bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful demand management in diagnostic immunology testing
Authors: Lilly Kristen , Proudlove Nathan , Bethune Claire
Published: December 2022

Aims

We investigated whether we could have a material and sustained impact on immunology test ordering by primary care clinicians by building evidence-based and explanatory algorithms into test ordering software.

Methods

A service evaluation revealed cases of over-requesting of antinuclear antibody, allergen-specific IgE and total IgE tests, and under-requesting of urine protein electrophoresis. We conducted a quality improvement programme to address this. We determined the most effective and efficient intervention would be to embed evidence-based and advice-based decision-support algorithms in the ordering software. Consultation with general practitioners revealed lack of knowledge and confidence about testing, and an appetite for support. We iteratively designed and implemented algorithms for the four sets of tests for the primary care practices in our catchment and made them available to other hospital trusts in our region. The ordering system now contains links to advice sheets for clinicians and their patients and to an email address for queries to the lab.

Results

We observe large (36% to 88%) reductions in testing activity (workload) for the over-requested tests and large (28%–135%) increases for the under-requested test. We show that these changes are sustained. There have been no complaints from the clinicians and queries to the lab are now minimal (less than one per month on average).

Conclusions

Embedding algorithms in the ordering software can be acceptable to clinicians and have a major and sustained impact on overuse or underuse of tests. The algorithms can be replicated by other hospital trusts.
One-year impact of a multicomponent, street-level design intervention in Mexico City on pedestrian crashes: a quasi-experimental study
Authors: Cárdenas-Cárdenas Luz Mery , Barrientos Gutiérrez Tonatiuh , Quistberg D Alex , Chias-Becerril Luis , Martínez-Santiago Armando , Reséndiz Lopez Héctor , Perez Ferrer Carolina
Published: December 2022

Background

Mexico City implemented thePasos Segurosprogramme to prevent pedestrian injuries and deaths at dangerous road intersections, which included street-level design changes, such as visible pedestrian crossings, sidewalk widening, refuge islands, lane reductions, pedestrian signals and adjustment of traffic light timing at these intersections. Few studies in low and middle-income countries (LMICs) have evaluated the effect of such interventions on pedestrian safety.

Aim

Assess the effectiveness of thePasos Segurosprogramme at reducing total, injury and fatal pedestrian-motor vehicle crashes.

Methods

Two-group quasi-experimental design. Monthly pedestrian crashes were obtained from the road incident database from Mexico City’s Citizen Contact Center. The programme’s effectiveness was evaluated by comparing 12 months preintervention to 12 months postintervention implementation using a negative binomial regression with random intercept with a difference-in-difference estimation. A qualitative comparative analysis was used to find the configuration of intersection characteristics and programme components associated with a decrease in pedestrian crashes.

Results

Total pedestrian crashes were reduced by 21% (RR 0.79; 95% CI 0.62 to 0.99) after implementation ofPasos Segurosprogramme. This reduction was observed for pedestrian injury crashes (RR 0.79; 95% CI 0.62 to 1.00) and for fatal crashes (RR 0.61; 95% CI 0.13 to 2.92) although not statistically significant for the latter. A decrease in pedestrian crashes was found at the most complex intersections where more of the programme components was implemented.

Conclusion

ThePasos Segurosprogramme successfully decreased total and injury pedestrian crashes. Similar interventions may improve walking safety in other LMIC cities.
Egalitarianism, moral status and abortion: a reply to Miller
Authors: Räsänen Joona
Published: December 2022

Calum Miller recently argued that a commitment to a very modest form of egalitarianism—equality between non-disabled human adults—implies fetal personhood. Miller claims that the most plausible basis for human equality is in being human—an attribute which fetuses have—therefore, abortion is likely to be morally wrong. In this paper, I offer a plausible defence for the view that equality between non-disabled human adults does not imply fetal personhood. I also offer a challenge for Miller’s view.
Novel use of continuous pericapsular nerve group (PENG) block technique for traumatic superior and inferior pubic rami fractures: a case report
Authors: Moorthy Aneurin , Choi Stephen , Safa Ben , McHardy Paul G , Niazi Ahtsham U
Published: December 2022

Background

Pubic rami fractures are painful injuries more commonly seen in the elderly with osteoporosis after high velocity trauma. In the most cases, management is conservative and non-operative with the goal to provide optimal pain relief to facilitate early mobilization and hospital discharge. Unfortunately, opioids remain the mainstay analgesic option and regional anesthesia techniques are limited but may include lumbar epidural anesthesia.

Case presentation

A female patient in her 80s presented to the emergency department of a level 1 trauma center following a high-speed motor vehicle collision. The patient suffered multiple non-life-threatening injuries. Notably, the patient was experiencing severe right groin and leg pain secondary to superior and inferior pubic rami fractures. Due to the severity of this pain, the patient was unable to mobilize or participate with physiotherapy. A lumbar epidural anesthesia technique was not deemed suitable and instead, we inserted a continuous pericapsular nerve group (PENG) block with a programmed intermittent bolus regimen. Immediate relief of pain was achieved and 48 hours later, the patient still reported satisfactory pain control and started to independently mobilize.

Conclusion

Analgesia options are limited in pubic rami fractures. We present the first published case of a novel use of the PENG block with a continuous catheter technique for the analgesic management of a traumatic superior and inferior pubic rami fracture. The clinical utility of this technique in pubic ramus fractures warrants further clinical investigation.
Added value of multiple autoantibody testing for predicting progression to inflammatory arthritis in at-risk individuals
Authors: Ponchel Frederique , Duquenne Laurence , Xie Xuanxiao , Corscadden Diane , Shuweihdi Farag , Mankia K , Trouw L A , Emery Paul
Published: December 2022

Background

Predicting progression to clinical arthritis in individuals at-risk of developing rheumatoid arthritis is a prerequisite to developing stratification groups for prevention strategies. Selecting accurate predictive criteria is the critical step to define the population at-risk. While positivity for anti-citrullinated protein antibodies (ACPA) remains the main recruitment biomarker, positivity for other autoantibodies (AutoAbs) identified before the onset of symptoms, may provide additional predictive accuracy for stratification.

Objective

To perform a multiple AutoAbs analysis for both the prediction and the time of progression to inflammatory arthritis (IA).

Methods

392 individuals were recruited based on a new musculoskeletal complaint and positivity for ACPA or rheumatoid factor (RF). ELISAs were performed for ACPA, RF, anti-nuclear Ab, anti-carbamylated protein (anti-CarP) and anti-collagen AutoAbs. Logistic and COX regression were used for analysis.

Results

Progression to IA was observed in 125/392 (32%) of cases, of which 78 progressed within 12 months. The AutoAbs ACPA, RF, anti-CarP were individually associated with progression (p<0.0001) and improved prediction when combined with demographic/clinical data (Accuracy >77%; area under the curve (AUC) >0.789), compared with prediction using only demographic/clinical data (72.9%, AUC=0.760). Multiple AutoAbs testing provided added value, with +6.4% accuracy for number of positive AutoAbs (AUC=0.852); +5.4% accuracy for AutoAbs levels (ACPA/anti-CarP, AUC=0.832); and +6.2% accuracy for risk-groups based on high/low levels (ACPA/RF/anti-CarP, AUC=0.837). Time to imminent progression was best predicted using ACPA/anti-CarP levels (AUC=0.779), while the number of positive AutoAbs was/status/risk were as good (AUC=0.778).

Conclusion

We confirm added value of multiple AutoAbs testing for identifying progressors to clinical disease, allowing more specific stratification for intervention studies.
Recommendations to advance equity in tobacco control
Authors: Mills Sarah D , Rosario Carrie , Yerger Valerie B , Kalb Marlene Donato , Ribisl Kurt M
Published: December 2022

Reducing racial and socioeconomic inequities in smoking has been declared a priority for tobacco control in the USA for several decades. Yet despite the rhetoric, these inequities persist and some have actually worsened over time. Although tobacco companies have targeted racially and ethnically diverse and lower-income tobacco users, which substantially contributes to these disparities, less attention has been given to the role of individuals and organisations within the tobacco control movement who have allowed progress in eliminating disparities to stagnate. We examine the failure of tobacco control professionals to ensure the widespread adoption of equity-focused tobacco control strategies. Review of major US tobacco control reports found that the focus on equity often stops after describing inequities in tobacco use. We suggest ways to advance equity in tobacco control in the USA. These recommendations fall across five categories: surveillance, interventions, funding, accountability and addressing root causes. Policy interventions that will have a pro-equity impact on smoking and related disease should be prioritised. Funding should be designated to tobacco control activities focused on eliminating racial and socioeconomic inequities in smoking, and tobacco control programmes should be held accountable for meeting equity-related goals.
Spatial patterns and environmental factors related to arsenic bioaccumulation in boreal freshwater fish
Authors: Kluke Calvin , Lescord Gretchen L. , Johnston Thomas A. , Kielstra Brian W. , Lock Alan , Bhavsar Satyendra , Gunn John M.
Published: December 2022

To better understand the spatial patterns in arsenic (As) bioaccumulation in freshwater systems, we investigated ecological, physical, and chemical factors associated with total arsenic concentrations ([As]) in lacustrine and riverine fish across Ontario, Canada, using a dataset of 3200 fish across 152 waterbodies. Assembled data of water chemistry, landscape characteristics, and stable carbon and nitrogen isotope ratios in muscle tissue were then used to assess factors related to As bioaccumulation. Results show that [As] were generally low across most species and waterbodies (i.e., <1 µg·g−1 wet in many inland fish). However, fish from northern coastal rivers had up to 23-fold higher [As] when compared with fish from landlocked sites. As concentrations increased slightly with the proportion of pelagic carbon in a fish's diet, although relationships varied among species and sites. Furthermore, principal component scores, representing landscape and water chemistry variables, were related to [As] in fish, but these relationships varied among species. These results will help improve the efficacy of fish contaminant monitoring by further identifying key physical and ecological variables related to higher [As] in fish.
Solving the fourth-order nonlinear boundary value problem by a boundary shape function method
Authors: Liu Chein-Shan , Li Botong
Published: December 2022

A method to construct the boundary shape function (BSF) and then two novel methods are developed to obtain the solutions of fourth-order singularly perturbed beam equation and nonlinear boundary value problem (BVP). In the first-type algorithm, the free function is a series of complete basis functions, while the corresponding BSFs are new bases. The trial functions with fractional powers exponential are suitable for the singularly perturbed beam equation under fixed-end and simply supported boundary conditions. With the aid of the BSF, we can improve the asymptotic and uniform approximations to exactly satisfy the prescribed boundary conditions. In the second-type algorithm, the solution of a nonlinear BVP is viewed as a boundary shape function, while the free function is regarded as a new variable. With this means, the fourth-order nonlinear BVP is exactly converted to an initial value problem with a new variable, the terminal value of which is unknown, when the initial conditions are given. The computed order of convergence and an error estimation are given. Numerical illustrations, including the singularly perturbed examples, show that the present methods, based on the new idea of the BSF, are highly effective, accurate, and fast convergent.
Improving colour computations in MadGraph5_aMC@NLO and exploring a $$1/N_c$$ expansion
Authors: Lifson Andrew , Mattelaer Olivier
Published: December 2022

In this paper, we present an extension of which is able to evaluate tree-level QCD matrix-elements up to $$2\rightarrow 6$$

2
→
6

(one more particle than before). To achieve this, we implemented Berends–Giele-like recursion, and re-implemented the way colour is computed such that we can now expand the colour matrix in powers of $$1/N_c$$

1
/

N
c

and truncate this expansion to a chosen order. For high multiplicity samples, even without truncating the colour matrix, the new implementation offers a speed gain compared to the previous code.
Exploring non standard interactions effects in T2HK and DUNE
Authors: Brahma Barnali , Giri Anjan
Published: December 2022

Neutrino oscillations in matter offer a novel path to investigate new physics. One of the main goals of neutrino experiments is to determine the CP phase, and the presence of new physics can alter the scenario. We assume that the observed difference, if any, in the CP phase is due to the possible non-standard interactions. We derive the relevant coupling strengths using the results of NO$$\nu $$
ν
A and T2K and study their effects in the next generation of long-baseline experiments: T2HK and DUNE. Our analysis reveals a significant impact on the sensitivity of atmospheric mixing angle $$\theta _{23}$$

θ
23

in the normal and inverted orderings. Furthermore, we observe discernible differences in probabilities for both experiments when non-standard interaction from $$e-\mu $$

e
-
μ

and $$e-\tau $$

e
-
τ

sectors are included.
Random Projection and Recovery for High Dimensional Optimization with Arbitrary Outliers
Authors: Huang Jiawei , Qin Ruizhe , Yang Fan , Ding Hu
Published: December 2022

Robust optimization problems have attracted considerable attention in recent years. In this paper, we focus on two fundamental robust optimization problems: SVM with outliers and [Formula: see text]-center clustering with outliers. The key obstacle is that the outliers can be located arbitrarily in the space (e.g., by an attacker), and thus they are actually quite challenging combinatorial optimization problems. Their computational complexities can be very high especially in high dimensional spaces. The Johnson–Lindenstrauss [Formula: see text]JL [Formula: see text] Transform is a popular random projection method for dimension reduction. Though the JL transform has been widely studied in the past decades, its effectiveness for dealing with high-dimensional optimizations with outliers has never been investigated before (to the best of our knowledge). Based on some novel insights from the geometry, we prove that the complexities of these two problems can be significantly reduced through the JL transform. Moreover, we prove that the solution in the dimensionality-reduced space can be efficiently recovered in the original [Formula: see text] space while the quality is still preserved. To study its performance in practice, we compare different JL transform methods with several other well known dimension reduction methods in our experiments.
A Novel YOLOv5 Deep Learning Model for Handwriting Detection and Recognition
Authors: Moustapha Maliki , Tasyurek Murat , Ozturk Celal
Published: December 2022

Computer Vision (CV) has become an essential field in Artificial Intelligence applications. Object detection and recognition (ODR) is one of the fundamental tasks of computer vision implementations. However, developing an efficient ODR model is still a significant problem. The model’s execution time and speed are the most critical features during the inference or detection and recognition process, which need to be improved using the latest object detection architectures. In this paper, the handwritten detection and recognition (HDR) model is developed based on previously known algorithms with their efficiency, such as Faster R-CNN and YOLOv4 in the first hand. On the other hand, two new models capable of detecting and recognizing handwritten digits using the latest ODR algorithm are proposed, one based on the latest YOLO family architecture (YOLOv5-HDR) with high speed and accuracy and the other using the transformers architecture (DETR). To the best of our knowledge, this is the first study to achieve a details comparison between YOLOv5 and transformers-based models in handwritten digit detection. Finally, the detailed performance analysis achieved by the paper proves that the YOLOv4-based model achieved the testing inference 13% faster than Faster R-CNN. However, the proposed YOLOv5-based model outperformed the YOLOv4 and the transformers-based one as it increased the testing execution time 25% faster than the YOLOv4, three times faster than the DETR model. A further adversarial attack test has been conducted to ensure the robust performance of the proposed model. Furthermore, numerical experiment results and their analyses demonstrate the robustness and effectiveness of the proposed YOLOv5-based model being the most stable for handwritten digit detection and recognition tasks.
Use of the Gouy–Stodola Theorem in Classical Mechanic Systems: A Study of Entropy Generation in the Simple Pendulum
Authors: Longaresi R. H. , Campos S. D.
Published: December 2022

Both classical mechanics and thermodynamics live in the core of physics. They are two different aspects of the same thing, one can say. The thermodynamic equivalent of a mechanical system is one of the main achievements of the 19th century. Regarding only thermodynamics, the introduction of entropy, roughly defined in many textbooks as the unuseful energy present in a physical system, is a victory of Rudolf Clausius. Unlike energy, entropy can be produced in a physical system under certain conditions. We can act to increase the degree of disorder (statistical mechanics) in a physical system. Here, we propose to apply the entropy generation [Formula: see text]) concept to the simple pendulum by using a very unknown result: the Gouy–Stodola theorem. When considering the ideal case, where only conservative forces act on the system, one has [Formula: see text], and the entropy variation is null. However, as shall be seen, the entropy variation is not null all the time. Considering a nonconservative force proportional to the pendulum velocity, the amplitude of oscillations decreases to zero as [Formula: see text] grows. Then, [Formula: see text] may be related with the energy dissipation, as stated by the Gouy–Stodola theorem. Hence, as shall be seen, the greater the strength of the nonconservative force, the greater are both the energy dissipation and the time rate of entropy variation.
Higgs in a Box: Investigating the Nature of a Scientific Discovery
Authors: Woithe Julia , Boselli Margherita , Chatzidaki Panagiota , Dahlkemper Merten Nikolay , Duggan Ruadh , Durey Guillaume , Herff Niklas , Horvat Anja Kranjc , Molaro Daniele , Scheerer Gernot Werner , Schmeling Sascha , Thill Patrick Georges , Wiener Jeff , Zoechling Sarah
Published: December 2022

The discovery of the Higgs boson by the ATLAS and CMS collaborations in 2012 concluded the longest search for a particle in the history of particle physics and was based on the largest and most complex physics experiments ever conducted, involving thousands of scientists and engineers from around the world. It provided crucial evidence for a theory developed in the 1960s that describes the existence of the invisible Brout–Englert–Higgs field and the effects of this field on the mass of elementary particles. After the discovery, the work on the theoretical prediction was awarded the Nobel Prize in Physics 2013. This discovery provides a prime example of modern science in the making and a fantastic opportunity to discuss important aspects of Nature of Science (NoS) in the classroom. In this article, we draw connections between (a) milestones in the discovery of the Higgs boson, (b) important aspects of NoS, and (c) hands-on activities with mystery boxes, which are an effective tool to enable students to experience elements of scientific discovery and explicitly reflect on NoS. We hope that this supports educators in bringing lively discussions about modern physics research into their classrooms.
Multi-level Attention-based Domain Disentanglement for BCDR
Authors: Zhang Xinyue , Li Jingjing , Su Hongzu , Zhu Lei , Shen Heng Tao
Published: December 2022

Cross-domain recommendation aims to exploit heterogeneous information from a data-sufficient domain (source domain) to transfer knowledge to a data-scarce domain (target domain). A majority of existing methods focus on unidirectional transfer that leverages the domain-shared information to facilitate the recommendation of the target domain. Nevertheless, it is more beneficial to improve the recommendation performance of both domains simultaneously via a dual transfer learning schema, which is known as bidirectional cross-domain recommendation (BCDR). Existing BCDR methods have their limitations, since they only perform bidirectional transfer learning based on domain-shared representations while neglecting rich information that is private to each domain. In this article, we argue that users may have domain-biased preferences due to the characteristics of that domain. Namely, the domain-specific preference information also plays a critical role in the recommendation. To effectively leverage the domain-specific information, we propose a
M
ulti-level
A
ttention-based
D
omain
D
isentanglement framework dubbed
MADD
for BCDR, which explicitly leverages the attention mechanism to construct personalized preference with both domain-invariant and domain-specific features obtained by disentangling raw user embeddings. Specifically, the domain-invariant feature is exploited by domain-adversarial learning while the domain-specific feature is learned by imposing an orthogonal loss. We then conduct a reconstruction process on disentangled features to ensure semantic-sufficiency. After that, we devise a multi-level attention mechanism for these disentangled features, which determines their contributions to the final personalized user preference embedding by dynamically learning the attention scores of individual features. We train the model in a multi-task learning fashion to benefit both domains. Extensive experiments on real-world datasets demonstrate that our model significantly outperforms state-of-the-art cross-domain recommendation approaches.
SIGCSE Technical Symposium 2023
Authors: Doyle Maureen , Stephenson Ben
Published: December 2022

The 2023 Technical Symposium will take place in Toronto, Canada from March 16-18, 2023 at the Metro Toronto Convention Centre. This is the first time that the Technical Symposium has been hosted outside of the United States, though it's not outside the United States by very much - the convention center is only 20 miles from the U.S. border as the crow flies. The symposium's theme, 'Prepared for Anything', continues to be highly applicable to many areas of our lives, perhaps more applicable than we would like as we continue to navigate the complexities of teaching in a world that continues to be disrupted by COVID-19.
Listening Within
Authors: Stephenson Chris
Published: December 2022

Events in 2020 created a moment of reckoning and a movement centered on and illuminating deeply ingrained patterns, processes, and prejudices of inequity and injustice faced by generations of Black Americans. Almost no institution was immune to probing questions concerning diversity, inclusion, and equity. Many professional membership organizations were also being asked to address the injustices manifested in their practices and traditions. Within ACM, however, the insider perspectives on this issue were not always clear. And so, from April until August 2021 I carried out research to determine whether ACM members, volunteers, staff and external experts believed that ACM should and could become a more diverse, inclusive, and equitable organization. This research is captured in a report entitled: All the Voices: Doing the Work to Improve Diversity, Equity, and Inclusion throughout ACM.
Getting Started with AdaWebPack
Authors: Reznik Max
Published: December 2022

This article introduces the AdaWebPack project recently presented at the 12th Ada Developer Room at FOSDEM 2022 [3]. The AdaWebPack project aims for providing a toolchain and Ada libraries to enable developing of web applications to be executed in a web browser.
A Work-Stealing Scheduler for Ada 2022, in Ada
Authors: Taft S Tucker
Published: December 2022

Ada 2022 includes parallel programming features that use lightweight logical threads of control on top of the heavier-weight Ada tasks. This talk will report on the work in progress to implement a work-stealing scheduler for these lightweight threads, in Ada itself.
Review of Feasible Computations and Provable Complexity Properties by Juris Hartmanis
Authors: Green Frederic
Published: December 2022

"It may only be a slight exaggeration to claim that in the 1930s we started to understand what is and is not effectively computable and that in the 1970s we started to understand what is and is not practically or feasibly computable. There is no doubt that the results about what can and cannot be effectively computed or formalized in mathematics have had a profound influence on mathematics, and, even more broadly, they have influenced our view of our scientific methods. We believe that the results about what can and cannot be practically computed will also have a major influence on computer science, mathematics, and even though more slowly, will affect other research areas and influence how we think about scientific theories." - Juris Hartmanis (from the Introduction)
Bulk and Surface Stabilization Process of Metastable Li-Rich Disordered Rocksalt Oxyfluorides as Efficient Cathode Materials
Authors: Shirazi Moghadam Y. , El Kharbachi A. , Melinte G. , Diemant T. , Fichtner M.
Published: December 2022

Manganese based disordered rocksalt systems have attracted attention as Co-free and high capacity cathode materials for Li-ion batteries. However, for a practical application these materials are considered as metastable and exhibit too limited cyclability. In order to improve the structural stability of the disordered rocksalt Li1+xMn2/3Ti1/3O2Fx (0 ≤ x ≤ 1) system during cycling, we have introduced a mild temperature heat treatment process under reducing atmosphere, which is intended to overcome the structural anomalies formed during the mechanochemical synthesis. The heat-treated samples presented better electrochemical properties, which are ascribed to a structural defect mitigation process both at the surface and in the bulk, resulting in improved crystal structure stability. In addition, the optimized particle size and the smaller BET surface area induced by the recrystallization contributes to the observed enhanced performance. Among the studied compositions, the heat treated Li2Mn2/3Ti1/3O2F sample displayed better electrochemical performance with a discharge capacity of 165 mAh g−1 after 100 cycles at 0.1 C (∼80% of the initial capacity), when combined with further conditioning of the cells. The results point explicitly towards a guided stabilization approach, which could have a beneficial effect regarding the application of DRS oxyfluoride materials for sustainable LIBs.
Endothelial miR-196b-5p regulates angiogenesis via the hypoxia/miR-196b-5p/HMGA2/HIF1α loop
Authors: Ren Ruizhe , Ma Kefan , Jiang Yuanqing , Chen Junbo , Kou Yaohui , Ge Zhen , Chen Zhaoming , Wei Xiyang , Yu Luyang
Published: December 2022

Angiogenesis is involved in development, reproduction, wound healing, homeostasis, and other pathophysiological events. Imbalanced angiogenesis predisposes patients to various pathological processes, such as angiocardiopathy, inflammation, and tumorigenesis. MicroRNAs (miRNAs) have been found to be important in regulating cellular processing and physiological events including angiogenesis. However, the role of miRNAs that regulate angiogenesis (angiomiRs) is not fully understood. Here, we observed a downregulation of the miR-196 family in endothelial cells upon hypoxia. Functionally, miR-196b-5p inhibited the angiogenic functions of endothelial cells in vitro and suppressed angiogenesis in Matrigel plugs and skin wound healing in vivo. Mechanistically, miR-196b-5p bound onto the 3′ untranslated region (UTR) of high-mobility group AT-hook 2 (HMGA2) mRNA and repressed the translation of HMGA2, which in turn represses HIF1α accumulation in endothelial cells upon hypoxia. Together, our results establish the role of endothelial miR-196b-5p as an angiomiR that negatively regulates endothelial growth in angiogenesis via the hypoxia/miR-196b-5p/HMGA2/HIF1α loop. miR-196b-5p and its regulatory loop could be an important addition to the molecular mechanisms underlying angiogenesis and may serve as potential targets for antiangiogenic therapy.
Diverse functions of apolipoprotein A-I in lung fibrosis
Authors: Wygrecka Malgorzata , Alexopoulos Ioannis , Potaczek Daniel P. , Schaefer Liliana
Published: December 2022

Apolipoprotein A-I (apoA-I) mediates reverse cholesterol transport (RCT) out of cells. In addition to its important role in the RTC, apoA-I also possesses anti-inflammatory and antioxidative functions including the ability to activate inflammasome and signal via toll-like receptors. Dysfunctional apoA-I or its low abundance may cause accumulation of cholesterol mass in alveolar macrophages, leading to the formation of foam cells. Increased numbers of foam cells have been noted in the lungs of mice after experimental exposure to cigarette smoke, silica, or bleomycin and in the lungs of patients suffering from different types of lung fibrosis, including idiopathic pulmonary fibrosis (IPF). This suggests that dysregulation of lipid metabolism may be a common event in the pathogenesis of interstitial lung diseases. Recognition of the emerging role of cholesterol in the regulation of lung inflammation and remodeling provides a challenging concept for understanding lung diseases and offers novel and exciting avenues for therapeutic development. Accordingly, a number of preclinical studies demonstrated decreased expression of inflammatory and profibrotic mediators and preserved lung tissue structure following the administration of the apoA-I or its mimetic peptides. This review highlights the role of apoA-I in lung fibrosis and provides evidence for its potential use in the treatment of this pathological condition.
Repeated freeze-thaw cycles in freeze-tolerant treefrogs: novel interindividual variation of integrative biochemical, cellular, and organismal responses
Authors: Yokum Elizabeth E. , Wascher Matthew , Goldstein David L. , Krane Carissa M.
Published: December 2022

The freeze-tolerant anuran Dryophytes chrysoscelis, Cope’s gray treefrog, mobilizes a complex cryoprotectant system that includes glycerol, glucose, and urea to minimize damage induced by freezing and thawing of up to 65% of body water. In this species’ eastern Northern American temperate habitat, oscillations of temperature above and below freezing are common; however, the effects of repeated freezing and thawing in this species are unstudied. The biochemical and physiological effects of repeated freeze-thaw cycles were therefore evaluated and compared with cold acclimation and single freeze-thaw episodes. Glycerol was elevated in plasma, liver, and skeletal muscle of both singly and repeatedly frozen and thawed animals compared with cold-acclimated frogs. In contrast, urea was unchanged by freezing and thawing, whereas glucose was elevated in singly frozen and thawed animals but was reduced toward cold acclimation levels after repeated bouts of freezing. Overall, the cryoprotectant system was maintained, but not further elevated, in all tissues assayed in repeatedly frozen and thawed animals. For repeated freeze-thaw only, hepatic glycogen was depleted and plasma hemoglobin, indicative of erythrocyte hemolysis, increased. Postfreeze recovery of locomotor function, including limb and whole body movement, was delayed with repeated freeze-thaw and was associated with glycerol accumulation and glycogen depletion. Individuals that resumed locomotor function more quickly also accumulated greater cryoinjury. Integrated analyses of cryoprotectant and cryoinjury accumulation suggest that winter survival of D. chrysoscelis may be vulnerable to climate change, limited by carbohydrate stores, cellular repair mechanisms, and plasticity of the cryoprotectant system.
T cell-specific deficiency in BBSome component BBS1 interferes with selective immune responses
Authors: Stump Madeliene , Guo Deng Fu , Rahmouni Kamal
Published: December 2022

Bsardet Biedl syndrome (BBS) is a genetic condition associated with various clinical features including cutaneous disorders and certain autoimmune and inflammatory diseases pointing to a potential role of BBS proteins in the regulation of immune function. BBS1 protein, which is a key component of the BBSome, a protein complex involved in the regulation of cilia function and other cellular processes, has been implicated in the immune synapse assembly by promoting the centrosome polarization to the antigen-presenting cells. Here, we assessed the effect of disrupting the BBSome, through Bbs1 gene deletion, in T cells. Interestingly, mice lacking the Bbs1 gene specifically in T cells ( T-BBS1−/−) displayed normal body weight, adiposity, and glucose handling, but have smaller spleens. However, T-BBS1−/− mice had no change in the proportion and absolute number of B cells and T cells in the spleen and lymph nodes. There was also no alteration in the CD4/CD8 lineage commitment or survival in the thymus of T-BBS1−/− mice. On the other hand, T-BBS1−/− mice treated with Imiquimod dermally exhibited a significantly higher percentage of CD3-positive splenocytes that was due to CD4 but not CD8 T cell predominance. Notably, we found that T-BBS1−/− mice had significantly decreased wound closure, an effect that was more pronounced in males indicating that the BBSome plays an important role in T cell-mediated skin repair. Together, these findings implicate the BBSome in the regulation of selective functions of T cells.
Hugan Buzure Induces Autophagy and Apoptosis in Hepatocellular Carcinoma by Inhibiting PI3K/Akt/mTOR Signaling Pathway
Authors: Meng Xiaoyi , Li Min , Qiao Ming , Li Xue , Yang Jianhua , Hu Junping
Published: December 2022

This study explored the effects of Hugan Buzure (HBR) on cell apoptosis and autophagy in hepatocellular carcinoma (HCC) and the molecular mechanisms of the PI3K/Akt/mTOR signaling pathway. HepG2 and Huh7 cell viability was detected by the tetramethylazolium salt colorimetric (MTT) method. Cell proliferation was measured using the colony formation method. Hoechst 33258 staining and flow cytometry were employed to detect apoptosis. In addition, immunofluorescence was carried out to evaluate the expression of LC3. Western blot was performed to detect the expression of Bcl-2, Bax, Caspase-3, LC3, Beclin1, p62 (SQSTM1), and PI3K/Akt/mTOR signal pathway-related proteins in HCC cells. This work verified that HBR reduced HepG2 and Huh7 cell proliferation in a concentration-dependent manner. Treatment with HBR caused an obvious improvement of the apoptosis rate, accompanied by the increase in Bax/Bcl2, Caspase3, LC3II, and Beclin1 levels, respectively. Furthermore, HBR downregulated the expression of p62, p-PI3K, p-Akt, and p-mTOR proteins. HBR combined with HCQ enhanced HBR-induced apoptosis. In conclusion, HBR induced autophagy and apoptosis through PI3K/Akt/mTOR signaling pathway, leading to HCC cell death. This research preliminarily suggested the potential role of HBR in the treatment of HCC.
Geochemical Characteristics and Organic Matter Accumulation of Wufeng-Longmaxi Shales in the Southeast of the Sichuan Basin of South China
Authors: Zhang Ying , Lyu Chengfu , Gao Xue , Dang Zhaoqing , Sun Zhaotong , Zhou Qianshan , Chen Guojun
Published: December 2022

The Upper Ordovician Wufeng Formation and Lower Silurian Longmaxi Formation black shales are the critical targets for shale gas exploration in the Sichuan Basin of South China. The enrichment of organic matter (OM) in shale is the basis for the generation of large-scale shale gas; however, its controlling factors in Wufeng-Longmaxi shales are still under debate, and few studies have focused on the edge of the Sichuan Basin. Based on the mineral composition, total organic carbon (TOC), and systematic inorganic geochemistry analysis of 72 core samples from Wufeng and Longmaxi formations in Well Xike 1, southeastern Sichuan Basin, the sedimentary conditions (palaeoclimate, palaeoredox, and palaeoproductivity) were reconstructed, and the controlling factors of OM enrichment were identified. The mineral compositions are dominated by quartz, clay minerals, calcite, and feldspar, associated with minor dolomite, pyrite, and anhydrite. The TOC contents (0.31%-6.84%, avg. 2.22%) show an upward decreasing trend from the Wufeng Formation to Longmaxi Formation. The chemical index of alteration (CIA) ranges from 65 to 71 (avg. 69), indicating warm and humid climate with moderate weathering. The diagrams of Al2O3-TiO2, TiO2-Zr, Zr/Sc-Th/Sc, La/Th-Hf, and La-Th-Sc jointly indicate the contribution from felsic and intermediate rock weathering. The P/Al, Cu/Al, and Ni/Al ratios suggest that marine paleoproductivity was relatively high in the Wufeng Formation and relatively low to moderate in the Longmaxi Formation. The V/Cr, V/Sc, U/Th, MoEF/UEF, and Corg/P ratios indicate that the bottom water was anoxic during the Wufeng Formation deposition and then fluctuating dysoxic and/or oxic in the overlying Longmaxi Formation. The TOC content was positively correlated with productivity proxies (P/Al, Cu/Al, and Ni/Al) as well as redox proxies (U/Th, V/Cr, MoEF/UEF, and Corg/P), indicating that the OM accumulation in Wufeng-Longmaxi shales is mainly controlled by high productivity and anoxic bottom water conditions.
Partially Measured State Estimation of Complex Dynamical Networks with Random Data Loss
Authors: Zhang Ke , Wang Nan , Hua Xingdong , Wang Xinwei , Wu Xu
Published: December 2022

The state estimation problem is a very important and interesting issue in the field of complex dynamical networks. Yet, the constructions of the state estimators in most existing literature studies all need to measure the output information of all nodes. However, the practical situation is that not all nodes could be measured to obtain the output information. Thus, in this paper, the state estimation is realized while only measuring the output data of partial nodes for a complex dynamical network with random data loss existing on its external communication links to the observers, where the lost data are compensated by the corresponding observer data. Depending on whether the network possesses the root strongly connected components that have a perfect matching, the choice problem of measured nodes and the construction problem of specific output matrices are discussed. By applying the Lyapunov stability theory and stochastic analysis method, a sufficient condition for state estimation is given. Through simulation experiments, the effectiveness of the proposed state estimation scheme is demonstrated.
Storytelling in Pregnancy and Childbirth: An Integrative Review of the Literature
Authors: Mahdavi Zahra , Amiri-Farahani Leila , Pezaro Sally
Published: December 2022

Background and Objectives. Storytelling is a common and popular way of conveying events, culture, ideas, and information. Stories have been used in various sciences to convey a particular concept that is influenced by the culture of individuals. Storytelling about childbirth may be useful to women in a number of ways. The objective of this review was to synthesize existing literature in relation to storytelling in the context of childbirth to inform future childbirth education programmes, interventions, and research. Methods. An integrative review of the literature was conducted, including peer-reviewed articles published between 2001 and 2022. The following databases were used to search for relevant studies: PubMed, CINAHL, PsycINFO, Web of Science, Ovid, Google Scholar, ScienceDirect, Cochrane Library, Magiran, Irandoc, and SID. A process of thematic synthesis was used to make sense of the data extracted. Results. Whilst 21 studies were retrieved, only 12 were relevant and thus met the inclusion criteria set. Two themes were identified from our thematic synthesis: (1) effects of childbirth storytelling on the storyteller and (2) effects of childbirth storytelling on the listener of the story. Subthemes included “reducing fear of childbirth,” “transferring information and raising awareness in line with community culture,” and “adjusting expectations.” Conclusion. The use of storytelling can be used as an effective method in educational interventions during pregnancy and childbirth. Due to limited high-quality intervention studies in this field, future studies could usefully be more robustly designed and incorporate digital storytelling methods to inform future directions.
Targeting MET and FGFR in Relapsed or Refractory Acute Myeloid Leukemia: Preclinical and Clinical Findings, and Signal Transduction Correlates
Authors: Chen Evan C. , Gandler Helen , Tošić Isidora , Fell Geoffrey G. , Fiore Ashlee , Pozdnyakova Olga , DeAngelo Daniel J. , Galinsky Ilene , Luskin Marlise R. , Wadleigh Martha , Winer Eric S. , Leonard Rebecca , O'Day Kelsey , de Jonge Adrienne , Neuberg Donna , Look A. Thomas , Stone Richard M. , Frank David A. , Garcia Jacqueline S.
Published: December 2022

Purpose:

Patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) have poor outcomes and require new therapies. In AML, autocrine production of hepatocyte growth factor (HGF) drives MET signaling that promotes myeloblast growth and survival, making MET an attractive therapeutic target. MET inhibition exhibits activity in AML preclinical studies, but HGF upregulation by the FGFR pathway is a common mechanism of resistance.

Patients and Methods:

We performed preclinical studies followed by a Phase I trial to investigate the safety and biological activity of the MET inhibitor merestinib in combination with the FGFR inhibitor LY2874455 for patients with R/R AML. Study Cohort 1 underwent a safety lead-in to determine a tolerable dose of single-agent merestinib. In Cohort 2, dose-escalation of merestinib and LY2874455 was performed following a 3+3 design. Correlative studies were conducted.

Results:

The primary dose-limiting toxicity (DLT) observed for merestinib alone or with LY2874455 was reversible grade 3 transaminase elevation, occurring in 2 of 16 patients. Eight patients had stable disease and one achieved complete remission (CR) without measurable residual disease. Although the MTD of combination therapy could not be determined due to drug supply discontinuation, single-agent merestinib administered at 80 mg daily was safe and biologically active. Correlative studies showed therapeutic plasma levels of merestinib, on-target attenuation of MET signaling in leukemic blood, and increased HGF expression in bone marrow aspirate samples of refractory disease.

Conclusions:

We provide prospective, preliminary evidence that MET and FGFR are biologically active and safely targetable pathways in AML.
Routine Ultrasound at 30th–33rd weeks versus 30th–33rd and 35th–37th weeks in Low-Risk Pregnancies: A Randomized Trial
Authors: Policiano Catarina , Mendes Jorge M. , Fonseca Andreia , Barros Joana , Vargas Sara , Cal Margarida , Martins Inês , Carvalho Catarina , Martins Diana , Clode Nuno , Graca Luis M.
Published: December 2022

Introduction: The aim of this study was to evaluate the accuracy of 35–37 weeks’ ultrasound for fetal growth restriction (FGR) detection and the impact of 30th–33rd weeks versus 30th–33rd and 35th–37th weeks’ ultrasound on perinatal outcomes. Methods: This was a randomized controlled trial that enrolled 1,061 low-risk pregnant women: 513 in the control group (routine ultrasound performed at 30th–33rd weeks) and 548 in the study group (with an additional ultrasound at 35th–37th weeks). FGR was defined as a fetus with an estimated fetal weight (EFW) below the 10th percentile. p values < 0.05 were considered statistically significant. Results: The ultrasound at 35–37 weeks had an overall accuracy of FGR screening of 94%. Spearman’s correlation coefficient between EFW and birthweight centile was higher for at 35–37 weeks’ ultrasound (ρ = 0.75) compared with 30–33 weeks’ ultrasound (ρ = 0.44). The study group had a lower rate of operative vaginal deliveries (24.4% vs. 39.3%, p = 0.005) and cesarean deliveries for nonreassuring fetal status (16.8% vs. 38.8%, p < 0.001). Discussion/Conclusion: A later ultrasound (35–37 weeks) had a high accuracy for detection of FGR and had a higher correlation between EFW and birthweight centiles. Furthermore, it was also associated with lower adverse perinatal outcomes compared to an earlier ultrasound.
PIK3R3 Missense and NOTCH2 Synonymous Single Nucleotide Polymorphisms Are Associated with Liver Cancer
Authors: Wang Baofeng , Min Weili , Zhang Wenjie , Liu Qiufang , Guo Xufeng , Zhan Jianshui , Lei Ming , Zan Ying , Ma Qingyong , Ma Hongbing
Published: December 2022

Background: Single nucleotide polymorphism (SNP) of candidate genes also affects the occurrence and prognosis of liver cancer. We mainly explored the effects of PIK3R3 and NOTCH2 polymorphisms on liver cancer risk among Chinese people. Methods: Four SNPs (rs785468, rs785467, rs3795666, and rs17024525 in PIK3R3 and NOTCH2) from 709 liver cancer patients and 700 healthy controls were genotyped using the Agena MassARRAY system. The correlation between SNPs and liver cancer risk was evaluated using logistic regression analysis. The SNP-SNP interactions were conducted by the multifactor dimensionality reduction method. Results: The results revealed that PIK3R3-rs785467 reduced the likelihood of liver cancer among Chinese Han people (p < 0.05). In addition, PIK3R3-rs785467 decreased the susceptibility to liver cancer in different populations (females, non-smokers, and age >55 years, p < 0.05). NOTCH2-rs3795666 reduced the susceptibility to liver cancer among males, drinkers, and patients aged >55 years (p < 0.05). Conclusions: Our results demonstrate that PIK3R3-rs785476 and NOTCH2-rs3795666 polymorphisms are responsible for decreasing the susceptibility of liver cancer development in the Chinese Han population.