < 0.001), OD (p < 0.001), LOS (p = 0.032), and TC (p < 0.001). VSP was associated with a mean 111.2 ± 37.9 minute reduction in OD (p = 0.004) compared to non‐VSP bony flaps. VSP was associated with higher itemized cost, but no increase in TC (p = 0.327).

Conclusions

Bony MR was used for higher complexity MR and was associated with increased TC, LOS, OD, and IT. VSP shortened OD with no significant increase in TC.
Reduced number of IFN‐γ producing cells in peripheral blood is a biomarker for patients with renal cell carcinoma
Authors: Wu Kun‐Jin , Yang Kun , Zhang Feng‐Ping , Liu Si‐Nan , Yang Kai‐Bo , Ma Xiao‐Hua , Zhang Xing , Ma Yan‐Fen , Geng Hui , Wang Zheng , Liu Chang , Lin Ting
Published: June 2022

Renal cell cancer (RCC) is the most lethal of all the common urologic cancers and constitutes 2.2% of all malignancy diagnoses. The incidence of RCC has been steadily increasing in recent decades. The classic risk factors of RCC include smoking, hypertension, obesity, genetics, and genetic mutations. Recent studies also revealed that RCC was an immunogenic tumor and affected by host immune status. Among the pan‐cance, RCC presented with the highest degree of immune infiltration, indicating RCC patients might benefit from immunotherapy. A new immune classification of RCC has been developed by Su et al. based on tumor‐infiltrating lymphocytes to guide clinical practice. However, these studies mainly focus on biomarkers derived from tumor microenvironment (TME), the biomarkers based on peripheral blood samples to RCC have rarely been described. We collected peripheral blood samples from RCC patients and their matched healthy controls and detected the number of IL‐2 and IFN‐γ producing cells by implementing an enzyme‐linked immunospot (ELISPOT) assay. This is the first study to report blood‐based immune biomarkers for RCC using an ELISPOT assay. Our results suggested the frequency of IFN‐γ producing cells but not IL‐2 producing cells was associated with RCC risk. These findings warrant further validation in larger prospective studies.
Targeting euchromatic histone lysine methyltransferases sensitizes colorectal cancer to histone deacetylase inhibitors
Authors: Bamberg Leonhard Valentin , Heigwer Florian , Wandmacher Anna Maxi , Singh Ambika , Betge Johannes , Rindtorff Niklas , Werner Johannes , Josten Julia , Skabkina Olga Valerievna , Hinsenkamp Isabel , Erdmann Gerrit , Röcken Christoph , Ebert Matthias P , Burgermeister Elke , Zhan Tianzuo , Boutros Michael
Published: June 2022

Epigenetic dysregulation is an important feature of colorectal cancer (CRC). Combining epigenetic drugs with other antineoplastic agents is a promising treatment strategy for advanced cancers. Here, we exploited the concept of synthetic lethality to identify epigenetic targets that act synergistically with histone deacetylase (HDAC) inhibitors to reduce the growth of CRC. We applied a pooled CRISPR‐Cas9 screen using a custom sgRNA library directed against 614 epigenetic regulators and discovered that knockout of the euchromatic histone‐lysine N‐methyltransferases 1 and 2 (EHMT1/2) strongly enhanced the antiproliferative effect of clinically used HDAC inhibitors. Using tissue microarrays from 1066 CRC samples with different tumor stages, we showed that low EHMT2 protein expression is predominantly found in advanced CRC and associated with poor clinical outcome. Cotargeting of HDAC and EHMT1/2 with specific small molecule inhibitors synergistically reduced proliferation of CRC cell lines. Mechanistically, we used a high‐throughput Western blot assay to demonstrate that both inhibitors elicited distinct cellular mechanisms to reduce tumor growth, including cell cycle arrest and modulation of autophagy. On the epigenetic level, the compounds increased H3K9 acetylation and reduced H3K9 dimethylation. Finally, we used a panel of patient‐derived CRC organoids to show that HDAC and EHMT1/2 inhibition synergistically reduced tumor viability in advanced models of CRC.
Circulating brain‐derived neurotrophic factor dysregulation and its linkage with lipid level, stenosis degree, and inflammatory cytokines in coronary heart disease
Authors: Xia Feng , Zeng Qingrong , Chen Jing
Published: June 2022

Background

Brain‐derived neurotrophic factor (BDNF) regulates the lipid metabolism, atherosclerosis plaque formation, and inflammatory process, while the study about its clinical role in coronary heart disease (CHD) is few. The present study intended to explore the expression of BDNF and its relationship with stenosis, inflammation, and adhesion molecules in CHD patients.

Methods

After serum samples were obtained from 207 CHD patients, BDNF, tumor necrosis factor‐alpha (TNF‐α), interleukin (IL)‐1β, IL‐6, IL‐8, IL‐17A, vascular cell adhesion molecule‐1 (VCAM‐1), and intercellular adhesion molecule‐1 (ICAM‐1) levels were determined using ELISA. Then, the BDNF level was also examined in 40 disease controls (DCs) and 40 healthy controls (HCs), separately.

Results

BDNF was lower in CHD patients than in DCs and HCs (median (95% confidential interval) value: 5.6 (3.5–9.6) ng/mL vs. 10.7 (6.1–17.0) ng/mL and 12.6 (9.4–18.2) ng/mL, both p < 0.001). BDNF could well distinguish CHD patients from DCs (area under the curve [AUC]: 0.739) and HCs (AUC: 0.857). BDNF was negatively associated with triglyceride (p = 0.014), total cholesterol (p = 0.037), and low‐density lipoprotein cholesterol (p = 0.008). BDNF was negatively associated with CRP (p < 0.001), TNF‐α (p < 0.001), IL‐1β (p = 0.008), and IL‐8 (p < 0.001). BDNF was negatively related to VCAM‐1 (p < 0.001) and ICAM‐1 (p = 0.003). BDNF was negatively linked with the Gensini score (p < 0.001).

Conclusion

BDNF reflects the lipid dysregulation, inflammatory status, and stenosis degree in CHD patients.
Scanning electron microscopy for identification of local strain of Aspergillus Parasiticus and its larvicidal efficacy against Aedes Aegypti and non‐target toxicity testing on fingerlings of Hypophthalmichthys Molitrix
Authors: Abrar Amina , Abbas Moneeza , Mehmood Salma , Ghani Nadia , Fatima Ammara , Shahzadi Rabia
Published: June 2022

Scanning electron microscopy proved to be helpful in identification of Aspergillus parasiticus. A. parasiticus has a worldwide occurrence with high entomopathogenic efficacy against Aedes aegypti. However, assessment of pathogenic effects of entomopathogenic fungi on non‐target organisms is required to evaluate its use as bio control agent. Aim of the present research is to study the parricidal activity of the local strain of A. parasiticus (MK371710) against A. aegypti and its toxicity assessment against aquatic model organism Hypophthalmichthys molitrix. A. parasiticus was isolated from the soil of Jallo Park, Lahore. The larvicidal effect of A. parasiticus was evaluated against fourth instar larvae of A. aegypti. Hundred percent of mortality of larvae was observed after exposure to 1 × 107 conidia/ml of fungal suspension after 72 h post treatment. The LC50 value of A. parsiticus in 24 h post treatment and 48 h post treatment was recorded as 1.0 × 107conidia/ml 2.99 × 105conidia/ml, respectively. However, an in‐depth understanding safety to non‐target organisms is necessary, if we are to properly control the action of these entomopathogenic fungi under natural conditions. For the toxicity assessment fingerlings of H. molitrix were exposed to conidial suspensions of A. parasiticus. Eye pop (64%), fin hemorrhage (33%), and scale infection (30%) were the major morphological effects observed during the study. Results reveal that although A. parasiticus is highly pathogenic to dengue vector but also have significant effects on organisms other than insects and its application as biological control agent requires safety considerations.

Highlights

Assessment of pathogenic effects of entomopathogenic fungi on non‐target organisms is required to evaluate its use as biocontrol agent.

SEM was used to identify the microscopic view of Aspergillus parasiticus.

Aim of the present research is to study the larvicidal activity of the local strain of A. parasiticus (MK371710) against Aedes aegypti and its toxicity assessment against aquatic model organism Hypophthalmichthys molitrix.
Solvability of mixed problems for the wave equation with reflection of the argument
Authors: Mussirepova Elmira , Sarsenbi Abdissalam A. , Sarsenbi Abdizhahan M.
Published: June 2022

The paper considers mixed problems for the wave equation with reflection of the argument, with a complex‐valued variable coefficient. The existence and uniqueness of solution of the studied problems is established by the method of separation of variables.
A compact tri‐band filter based on a dual‐capacitively loaded triple‐mode substrate integrated waveguide resonator
Authors: Jing Huaishu , Zhang Yonghong , Qu Lili , Jing Shouzhao , Liu Jiawei , Bo Xiaole
Published: June 2022

This letter presents a compact tri‐band filter using a dual‐capacitively loaded (DCL) substrate integrated waveguide (SIW) triple‐mode resonator. The frequencies of TE101, TE102, and TE103 are shifted lower by the capacitive loading effect, which is achieved by the DCL structure. A compact tri‐band example filter is then built by using two DCL triple mode SIW  resonators. Following that, seven transmission zeros are generated to improve filter selectivity by vertical coupling of two cavities. The area of the filter occupies only 0.46 λg2. The measured results demonstrate that this compact tri‐band filter has the advantages of flexible control of passbands, easy interconnection with other planar radio frequency components, making it promising for millimeter wave implementations and 3D‐integrated systems.
Gradient‐echo‐train‐based sub‐millisecond periodic event encoded dynamic imaging with random (k, t)‐space undersampling: k‐tget‐SPEEDI
Authors: Luo Qingfei , Zhong Zheng , Sun Kaibao , Scotti Alessandro , Zhou Xiaohong Joe
Published: June 2022

Purpose

The gradient‐echo‐train‐based Sub‐millisecond Periodic Event Encoded Dynamic Imaging (get‐SPEEDI) technique provides ultrahigh temporal resolutions (∼0.6 ms) for detecting rapid physiological activities, but its practical adoption can be hampered by long scan times. This study aimed at developing a more efficient variant of get‐SPEEDI for reducing the scan time without degrading temporal resolution or image quality.

Methods

The proposed pulse sequence, named k‐t get‐SPEEDI, accelerated get‐SPEEDI acquisition by undersampling the k‐space phase‐encoding lines semi‐randomly. At each time frame, k‐space was fully sampled in the central region whereas randomly undersampled in the outer regions. A time‐series of images was reconstructed using an algorithm based on the joint partial separability and sparsity constraints. To demonstrate the performance of k‐t get‐SPEEDI, images of human aortic valve opening and closing were acquired with 0.6‐ms temporal resolution and compared with those from conventional get‐SPEEDI.

Results

k‐t get‐SPEEDI achieved a 2‐fold scan time reduction over the conventional get‐SPEEDI (from ∼6 to ∼3 min), while achieving comparable SNRs and contrast‐to‐noise ratio (CNRs) for visualizing the dynamic process of aortic valve: SNR/CNR 70/38 vs. 73/39 in the k‐t and conventional get‐SPEEDI scans, respectively. The time courses of aortic valve area also matched well between these two sequences with a correlation coefficient of 0.86.

Conclusions

The k‐t get‐SPEEDI pulse sequence was able to half the scan time without compromising the image quality and ultrahigh temporal resolution. Additional scan time reduction may also be possible, facilitating in vivo adoptions of SPEEDI techniques.
Systematic Dimensional Analysis of the Scaling Relationship for Gradient and Shim Coil Design Parameters
Authors: Lee Seung‐Kyun , Bernstein Matt A.
Published: June 2022

Purpose

To demonstrate systematic, linear algebra–based, dimensional analysis to derive a scaling relationship among the design parameters of MRI gradient and harmonic shim coils.

Theory and Methods

The dimensions of five physical quantities relevant for gradient coil design (inductance, gradient amplitude, inner diameter [], current, and the permeability of free space) were decomposed into fundamental units, and their exponents were arranged into a dimensional matrix. The resulting set of homogenous equations was solved using standard linear algebraic methods. Inclusion of the number of turns as an additional unit yielded a 5 × 5 dimensional matrix with a unique, nontrivial solution. The analysis was extended to harmonic shim coils. The gradient coil scaling relationship was compared with data from 24 published gradient coil sets.

Results

Only when the unit of turns was included did the linear algebra–based analysis uniquely produce the known scaling relationship that gradient inductance is proportional to gradient efficiency squared times . By applying the same methodology to anlth order shim coil, a novel result is obtained: Shim inductance is proportional to its efficiency squared times . The predicted power‐law relationship between inductance‐normalized gradient efficiency and the diameter accounted for > 92% of the efficiency variation of the surveyed gradient coils. A dimensionless parameter is proposed as an intrinsic figure‐of‐merit of gradient coil efficiency.

Conclusion

Systematic application of linear algebra–based dimensional analysis can provide new insight in gradient and shim coil design by revealing fundamental scaling relations and helping to guide the design and comparison of coils with different diameters.
Correcting for imaging gradients–related bias of T2 relaxation times at high‐resolution MRI
Authors: Bnaiahu Natalie , Omer Noam , Wilczynski Ella , Levy Shir , Blumenfeld‐Katzir Tamar , Ben‐Eliezer Noam
Published: June 2022

Purpose

High‐resolution animal imaging is an integral part of preclinical drug development and the investigation of diseases' pathophysiology. Quantitative mapping of T2 relaxation times (qT2) is a valuable tool for both preclinical and research applications, providing high sensitivity to subtle tissue pathologies. High‐resolution T2 mapping, however, suffers from severe underestimation of T2 values due to molecular diffusion. This affects both single‐echo and multi‐echo spin echo (SSE and MESE), on top of the well‐known contamination of MESE signals by stimulated echoes, and especially on high‐field and preclinical scanners in which high imaging gradients are used in comparison to clinical scanners.

Methods

Diffusion bias due to imaging gradients was analyzed by quantifying the effective b‐value for each coherence pathway in SSE and MESE protocols, and incorporating this information in a joint T2‐diffusion reconstruction algorithm. Validation was done on phantoms and in vivo mouse brain using a 9.4T and a 7T MRI scanner.

Results

Underestimation of T2 values due to strong imaging gradients can reach up to 70%, depending on scan parameters and on the sample's diffusion coefficient. The algorithm presented here produced T2 values that agreed with reference spectroscopic measurements, were reproducible across scan settings, and reduced the average bias of T2 values from −33.5 ± 20.5% to −0.1 ± 3.6%.

Conclusions

A new joint T2‐diffusion reconstruction algorithm is able to negate imaging gradient–related underestimation of T2 values, leading to reliable mapping of T2 values at high resolutions.
Pregnancy outcomes in patients with congenital myasthenic syndromes
Authors: O'Connell Karen , Rooney Tatiana , Alabaf Setareh , Ramdas Sithara , Beeson David , Palace Jacqueline
Published: June 2022

Introduction/Aims

The congenital myasthenic syndromes (CMS) are a heterogeneous group of inherited disorders that affect neuromuscular junction transmission. Data on pregnancy outcomes in women with CMS are limited due to their infrequency. In this study we explored pregnancy with CMS in a large cohort of women attending a national specialty clinic in England.

Methods

All women with CMS who had a documented pregnancy were invited to complete a questionnaire assessing clinical status during pregnancy and postpartum, pregnancy outcomes, fetal outcomes, and medication use during pregnancy.

Results

Among 16 women with CMS (acetylcholine receptor deficiency [CHRNE], slow channel syndrome [CHRNA1], DOK7, RAPSYN and glycosylation [DPAGT1 and GFPT1]), 27 pregnancies were recorded: 26 single pregnancies and 1 twin pregnancy. Symptom worsening was reported in 63% of pregnancies, but recovery to baseline function was seen in all but one patient. Miscarriage and cesarean section occurred in 31% and 33% of the women, respectively. Over half of the patients continued taking their medication during pregnancy, which included pyridostigmine (n = 10), 3,4‐diaminopyridine (n = 9), ephedrine (n = 3), salbutamol (n = 3), and quinidine (n = 1). No fetal malformations were recorded.

Discussion

Our results show that clinical worsening during pregnancy was common but rarely persistent. The majority of women with CMS can safely plan pregnancy, but close follow‐up is required from their neurology and obstetric teams. Although we identified no safety concerns, continued medication use should be reviewed on a case‐by‐case basis.
Langerhans cell histiocytosis of single‐system multifocal bone, including the mandible, in a 22‐month‐old child: A case report
Authors: Sakai Kiyoshi , Yamamoto Noriyuki , Yamaguchi Satoshi , Okabe Kazuto , Koma Yoshiro , Hibi Hideharu
Published: June 2022

Background

Langerhans cell histiocytosis (LCH) is a rare disease in which antigen‐presenting Langerhans cells proliferate abnormally.

Case Presentation

We report a case of a 22‐month‐old boy who presented with left cheek swelling. A palpable bony bulge was noted at the left mandibular angle and a malignant tumor was suspected. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed an area of bone resorption from the left mandibular angle to the mandibular branch. Positron emission tomography (PET)‐CT revealed accumulation in the left mandible, left femoral diaphysis, and L1 vertebra. The patient was diagnosed with multiple‐bone LCH and underwent chemotherapy.

Conclusion

Four years after treatment, the patient is doing well and has no recurrence.
Objectively measured physical activity among treatment seeking children and adolescents with severe obesity and normal weight peers
Authors: Danielsen Yngvild S. , Skjåkødegård Hanna F. , Mongstad Marit , Hystad Sigurd W. , Olsson Sven J. G. , Kleppe Malin , Juliusson Petur B. , Frisk Bente
Published: June 2022

Background

Treatment seeking children and adolescents with severe obesity often experience barriers to physical activity. Studies objectively measuring physical activity in this group and investigating explanatory factors for physical activity levels could inform clinical practice.

Objectives

This study aimed to compare objectively measured physical activity levels among treatment seeking children and adolescents with severe obesity and normal weight peers, and to investigate explanatory factors for time spent in moderate physical activity and vigorous physical activity among children and adolescents with severe obesity.

Methods

Children with severe obesity (n = 85) were matched 1:1 by age, gender, and the season for accelerometer measurements with normal weight peers (n = 85). Children wore accelerometers for seven consecutive days, yielding measures of physical activity, sleep duration and timing. Parents reported on screen time, parental body mass index and participation in organized sports.

Results

Children and adolescents with severe obesity spent significantly less time in moderate physical activity (12 min, p < 0.001) and vigorous physical activity (21 min, p < 0.001) per day compared to normal weight peers. No difference for time spent in sedentary activity was found between groups. For participants with severe obesity, age ≤12 years (p = 0.009) and participation in organized sports (p = 0.023) were related to more moderate physical activity, while age ≤12 years (p = 0.038) and early sleep timing (p = 0.019) were related to more vigorous physical activity.

Conclusion

Children and adolescents with severe obesity were less physically active than their normal weight peers. Factors related to more moderate and vigorous physical activity in children with severe obesity were lower age, participation in organized sports and earlier sleep timing.
The role of demonstration projects as policy instruments in the development of nonprofit organizations: Beyond instrumentality
Authors: Liu Zejin , Van de Walle Steven
Published: June 2022

Demonstration projects have been widely used to demonstrate new technologies and practices to stimulate broader deployment and implementation. Apart from this technical and explicit function, demonstration projects also serve social and implicit functions that have received limited attention. This study examines the ways in which demonstration projects are drawn upon as policy instruments. Building on the political sociology approach to policy instruments, this study employs a qualitative case study design to investigate the roles of 2989 centrally funded demonstration projects in the Chinese nonprofit area. The results reveal that demonstration projects can be used not only in a technical sense for effectively addressing public problems but also in a social sense as an opportunity for justifying public action and power within a particular area in the name of public values.
EndoBarrier treatment for longstanding type 2 diabetes and obesity: outcomes one year after EndoBarrier in 90 consecutively treated patients
Authors: Ryder Robert EJ , Yadagiri Mahi , Burbridge Wyn , Irwin Susan P , Gandhi Hardeep , Bashir Tahira , Allden Rachael A , Wyres Melanie , Cull Melissa , Bleasdale John P , Fogden Edward N , Anderson Mark R , Gupta Piya Sen
Published: June 2022

Aims: EndoBarrier is a 60cm duodenal–jejunal bypass liner endoscopically implanted for up to one year and designed to mimic the by‐pass part of Roux‐en‐Y bariatric surgery. We aimed to assess the safety and efficacy of EndoBarrier in patients with suboptimally‐controlled diabesity.

Methods: Between July 2013 and November 2017 we implanted 90 EndoBarriers in a single centre with all removed by November 2018. Outcomes were monitored in a registry.

Results: All 90 patients have completed one‐year post EndoBarrier removal and, of these, 71/90 (79%) – age 51.3 ± 8.6 years, 46% male, 52% White ethnicity, diabetes duration 13.0 (7.0–17.0) years, 59% insulin‐treated, BMI 41.1 ± 6.5kg/m2) – attended follow‐up and 19/90 (21%) did not attend follow‐up. During EndoBarrier implantation, mean ± SD HbA1c fell by 19.5 ± 18.4mmol/mol from 78.1 ± 18.9 to 58.6 ± 13.6mmol/mol (p < 0.001), weight by 15.9 ± 8.6kg from 118.4 ± 27.0 to 102.4 ± 27.7kg (p < 0.001), systolic BP from 139.0 ± 15.0mmHg to 126.6 ± 17.6mmHg (p < 0.001), cholesterol from 4.8 ± 1.2 to 4.0 ± 1.0mmol/L (p < 0.001), and serum alanine‐aminotransferase (marker of liver fat) from 31.0 ± 16.5 to 19.8 ± 11.5U/L (p < 0.001). Median (IQR) total daily insulin dose reduced from 98 (53–163) to 30 (0–63) units (p < 0.001). Eleven of 42 (26.2%) insulin treated patients discontinued insulin. One year post‐EndoBarrier 32/71 (45%) demonstrated fully‐sustained improvement, 25/71 (35%) partially‐sustained improvement and 14/71 (20%) reverted to baseline. Of those deteriorating, 10/14 (71%) had depression and/or bereavement. Thirteen of 90 (14%) patients required early EndoBarrier removal: five for gastrointestinal haemorrhage, two for liver abscess, one for non‐hepatic intra‐abdominal abscess, and five for gastrointestinal symptoms. All made a full recovery.

Conclusion: Our data demonstrate EndoBarrier as highly effective in patients with refractory diabesity, with maintenance of significant improvement one year after removal in 80% of cases. As it requires only an endoscopic procedure, EndoBarrier treatment is relatively simple and non‐invasive and it deserves further investigation. Copyright © 2022 John Wiley & Sons.
National audit of children and young people with type 2 diabetes shows rising trend in contributory factors of serious concern
Authors: Chaplin Steve
Published: June 2022

The latest results of the National Diabetes Audit and the National Paediatric Diabetes Audit together have identified serious concerns regarding the rising incidence of type 2 diabetes in children and young people. Obesity and deprivation play a major part; this and improvements in treatment delivery need to be addressed. Steve Chaplin reports.
Reduced risk of NSAID‐Induced adverse events with concomitant use of misoprostol (MICRO study)
Authors: Munger Mark A. , Nelson Scott D. , Teng Chia‐Chen , Cheung Alfred K. , Sauer Brian C.
Published: June 2022

Background

Non‐steroidal anti‐inflammatory drugs (NSAIDs) are one of the most frequently used medications for pain, even though they increase the risk for adverse cardiovascular events.

Objectives

The objective of this study was to determine cardiovascular, cerebrovascular, and renal event rates between NSAIDs versus NSAIDs plus misoprostol.

Methods

A population‐based historical cohort of U.S. veterans receiving prescription NSAIDs (1,681,609) versus NSAIDs plus misoprostol (5972 misoprostol users) was followed for 5 years. In an intent‐to‐treat analysis, NSAID and NSAID plus misoprostol groups were compared using propensity score‐weighted Poisson regression models to estimate incident rate ratio (IRR) and Cox regression to estimate hazard ratio (HR).

Results

The most prescribed NSAIDs were diclofenac and ibuprofen. The mean follow‐up was 35.2 ± 14.5 months. There were 439 total cardio‐renal events (5.62/1000 patient‐months) in the NSAID group and 419 patients (5.01/1000 patient‐months) in the NSAID plus misoprostol group (Hazard Ratio (HR): 0.89; 95% confidence interval [CI]: 0.78–1.019; p = 0.09). The risk of cardiovascular event was lower in the NSAID plus misoprostol group (HR: 0.56; 95% CI: 0.34–0.93; p < 0.0001). Cerebrovascular event rates were lower in the NSAID plus misoprostol group (HR: 0.74; 95% CI: 0.60–0.94, p < 0.0001) and for renal (HR: 0.67; 95% CI: 0.49–0.89, p < 0.0001) events. All‐cause mortality rate was not different between the two groups (HR: 1.05; 95% CI: 0.88–1.25, p = 0.61).

Conclusion

Compared with NSAID use alone, the concomitant use of NSAID plus misoprostol is associated with a reduced risk of NSAID‐induced cardiovascular, cerebrovascular, and renal adverse events. These data support the development of a safer NSAID when combined with misoprostol.
Measurement properties of the Falls Efficacy Scale‐International (FES‐I) in persons with late effects of polio: A cross‐sectional study
Authors: Brogårdh Christina , Lexell Jan , Westergren Albert
Published: June 2022

Background

Fear of falling (FoF) is very common in persons with late effects of polio (LEoP). An internationally recognized rating scale to assess FoF is the Falls Efficacy Scale‐International (FES‐I). Yet, there is limited knowledge about its measurement properties in persons with LEoP.

Objective

To investigate the measurement properties of the FES‐I (16‐item version) and the short FES‐I (7‐item version) in persons with LEoP.

Design

Explorative factor analysis and Rasch model analysis of cross‐sectional data.

Setting

University hospital.

Participants

A total of 321 persons with LEoP (mean age ± standard deviation [SD] 70 ± 10 years, 173 women).

Main Outcome Measurement

The FES‐I and the short FES‐I, comprising four response options about concerns of falling ranging from 1 (not at all concerned) to 4 (very concerned).

Methods

Data were collected by a postal survey. First, a factor analysis was performed to investigate the unidimensionality of the scale. Thereafter, a Rasch model analysis was used to further analyze the measurement properties of the FES‐I and the short FES‐I, such as local dependency, targeting, hierarchical order of items, Differential Item Functioning (DIF), response category functioning and reliability (Person Separation Index, PSI). Raw score transformation to interval measurements was also performed.

Results

The factor analysis revealed that the FES‐I was unidimensional, even though the Rasch analysis showed some misfit to the Rasch model and local dependency. Targeting for the FES‐I and the short FES‐I was somewhat suboptimal as the participants on average reported less FoF than expected. A negligible gender DIF was found for two items in the FES‐I and for one item in the short FES‐I. Reliability was high (PSI >0.86), and the response category thresholds worked as intended for both the FES‐I and the short FES‐I.

Conclusion

The FES‐I and the short FES‐I have sufficient measurement properties in persons with LEoP. Both versions can be used to assess fear of falling (or FoF) in this population.
Who's Afraid of the Supersymmetric Dark? The Standard Model vs Low‐Energy Supergravity
Authors: Burgess C.P. , Quevedo F.
Published: June 2022

Use of supergravity equations in astronomy and late‐universe cosmology is often criticized on three grounds: (i) phenomenological success usually depends on the supergravity form for the scalar potential applying at the relevant energies; () the low‐energy scalar potential is extremely sensitive to quantum effects involving very massive particles and so is rarely well‐approximated by classical calculations of its form; and () almost all Standard Model particles count as massive for these purposes and none of these are supersymmetric. Why should Standard Model loops preserve the low‐energy supergravity form even if supersymmetry is valid at energies well above the electroweak scale? We use recently developed tools for coupling supergravity to non‐supersymmetric matter to estimate the loop effects of heavy non‐supersymmetric particles on the low‐energy effective action, and provide evidence that the supergravity form is stable against integrating out such particles (and so argues against the above objection). This suggests an intrinsically supersymmetric picture of Nature where supersymmetry survives to low energies within the gravity sector but not the visible sector (for which supersymmetry is instead non‐linearly realized). We explore the couplings of both sectors in this picture and find that the presence of auxiliary fields in the gravity sector makes the visible sector share many features usually attributed to linearly realized supersymmetry although (unlike for the MSSM) a second Higgs doublet is not required for all Yukawa couplings to be non‐vanishing and changes the dimension of the operator generating the Higgs mass. We discuss the naturalness of this picture and some of the implications it might have when searching for dark‐sector physics.
Inflammatory bowel disease‐related periostosis
Authors: Yuan Yilin , Mu Rong
Published: June 2022

Key point

Periosteal reaction and bone absorption could be manifested in ulcerative colitis.
Mechanical design and wheel–leg–body cooperation control of a step‐climbing robot
Authors: Liu Chong , Zhang Xinde , Wu Renqiong , Wang Shixiong , Wang Ruchao , Lu Zhiguo , Xiao Yinhe , Li Songhao , Wu Zhuohang
Published: June 2022

This paper proposes the mechanical design and wheel–leg–body cooperation control of a robot capable of climbing stairs for the RoboMaster competition. The robot is comprised of a robot body and four legs with wheels on each end. The front and hind legs composed of the linkages and sliders complete the climbing stairs motion under the coordination of the motors and the cylinders. The dynamic stair‐climbing motion is realized by control the wheel speed and leg motion corresponding to the body motion of the robot relative to the stair environment. Compared with the common split stair climbing designed, the robot can dynamically climb the stairs without losing the forward speed, which makes climbing stairs more smoothly while retaining the ability to move on the flat. Experimental results demonstrate that the robot can climb stairs with a riser height up to 20 cm and a tread depth more than 80 cm. And the process of climbing each stair is reduced to 1–2 s.