bluuebunny/crossref_metadata_2025 huggingface dataset:
A source‐driven probabilistic forwarding and caching strategy in NDN and SDN‐based NDN
Authors: Iqbal Shahid Md. Asif , Asaduzzaman  , Hoque Mohammed Moshiul
Published: January 2022

NDN forwarding strategies are mainly developed receiver‐driven, where Interest forwarding and Data (content) delivery are controlled from the consumers' viewpoint. The receiver‐driven strategies are greedy by nature and emphasize optimizing the Interest forwarding, which is far from the performance bottleneck as an Interest is of tiny size in compared with a content's size. Thus, optimizing the content delivery can improve the forwarding performance. Moreover, source‐driven optimization of content delivery can alleviate the greedy nature of its counterpart. In this work, a source‐driven forwarding strategy is proposed where the content sources respond to Interest requests in a distributed manner. The content requests hit all the sources, but the sources respond probabilistically such that the content retrieval overhead and latency are minimized. The strategy consents the nearer sources to set a high probability of reacting with the matching content. On the contrary, the distant sources answer with an Offer to save transmission overhead. Besides, a caching strategy is proposed, an integral part of the source‐driven scheme, that caches diverse contents considering the gap between successive copies and content availability while admitting new contents. Next, we extend the source‐driven probabilistic forwarding strategy to operate in SDN‐based NDN architecture. The SDN‐based solution controls the content delivery phase using the global knowledge of NDN cache states. Simulation study conducted using ndnSIM reveals that the proposed forwarding and caching strategy improves user satisfaction and network performance in terms of different performance metrics such as transmission overhead, latency, and cache hit.
Discussion on China's anti‐epidemic response based on the Protocol on Prevention and Control of Coronavirus Disease 2019 from Chinese Authority
Authors: Zhao Zhihui , Zhou Yi , Li Weihong , Fan Xiaohong , Huang Qingsong , Tang Zhaohui , Li Han , Wang Jiexin , Li Jialiang , Wu Jing
Published: January 2022

Eight versions of the Protocol on Prevention and Control of Coronavirus Disease 2019 (COVID‐19) (the Protocol) were issued successively by the Chinese authority to guide the local responses since the first COVID‐19 case appeared in Wuhan, China. This study aimed to investigate the evolution of the overall strategy and specific measures in these Protocols, and several recommendations were provided after analysing China's response to the epidemic resurgence. As a result, we found a gradual expanding trend in case surveillance, early screening, and epidemiological investigation, as well as a progressively rigorous tendency in isolation measures and close contact management. With the Protocol's guidance, China had achieved success in several recent fights against domestic COVID‐19 resurgences. The city lockdown and multiple city‐wide nucleic acid tests adopted were deemed necessary in COVID‐19 resurgence's battle. Besides, the large‐scale distance centralised quarantine, which is, quarantine in a purpose‐built isolation station away from communities where people under quarantine lived, was promoted in rural areas. China's anti‐epidemic achievements provide ideas for the global battle against COVID‐19.
Blue coloured haüyne from Mt. Vulture (Italy) volcanic rocks: SEM‐EDS and Raman investigation of natural and heated crystals
Authors: Caggiani Maria Cristina , Mangone Annarosa , Acquafredda Pasquale
Published: January 2022

Haüyne mineral, belonging to sodalite group, characterizes two lithotypes of Mount Vulture area (Italy): phonolite of Toppo San Paolo and haüynophyre of Melfi. In the latter, haüyne phenocrysts can appear colourless‐white, grey‐to‐black or blue in colour. The blue colour of these crystals—sometimes in literature classified as lazurite—is known to be due to the presence of
polysulphides radical anion chromophores. Since it has been previously observed that heating these rocks up to 750 °C in oxidizing conditions leads haüyne crystals to acquire the blue colour, it was decided to investigate the reasons of this chromatic transformation. SEM‐EDS and Raman spot microanalyses were performed on single crystals of the pristine rocks; furthermore, detailed X‐ray and Raman maps were carried out on two white and two black haüyne crystals of haüynophyre before and after heating up to 750 °C. This allowed to investigate the role of very fine inclusions in the chromatic change: the sulphur‐, barium‐ and iron‐based species included in haüyne, principally ‘pyrrhotite‐like’ crystals and baryte, with the increasing of temperature and under control of oxygen and sulphur fugacity, give rise to the formation of new phases, chiefly haematite and new baryte crystals and of
groups.
Eye movement desensitization and reprocessing for the treatment and early intervention of trauma among first responders: A systematic review
Authors: Morris Heather , Hatzikiriakidis Kostas , Savaglio Melissa , Dwyer Jenny , Lewis Catrin , Miller Robyn , Skouteris Helen
Published: January 2022

First responders are exposed to repetitive work‐related trauma and, thus, are at risk of developing posttraumatic stress disorder (PTSD). Eye‐movement desensitization and reprocessing (EMDR) is a psychotherapy intervention designed to treat symptoms of posttraumatic stress. We conducted a systematic review to examine the viability of EMDR among first responders. The primary aim of this review was to identify studies that have trialed EMDR among first responders and evaluate its effectiveness in reducing trauma‐related symptoms; a secondary aim was to identify whether EMDR has been used as an early intervention for this cohort and determine its effectiveness as such. Four databases were searched. Studies were included if they evaluated the extent to which EMDR was effective in alleviating symptoms stemming from work‐related trauma exposure among first responders. The findings from each study were reported descriptively, and eight studies that evaluated the efficacy of EMDR in this population were included. There was substantial variation in how EMDR was implemented, particularly in the type, duration, frequency, and timing. The findings suggest that EMDR can alleviate symptoms of work‐related trauma exposure among first responders; however, findings regarding early intervention were inconclusive, and a methodological quality assessment revealed that all studies were classified as being of either weak or medium quality. Although this review provides preliminary insights into the effectiveness of EMDR for first responders, the conclusions that can be drawn from the literature are limited, and the findings highlight several gaps in the literature.
A clinical signature predicting the malignant transformation of inflammatory myofibroblastic tumor in the head and neck
Authors: Peng Cangbang , Chen Ming Tao , Liu Zheqi , Guo Yibo , Zhang Yu , Ji Tong
Published: January 2022

Background

Inflammatory myofibroblastic tumors in the head and neck (HNIMTs) sometimes show aggressive clinical features and can be diagnosed as HNIMT with malignant transformation.

Methods

The clinicopathological features of 45 HNIMTs with or without malignant transformation were retrospectively investigated. Logistic regression and receiver operating characteristic analysis were used to establish the predictive model.

Results

HNIMT with malignant transformation was associated with worse prognosis. HNIMT with a tumor size of >4.4 cm, tumors located in the maxillary sinus, or a preoperative neutrophil‐to‐lymphocyte ratio (NLR) greater than 1.958 were associated with higher chance of malignant transformation, with an AUC value of 0.9189. Postoperative radiotherapy could benefit HNIMT patients with high risk of malignant transformation.

Conclusions

HNIMT patients with a tumor size of >4.4 cm, tumors located in the maxillary sinus, and a preoperative NLR over 1.958 were associated with a higher risk of malignant transformation. These patients can benefit from postoperative radiotherapy.
Diagnosis of lymph node metastasis in head and neck squamous cell carcinoma using deep learning
Authors: Tang Haosheng , Li Guo , Liu Chao , Huang Donghai , Zhang Xin , Qiu Yuanzheng , Liu Yong
Published: January 2022

Background

To build an automatic pathological diagnosis model to assess the lymph node metastasis status of head and neck squamous cell carcinoma (HNSCC) based on deep learning algorithms.

Study Design

A retrospective study.

Methods

A diagnostic model integrating two‐step deep learning networks was trained to analyze the metastasis status in 85 images of HNSCC lymph nodes. The diagnostic model was tested in a test set of 21 images with metastasis and 29 images without metastasis. All images were scanned from HNSCC lymph node sections stained with hematoxylin–eosin (HE).

Results

In the test set, the overall accuracy, sensitivity, and specificity of the diagnostic model reached 86%, 100%, and 75.9%, respectively.

Conclusions

Our two‐step diagnostic model can be used to automatically assess the status of HNSCC lymph node metastasis with high sensitivity.

Level of evidence

NA.
Quantum Susceptibilities in Time‐Domain Sampling of Electric Field Fluctuations
Authors: Kizmann Matthias , Moskalenko Andrey S. , Leitenstorfer Alfred , Burkard Guido , Mukamel Shaul
Published: January 2022

Electro‐optic sampling has emerged as a new quantum technique enabling measurements of electric field fluctuations on subcycle time scales. In a second‐order nonlinear material, the fluctuations of a terahertz field are imprinted onto the polarization properties of an ultrashort probe pulse in the near infrared. The statistics of this time‐domain signal are calculated, incorporating the quantum nature of the involved electric fields right from the beginning. A microscopic quantum theory of the electro‐optic process is developed adopting an ensemble of noninteracting three‐level systems as a model for the nonlinear material. It is found that the response of the nonlinear medium can be separated into a conventional part, which is exploited also in sampling of coherent amplitudes, and quantum contributions, which are independent of the state of the terahertz input. Interactions between the three‐level systems which are mediated by terahertz vacuum fluctuations are causing this quantum response. Conditions under which the classical response serves as a good approximation of the electro‐optic process are also determined and how the statistics of the sampled terahertz field can be reconstructed from the electro‐optic signal is demonstrated. In a complementary regime, electro‐optic sampling can serve as a spectroscopic tool to study the pure quantum susceptibilities of matter.
Features of successful interventions to improve adherence to inhaled corticosteroids in children with asthma: A narrative systematic review
Authors: Pearce Christina J. , Chan Amy H. Y. , Jackson Tracy , Fleming Louise , Foot Holly , Bush Andy , Horne Rob
Published: January 2022

Introduction

Nonadherence to inhaled corticosteroids (ICSs) in children with asthma leads to significant morbidity and mortality. Few adherence interventions have been effective and little is known about what contributes to intervention effectiveness. This systematic review summarizes the efficacy and the characteristics of effective interventions.

Methods

Six databases were systematically searched on October 3, 2020 for randomized control trials measuring adherence to ICS in children with asthma. A narrative synthesis was conducted focusing on intervention efficacy and study reliability. Intervention content was coded based on the National Institute for Health and Care Excellence guidelines for medicines adherence (the Perceptions and Practicalities Approach, PAPA) and behavior change techniques (BCTs), to determine the effective aspects of the intervention.

Results

Of 240 studies identified, 25 were eligible for inclusion. Thirteen of the 25 studies were categorized as being highly reliable. Nine of the 13 interventions were effective at increasing adherence and 6 of those met the criteria for a PAPA intervention. Techniques targeting perceptions and practicalities in successful interventions included rewards, reminders, feedback and monitoring of adherence, pharmacological support, instruction on how to take their ICS/adhere, and information about triggers for symptoms and nonadherence.

Conclusion

Adherence interventions in children with asthma have mixed effectiveness. Effective intervention studies were more frequently of higher quality, were tailored to individuals' perceptual and practical adherence barriers, and used multiple BCTs. However, due to the small number of included studies and varying study design quality, conclusions drawn here are preliminary. Future research is needed to test a PAPA‐based intervention with a rigorous study design.
Berkeley Madonna Version 10–A simulation package for solving mathematical models
Authors: Marcoline Frank V. , Furth John , Nayak Smita , Grabe Michael , Macey Robert I.
Published: January 2022

Berkeley Madonna is a software program that provides an easy and intuitive environment for graphically building and numerically solving mathematical equations. Our users range from college undergraduates with little or no mathematical experience to academic researchers and professionals building and simulating sophisticated mathematical models that represent complex systems in the biological, chemical, and engineering fields. Here we briefly describe our recent advances including a new Java‐based user interface introduced in Version 9 and our transition from a 32‐ to 64‐bit architecture with the release of Version 10. We take the reader through an example tutorial that illustrates how to construct a mathematical model in Berkeley Madonna while highlighting some of the recent changes to the software. Specifically, we construct a standard pharmacokinetic model of the antifungal medication amphotericin B taken from the literature and discuss aspects related to model building, key numerical considerations, data fitting, and graphical visualization. We end by discussing planned functionality and features intended for future releases.
The sonographer's use of spectral Doppler in the common femoral vein for the assessment of iliac vein obstructions: A retrospective audit
Authors: Rae Daniel
Published: January 2022

Introduction

Iliac vein obstructions account for 2%–3% of all lower limb deep vein thromboses (DVT). Delayed diagnosis can lead to a higher risk of limb ischemia in the acute setting and post‐thrombotic syndrome in the chronic setting. The purpose of this audit was to determine whether sonographers were taking and interpreting waveforms correctly at the common femoral vein (CFV).

Methods

A retrospective audit was performed of all the DVT patients (n = 375) over the course of 3 months. Changes in phasicity during Valsalva, respiration or augmentation of the spectral waveform at the CFV was recorded.

Results

Within the cohort group of 375 examinations assessed. Only 277 (74%) patients had spectral traces taken at the level of the CFV. 29 (10%) patients had persistent monophasic waveforms that did not change significantly when a Valsalva manoeuvre was performed, eight patients (2%) had confirmed iliofemoral vein obstruction with either ultrasound or computed tomography venogram.

Conclusion

The audit results show that spectral traces at the CFV are not always being taken or assessed effectively in clinical practice for various reasons; highlighting a potential clinical risk. With a combination of education, improved department protocols and workflow strategies, the standard of sonography should be improved.
Differentiating right ventricular remodelling from cardiac pathology in athletes
Authors: Allwood Richard P.
Published: January 2022

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a leading cause of sudden cardiac death in young people and athletes. Prominent right ventricular remodelling can occur in highly trained endurance athletes, raising concern about underlying right ventricular pathology, such as ARVC. Distinguishing between physiological adaptation and cardiac pathology in athletes can be challenging, particularly in elite endurance athletes. This article describes a systematic approach used in sports cardiology to review the physiological adaptation of the right ventricle to exercise and the overlap with ARVC, focusing on the diagnostic investigations used to distinguish between athlete's heart and ARVC.
Propofol‐dexmedetomidine continuous infusion in a dog with pulmonic stenosis undergoing balloon valvuloplasty
Authors: Viilmann Inga , Vettorato Enzo
Published: January 2022

A 6‐month‐old, 4 kg, male pomeranian, was referred for investigations of a heart murmur found during a routine clinical examination. A severe valvular pulmonic stenosis was diagnosed and medical management with atenolol was started. One month later, the dog underwent percutaneous balloon valvuloplasty. Anaesthesia was maintained with propofol‐dexmedetomidine continuous infusion, and a minimally invasive cardiac output monitor was used to assess haemodynamic variations. Intraoperatively, lidocaine was started because the frequency of the premature ventricular complexes increased before ballooning. A reduction in pressure gradient across the pulmonic valve was achieved. No other intraoperative complications were recorded. Recovery from general anaesthesia was uneventful, and the dog was discharged from the hospital 26 hours following the procedure.
Addressing racial/ethnic inequities in vaccine hesitancy and uptake: lessons learned from the California alliance against COVID-19
Authors: AuYoung Mona , Rodriguez Espinosa Patricia , Chen Wei-ting , Juturu Preeti , Young Maria-Elena De Trinidad , Casillas Alejandra , Adkins-Jackson Paris , Hopfer Suellen , Kissam Ed , Alo Audrey Kawaiopua , Vargas Roberto A. , Brown Arleen F. ,   And the STOP COVID-19 C. A. Communications Working Group
Published: January 2022

Lack of trust in biomedical research, government, and health care systems, especially among racial/ethnic minorities and under-resourced communities, is a longstanding issue rooted in social injustice. The COVID-19 pandemic has further highlighted existing health and socioeconomic inequities and increased the urgency for solutions to provide access to timely, culturally, and linguistically appropriate evidence-based information about COVID-19; and ultimately to promote vaccine uptake. California’s statewide alliance STOP COVID-19 CA (comprising eleven sites), leverages long standing community partnerships to better understand concerns, misinformation, and address racial/ethnic inequities in vaccine hesitancy and uptake. Using data from the California CEAL Communication Working Group, we demonstrate the wide range of strategies, communication methods, languages, and trusted messengers that have been effective in reaching diverse communities across the state. We also showcase challenges and lessons learned, such as the importance of including trusted community partners to share information or provide vaccines. These approaches, rooted in community engagement, are crucial for addressing inequities and responding to future public health emergencies.
Soil water repellence increased early wheat growth and nutrient uptake
Authors: Yeap S. G. H. , Bell R. W. , Scanlan C. , Stefanova K. , Harper R. , Davies S.
Published: January 2022

Purpose

Soil water repellence causes uneven soil wetting which can constrain dryland crop and pasture establishment and yield. The same processes are likely to affect nutrient availability from soil and fertiliser, but the effects of repellence on crop growth and nutrition per se have seldom been reported. Here, we investigated early wheat (Triticum aestivum cv. Mace) growth and nutrient uptake responses to repellence.

Methods

Wheat was furrow-sown in severely repellent sandy loam soil (with a wettable furrow base to allow for germination) or completely wettable soil, under uniform plant density and variable topsoil thickness (20 or 100 mm) and fertiliser band placement (below or away from the seed). Tiller number, shoot dry matter, shoot N concentration, total nutrient uptake, and root length density (RLD) were determined.

Results

Contrary to expectations, repellence significantly increased tiller number (by up to 2 tillers per plant), shoot dry matter (by 82%), shoot N concentration (by 0.3% N), and total nutrient uptake (by 87%) at 51 days after sowing, regardless of topsoil thickness and fertiliser placement. In the furrow, RLD of repellent treatments was also nearly double that in wettable treatments when fertiliser was banded below the seed. Results suggest that preferential soil wetting of the furrow in repellent treatments favoured plant nutrient uptake under regular but low water supply.

Conclusion

We conclude that for water-repellent soils with limited water supply, water harvesting techniques such as furrow sowing and banding wetting agents could boost water and nutrient uptake and early crop growth.
Learning 3D Semantic Scene Graphs with Instance Embeddings
Authors: Wald Johanna , Navab Nassir , Tombari Federico
Published: January 2022

A 3D scene is more than the geometry and classes of the objects it comprises. An essential aspect beyond object-level perception is the scene context, described as a dense semantic network of interconnected nodes. Scene graphs have become a common representation to encode the semantic richness of images, where nodes in the graph are object entities connected by edges, so-called relationships. Such graphs have been shown to be useful in achieving state-of-the-art performance in image captioning, visual question answering and image generation or editing. While scene graph prediction methods so far focused on images, we propose instead a novel neural network architecture for 3D data, where the aim is to learn to regress semantic graphs from a given 3D scene. With this work, we go beyond object-level perception, by exploring relations between object entities. Our method learns instance embeddings alongside a scene segmentation and is able to predict semantics for object nodes and edges. We leverage 3DSSG, a large scale dataset based on 3RScan that features scene graphs of changing 3D scenes. Finally, we show the effectiveness of graphs as an intermediate representation on a retrieval task.
A pilot study on comparison of subjective titration versus remotely controlled mandibular positioning during polysomnography and drug-induced sleep endoscopy, to determine the effective protrusive position for mandibular advancement device therapy
Authors: Kazemeini Elahe , Op de Beeck Sara , Vroegop Anneclaire , Van Loo Dorine , Willemen Marc , Verbraecken Johan , Braem Marc J. , Vanderveken Olivier M. , Dieltjens Marijke
Published: January 2022

Study objectives

The aim of this pilot study was to evaluate the clinical effectiveness of subjective titration versus objectively guided titration during polysomnography (PSG) and drug-induced sleep endoscopy (DISE) in mandibular advancement device (MAD) therapy for patients with obstructive sleep apnea (OSA).

Methods

In this pilot cross-over study, patients underwent three titration procedures in randomized order: (1) subjective titration, (2) PSG-guided titration using a remotely controlled mandibular positioner (RCMP) and (3) DISE-assisted titration using RCMP. After each titration procedure, patients used the MAD for 1 month at the targeted protrusion obtained according to the preceding titration procedure. For each procedure, a follow-up PSG was performed after 1 month of MAD use in order to evaluate the efficacy of the MAD.

Results

Ten patients were included in the study. Overall, no significant differences in targeted optimal protrusion compared to maximal comfortable protrusion among the three titration methods were observed. There was no significant difference in reduction in AHI. In this study, PSG titration correctly classified 50% of patients as ‘responder’. A higher predictive accuracy was found for DISE titration with a sensitivity of 83.3% and a specificity of 100%.

Conclusions

This pilot randomized cross-over trial showed no differences in optimal mandibular positioning and corresponding efficacy of MAD between subjective titration, DISE titration or PSG titration.
Arsenic Detection Using Surface Plasmon Resonance Sensor With Hydrous Ferric Oxide Layer
Authors: Mustapha Kamil Yasmin , Al-Rekabi Sura Hmoud , Abu Bakar Muhammad Hafiz , Fen Yap Wing , Mohammed Husam Abduldaem , Mohamed Halip Nor Hafizah , Alresheedi Mohammed Thamer , Mahdi Mohd Adzir
Published: January 2022

The lethality of inorganic arsenic (As) and the threat it poses have made the development of efficient As detection systems a vital necessity. This research work demonstrates a sensing layer made of hydrous ferric oxide (Fe2H2O4) to detect As(III) and As(V) ions in a surface plasmon resonance system. The sensor conceptualizes on the strength of Fe2H2O4 to absorb As ions and the interaction of plasmon resonance towards the changes occurring on the sensing layer. Detection sensitivity values for As(III) and As(V) were 1.083 °·ppb−1 and 0.922 °·ppb−1, respectively, while the limit of detection for both ions was 0.6 ppb. These findings support the feasibility and potential of the sensor configuration towards paving future advancement in As detection systems.
Low-Drift Closed-Loop Fiber Optic Gyroscope of High Scale Factor Stability Driven by Laser With External Phase Modulation
Authors: Yan Jingtao , Miao Lijun , Shen Heliang , Shu Xiaowu , Huang Tengchao , Che Shuangliang
Published: January 2022

In view of the poor scale factor stability of the interferometric fiber optic gyroscope (IFOG), it is a creative method to use laser to drive the IFOG for its better frequency stabilization characteristics instead of the broadband light source. As the linewidth of laser is narrow, the errors of coherent backscattering, polarization coupling, and Kerr effect are reintroduced which cause more noise and drift. This paper studies laser spectrum broadening based on external phase modulation of Gaussian white noise (GWN). The theoretical analysis and test results indicate that this method has a good effect on spectrum broadening and can be used to improve the performance of the laser-driven IFOG. In the established closed-loop IFOG, a four-state modulation (FSM) is adopted to avoid temperature instability of the multifunction integrated-optic chip (MIOC) and drift caused by the electronic circuit in demodulation. The experimental results show that the IFOG driven by broadened laser has the angular random walk noise of 0.003 8 °/√h and the drift of 0.017 °/h, which are 62% and 66% better than those without modulation respectively, of which the drift has reached the level of the broadband light source. Although the noise still needs further reduction, its scale factor stability is 0.38 ppm, which has an overwhelming advantage compared with the traditional IFOG.
Skew Polynomial Rings: the Schreier Technique
Authors: Ánh Phạm Ngọc
Published: January 2022

Schreier bases are introduced and used to show that skew polynomial rings are free ideal rings, i.e., rings whose one-sided ideals are free of unique rank, as well as to compute a rank of one-sided ideals together with a description of corresponding bases. The latter fact, a so-called Schreier-Lewin formula (Lewin Trans. Am. Math. Soc.145, 455–465 1969), is a basic tool determining a module type of perfect localizations which reveal a close connection between classical Leavitt algebras, skew polynomial rings, and free associative algebras.
Revisiting the Limits of Atmospheric Temperature Retrieval From Cosmic‐Ray Measurements
Authors: Riádigos Irma , González‐Díaz Diego , Pérez‐Muñuzuri Vicente
Published: January 2022

A priori, cosmic‐ray measurements offer a unique capability to determine the vertical profile of atmospheric temperatures directly from ground. However, despite the increased understanding of the impact of the atmosphere on cosmic‐ray rates, attempts to explore the technological potential of the latter for atmospheric physics remain very limited. In this paper, we examine the intrinsic limits of the process of cosmic‐ray data inversion for atmospheric temperature retrieval, by combining a detection station at ground with another one placed at an optimal depth, and making full use of the angular information. With that aim, the temperature‐induced variations in cosmic rays (c.r.) rates have been simulated resorting to the theoretical temperature coefficients WT(h, θ, Eth) and the temperature profiles obtained from the ERA5 atmospheric reanalysis. Muon absorption and Poisson statistics have been included to increase realism. The resulting c.r. sample has been used as input for the inverse problem and the obtained temperatures compared to the input temperature data. Relative to early simulation works, performed without using angular information and relying on underground temperature coefficients from a suboptimal depth, our analysis shows a strong improvement in temperature predictability for all atmospheric layers up to 50 hPa, nearing a factor 2 error reduction. Furthermore, the temperature predictability on 6‐h intervals stays well within the range 0.8–2.2 K. Most remarkably, we show that it can be achieved with small‐area m2‐scale muon hodoscopes, amenable nowadays to a large variety of technologies. For mid‐latitude locations, the optimal depth of the underground station is around 20 m.
Hydro‐Mechanical Measurements of Sheared Crystalline Rock Fractures With Applications for EGS Collab Experiments 1 and 2
Authors: Meng Meng , Frash Luke P. , Li Wenfeng , Welch Nathan J. , Carey J. William , Morris Joseph , Neupane Ghanashyam , Ulrich Craig , Kneafsey Timothy
Published: January 2022

We present hydro‐mechanical measurements that characterize shear on natural fractures in schist, amphibolite, and rhyolite specimens from the enhanced geothermal system (EGS) Collab Project's Experiment 1 and 2 sites (E1 and E2) at the Sanford Underground Research Facility. We employed a triaxial direct shear method augmented with X‐ray imaging to perform hydroshearing (injection‐induced shearing) and mechanical shearing on naturally fractured specimens at in situ stress conditions. Measurements included fracture permeability, strength, stress‐dependent aperture, shear dilation, and frictional strength. Results reveal that in situ natural fractures must be permeable, weak, and shear‐oriented to be hydrosheared, and only a subset of the observable in situ fractures were suitable. When sheared, the fracture permeability typically increased by a factor of 10 or more and this increase was retained over time. However, shear slip did not always result in permeability increase. High phyllosilicate content associated with exceptionally weak fractures exhibited poor or even decreased permeability after stimulation. These measurements in combination with site data were used to conduct a slip‐tendency analysis for different fracture sets, and we selected the top candidate natural fractures for hydroshearing at the EGS Collab sites. We also found that the lower in situ shear stress and stronger fractures at the E2 site make hydroshearing more challenging than at the E1 site. Overall, the methods and analysis used in our work can be applied to any geothermal project to identify in situ joint sets that are best suited for hydroshearing, which in turn can help to optimize well placement and energy production.
T cell apoptosis characterizes severe Covid-19 disease
Authors: André Sonia , Picard Morgane , Cezar Renaud , Roux-Dalvai Florence , Alleaume-Butaux Aurélie , Soundaramourty Calaiselvy , Cruz André Santa , Mendes-Frias Ana , Gotti Clarisse , Leclercq Mickaël , Nicolas Alexandre , Tauzin Alexandra , Carvalho Alexandre , Capela Carlos , Pedrosa Jorge , Castro António Gil , Kundura Lucy , Loubet Paul , Sotto Albert , Muller Laurent , Lefrant Jean-Yves , Roger Claire , Claret Pierre-Géraud , Duvnjak Sandra , Tran Tu-Anh , Racine Gina , Zghidi-Abouzid Ouafa , Nioche Pierre , Silvestre Ricardo , Droit Arnaud , Mammano Fabrizio , Corbeau Pierre , Estaquier Jérôme
Published: January 2022

Severe SARS-CoV-2 infections are characterized by lymphopenia, but the mechanisms involved are still elusive. Based on our knowledge of HIV pathophysiology, we hypothesized that SARS-CoV-2 infection-mediated lymphopenia could also be related to T cell apoptosis. By comparing intensive care unit (ICU) and non-ICU COVID-19 patients with age-matched healthy donors, we found a strong positive correlation between plasma levels of soluble FasL (sFasL) and T cell surface expression of Fas/CD95 with the propensity of T cells to die and CD4 T cell counts. Plasma levels of sFasL and T cell death are correlated with CXCL10 which is part of the signature of 4 biomarkers of disease severity (ROC, 0.98). We also found that members of the Bcl-2 family had modulated in the T cells of COVID-19 patients. More importantly, we demonstrated that the pan-caspase inhibitor, Q-VD, prevents T cell death by apoptosis and enhances Th1 transcripts. Altogether, our results are compatible with a model in which T-cell apoptosis accounts for T lymphopenia in individuals with severe COVID-19. Therefore, a strategy aimed at blocking caspase activation could be beneficial for preventing immunodeficiency in COVID-19 patients.
Palladium-catalyzed intermolecular alkynylcarbonylation of unactivated alkenes: easy access to β-alkynylcarboxylic esters
Authors: Li Xiang , Chen Pinhong , Liu Guosheng
Published: January 2022

A palladium-catalyzed intermolecular alkynylcarbonylation of unactivated alkenes has been established, providing β-alkynylcarboxylic esters efficiently from simple alkenes.
AHR EXPRESSION ON VIL1-EXPRESSING COLONIC EPITHELIAL CELLS IS ESSENTIAL FOR I3C-MEDIATED PROTECTION AGAINST COLITIS
Authors: Saxena Archana , Mitchell Chandani , Stanley Shanieka , Wilson Keisha , Rutkovsky Alex , Wisniewski P J , Dopkins Nicholas , Nagarkatti Mitzi , Nagarkatti Prakash , Busbee Philip
Published: January 2022

Ulcerative colitis (UC) is a chronic, idiopathic inflammatory disease that affects the colon and is characterized by localized tissue injury and disruption of the intestinal epithelial barrier. Pathophysiology of UC includes genetic predisposition, epithelial barrier defects, dysregulated immune responses, microbial dysbiosis, and environmental factors. Several therapeutic interventions for colitis have been identified, but many current treatments have various negative side effects, which is alarming given the incidence of UC is increasing around the world. Thus a search for safe therapeutic strategies to control the pathogenesis of colitis is still greatly needed. Previous studies from our laboratory reported that indole-3-carbinol (I3C), a natural plant product and ligand for the aryl hydrocarbon receptor (AhR), exhibited protective effects against colitis through innate lymphoid type 3 (ILC3) cells in an interleukin-22 (IL-22) dependent manner. The aim of this study was to ascertain the possible role of AhR in vil1-expressing colonic epithelial cells (CECs) during I3C-mediated protection against colitis. Using in vivo mouse studies and in vitro primary CEC organoid cultures, we investigated how key intestinal regulatory mediators (e.g. mucins and anti-microbial peptides, or AMPs) were altered in the absence or presence of AhR in CECs during I3C treatment under colitis or colitis-like conditions. We generated conditional AhR knockout mice in vil1-expressing CECs using the cre-flox system and induced colitis using the dextran sodium sulfate (DSS) model. Our results showed that the mice with AhR deficiency in CECs (AV mice) lost the protective effects of I3C treatment during colitis. Results showed that AV mice had a higher disease score and increased inflammation in the colon when compared to wild type (WT) or littermate (LM) controls. In addition, after treatment with I3C during DSS-induced colitis, AV mice were not able to prevent colitis-associated gut microbial dysbiosis even though flow cytometry analysis revealed AV mice were still capable of increasing IL-22 production by ILC3s in the colon. This suggested that the IL-22-ILC3 immune cell response was not the only major mechanism involved in I3C-mediated protection against colitis and regulation of the gut microbiome. Whole transcriptome analysis of RNA isolated from enriched CECs of experimental mice was performed and results showed significant altered expression of several microRNAs, mucins (muc3 and muc13), and tight junction proteins in AV mice when compared to wild type (WT) or littermate (LM) controls. PCR gene expression data and direct effects of I3C on CECs using colonic organoids from WT and AV mice validated these results. Collectively, these data showed that AhR expression in CECs play a critical role in I3C-mediated prevention of colitis.
EFFECTIVENESS OF ANTI-TNF THERAPY COMPARED TO IMMUNE MODULATOR FOR PREVENTION OF SURGICAL RECURRENCE IN PEDIATRIC CD
Authors: Egberg Matthew , Zhang Xian , Phillips Michael , Kappelman Michael
Published: January 2022

BACKGROUND

Crohn’s disease (CD) is an immune-mediated, chronic inflammatory disease without a present cure. Surgical intervention for disease complications is common among CD patients, however post-operative strategies to prevent disease recurrence represent a critical knowledge gap, particularly in the pediatric CD population. Although adult CD data suggest effectiveness of anti-Tumor Necrosis Factor (TNF) therapies for prevention of recurrence, similar evidence is scarce for the pediatric population. We sought to evaluate the effectiveness of anti-TNF monotherapy compared to immune modulator (methotrexate or thiopurine) monotherapy for prevention of surgical recurrence in pediatric CD patients using a large, geographically diverse administrative claims database.

METHODS

We analyzed pediatric (≤18 years) patients with CD who underwent ≥1 intestinal resection within the IQVIA Legacy PharMetrics Adjudicated Claims database between 2007 and 2018. IQVIA data contain longitudinal, de-identified patient-level claims for medical, surgical, and pharmacy encounters. IQVIA captures over 100 health plans with nearly 80 million insurance plan enrollees. We selected patients with ≥1 International Classification of Diseases 9thor 10thclinical modification (ICD-9/10) code for CD and ≥1 Current Procedural Terminology (CPT) code for a large and/or small bowel resection. We excluded patients with ≥3 encounters with an ICD-9/10 diagnosis code for ulcerative colitis (UC) or ≥1 UC code in the month of the index resection. We identified patients prescribed anti-TNF monotherapy and those prescribed immune modulators (thiopurine or methotrexate) monotherapy within 90 days of resection and compared rates of surgical recurrence. Analyses included descriptive statistics for the post-surgical cohort as well as time to surgical recurrence using Kaplan-Meier curves.

RESULTS

A total of 399 pediatric CD patients underwent an intestinal resection between 2007-2018 within the IQVIA database. Among those, 212 were prescribed either an anti-TNF monotherapy (109; 51%) or immune modulator monotherapy (103; 49%) within 90 days of resection. The median age of the treated cohort was 16 years (interquartile range (IQR) 14, 17) with 48% females. Over 60% of intestinal resections were ileo-cecectomies/colectomies. Thirteen (6.1%) patients required a repeat resection. Differences in median time to surgical recurrence were not statistically significant (Figure 1). Post-operative therapy was highly correlated with pre-operative therapy (p-value <0.001).

CONCLUSION

Our results do not suggest a clear benefit of anti-TNF monotherapy versus immune modulator therapy for post-operative prophylaxis of pediatric Crohn’s disease. Randomized comparative effectiveness trials evaluating a range of outcomes including clinical and endoscopic recurrence are needed.
SAFFRON AS AN ADJUVANT THERAPY IN ULCERATIVE COLITIS PATIENTS
Authors: Ashktorab Hassan , Oppong-Twene Philip , Maecker Holden Terry , Chirumamilla Lakshmi , Kibreab Angesom , Nabi Eiman , Laiyemo Adeyinka , Brim Hassan
Published: January 2022

BACKGROUND

In the search for alternative or supplemental treatment for Ulcerative Colitis (UC), we studied saffron (Crocus Sativus) in a UC clinical trial, as an additional intervention to improve clinical manifestations of UC through its anti-inflammatory and anti-reactive oxygen species properties.

METHODS

This study is an open-label single-center pilot study conducted at Howard University. Patients with UC (n=3) in remission with mild-moderate disease received 50mg of Saffron twice daily for a period of 8-weeks. Inflammatory markers CRP measured in serum, calprotectin in feces, and the others (TNFα, INFγ, IL-6, IL-2, IL-17a, and IL-10) from PMA/ionomycin stimulated PBMCs by CyTOF, at baseline compared to 8-weeks Saffron treatment. Partial Mayo scoring was used for clinical response, the health-related quality of life questionnaire (HQoL) along with Hamilton Depression Rating Scale (HDRS) was used to assess the patient’s quality of Life as the primary endpoints. 16sDNA was performed on stool DNA for gut microbiome.

RESULTS

Significant calprotectin improvement was noticed in 2 out of 3 patients receiving saffron after 8 weeks compared to baseline. There was an improvement of Partial Mayo Score, pro-inflammatory markers TNFα, INFγ, IL-6, IL-2, IL-17a decreased while anti-inflammatory IL-10 increased. A wash-out period of 8 weeks reversed the calprotectin improvement while the second cycle of saffron treatment restored the calprotectin improvement level after 8-week in the 2 patients enrolled in the washout period. There was no drug-related adverse event during the study. Saffron’s effects on the gut microbiome composition in UC patients showed a decrease in gamma Proteobacteria, and enrichment in Ruminococcaceae.

CONCLUSIONS

Saffron improved clinical response for the main UC indicator fecal calprotectin and in Partial Mayo Scores. We observed significant improvement in patient’s symptoms such as abdominal pain, diarrhea, and rectal bleeding. Therefore, using saffron supplements, along with conventional medicines, may have beneficial impacts on UC patients and reduce the need for immunosuppressants in these patients.
SIMPLE SUGAR TRIGGERS SPONTANEOUS COLITIS DEVELOPMENT INIL10
-/- MICE
Authors: Khan Shahanshah , Zaki Hasan
Published: January 2022

The Western diet characterized by high fat and high sugar is considered a risk factor for inflammatory bowel disease (IBD) such as colitis. However, the precise role of sugar in colitis pathogenesis is poorly understood. We, therefore, investigated the role of glucose, a simple sugar, in colitis pathogenesis using IBD susceptible Il10-/- mice. We fed healthy 14-week old Il10-/- mice with 10% glucose in drinking water for 5 week and monitored body weight changes. Sugar fed Il10-/- mice spontaneously developed severe colitis, characterized by higher body weight loss and increased diarrhea, and shorter colon lengths. In agreement, there was higher expression of pro-inflammatory cytokines and chemokines in glucose-fed mice. Since colitis induction in Il10-/- mice is microbiota dependent, development of spontaneous colitis is often irregular. To induce colitis uniformly in all mice, glucose-fed and control Il10-/- mice were treated with a piroxicam-fortified diet. Alternatively, healthy Il10-/- mice were administered with a piroxicam-fortified diet for 5 days followed by feeding with high-glucose or regular drinking water. In both instances, glucose-fed Il10-/- mice lost more body weight and developed worse colitis. Increased colitis pathogenesis of glucose-fed Il10-/- mice was associated with increased inflammatory response, activation of inflammatory signaling pathways, induction of cell death, and erosion of mucus layer. Consistent to reduced mucus layer, there was increased bacterial colonization on the colonic mucosa and higher activity of bacteria-derived mucolytic enzymes in the gut lumen of sugar-fed Il10-/- mice. Notably, high sugar diets altered the composition of gut microbiota, particularly the abundance of mucus degrading bacteria, such as Akkermansia muciniphila and Bacteroides sp., was increased. Together these data suggest that high-sugar diet predisposes spontaneous colitis and enhances colitis pathogenesis by promoting the growth of mucus degrading bacteria in the gut of Il10-/- mice.
BURDEN OF ILLNESS OF OSTEOPOROTIC FRACTURES COMPARED TO OTHER SERIOUS DISEASES AMONG IBD PATIENTS
Authors: Tariq Raseen , Tahir Muhammad Waqas , Tahir Zoya , Zaheer Faizan , Wahab Abdul
Published: January 2022

INTRODUCTION

Inflammatory bowel disease (IBD) patients are off and on treated with steroids which is associated with increased risk of osteoporosis and fragility fractures. We conducted an analysis to study the burden of osteoporotic fractures compared to acute myocardial infarction (AMI) or stroke in hospitalized patients with IBD.

METHODS

We used the National Inpatient Sample database from 2007 through 2014, to identify patients admitted with primary or secondary diagnosis of IBD using the ICD-9 codes. We identified primary diagnosis of osteoporotic fractures (excluding traumatic injuries, open fracture, readmission indicators), acute myocardial infarction and stroke using respective diagnostic codes. We analyzed trends in nationwide estimates for annual admissions, age at admission, length of stay (LOS), in-patient mortality and total hospital charge (adjusted for inflation).

RESULTS

Over the eight-year study period, there were an estimated 2,296,145 admissions with IBD. Overall, hip fractures as primary diagnosis accounted for 0.5% of these hospitalizations, non-hip fractures for 0.6%, AMI for 0.8% and stroke for 0.6%. Among patients over 50 years old, the prevalence was 1.0% for hip fractures, 0.9% for non-hip fractures, 1.3% for AMI and 1.0% for stroke. Temporal trend was unchanged over the studied period. More females were admitted with fractures (70.5%) and strokes (55.7%) as compared to AMI (42.4%). Highest mortality was seen among patients admitted for stroke (7.1%), followed by AMI (4.1%) and fractures where mortality with hip fractures was significantly higher than non-hip fractures (2.7% vs 1.7%, p<0.05). The median age for patients with hip fractures was 78, much higher than for non-hip fractures (72), which was close to age for stroke (71), but higher than AMI (67). Mean LOS for stroke was 5.9 days, followed by hip fractures 5.8 days, non-hip fractures 5.6 days, and AMI 5.2 days. Mean charge for hospitalization was similar for hip fractures and non-hip fractures, ($52,399 vs $50,545) which was less than that for stroke ($55,569) and AMI ($70,970). After adjusting for inflation, there was a trend of increase in charge for all four admission diagnoses (Figure 1).

CONCLUSION

Proportion of IBD patients admitted primarily for nontraumatic fractures is similar to stroke admission, particularly in patients older than 50. Hip fractures are more common than non-hip fractures. Mortality is higher with hip fractures than non-hip fractures. LOS among studied causes is highest for hip fractures and stroke. Cost of hospitalization although not as much with fractures than AMI, showed a rising trend during the study period.