bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Thromboelastography to Predict Thrombotic Complications in Pediatric and Neonatal Extracorporeal Membranous Oxygenation
Authors: Henderson Natalie , Sullivan Janice E. , Myers John , Wells Terri , Calhoun Aaron , Berkenbosch John , Tzanetos Deanna Todd
Published: July 2023

The objectives of this study were to investigate the correlation between thromboelastography (TEG) and conventional measures of anticoagulation, and to determine optimum values for citrated kaolin TEG R time (TEG RCK) and anti-Xa activity that would minimize both bleeding and thrombotic complications in pediatric and neonatal patients requiring extracorporeal membranous oxygenation (ECMO). A retrospective chart review of patients requiring veno-venous (VV) and venoarterial (VA) ECMO was performed. Combined medical and cardiac ICU within a single-center, tertiary care, freestanding, children’s hospital. Non-pregnant patients <18 years and >2 kilograms requiring VV or VA ECMO from July 2013 through July 2015. Anti-Xa (OR = 0.62, 95% CI 0.53–0.72, p < .001) and TEG RCK (OR = 1.19, 95% CI 1.07–1.34, p = .003) were the only independent predictors for a significant thrombotic event. Receiver operating characteristic curves and traditional epidemiological data (sensitivity, specificity, PPV, NPV) were used to determine optimal target Anti-Xa and TEG RCK values. No independent predictors for significant bleeding events were identified in this cohort. A anti-Xa activity of .25 IU/mL (sensitivity = 81%, specificity = 67%, PPV = 81%, NPV = 58%) and TEG RCK time of 17.85 minutes (sensitivity = 84%, specificity = 68%, PPV = 82%, NPV = 59%) were established as the optimal thresholds for preventing thrombotic events. Anti-Xa and TEG RCK were independent predictors of thrombosis in this cohort of pediatric and neonatal ECMO patients. Targeting an anti-Xa activity greater than .25 IU/mL and a TEG RCK greater than 17.85 minutes may minimize the risk of thrombosis in pediatric and neonatal ECMO patients. Future investigation should evaluate targets for anti-Xa and TEG RCK, which additionally minimize the risk of significant bleeding in this patient population.
The Novel Use of a Low Prime Modified Ultrafiltration Apparatus in a 13-kg Jehovah’s Witness Patient: A Case Report
Authors: Datt Bharat , Munro Hamish M. , DeCampli William M.
Published: July 2023

Modified ultrafiltration (MUF) is used in neonates and infants to reduce volume overload and increase oxygen-carrying capacity post cardiopulmonary bypass (CPB). In addition, it decreases edema, attenuates complementation activation and immunogenic response to CPB. Hemodilution in the pediatric patient has always been a challenge, countered in part by miniaturization of CPB circuits. We describe a case in which we maintained an acceptable hematocrit level greater than 24%, considered the nadir below which the adverse effects of hemodilution can become evident. We performed this by the novel use of an intravenous warming device (enFlow, Vyaire Medical, Mettawa, IL) to reduce the prime volume of our MUF circuit by more than 50%. We present the case and discuss the advantages and disadvantages of using a low-prime MUF circuit. We were able to conduct “bloodless” CPB, with the use of acute normovolemic hemodilution, miniaturization of the CPB and MUF circuits.
Microfluidic Point-of-Care Ecarin-Based Clotting and Chromogenic Assays for Monitoring Direct Thrombin Inhibitors
Authors: Alouidor Benjamin , Sweeney Robin E. , Tat Trinny , Wong Raymond K. , Yoon Jeong-Yeol
Published: July 2023

Direct thrombin inhibitors (DTIs), such as bivalirudin and dabigatran, have maintained steady inpatient and outpatient use as substitutes for heparin and warfarin, respectively, because of their high bioavailability and relatively safe “on-therapy” range. Current clinical methods lack the capacity to directly quantify plasma DTI concentrations across wide ranges. At present, the gold standard is the ecarin clotting time (ECT), where ecarin maximizes thrombin activity and clotting time is evaluated to assess DTIs’ anticoagulation capability. This work focused on the development of a microfluidic paper analytic device (µPAD) that can quantify the extent of anticoagulation as well as DTI concentration within a patient’s whole blood sample. Capillary action propels a small blood sample to flow through the nitrocellulose paper channels. Digital images of whole blood migration are then captured by our self-coded Raspberry Pi and/or the Samsung Galaxy S8 smartphone camera. Both the flow length and the blue absorbance from the plasma front on the μPAD were measured, allowing simultaneous, dual assays: ecarin clotting test (ECT) and ecarin chromogenic assay (ECA). Statistically significant (p < .05) changes in flow and absorbance were observed within our translational research study. Currently, there are no quantitative, commercially available point-of-care tests for the ECT and ECA within the United States. Both the ECT and ECA assays could be instrumental to differentiate between supratherapeutic and subtherapeutic incidents during bridging anticoagulant therapy and limit the unwarranted use of reversal agents.
Improving Decreased Heater–Cooler Efficiency as a Result of Heater–Cooler Infection Control Strategy
Authors: Blakey Adam K. , Holt David W.
Published: July 2023

Heater–cooler units (HCUs) play a vital role in temperature management during cardiopulmonary bypass. In recent years, HCUs have been shown to play a significant role in the propagation of bacteria causing patient infection and significant harm. As a result, various institutions across the world have begun moving the HCU either far away or outside of the operative theater entirely. The purpose of this study was to examine the effect that the increased length of HCU water lines have on the ability of the device to heat and cool. We hypothesized that the increase in water line distance leads to a decrease in HCU efficiency and that insulating the water lines would blunt the effect of this increase in distance. Five water line conditions were compared under two cooling and two warming ranges. Short water lines, long water lines, and long water lines with foam, rubber, or tape insulation were compared. Cooling from an arterial line temperature of 26.7–19.7°C showed no difference between conditions with the exception that every long line condition takes significantly longer to cool than short water lines. Cooling from 35.6 to 28.6°C revealed that all insulations reduce the cooling time compared with long water lines without insulation, but only foam insulation reduces to the level of the short water lines. During warming conditions, all insulations reduced the warming time compared with long uninsulated water lines, but none were comparable with short water lines. Increased water line length leads to a decrease in HCU efficiency. Insulation is effective at increasing efficiency of long water lines, but only at warmer temperatures and not to the level of short water lines. Only foam-insulated long water lines were able to match the efficiency of short water lines, but only across a single temperature range.
Gravity Venous Drainage and the 3/8-Inch Venous Line: What Would Poiseuille Do?
Authors: Datt Bharat , Pourmoghadam Kamal K. , Munro Hamish M. , DeCampli William M.
Published: July 2023

The 1/2″ venous line has long been the drainage tubing diameter of choice for adult patients undergoing cardiac surgery. However, several programs use a smaller diameter venous line when used in conjunction with kinetic-assisted venous drainage or vacuum-assisted venous drainage. In 2014, our perfusion team made an institution-wide effort to miniaturize the cardiopulmonary bypass (CPB) circuit for children. One of our changes was the transition to a 3/8″ diameter venous line for drainage, even in our larger patients (up to 80 kg). We reviewed the current literature on this topic and delineated the various parameters required to be able to use the 3/8″ venous line with gravity drainage with the aim of using it on patients up to 115 kg with the appropriate venous reservoir. We have successfully used the 3/8″ venous line in more than 40 of our larger patients (35–90 kg) without the need for assisted venous drainage. We were able to reduce CPB prime from 625 ± 118 to 425 ± 52 mL before retrograde autologous priming (RAP)/venous autologous priming (VAP). The prime was further reduced to 325 ± 66 mL after RAP/VAP. Homologous blood utilization was reduced from 217 ± 311 mL to 27 ± 77 mL. Both results were statistically significant. We hypothesize that taking into account two of the parameters of Poiseuille’s law, namely length and diameter, it is possible to safely drain large children and mid-size adults via gravity venous drainage and the 3/8″ venous line. This technique allows reducing prime volume, simplifies CPB circuits with increased safety and potentially reduces the need for homologous blood transfusion.
Platelet Refractoriness in a Pediatric ECMO Patient: A Case Report
Authors: Gill Martin
Published: July 2023

Thrombocytopenia is a life-threatening condition, the severity of which is exacerbated further if the patient requires anticoagulation and is refractory to platelet transfusion. This is the first report of an infant undergoing extracorporeal support with immune-mediated platelet refractoriness. A 19-month-old girl, with a complex cardiac history, required extracorporeal support because of deterioration 8 days post-cardiac surgery. The child suffered from ongoing thrombocytopenia, unresponsive to multiple platelet transfusions. An incremental rise in the platelet count was achieved following transfusion of human leukocyte antigen–matched platelets, although this was unsuccessful with subsequent transfusions of matched platelets. Following 7 days on extracorporeal membrane oxygenation (ECMO), without cardiac improvement and likely poor prognosis, treatment was withdrawn and the patient died. The management of immune-mediated platelet refractoriness, in an anticoagulated patient on ECMO, requires early diagnosis and timely intervention to achieve a good outcome for the child. An understanding of the condition and a multidisciplinary approach to its treatment will assist in effective direction of medical therapy.
Transition from Hemochron Response to Hemochron Signature Elite Activated Clotting Time Devices in a Congenital Cardiac Surgery Practice
Authors: Matte Gregory S. , Howe Robert J. , Ibla Juan , Emani Sirisha , Emani Sitaram M.
Published: July 2023

Heparin is the primary anticoagulant used during cardiac surgery to prevent thrombosis due to cardiopulmonary bypass (CPB)–related activation of the hemostatic system. The efficacy of heparin in the operating room is generally determined by activated clotting time (ACT) point-of-care tests performed throughout the procedure. In an effort to transition to the Hemochron Elite which requires approximately 1/10th the sampling volume of blood, we conducted a prospective study in 260 pediatric patients undergoing CPB. ACT tests were performed during CPB with a total of 260 pre-bypass and 1,117 on-bypass ACT values recorded. All samples were run simultaneously on both ACT devices. Several therapeutic cut-off possibilities ranging from >380 to >480 seconds were evaluated to ascertain the ACT level on the Elite device which best correlated with results from the Response device. Linear regression was used to determine correlation. The correlation between the two methods was moderate with a Pearsonrof .6 and .4 for pre-bypass bolus ACT values and on-bypass ACT values, respectively. As the therapeutic ACT cut-off values were lowered from 480 to 380 seconds on the Elite device relative to the Response device (>480 seconds) for the on-bypass heparin samples, more patients would be under-dosed (incidence rising from 1 to 2%) and fewer patients would be overdosed (incidence decreasing from 32 to 5%) and the percent correlation between devices increased from 67 to 93%. A similar trend was observed with the pre-bypass heparin bolus samples. There was no significant effect of temperature on the ACT values comparing both devices. A therapeutic ACT value of >400 seconds for CPB with the Hemochron Elite device reasonably approximates a therapeutic ACT value of >480 seconds on the Hemochron Response device in our congenital cardiac surgery practice. Transitioning to the Elite device significantly reduces the overall sampling volume required for ACT monitoring during cardiac surgery.
„State of the Art in der Therapie der Adipositas“
Authors: Schulze zur Wiesch Clarissa , Lautenbach Anne , Aberle Jens
Published: July 2023

Laut der WHO sind Übergewicht und Adipositas in Europa jährlich für mehr als 1,2 Millionen Todesfälle verantwortlich, was mehr als 13 % der Gesamtsterblichkeit in der Region entspricht. Gemäß des Obesity Report von 2022 werden erhebliche Anstrengungen erforderlich werden, um die Menschen wieder zu einer gesünderen Lebensweise und mehr körperlicher Aktivität zu bewegen. Therapeutische Maßnahmen im Rahmen einer eskalierenden Stufentherapie sollten Strategien für eine gezielte
Gewichtsreduktion und einen langfristigen Gewichtserhalt umfassen. Ein wichtiges gesundheitspolitisches Ziel sollte der bessere Zugang zu diesen Therapieoptionen sein mit einem zusätzlichen Fokus auf die Primärprävention.
Psychiatrisch pflegerischer Konsildienst
Authors: Jansen Heike , Feuchtinger Johanna , Wyllegalla Christian , Müller Martin , Roth Andreas , Kusserow Anja , Heine Daniela , Moser Esther
Published: July 2023

Um psychiatrisch erkrankte Patient*innen in der Somatik ganzheitlich pflegen zu können, erhalten somatisch Pflegende zeitnah Unterstützung durch den psychiatrisch pflegerischen Konsildienst. Im Schwerpunkt stellen wir Ihnen das Projekt des Universitätsklinikums Freiburg vor.
Hier darf ich sein, wie ich bin
Authors: Dann Christine
Published: July 2023

Wie sieht die Arbeit in einer 24-Stunden-Betreuung aus, welche Kompetenzen brauchen die Mitarbeitenden und welche Bedürfnisse haben die Bewohner? Antworten liefert unsere Autorin in einem eindrucksvollen Erfahrungsbericht.
Auswirkungen der COVID-19-Pandemie auf die Versorgung von Menschen mit Diabetes mellitus in Deutschland: ein Scoping Review-Update
Authors: Friedrichs Paula , Schmidt Kerstin , Hauner Hans
Published: July 2023

Bei der vorliegenden Arbeit handelt es sich um ein Scoping Review-Update zu den Auswirkungen der COVID-19-Pandemie auf die Versorgung von Menschen mit Diabetes in Deutschland. Dazu wurde eine systematische Literaturrecherche in Literatur- und Forschungsdatenbanken (BELIT, LIVIVO, DNB, CORDIS, MediaTUM, GEPRIS und PubMed), sowie mit Google und Google Scholar durchgeführt. Auf diese Weise konnten 30 Studien zur Versorgung von Menschen mit Diabetes im Verlauf der COVID-19-Pandemie identifiziert und in die Datenextraktion eingeschlossen werden. Die eingeschlossenen Studien wurden hinsichtlich ihrer methodischen Qualität bewertet. Thematisch bezogen sich die identifizierten Studien auf die folgenden Versorgungsbereiche: ambulante Versorgung, stationäre Versorgung, Arzneimittelversorgung, Psychosoziales, Disease-Management-Programme, Qualität der Diabeteseinstellung, Diabetes-Schulung, Telemedizin und Mortalität. Die Beobachtungszeiträume fast aller Studien umfassten mindestens die Anfangsphase der Pandemie (März bis Mai 2020) und gingen nicht über das Ende der 2. Welle hinaus (April 2021).

Der Großteil der Studien zeigte keine gravierenden bzw. lediglich kurzfristige Effekte der COVID-19-Pandemie auf die Versorgung von Menschen mit Diabetes. Es gab vor allem in der Anfangsphase der Pandemie weniger Diabetes-Diagnosen im ambulanten und stationären Bereich. Weiter fand sich ein zeitweiser Anstieg diabetischer Ketoazidosen bei der Erstmanifestation von Kindern und Jugendlichen mit Typ-1-Diabetes und es gab Anhaltspunkte für eine höhere Rate von Majoramputationen bei Personen mit Typ-2-Diabetes.

Zusammenfassend legen die hier gefundenen Studien mit deutlich besserer Datenlage nahe, dass die Mehrzahl der Menschen mit Diabetes während der COVID-19-Pandemie medizinisch adäquat versorgt war. Einen wichtigen Beitrag dazu leistete wahrscheinlich der Einsatz der Telemedizin. So wurden Telefon- oder Videokonsultationen häufig genutzt, um die medizinische Versorgung zu gewährleisten, ohne dass ein persönlicher Kontakt nötig war. Diese Erfahrungen sollten genutzt werden, um telemedizinische Ansätze auch zukünftig in der Versorgung von Menschen mit Diabetes stärker einzusetzen.
Motion Capture statt Goniometer – Computergestützte ROM-Messung und Dokumentation
Authors: Schäfer Katharina , Johnen Laura , Balster Jella , Buhr Mirijam , Brandl Christopher
Published: July 2023

Eine spannende Forschungsarbeit zeigt, wie Physiotherapeut*innen das Bewegungsausmaß schnell, einfach und kostengünstig digital erfassen können. Die Daten werden automatisch analysiert, dokumentiert und die Verlaufskontrolle optimiert. Das innovative Konzept ist evidenzbasiert und praxisorientiert, stößt aber auf Hindernisse wie den Mangel an Therapeut*innen, veraltete Technik und fehlendes Know-How.
Management of Brachial Plexus Birth Injuries at British Columbia Children's Hospital
Authors: Verchere Cynthia , Durlacher Kim , Bellows Doria
Published: July 2023

A multidisciplinary team at BC Children's Hospital provides brachial plexus birth injury management for our provincial catchment area. Although compared with many centers we service a relatively small clinic population, we have the benefit of universal health care, province-wide reach, and accessible research infrastructure. In 2008, we created the Sup-ER protocol, which includes an orthosis that passively positions the neonatal shoulder into more idealized glenohumeral contact during early growth. We have since shown that our Sup-ER patients have better shoulder outcomes, require less brachial plexus surgery, and need fewer shoulder tendon transfers than those patients treated in our clinic prior to 2008. We have also found that the rate and degree of elbow flexion contractures are reduced compared with results reported in the literature.
Detection of Antibiotic Resistance and Biofilm- Producing Ability of Staphylococcus Species in Clinical Isolates
Authors: Singh Shila Kumari , Bhattacharjee Minakshi , Unni Balagopalan , Kashyap Rajpal Singh
Published: July 2023

Background

Staphylococci are responsible for life-threatening infections in hospitals and community. Their ability to produce multiple virulence factors and antibiotic resistance is an important reason of high mortality in staphylococcal infections. Biofilm production by these organisms makes it difficult to treat. Most of the treating antibiotics are failing and making it a matter of concern.

Aims

This study aims to detect the increased antibiotic resistance in biofilm-producing Staphylococcus and to compare the performance of three potential methods of detection.

Methods

A total of 81 isolates of staphylococci including coagulase negative staphylococci (CoNs), methicillin resistant S. aureus (MRSA), and methicillin sensitive S. aureus (MSSA) are included in this study. After the identification, an antibiotic sensitivity test was performed. Biofilm detection was done by three different methods: Congo red agar method, tube adherence method, and microtiter plate method.

Result

Out of the 81 samples, 37 CoNs, 17 MRSA, and 27 MSSA were identified. Out of them we got 43 (53%) biofilm producers by Congo red agar method, 40 (49%) by tube adherence method, and 52 (64%) producers by tissue culture plate/microtiter plate method. Most of the biofilm producers showed multiple drug resistance.

Conclusion

We found out that the microtiter plate method is sensitive and reliable as compared with the other two methods. Antibiotic resistance was found to be very common in biofilm producers. This was due to the resistance developed as a result of the matrix that does not let the antibiotic bind with the organisms. This can make the treatment of Staphylococcus very difficult in the future as the rate of drug resistance is faster as compared with newly emerging antibiotics.
Detection of two-dimensional small polarons at oxide interfaces by optical spectroscopy
Authors: Tang Chi Sin , Zeng Shengwei , Wu Jing , Chen Shunfeng , Naradipa Muhammad A. , Song Dongsheng , Milošević M. V. , Yang Ping , Diao Caozheng , Zhou Jun , Pennycook Stephen J. , Breese Mark B. H. , Cai Chuanbing , Venkatesan Thirumalai , Ariando Ariando , Yang Ming , Wee Andrew T. S. , Yin Xinmao
Published: July 2023

Two-dimensional (2D) perovskite oxide interfaces are ideal systems to uncover diverse emergent properties, such as the arising polaronic properties from short-range charge–lattice interactions. Thus, a technique to detect this quasiparticle phenomenon at the buried interface is highly coveted. Here, we report the observation of 2D small-polarons at the LaAlO3/SrTiO3 conducting interface using high-resolution spectroscopic ellipsometry. First-principles investigations show that interfacial electron–lattice coupling mediated by the longitudinal phonon mode facilitates the formation of these polarons. This study resolves the long-standing question by attributing the formation of interfacial 2D small polarons to the significant mismatch between experimentally measured interfacial carrier density and theoretical values. Our study sheds light on the complexity of broken periodic lattice-induced quasi-particle effects and its relationship with exotic phenomena at complex oxide interfaces. Meanwhile, this work establishes spectroscopic ellipsometry as a useful technique to detect and locate optical evidence of polaronic states and other emerging quantum properties at the buried interface.
Enhanced photoconductivity of hybrid 2D-QD MoS2–AgInS2 structures
Authors: Kondratenko Serhiy , Datsenko Oleksandr I. , Babich Danylo , Dzhagan Volodymyr , Pan Yang , Rahaman Mahfujur , Selyshchev Oleksandr , Zahn Dietrich R. T.
Published: July 2023

This study describes the fabrication of hybrid two-dimensional (2D)-quantum dot (QD) MoS2–AgInS2 photoconductive devices through the mechanical pressing of a MoS2 flake onto an AgInS2 QD film. The devices exhibit an enhanced photoresponse at both continuous and modulated optical excitations, compared with the bare MoS2 or AgInS2 layer, due to the formation of a built-in electric field near the MoS2/AgInS2 interface. The continuous wave photoresponse is significantly higher due to the effective photoconductive gain when electrons flow freely through the MoS2 flake, whereas holes are effectively trapped in AgInS2 QDs. The study highlights the potential of hybrid 2D-QD MoS2–AgInS2 devices for photovoltaic and optoelectronic applications.
Novel applications of generative adversarial networks (GANs) in the analysis of ultrafast electron diffraction (UED) images
Authors: Daoud Hazem , Sirohi Dhruv , Mjeku Endri , Feng John , Oghbaey Saeed , Miller R. J. Dwayne
Published: July 2023

Inferring transient molecular structural dynamics from diffraction data is an ambiguous task that often requires different approximation methods. In this paper, we present an attempt to tackle this problem using machine learning. Although most recent applications of machine learning for the analysis of diffraction images apply only a single neural network to an experimental dataset and train it on the task of prediction, our approach utilizes an additional generator network trained on both synthetic and experimental data. Our network converts experimental data into idealized diffraction patterns from which information is extracted via a convolutional neural network trained on synthetic data only. We validate this approach on ultrafast electron diffraction data of bismuth samples undergoing thermalization upon excitation via 800 nm laser pulses. The network was able to predict transient temperatures with a deviation of less than 6% from analytically estimated values. Notably, this performance was achieved on a dataset of 408 images only. We believe that employing this network in experimental settings where high volumes of visual data are collected, such as beam lines, could provide insights into the structural dynamics of different samples.
The contribution of Compton ionization to ultrafast x-ray scattering
Authors: Ziems Karl Michael , Simmermacher Mats , Gräfe Stefanie , Kirrander Adam
Published: July 2023

We investigate the role of Compton ionization in ultrafast non-resonant x-ray scattering using a molecular model system, which includes the ionization continuum via an orthonormalized plane wave ansatz. Elastic and inelastic components of the scattering signal, as well as coherent-mixed scattering that arises from electron dynamics, are calculated. By virtue of a near-quantitative distinction between scattering related to electronic transitions into bound and continuum states, we demonstrate how Compton ionization contributes to the coherent-mixed component. Analogous to inelastic scattering, the contribution to the coherent-mixed signal is significant and particularly manifests at intermediate and high-momentum transfers. Strikingly, for molecules with inversion symmetry, the exclusion of bound or continuum transitions may lead to the prediction of spurious coherent-mixed signals. We conclude that qualitative and quantitative accuracies of predicted scattering signals on detectors without energy resolution require that elements of the two-electron density operator are used. This approach inherently accounts for all accessible electronic transitions, including ionization.
Effect of temperature and moisture on the field distortion in synthetic ester induced by space charge accumulation
Authors: Yu Rui , Matharage Shanika , Wang Zhongdong
Published: July 2023

Electric field distortion caused by space charge accumulation is one of the challenges in the development of insulating liquid immersed converter transformers and battery energy storage. This paper studies the impact of temperature and moisture content on field distortion in synthetic ester through an improved computational model incorporating the time-development permittivity of insulating liquid, and the test results indicated highly accurate simulation results of electric field distribution can be produced compared with the previous model. Charge mobility and charge density in synthetic ester were extracted from frequency dielectric spectroscopy test results, which were then used to calculate field distortion by the developed computational model. Simulation results indicated that the field distortion in synthetic ester decreases with temperature due to the enhanced permittivity caused by space charge accumulation, while it increases with moisture content due to the increased charge density from the dissociation of water.
A fault detection method for induction motors with sliding mode observers based on stochastic resonance and the Teager energy operator
Authors: Zhong Guanglin , Yu Wenxin , Wang Junnian
Published: July 2023

To accurately and sensitively track the stator current of an induction motor (IM) and detect faults, stochastic resonance (SR) and the Teager energy operator (TEO) are combined to detect a fault in the residual stator current of a sliding mode observer (SMO) under strong noise interference and complex weak fault conditions. First, a new reaching law is constructed to establish an SMO for better state tracking. Second, SR is used to absorb noise and amplify the detection residuals of the SMO, and the output results are estimated by the TEO in the time domain to achieve fault detection. Finally, the detection results of the IM stator and rotor winding faults and sensor intermittent faults are presented. The experimental results show that the SMO has higher state tracking accuracy and a faster rate of convergence. Moreover, the residual of the stator current is processed by SR and the TEO, and the effectiveness of fault detection is enhanced.
Sparse random similarity feature decomposition and its application in gear fault diagnosis
Authors: Liu Feng , Cheng Junsheng , Hu Niaoqing , Cheng Zhe , Yang Yu
Published: July 2023

As a new signal decomposition method, sparse random mode decomposition (SRMD) does not depend on the signal sampling process and has good anti-mode aliasing performance. However, SRMD needs preset decomposition parameters and cannot perform accurate decomposition for strong noise interference signals. Thus, this paper proposes a sparse random similarity feature decomposition (SRSFD) method to overcome the problems of SRMD. Firstly, SRSFD utilizes the windowed sinusoidal function to randomly generate time–frequency features. Then, by solving sparse optimization problem, the sparse random feature approximation of the input signal can be obtained and its corresponding time–frequency features can be applied to reconstruct the initial signal components. Finally, the initial signal components are regrouped by using periodic similarity to obtain the final components. The analytical results of simulation and actual gear fault signals show that SRSFD can effectively achieve adaptive signal decomposition and has better decomposition performance and noise robustness compared with existing methods.
Impact of individual behavior adoption heterogeneity on epidemic transmission in multiplex networks
Authors: Huo 霍 Liang’an 良安 , Yu 于 Yue 跃
Published: July 2023

In recent years, the impact of information diffusion and individual behavior adoption patterns on epidemic transmission in complex networks has received significant attention. In the immunization behavior adoption process, different individuals often make behavioral decisions in different ways, and it is of good practical importance to study the influence of individual heterogeneity on the behavior adoption process. In this paper, we propose a three-layer coupled model to analyze the process of co-evolution of official information diffusion, immunization behavior adoption and epidemic transmission in multiplex networks, focusing on individual heterogeneity in behavior adoption patterns. Specifically, we investigate the impact of the credibility of social media and the risk sensitivity of the population on behavior adoption in further study of the effect of heterogeneity of behavior adoption on epidemic transmission. Then we use the microscopic Markov chain approach to describe the dynamic process and capture the evolution of the epidemic threshold. Finally, we conduct extensive simulations to prove our findings. Our results suggest that enhancing the credibility of social media can raise the epidemic transmission threshold, making it effective at controlling epidemic transmission during the dynamic process. In addition, improving an individuals’ risk sensitivity, and thus their taking effective protective measures, can also reduce the number of infected individuals and delay the epidemic outbreak. Our study explores the role of individual heterogeneity in behavior adoption in real networks, more clearly models the effect of the credibility of social media and risk sensitivity of the population on the epidemic transmission dynamic, and provides a useful reference for managers to formulate epidemic control and prevention policies.
Prediction of superionic state in LiH2 at conditions enroute to nuclear fusion
Authors: Li 李 Fude 福德 , Wang 王 Hao 豪 , Li 李 Jinlong 津龙 , Geng 耿 Huayun 华运
Published: July 2023

Hydrogen and lithium, along with their compounds, are crucial materials for nuclear fusion research. High-pressure studies have revealed intricate structural transitions in all these materials. However, research on lithium hydrides beyond LiH has mostly focused on the low-temperature regime. Here, we use density functional theory and ab initio molecular dynamics simulations to investigate the behavior of LiH2, a hydrogen-rich compound, near its melting point. Our study is particularly relevant to the low-pressure region of the compression pathway of lithium hydrides toward fusion. We discovered a premelting superionic phase transition in LiH2 that has significant implications for its mass transportation, elastic properties, and sound velocity. The theoretical boundary for the superionic transition and melting temperature was then determined. In contrast, we also found that the primary compound of lithium hydrides, LiH, does not exhibit a superionic transition. These findings have important implications for optimizing the compression path to achieve the ignition condition in inertial confinement fusion research, especially when lithium tritium-deuteride (LiTD) is used as the fuel.
Simulation of gas–liquid two-phase flow in a flow-focusing microchannel with the lattice Boltzmann method
Authors: Feng 冯 Kai 凯 , Yang 杨 Gang 刚 , Zhang 张 Huichen 会臣
Published: July 2023

A lattice Boltzmann method for gas–liquid two-phase flow involving non-Newtonian fluids is developed. Bubble formation in a flow-focusing microchannel is simulated by the method. The influences of flow rate ratio, surface tension, wetting properties, and rheological characteristics of the fluid on the two-phase flow are analyzed. The results indicate that the flow pattern transfers from slug flow to dry-plug flow with a sufficiently small capillary number. Due to the presence of three-phase contact lines, the contact angle has a more significant effect on the dry-plug flow pattern than on the slug flow pattern. The deformation of the front and rear meniscus of a bubble in the shear-thinning fluid can be explained by the variation of the capillary number. The reduced viscosity and increased contact angle are beneficial for the drag reduction in a microchannel. It also demonstrates the effectiveness of the current method to simulate the gas–liquid two-phase flow in a microchannel.
A comprehensive review on recent developments of natural fiber composites synthesis, processing, properties, and characterization
Authors: Shebaz Ahmed J P , Satyasree Karedla , Rohith Kumar R , Meenakshisundaram Omkumar , Shanmugavel Sudarsan
Published: July 2023

The escalation of ecological awareness and sustainability has motivated many researchers to foster bio-composite studies and advancement in employing natural fibers and resin. During the last few decades, composites have emerged with various environmental impacts such as degradation, incineration, and toxicity. The credence is that bio-composite materials will downsize the need for environmentally and economically synthetic polymers. To enhance the degradability to the maximum extent, natural resin and natural fiber must be acquired from natural resources. A sequence of treatments must be followed throughout the resin synthesis process to obtain a usable and effective form of natural resin. Natural fibers are becoming more and more dominant over synthetic fibers because of their superior strength, stiffness, durability, and lack of toxicity. In comparison to synthetic fibers, biocomposites have the potential to diminish material expenses while improving mechanical properties. The processing techniques of compression molding, injection molding, and extrusion are frequently employed for biopolymer composite preparations. The ultimate properties of the composite are determined by the degree of adhesion between the matrix and fiber. To assess the mechanical and thermal properties of biocomposites, tests such as tensile, flexural, impact, thermogravimetric analysis, and dynamic mechanical analyzer are conducted. Many applications of bio-composites have created new opportunities for research and business ventures. Bio-composites are non-abrasive, degradable, and used for various purposes like packaging, medicine, agriculture, and the automotive industry. The undesirable factors like degradation, incineration, and recycling problem of non-biodegradable composite have induced the research and evolution of bio-composite. This decisive review would manifest a summary concerning the framework of natural resins, natural fibers, and bio-composites, the factors affecting the characteristics of bio-composites, and the future prospects for this field.
On unipotent representations of ramified 𝑝-adic groups
Authors: Solleveld Maarten
Published: July 2023

Let

G
G

be any connected reductive group over a non-archimedean local field. We analyse the unipotent representations of

G
G

, in particular in the cases where

G
G

is ramified. We establish a local Langlands correspondence for this class of representations, and we show that it satisfies all the desiderata of Borel as well as the conjecture of Hiraga, Ichino and Ikeda about formal degrees.

This generalizes work of Lusztig and of Feng, Opdam and the author, to reductive groups that do not necessarily split over an unramified extension of the ground field.
CAMEL NANOBODIES NEUTRALIZE SARS-COV-2 VARIANTS
Authors: Hong Jessica , Kwon Hyung Joon , Cachau Raul , Butay Kevin John , Duan Zhijian , Li Dan , Ren Hua , Hsieh Chao-Ming , Dandey Venkata P , Borgnia Mario J , Xie Hang , Ho Mitchell
Published: July 2023

Background and Significance

With the emergence of SARS-CoV-2 variants during the global pandemic from 2020 to 2023, there is need for broadly neutralizing antibodies. Due to their small size and unique conformations, nanobodies can recognize protein cavities that are not accessible to conventional antibodies.

Methods and Results

Here, we used phage display libraries built from dromedary camels to isolate two VHH nanobodies (7A3 and 8A2), which have high affinity for the receptor-binding domain (RBD) of the SARS-CoV-2 spike. Cryo-EM complex structures revealed that 8A2 binds the RBD in its up mode and 7A3 targets a conserved and deeply buried site in the spike regardless of the conformational state of the RBD. At a dose of ≥5 mg/kg, nanobody 7A3 efficiently protected K18-hACE2 transgenic mice from the lethal challenge of SARS-CoV-2 variants B.1.351 or B.1.617. With the addition of omicron variant, a new VHH nanobody (J1B4) was isolated to target the S2 subunit of the SARS-CoV-2 spike that can bind across many variants including omicron. Trispecific nanobodies were made using 7A3, 8A2, and J1B4 which had increased binding signals compared to the nanobodies alone. Using this method, we hope to create a therapeutic that is able to broadly neutralize not only all pre-existing variants of SARS-CoV-2, but also be effective towards future SARS-CoV related variants.

Conclusions and Future Directions

By combining nanobodies targeting the RBD of the S1 subunit (7A3+8A2) with a nanobody targeting the S2 subunit (J1B4), we can increase the chance of protection against all SARS-CoV-2 infections. Due to the increased protein binding of the trispecific compared to individual nanobodies alone, it shows great promise that the trispecific may be able to enhance its activity across all variants. Nanobody-based therapeutics may be developed as a nasal spray which can be self-administered and inhaled directly to the lungs to treat the infection at its source.
DEVELOPMENT OF A SELECTIVE CD16A-BASED NK CELL ENGAGER UTILIZING ANTIBODIES TARGETING A SINGLE AMINO ACID VARIATION
Authors: Liao Wuxiang , Tumanut Christine , Li Lin , Corper Adam , Challa Dilip , Chang Alex , Begum Hydari , Farokhi Elinaz , Woods Catherine , Fan Xiaomin
Published: July 2023

Background and Significance

Natural killer (NK) cells play a vital role in the human innate immune system and are being explored as a promising approach for cancer immunotherapy. Of particular interest are NK cell engagers that can target and activate NK cells to attack cancer cells. In this study, we developed novel NK cell engagers by targeting the NK cell activating receptor CD16a using antibodies that selectively distinguish between CD16a on NK cells and CD16b on granulocytes, which are highly homologous to each other.

Methods and Results

To generate antibodies with high developability, we employed a rational design approach to construct large yeast display libraries of human antibodies. This approach was based on the analysis of a deep sequencing dataset of human antibodies from over 500 individuals, which allowed us to determine the natural amino acid usage patterns of human antibody CDRs and mimic human antibody repertoires.

Through screening these libraries, we discovered two classes of antibody clones that selectively recognize CD16a without cross-reactivity to CD16b. Epitope mapping revealed that a single amino acid difference confers over 10,000-fold selectivity for one class of antibody clones, while for the other class a second unique epitope on CD16a was identified.

To evaluate the activity of these antibody clones, we produced bispecific antibody clones with one arm targeting CD16a and the other arm targeting a tumor-associated antigen (TAA). Our results demonstrated potent tumor cell-dependent activation of NK cells and effective killing of tumor cells. Several of these antibodies had greatly enhanced resistance to human IgG inhibition in killing target cells. Significantly, our anti-CD16a antibody clones exhibited superior performance compared to leading reference anti-CD16a clones in two distinct NK cell engager formats. This included higher affinity for CD16a, higher thermostability, and more potent killing activity both in the absence and presence of 10 mg/mL human IgGs as competitors.

Conclusion

Our findings indicate that anti-CD16a antibody-based NK cell engagers have significant potential for cancer immunotherapies.
TARGETING TREG CELLS BY TNFR2 ANTIBODY INDUCES TUMOR REGRESSION IN VIVO
Authors: Yi Zuoan David , He Chong , Hso Yueh-Mei , Strainic Michael , Yin Yong , Zhai Wenwu
Published: July 2023

Background

Tumor necrosis factor receptor 2 (TNFR2) is considered an appealing target due to its low-level expression on immune cells, but it could be upregulated on regulatory T cells (Tregs) in the tumor microenvironment which plays key roles in Treg proliferation and function. It has been demonstrated that Tregs with high TNFR2 expression were the most suppressive subsets among all Treg populations in the tumor. While early studies showed that TNFR2 co-stimulates naïve T cells, it has been revealed later that TNFR2 also limits CD8+ T-cell-mediated viral clearance and anti-tumor immunity by inducing rapid contraction of CD8+ T cells. Consistent with these findings, several publications reported that anti-TNFR2 antibody treatment exhibited robust antitumor efficacy. In short, TNFR2 signaling is critical in regulating immune response in different diseases. In the current study, the anti-human TNFR2 antibody SBT-1901 was developed and the anti-tumor activity was evaluated.

Materials and methods

SBT-1901 was generated through hybridoma and humanization technologies. The binding affinity and specificity were tested by ELISA, FACS, and OCTET. The function of SBT-1901 was tested in TNFR2-Fas overexpressing Ramos cells and in Treg proliferation assay. The in vivo anti-tumor activity and pharmacokinetics of SBT-1901 were evaluated in the human TNFR2 transgenic mouse model (Biocytogen) bearing MC38 tumor.

Results

SBT-1901 binds to the extracellular domain of human and cynomolgus TNFR2 with the affinity of single digit-nanomolar. It competes with TNFα for binding to TNFR2 receptor and inhibits TNFα-induced TNFR2-Fas overexpressing RAMOS cell death. SBT-1901 also blocks TNFα induced Treg proliferation in human PBMC. In addition, SBT-1901 significantly inhibits MC38 tumor growth in a dose-dependent manner as a monotherapy and enhances anti-tumor efficacy of mPD-1 antibody in a combination study in human TNFR2 transgenic mouse model. SBT-1901 is currently under preclinical development.

Conclusions

Our studies show that SBT-1901 exhibits a very potent anti-tumor efficacy in vivo as a single agent or the combination. Therefore, it is highly valuable to further develop SBT-1901 for human cancer treatment.
ESTABLISHMENT OF AN ULTRA HIGH-THROUGHPUT PROTEIN PRODUCTION PLATFORM (ULTRA 96) FOR EARLY STAGE IN VITRO STUDIES
Authors: Jiang Kai , Li Huishuai , Tang Chuanlong , Zhang Dawei , Zhang Xuejian , Zhang Ying , Zhao Zhengyang , Zhou Jun , Lu Mengjie , Xiao Yongsheng , Feng Zhumei , Wu Jiansheng
Published: July 2023

Proteins are known as the building blocks of life which play many critical roles in the body. In early stage drug discovery, numerous μg to mg scale high quality proteins need to be produced for in vitro functional studies and therapeutic evaluation, including antigens, monoclonal antibodies (mAb), bispecific antibodies (bsAbs) as well as other Fc fusion proteins. High-throughput production (HTP) of various proteins with high quality in very short time is a big challenge in industry. Here we present how WuXi Biologics has created a powerful ultra HTP protein production platform (termed as “Ultra 96”) that can automatically produce proteins within 3 weeks with one step purification at 1~3mL expression scale by using 96 and 24 well DWP. High titer of expression, high quality of products, short timeline as well as low cost make “Ultra 96” a robust platform which can empower our clients and dramatically accelerate their early stage drug discovery projects.
DEVELOPMENT OF A METHOD FOR PRODUCING FAB/F(AB’)2 FRAGMENTS FROM A FULL-LENGTH MONOCLONAL ANTIBODY FOR BIOANALYTICAL ASSAYS
Authors: Zhang Hefeng , Zhu Lingling , Zou Emily , Liang Yu , Zou Linglong
Published: July 2023

Background

Monoclonal antibodies (mAb) comprise of two Fab fragments and one Fc fragment or one F(ab)’2 fragment and one Fc fragment. While a full-length mAb is frequently used as an assay reagent for bioanalysis, mAb fragments are required in certain cases. For example, to build a sandwich assay for detection of anti-drug antibodies (ADA) for therapeutic antibodies, Fab or F(ab)’2 fragment is used instead of a full-length mAb as capture reagent. This is because therapeutic antibodies, either humanized or fully human, are in many ways indistinguishable from the ADA generated in patients, especially in Fc fragment. When ADA detection methods utilizes anti-human Fc antibodies as the detection reagent, the full-length mAb drug will be directly bound by the detection reagent, causing interference. Preparation of a Fab or F(ab)’2 fragment is therefore needed.

Methods and results

We are developing a method for enzymatic digestion of therapeutic antibodies to generate monovalent Fab or bivalent F(ab’)2 fragments in this study. With such reagents becoming available, a sandwich ADA assay formats can be expanded to allow anti-human Fc antibodies as detection regents. To standardize the method, we explored various enzymatic conditions, including type of enzymes (i.e., pepsin, papain, and IdeS Protease), digestion-time (1, 2, 4, and 6 h), enzyme to antibody ratio (1:10, 1:20, and 1:40 w/w), IgG species and isotypes (human IgG1-κ, IgG1-λ, and IgG4-κ). The enzymatic hydrolysates were quantified by NanoDrop and purified by dialysis (10K MWCO) and Protein A/G/L magnetic bead methods. The effective recovery of truncated antibodies was > 90%, as assessed by reduced/non-reduced SDS-PAGE and ELISA analysis. Digestion of human IgG1 and IgG4 with pepsin resulted into a complete cleavage into F(ab')2 fragments and degradation of Fc fragments. While IdeS Protease produced an equivalent quantity of F(ab’)2 and Fc fragments with a similar efficiency, removal of the intact Fc fragment was required as an additional step. If the Fab fragments were desired, papain could be used with yield being over 90%. We have subsequently utilized either Fab or F(ab’)2 as a capture reagent for ADA detection.

Conclusion

We have successfully developed the enzymatic digestion method to prepare Fab or F(ab’)2 fragments. The optimized conditions described here are broadly applicable to different IgG isotypes across many therapeutic antibodies.