bluuebunny/crossref_metadata_2025 huggingface dataset:
The novel HLA‐B*13:01:21 allele identified by Sanger dideoxy nucleotide sequencing in a Chinese individual
Authors: Zhang Yan‐fen , Zheng Zhong‐zheng , Du Ke‐ming , An Lin , Gao Da
Published: December 2022

HLA‐B*13:01:21 differs from HLA‐B*13:01:01:01 by one nucleotide in exon 2.
Comprehensive research on the distribution of HLA‐DRB1 in Chinese populations
Authors: Fan Baitong , Huang Xiaoqin , Zhang Xiaochao , Huang Lifan , Yang Zhaoqing , Ma Shaohui , Chu Jiayou , Huang Kai , Weng Yuting , Zhang Lin , Lin Keqin , Sun Hao
Published: December 2022

By presenting antigen peptides, HLA‐DRB1 plays an important role in the immune system. However, the allele frequency of HLA‐DRB1 exon 2 across China has not been comprehensively studied, especially in minority populations. We sampled 3757 individuals from 59 population. The HLA‐DRB1 region from 212 to 463 bp (NM_002124.4 exon 2) in each population was sequenced by Sanger sequencing and genotyped via SBTengine® software, and the allele frequency was calculated by GenAlEx 6.5. Eighty‐two DRB1 alleles were identified. The expected heterozygosity of DRB1 was lower in the south than in the north, which was inconsistent with the Y chromosome and mitochondrial DNA results. The Mantel test and nonparametric correlation analysis showed that the correlations of the genetic distance with geographical distance and of DRB1 allele frequencies with latitude weakened after the southern and northern groups were considered separately. Principal coordinate analysis showed that populations speaking the same languages were not codistributed. Compared with other genetic markers, the distribution of DRB1 seems less affected by geographic distance and ethnic origin. Local factors such as gene flow with neighbouring populations, geographic isolation or natural selection are important forces shaping the DRB1 gene pool of local populations.
The novel HLA‐A*24:561:02 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual
Authors: Yu Jie‐chen , Zheng Zhong‐zheng , Du Ke‐ming , An Lin , Xu Li‐li
Published: December 2022

HLA‐A*24:561:02 differs from HLA‐A*24:02:01:01 by one nucleotide in exon 3.
The novel HLA‐C*15:02:58 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual
Authors: Zhao Yan‐qiu , Zheng Zhong‐zheng , Du Ke‐ming , An Lin , Fan Sheng‐jin
Published: December 2022

HLA‐C*15:02:58 differs from HLA‐C*15:02:01:01 by one nucleotide in exon 1.
Investigations on the Splitter Structure to Improve the Aerodynamic Performance of Gas Turbine Exhaust Diffuser at Different Swirl Angles
Authors: Dong Yuxuan , Li Zhigang , Li Jun
Published: December 2022

To weaken the flow separation in the exhaust diffuser under real operating conditions and increase the static pressure recovery coefficient of the exhaust diffuser, an exhaust diffuser structure with splitters was proposed. Based on verifying the reliability of the numerical method, the paper numerically explores the influence of the height and width of the splitter on the aerodynamic performance of the exhaust diffuser under three different inlet swirl angles by solving three-dimensional Reynolds-Averaged Navier–Stokes (RANS). The results show that the introduction of the splitter structure into the exhaust diffuser can effectively suppress the separation vortex near the strut, improve the flow state at the exhaust diffuser outlet, and further increase the static pressure recovery coefficient of the exhaust diffuser. The optimal splitter structure can be obtained by comparing the effects of the splitter height and width on the static pressure recovery performance of the exhaust diffuser under different inlet swirl angles. When the inlet swirl angles are 16 degs, 28 degs, and 38 degs, compared with the original exhaust diffuser without splitters, the optimal splitter structure can increase the static pressure recovery coefficient of the exhaust diffuser by 0.036, 0.096, and 0.146, respectively, with a relative increase of 7.3%, 34.2%, and 76.2%. The introduction of the splitter structure helps to improve the aerodynamic performance of the exhaust diffuser.
Direct-to-Chip Two-Phase Cooling for High Heat Flux Processors
Authors: Heydari Ali , Manaserh Yaman , Abubakar Ahmad , Caceres Carol , Miyamura Harold , Ortega Alfonso , Rodriguez Jeremy
Published: December 2022

Due to the surge in electronics power density, single-phase liquid cooling technologies are emerging to replace legacy air-cooling technologies. However, this surge in electronics power densities is accelerating abruptly, which will cause a single-phase liquid cooling operational lifetime to be much shorter than air cooling. Accordingly, it is essential to look for alternative cooling technologies such as two-phase cooling to replace liquid cooling when its time is up. This work presents comprehensive analyses of two-phase rack-level cooling systems deployment. These analyses can be divided into three main categories which are benchtop testing, rack-level deployment, and choosing a green refrigerant replacement. On the benchtop part of the project, five different cold plates that have different internal geometry are considered. These cold plates are used to build cooling loops with various configurations namely parallel, serial, and hybrid (parallel and serial). An EES code is used to design and evaluate the cold plates and cooling loops based on the existing correlations and modeling techniques. To evaluate this code, a benchtop two-phase experimental setup is built. This setup is designed to test single cold plates and full cooling loops while maintaining system stability. In this setup, high-power-density TTVs with 2.5 kW rated heaters are used to test these cold plates and cooling loops. The work on the benchtop level is just a preparation stage for the rack level deployment, where a custom-built CDU distributes refrigerant to the cooling loops through rack and row manifolds. These cooling loops are placed in multiple racks and attached to TTVs to simulate the thermal load of high-power density servers. In this part of the study, some design perspectives are introduced, and the impact of different operational parameters on CDU performance is explored. The last part of this study discusses the criteria for choosing a green refrigerant to replace existing high GWP ones. Most commonly used refrigerants such as R134a are expected to be phased out very soon due to their high GWP. Therefore, it is necessary to look for an alternative green refrigerant that can be adopted in the system without significantly impacting its performance. Preliminary results showed that R1234yf is the most appropriate replacement for R134a in two-phase rack-level cooling systems.
Pool Boiling Heat Transfer in Dielectric Fluids and Impact of Surfaces on the Repeatability
Authors: Emir Tolga , Yazici Yakup Gokalp , Budakli Mete , Arik Mehmet
Published: December 2022

This study presents an experimental investigation on the nucleate boiling heat transfer (NBHT) in deionized (DI) water and HFE-7100 on bare copper surfaces. The experiments were performed under atmospheric condition at 0 and 10 K subcooling levels. The primary objective was to understand the effect of fluid property on critical heat flux (CHF) and heat transfer performance, where the occurrence of surface oxidation over the entire set of experiments were investigated for a range of operating conditions. In order to determine the onset and development of the latter phenomenon, experiments for the complete boiling process have been repeated three times under similar conditions. A detailed visualization study with a high-speed camera has been utilized to capture the dynamics of bubble formation and departure. Additionally, high-resolution microscopic images were captured, and contact angle measurements were used to express the experimental results conveniently. Microscopic images showed that using DI water leads to an intensified oxidization on the heater surface, while HFE-7100 yields a minor occurrence of oxide layer on the copper surfaces. The results indicated that CHF values remain constant for water at 0 K; however, a remarkable increase was observed for 10 K subcooling from the first to third run of successive measurements.
Liquid to Liquid Cooling for High Heat Density Liquid Cooled Data Centers
Authors: Heydari Ali , Shahi Pardeep , Radmard Vahideh , Eslami Bahareh , Chowdhury Uschas , Saini Satyam , Bansode Pratik , Miyamura Harold , Agonafer Dereje , Rodriguez Jeremy
Published: December 2022

Removal of heat is becoming a major challenge in today’s data centers. Computing-intensive applications such as artificial intelligence and machine learning are pushing data center to compute intensive systems, such as GPU, CPU, and switches to their extreme limits. Racks of IT can approach up to 100kW of heat dissipation challenging traditional data center designs for enterprises and cloud service providers. Direct-to-chip liquid cooling utilizing cold plates is becoming a common method of removing heat from high heat density data center server racks. There are various methods of applying liquid cooling to data centers to address the high heat density components such as liquid to liquid (L2L), liquid to air (L2A), and liquid to single phase refrigerant (L2R). This study aims to investigate the thermo-hydraulic performance of the L2L cooling systems using cooling distribution units (CDUs). CDUs provide a cold secondary coolant (Propylene Glycol 25%) into the cooling loops of liquid-cooled server racks, with the CDUs providing liquid to liquid heat exchange between the primary facility water and secondary liquid used for cold plates. This study uses Thermal Test Vehicles (TTVs) which have been built to reproduce and simulate high heat density servers. Four different cooling loops are characterized experimentally, and detailed analytical and numerical simulations using CFD are developed for analyzing the cooling characteristics of the entire L2L cooling loop, including the CDU, for removing heat from the cold plates. Detailed Flow Network Modeling (FNM) has been performed to analyze precise hydraulic modeling of the secondary fluid flow, from the CDUs to the cooling loops, for predicting pressure drop and flow rate of the secondary coolant. A FNM properly sizes the pumping requirements of the L2L cooling system. Additionally, a system calculator has been created for quickly sizing all secondary loop piping for L2L heat exchanger deployments.
Comparative Study of Single-Phase Immersion Cooled Two Socket Server in Tank and Sled Configurations
Authors: Sivaraju Krishna Bhavana , Bansode Pratik , Gupta Gautam , Lamotte-Dawaghreh Jacob , Saini Satyam , Simon Vibin , Herring Joseph , Karajgikar Saket , Mulay Veerendra , Agonafer Dereje
Published: December 2022

Submerging a cluster of servers inside a large tank is the customary way of employing single-phase immersion cooling. But this approach requires a complete renovation of existing air-cooled infrastructure. A practical approach to convert an air-cooled data center to immersion cooled data center can be retaining the rack and server arrangements and supplying each server with immersion liquid in sled configuration – retaining horizontal position. The present study aims at characterizing the thermal performance of a 2-socket server in sled and tank configurations using CFD. In the tank configuration model, the server is immersed vertically with the coolant supply from bottom to top as in the case of a typical single-phase immersion deployments. In the sled configuration, the server orientation is retained (horizontally) and the fluid supply is modeled as an inlet and outlet manifold connected to the same side of the server. The CFD modeling approach is aimed to determine the heat transfer behavior of the server in two configurations being looked at was done for a commercially available dielectric immersion liquid, EC 110. A detailed baseline geometry of the server was first simplified, considering only the components that are significant source of heat and/or impact the server flow characteristics. Some of the components considered for analysis include CPU, storage drives and memory modules. The performance of the server in two configurations is compared to determine the efficiency of both the server configurations while ensuring the components do not exceed their respective thermal threshold. Component temperatures are obtained by varying the coolant flow rates and dielectric temperatures.
CFD Analysis of Heat Capture Ratio in a Hybrid Cooled Server
Authors: Shalom Simon Vibin , Reddy Lochan Sai , Shahi Pardeep , Valli Amrutha , Saini Satyam , Modi Himanshu , Bansode Pratik , Agonafer Dereje
Published: December 2022

Rising power densities at the server level due to increasing performance demands are being met by using efficient thermal management methods such as direct-to-chip liquid cooling. The use of cold plates that are directly installed yields a lower thermal resistance path from the chip to the ambient. In a hybrid-cooled server arrangement, high-heat-generating components are cooled with water or a water-based fluid, while the rest of the components are cooled with air using server-level fans. It is imperative to characterize the heat capture ratio for various server boundary conditions to ascertain the best possible liquid and airflow rates and temperatures. These parameters serve as inputs in defining the Total Cost of Ownership (TCO). The present investigation numerically evaluates the heat capture ratio in a hybrid cooled server for peak server load and varying inlet temperature for air and liquid. The CFD model of a Cisco Series C220 server with direct-to-chip liquid-cooled CPUs was developed. The cold plate for the CPU was experimentally characterized for pressure drop and thermal resistance characteristics and a black-box model was used for CFD simulations using 25% propylene glycol as the coolant. The heat capture ratio value was obtained under the varied temperature and flow rate boundary conditions of air and liquid. Based on the heat capture ratio values obtained, optimum values of inlet temperatures and flow rates are recommended for air and liquid for the server being investigated.
Mechanical and Electrical Properties of Additively Printed Circuits With Magnetically Orientated Anisotropic Conductive Adhesive Attachment for FHE Applications
Authors: Lall Pradeep , Narangaparambil Jinesh , Miller Scott
Published: December 2022

Developing component attachment techniques with low-temperature processing is required to implement flexible hybrid electronics utilizing additively printed circuits. Additive electronics may be made on several substrates such as Polyimide, PET, and PEN. While polyimide may be processed at standard reflow temperatures, thermally stabilized PET and PEN require a peak processing temperature of less than 150 °C. A variety of novel solder materials have emerged that can be worked at temperatures lower than 150 degrees Celsius. The low temperature also provides the added benefits of less warpage, less energy use, and a reduced carbon footprint. The process-performance-reliability relationships for the printed magnetically oriented conductive adhesive on the printed conductive metallization have been investigated in this work. Young’s modulus of the bonding material has been evaluated using the nanoindentation technique. Characterization of the frequency-performance of surface mount component attachments on additively printed metallization was used to study electrical and mechanical performance. The performance of the interconnects was compared to the COTS predefined tolerance limits. In flex-to-install applications, the reliability and performance deterioration of additively printed circuits have been measured. The interconnection reliability is also tested for dynamic flexing conditions for cycles to failure. Optical imaging has also been used to investigate the intermetallics at the interface of conductive adhesive and additively printed circuits.
AI-Based Reliability Assessment of Power Electronic Systems
Authors: McCluskey F. Patrick , Buxbaum Clifton , Mazumder Sudip K. , Sarwat Arif , Ursino Matt , Russell Miles C.
Published: December 2022

One of the most important elements for market acceptance of new technologies is ensuring reliability. Nowhere is this truer than in the shift from well characterized fossil fuel technologies to newer renewable and sustainable energy technologies. The key enabling technology driving these shifts is the development of power converters and inverters. Conventional approaches to assess reliability of these devices have severe drawbacks. Frequent redesigns, often with new parts having no historical data, limit the usefulness of methods based on historical data. Conversely, physics-of-failure approaches often do not capture the most relevant failure mechanisms, including those related to operationally induced electrical overstress and software. In this paper, we will discuss a revolutionary new reliability assessment approach that utilizes advancements in artificial intelligence (AI), machine learning, and data analytics, along with new techniques for characterizing and modeling failure mechanisms to improve power electronics reliability.

The reliability assessment method combines AI and machine learning algorithms for analyzing field failure data, with top down models that translate the impacts of grid-connected and grid-parallel mode dynamics and mode-transition dynamics on power systems, and reliability physics degradation models for key failure mechanisms that simulate the effects of both electrical and environmental degradation under field operational stresses. These models can be embedded in digital twins created specifically to replicate the design of current and new inverters. The output of these digital twins reflects the effects of aging and component degradation on system performance and will be transferable to multiple power electronic systems and platforms.
The acoustic realization of contrastive focus by 6-year-old Australian English-speaking children
Authors: Yuen Ivan , Xu Rattanasone Nan , Schmidt Elaine , Holt Rebecca , Demuth Katherine
Published: December 2022

Children as young as five have some ability to produce contrastive focus [Wells et al. (2004) J. Child Lang. 31, 749–778]. However, adult listeners' ability to identify the location of contrastive focus depends on whether the speech came from a 4-, 7-, or 11-year-old [Patel and Brayton (2009) J. Speech. Lang. Hear. Res. 52, 790–801]. Recent acoustic studies have also reported the use of F0 vs duration in contrastive focus productions by American English–speaking 2-year-olds [Thorson and Morgan (2021) J. Child Lang. 48, 541–568] and 4-year-olds [Wonnacott and Watson (2008) Cognition 107, 1093–1101], respectively. This study, therefore, evaluated the extent to which older 6-year-olds, with more language experience, used F0 and/or duration when producing contrastive focus, and compared this to adult speech. Monosyllabic and disyllabic adjective + noun targets (e.g., green ball) in utterance medial and final position were elicited from 20 Australian English–speaking 6-year-olds and 14 adults in adjective focus and noun focus conditions. Although both adults and children used high F0, only adults consistently used word and stressed syllable duration as well. This suggests that children may master the different acoustic cues to contrastive focus at different stages of development, with late cue integration.
Sonic boom reflection over urban areas
Authors: Dragna Didier , Emmanuelli Ariane , Ollivier Sébastien , Blanc-Benon Philippe
Published: December 2022

Sonic boom propagation over urban areas is studied using numerical simulations based on the Euler equations. Two boom waves are examined: a classical N-wave and a low-boom wave. Ten urban geometries, generated from the local climate zone classification [Stewart and Oke (2012), Bull. Am. Meteorol. Soc. 93(12), 1879–1900], are considered representative of urban forms. They are sorted into two classes, according to the aspect ratio of urban canyons. For compact geometries with a large aspect ratio, the noise levels and the peak pressure, especially for the N-wave, are highly variable between canyons. For open geometries with a small aspect ratio, these parameters present the same evolution in each urban canyon, corresponding to that obtained for isolated buildings. A statistical analysis of the noise levels in urban canyons is then performed. For both boom waves, the median of the perceived noise levels mostly differs by less than 1 dB from the value obtained for flat ground. The range of variation is greater for open geometries than for compact ones. Finally, low-frequency oscillations, associated with resonant modes of the canyons, are present for both compact and open geometries. Their amplitude, frequency and decay rate vary greatly from one canyon to another.
Improving stretchability of associative polymers through tuning density of the secondary interactionsa)
Authors: Wu Shilong , Yang Huanhuan , Chen Quan
Published: December 2022

The macroscopic stretchability of ionomer melts strongly relies on the structural evolution during the elongational flow. It has been noted that the introduction of the secondary associations weaker than the ionic association can improve the stretchability. To understand the mechanism, this study examines the stretchability of unentangled ionomers containing a fixed number of ionic groups per chain, fion≅4, but a varied number of hydrogen bonds per chain, fH = 5.5–27. The stretchability that is reflected in the maximum Hencky strain achieved before rupture shows nonmonotonous change with fH: the stretchability improves with increasing fH from 5.5 to 14 while it decreases upon further increasing fH to 27. The former improvement is attributed to the slowing down of chain retraction after the strain-induced dissociation of ionic groups. The slowing down would suppress the formation of defects or small cracks that potentially grow into the fracture. This mechanism, i.e., strain-induced dissociation followed by the chain retraction, holds only in a window where the elongational rate is faster than the ionic dissociation rate but slower than the chain retraction rate. This window narrows down with increasing fH, which probably leads to the decrease of stretchability at high fH = 27.
Physical Educators’ Perceptions and Experiences of Teaching Students With Mobility Disabilities
Authors: Benzinger Jacob , Crane Jeff R. , Coppola Angela M. , Hancock David J.
Published: December 2022

Schools can support physical education (PE) among students with mobility disabilities (SMDs). However, previous research has indicated that people and resources in the school environment have served as facilitators and barriers to engaging SMDs in PE. Thus, the purpose of this pragmatic, qualitative study was to explore physical educators’ perceptions and experiences of teaching SMDs to learn how to develop a PE environment supportive of SMDs. Eleven K-8 PE teachers who taught SMDs engaged in semistructured interviews. A thematic analysis revealed three themes describing facilitators and barriers of a supportive PE environment for SMDs: (a) teacher planning, (b) students in the PE environment, and (c) resources and support. These findings provide context to PE environments for SMDs and highlight a need for increased communication and collaboration with students with or without mobility disabilities, training or professional development for PE teachers to develop skills for adapted PE, and financial and personnel support.
Why Do Unfairly Paid Trainees Persist? Pay Fairness and Human Capital Investment in Development Leagues
Authors: McLeod Christopher M. , Agha Nola
Published: December 2022

Pay fairness and human capital theories make different predictions about trainees’ occupational turnover in situations where trainees perceive unfair pay but receive huge potential returns from training. Therefore, the purpose of this study was to examine how pay fairness and human capital investment combined to explain why trainees are motivated to persist in employment when they perceive unfair pay. Cross-sectional survey data from 144 minor league baseball players showed that athletes perceived unfair pay but had low occupational turnover intentions because they perceived high learning achievement and expected to play in Major League Baseball eventually. Perceptions of unfair pay only increased occupational turnover intentions under certain conditions, such as when athletes had low expectations of playing at least one game in Major League Baseball in the next 3 years. The results support a framework that combines human capital theory and pay fairness theories to explain boundary conditions for trainee motivation.
StripeDiff: Model-based algorithm for differential analysis of chromatin stripe
Authors: Gupta Krishan , Wang Guangyu , Zhang Shuo , Gao Xinlei , Zheng Rongbin , Zhang Yanchun , Meng Qingshu , Zhang Lili , Cao Qi , Chen Kaifu
Published: December 2022

Multiple recent studies revealed stripes as an architectural feature of three-dimensional chromatin and found stripes connected to epigenetic regulation of transcription. Whereas a couple of tools are available to define stripes in a single sample, there is yet no reported method to quantitatively measure the dynamic change of each stripe between samples. Here, we developed StripeDiff, a bioinformatics tool that delivers a set of statistical methods to detect differential stripes between samples. StripeDiff showed optimal performance in both simulation data analysis and real Hi-C data analysis. Applying StripeDiff to 12 sets of Hi-C data revealed new insights into the connection between change of chromatin stripe and change of chromatin modification, transcriptional regulation, and cell differentiation. StripeDiff will be a robust tool for the community to facilitate understanding of stripes and their function in numerous biological models.
Adaptive optimal control of entangled qubits
Authors: Goodwin David L. , Singh Pranav , Foroozandeh Mohammadali
Published: December 2022

Developing fast, robust, and accurate methods for optimal control of quantum systems comprising interacting particles is one of the most active areas of current science. Although a valuable repository of algorithms is available for numerical applications in quantum control, the high computational cost is somewhat overlooked. Here, we present a fast and accurate optimal control algorithm for systems of interacting qubits, QOALA (quantum optimal control by adaptive low-cost algorithm), which is predicted to offer

O

(
M
2
) speedup for an
M
-qubit system, compared to the state-of-the-art exact methods, without compromising overall accuracy of the optimal solution. The method is general and compatible with diverse Hamiltonian structures. The proposed approach uses inexpensive low-accuracy approximations of propagators far from the optimum, adaptively switching to higher accuracy, higher-cost propagators when approaching the optimum. In addition, the utilization of analytical Lie algebraic derivatives that do not require computationally expensive matrix exponential brings even better performance.
Optimized ACE2 decoys neutralize antibody-resistant SARS-CoV-2 variants through functional receptor mimicry and treat infection in vivo
Authors: Torchia James A. , Tavares Alexander H. , Carstensen Laura S. , Chen Da-Yuan , Huang Jessie , Xiao Tianshu , Mukherjee Sonia , Reeves Patrick M. , Tu Hua , Sluder Ann E. , Chen Bing , Kotton Darrell N. , Bowen Richard A. , Saeed Mohsan , Poznansky Mark C. , Freeman Gordon J.
Published: December 2022

As severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) evolves to escape natural antibodies, it also loses sensitivity to therapeutic antibody drugs. By contrast, evolution selects for binding to ACE2, the cell-surface receptor required for SARS-CoV-2 infection. Consistent with this, we find that an ACE2 decoy neutralizes antibody-resistant variants, including Omicron, with no loss in potency. To identify design features necessary for in vivo activity, we compare several enzymatically inactive, Fc effector–silenced ACE2-Fc decoys. Inclusion of the ACE2 collectrin-like domain not only improves affinity for the S protein but also unexpectedly extends serum half-life and is necessary to reduce disease severity and viral titer in Syrian hamsters. Fc effector function is not required. The activity of ACE2 decoy receptors is due, in part, to their ability to trigger an irreversible structural change in the viral S protein. Our studies provide a new understanding of how ACE2 decoys function and support their development as therapeutics to treat ACE2-dependent coronaviruses.
A randomized controlled trial showing safety and efficacy of a whole sporozoite vaccine against endemic malaria
Authors: Sirima Sodiomon B. , Ouédraogo Alphonse , Tiono Alfred B. , Kaboré Jean M. , Bougouma Edith C. , Ouattara Maurice S. , Kargougou Désiré , Diarra Amidou , Henry Noelie , Ouédraogo Issa N. , Billingsley Peter F. , Manoj Anita , Abebe Yonas , KC Natasha , Ruben Adam , Richie Thomas L. , James Eric R. , Joshi Sudhaunshu , Shrestha Biraj , Strauss Kathy , Lyke Kirsten E. , Plowe Christopher V. , Potter Gail E. , Cox Catherine , Jones Walter , Sim B. Kim Lee , Hoffman Stephen L. , Laurens Matthew B.
Published: December 2022

A highly effective malaria vaccine remains elusive despite decades of research.
Plasmodium falciparum
sporozoite vaccine (PfSPZ Vaccine), a metabolically active, nonreplicating, whole parasite vaccine demonstrated safety and vaccine efficacy (VE) against endemic
P. falciparum
for 6 months in Malian adults receiving a five-dose regimen. Safety, immunogenicity, and VE of a three-dose regimen were assessed in adults in Balonghin, Burkina Faso in a two-component study: an open-label dose escalation trial with 32 participants followed by a double-blind, randomized, placebo-controlled trial (RCT) with 80 participants randomized to receive three doses of 2.7 × 10
6
PfSPZ (
N
 = 39) or normal saline (
N
 = 41) just before malaria season. To clear parasitemia, artesunate monotherapy was administered before first and last vaccinations. Thick blood smear microscopy was performed on samples collected during illness and every 4 weeks for 72 weeks after last vaccinations, including two 6-month malaria transmission seasons. Safety outcomes were assessed in all 80 participants who received at least one dose and VE for 79 participants who received three vaccinations. Myalgia was the only symptom that differed between groups. VE (1 − risk ratio; primary VE endpoint) was 38% at 6 months (
P
 = 0.017) and 15% at 18 months (0.078). VE (1 − hazard ratio) was 48% and 46% at 6 and 18 months (
P
 = 0.061 and 0.018). Two weeks after the last dose, antibodies to
P. falciparum
circumsporozoite protein and PfSPZ were higher in protected versus unprotected vaccinees. A three-dose regimen of PfSPZ Vaccine demonstrated safety and efficacy against malaria infection in malaria-experienced adults.
Senolytic treatment preserves biliary regenerative capacity lost through cellular senescence during cold storage
Authors: Ferreira-Gonzalez Sofia , Man Tak Yung , Esser Hannah , Aird Rhona , Kilpatrick Alastair M. , Rodrigo-Torres Daniel , Younger Nicholas , Campana Lara , Gadd Victoria L. , Dwyer Benjamin , Aleksieva Niya , Boulter Luke , Macmillan Mark T. , Wang Yinmiao , Mylonas Katie J. , Ferenbach David A. , Kendall Timothy J. , Lu Wei-Yu , Acosta Juan Carlos , Kurian Dominic , O’Neill Stephen , Oniscu Gabriel C. , Banales Jesus M. , Krimpenfort Paul J. , Forbes Stuart J.
Published: December 2022

Liver transplantation is the only curative option for patients with end-stage liver disease. Despite improvements in surgical techniques, nonanastomotic strictures (characterized by the progressive loss of biliary tract architecture) continue to occur after liver transplantation, negatively affecting liver function and frequently leading to graft loss and retransplantation. To study the biological effects of organ preservation before liver transplantation, we generated murine models that recapitulate liver procurement and static cold storage. In these models, we explored the response of cholangiocytes and hepatocytes to cold storage, focusing on responses that affect liver regeneration, including DNA damage, apoptosis, and cellular senescence. We show that biliary senescence was induced during organ retrieval and exacerbated during static cold storage, resulting in impaired biliary regeneration. We identified decoy receptor 2 (DCR2)–dependent responses in cholangiocytes and hepatocytes, which differentially affected the outcome of those populations during cold storage. Moreover, CRISPR-mediated DCR2 knockdown in vitro increased cholangiocyte proliferation and decreased cellular senescence but had the opposite effect in hepatocytes. Using the p21
KO
model to inhibit senescence onset, we showed that biliary tract architecture was better preserved during cold storage. Similar results were achieved by administering senolytic ABT737 to mice before procurement. Last, we perfused senolytics into discarded human donor livers and showed that biliary architecture and regenerative capacities were better preserved. Our results indicate that cholangiocytes are susceptible to senescence and identify the use of senolytics and the combination of senotherapies and machine-perfusion preservation to prevent this phenotype and reduce the incidence of biliary injury after transplantation.
Green light analgesia in mice is mediated by visual activation of enkephalinergic neurons in the ventrolateral geniculate nucleus
Authors: Tang Yu-Long , Liu Ai-Lin , Lv Su-Su , Zhou Zi-Rui , Cao Hong , Weng Shi-Jun , Zhang Yu-Qiu
Published: December 2022

Green light exposure has been shown to reduce pain in animal models. Here, we report a vision-associated enkephalinergic neural circuit responsible for green light–mediated analgesia. Full-field green light exposure at an intensity of 10 lux produced analgesic effects in healthy mice and in a model of arthrosis. Ablation of cone photoreceptors completely inhibited the analgesic effect, whereas rod ablation only partially reduced pain relief. The analgesic effect was not modulated by the ablation of intrinsically photosensitive retinal ganglion cells (ipRGCs), which are atypical photoreceptors that control various nonvisual effects of light. Inhibition of the retino–ventrolateral geniculate nucleus (vLGN) pathway completely abolished the analgesic effects. Activation of this pathway reduced nociceptive behavioral responses; such activation was blocked by the inhibition of proenkephalin (Penk)–positive neurons in the vLGN (vLGN
Penk
). Moreover, green light analgesia was prevented by knockdown of
Penk
in the vLGN or by ablation of vLGN
Penk
neurons. In addition, activation of the projections from vLGN
Penk
neurons to the dorsal raphe nucleus (DRN) was sufficient to suppress nociceptive behaviors, whereas its inhibition abolished the green light analgesia. Our findings indicate that cone-dominated retinal inputs mediated green light analgesia through the vLGN
Penk
-DRN pathway and suggest that this signaling pathway could be exploited for reducing pain.
Repurposing Tamoxifen as Potential Host-Directed Therapeutic for Tuberculosis
Authors: Boland Ralf , Heemskerk Matthias T. , Forn-Cuní Gabriel , Korbee Cornelis J. , Walburg Kimberley V. , Esselink Jeroen J. , Carvalho dos Santos Carina , de Waal Amy M. , van der Hoeven Daniel C. M. , van der Sar Elisa , de Ries Alex S. , Xie Jiajun , Spaink Herman P. , van der Vaart Michiel , Haks Mariëlle C. , Meijer Annemarie H. , Ottenhoff Tom H. M.
Published: December 2022

Tuberculosis (TB) is the world's most lethal infectious disease caused by a bacterial pathogen,
Mycobacterium tuberculosis
. This pathogen evades the immune defenses of its host and grows intracellularly in immune cells, particularly inside macrophages.
Myelin oligodendrocyte glycoprotein (MOG) antibody-associated longitudinally extensive transverse myelitis (LETM) and primary Sjogren syndrome: a rare association
Authors: Sahoo Debananda , Dash Anil , Dey Anupam , Devi Sujata
Published: December 2022

Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a recent addition to the field of central nervous system inflammatory disorders. It can have a wide range of presentations, including optic neuritis, transverse myelitis, acute disseminated encephalomyelitis or any combination of these. The aquaporin-4-positive neuromyelitis optica (NMO) is a close differential owing to the similar clinical presentation. There is a proven association between NMO and autoimmunity, whereas such an association is yet to be established in the case of MOGAD. Here we describe the case of a woman in her 30s presenting with sudden-onset quadriparesis with sensory and autonomic involvement who was diagnosed with MOGAD (cervicothoracic longitudinally extensive transverse myelitis) and found to have primary Sjogren syndrome on further workup. This association between MOGAD and autoimmunity should be kept in mind, as diagnosis of the former should alert the physician to the possibility of the latter’s existence and the need to initiate an appropriate workup.
Recurrent pneumonia post atrial fibrillation ablation: do not forget to look for pulmonary vein stenosis
Authors: Mizuno Aki , Mauler-Wittwer Sarah , Muller Hajo , Noble Stephane
Published: December 2022

A man in his 50s presented with persistent chest pain, haemoptysis, cough and dyspnoea 5 months after undergoing catheter ablation for atrial fibrillation (AF). Several chest CT scans suggested pneumonia. Despite adequate treatment for recurrent pneumonia, symptoms persisted. While reviewing the initial chest CT, a partial venous infarction of the left lower lobe associated with severe left inferior pulmonary vein stenosis (PVS) was diagnosed. Stenting of the left inferior pulmonary vein with a vascular bare metal stent was performed, guided by fluoroscopy and transoesophageal echocardiography. Dual antiplatelet therapy (aspirin/clopidogrel) was introduced for 3 months, followed by long-term aspirin monotherapy. The treatment resulted in relief of his symptoms and the resolution of pulmonary opacities on chest CT. Despite low frequency, AF ablation remains the most common cause of acquired PVS. As highlighted in this case, symptoms are not specific and include recurrent pulmonary infection with delayed management.
Combination of endoscopic internal thoracic artery harvest and proximal anastomoses on the descending aorta in minimally invasive coronary artery bypass grafting
Authors: Goto Yoshihiro , Takagi Sho , Yanagisawa Junji , Nakasu Akio
Published: December 2022

Minimally invasive coronary artery bypass grafting is less invasive. Proximal anastomoses at the ascending aorta, in contrast, are technically difficult to perform because of the limited field of view. A man in his 60s undergoing haemodialysis required minimally invasive coronary artery bypass grafting for left anterior descending artery and circumflex arterial restenosis. We successfully performed minimally invasive coronary artery bypass grafting with a proximal graft anastomosis of the descending aorta. A thoracotomy was performed to extend the lateral approach to the descending aorta. We performed a minithoracotomy using three-dimensional endoscopy for internal thoracic artery harvesting. Endoscopic internal thoracic artery harvesting minimises incision length. The combination of endoscopic and lateral thoracotomy incisions in minimally invasive coronary artery bypass grafting enabled small and lateral thoracotomy incisions.
Life-threatening rupture of interstitial ectopic pregnancy: a rare presentation of metastatic invasive mole
Authors: Figueiredo Joana , Tomé Ana , Nazaré Patrícia , Antunes Sofia Carralas
Published: December 2022

An invasive mole is an uncommon type of gestational trophoblastic disease, and if considering its implantation in an interstitial extrauterine location, we are facing a rarer condition.

There are 14 cases described of interstitial ectopic gestational trophoblastic disease. As far as we know, we present the third case of invasive mole within interstitial location, in this case with pulmonary metastases.

The diagnosis of an interstitial implantation is challenging. Our patient was initially diagnosed with an intrauterine hydatidiform molar pregnancy, and a uterine aspiration was performed. Two weeks later, she presented with haemodynamical instability due to a severe haemoperitoneum. A laparotomy was immediately performed and revealed a ruptured interstitial pregnancy with molar vesicle extrusion. Besides its rarity, we highlight the clinical presentation with hypovolaemic shock due to rupture of ectopic pregnancy in a young nulliparous woman, which required an emergent surgical approach with lifesaving purpose while preserving future fertility.
Epidemiology of iron deficiency among adolescents aged 10–19 years old in Qatar: a cross-sectional study
Authors: Aabdien Mohamed , Al Kaabi Noora , Al-Kohji Sadriya Mohammed S , Selim Nagah
Published: December 2022

Objective

To estimate the magnitude and the determinants of iron deficiency among adolescents aged 10–19 years in the State of Qatar.

Design

A cross-sectional study design was used to conduct the study.

Setting

Primary healthcare centres covering the three main geographical areas. One health centre was selected randomly from each region catchment areas: Northern, Central and Western.

Participants

Four hundred and fifty adolescents aged 10–19 years of all nationalities were enrolled in the study.

Outcome measures

Serum ferritin cut-off level used to diagnose iron deficiency (<15 µg/L), with normal C reactive protein.

Results

The mean age of the participants was 14.00±2.920, and more than half of the participating adolescents were among 10–14 years old age group (56.9%). Fifty-five per cent of the study participants were Non-Qatari, and females consisted of 70.0% of the participants. The prevalence of iron deficiency was 26.4%. Iron deficiency was significantly associated with gender, nationality, attaining menarche and consumption of iron absorption enhancers (citrus fruits and juice).

Conclusion

Iron deficiency among adolescents is of moderate public health concern in the country, according to the classification of the WHO. The estimated prevalence of iron deficiency was close to what was found in other low-income and middle-income countries; however, it is still behind the developed countries. Gender, attaining menarche and dietary habits are among the important factors that are associated with iron deficiency. Thus, there is a need to coordinate efforts and resources to address this issue by implementing effective strategies at the community and primary healthcare levels.
Effect of remote patient monitoring for patients with chronic kidney disease who perform dialysis at home: a systematic review
Authors: Nygård Henriette Tyse , Nguyen Lien , Berg Rigmor C
Published: December 2022

Objective

The purpose of the systematic review was to assess the effectiveness of remote patient monitoring (RPM) follow-up compared with standard care, for patients with chronic kidney disease (CKD) who perform dialysis at home.

Methods

We conducted a systematic review in accordance with international guidelines. We performed systematic searches for publications from 2015 to 2021 in five databases (eg, Medline, Cinahl, Embase) and a search for grey literature in reference lists. Included effect measures were quality of life, hospitalisation, technical failure as the cause for transfer to a different dialysis modality, infections and time patients use for travel. Screening of literature, data extraction, risk-of-bias assessment and certainty of evidence assessment (using the Grading of Recommendations Assessment, Development and Evaluation approach) were done by two researchers. We conducted meta-analyses when possible.

Results

Seven studies met the inclusion criteria, of which two were randomised controlled trials and five were retrospective cohort studies with control groups. The studies included 9975 participants from 5 countries, who were a good representation of dialysis patients in high-income and upper-middle-income countries. The patients were on peritoneal dialysis (six studies) or home haemodialysis (one study). There was very low certainty of evidence for the outcomes, except for hospitalisations: there was low certainty evidence from three cohort studies for fewer hospitalisation days in the RPM group. No studies included data for time patients used for travel.

Conclusion

We found low to very low certainty evidence that indicate there may be positive effects of RPM follow-up, in comparison to standard care only, for adult patients with CKD who perform dialysis at home. Offering RPM follow-up for home dialysis patients as an alternative or supplement to standard care appears to be safe and provide health benefits such as fewer hospitalisation days. Future implementation should be coupled with robust, high-quality evaluations.

PROSPERO registration number

CRD42021281779.
Biofeedback Enabled CALM (BeCALM)—the feasibility of biofeedback on procedural anxiety during radiation therapy: study protocol for a pilot randomised controlled trial
Authors: Forbes Erin , Clover Kerrie , Baker Amanda L , McCarter Kristen Louise , Oultram Sharon , Kumar Mahesh , Wratten Chris , Tieu Minh Thi , Nixon Jodie , Britton Ben
Published: December 2022

Introduction

Patients undergoing treatment for cancer who require radiation therapy (RT) report anxiety specifically relating to the RT procedure. Procedural anxiety can be detrimental to treatment delivery, causing disruptions to treatment sessions, or treatment avoidance. Acute procedural anxiety is most commonly managed with anxiolytic medication. There is a need for effective, non-pharmacological interventions for patients not suitable for, or who prefer to avoid, anxiolytic medication. The primary objectives of this pilot trial are to evaluate the: (1) feasibility of conducting the Biofeedback Enabled CALM (BeCALM) intervention during RT treatment sessions; (2) acceptability of the BeCALM intervention among patients; and (3) acceptability of the BeCALM intervention among radiation therapists. The secondary objective of this pilot trial is to examine the potential effectiveness of the BeCALM intervention delivered by radiation therapists to reduce procedural anxiety during RT.

Methods and analysis

This is a pilot randomised controlled trial. A researcher will recruit adult patients with cancer (3-month recruitment period) scheduled to undergo RT and meeting eligibility criteria for procedural anxiety at the Calvary Mater Hospital, Newcastle (NSW), Australia. Participants will be randomly assigned to receive treatment as usual or the BeCALM intervention (biofeedback plus brief breathing techniques). The primary outcomes are feasibility (measured by recruitment, retention rates and percentage of treatment sessions in which the intervention was successfully delivered); radiation therapists perceived feasibility and acceptability (survey responses); and patient perceived acceptability (survey responses). Secondary outcome is potential effectiveness of the intervention (as measured by the State Trait Anxiety Inventory—State subscale; the Distress Thermometer; and an analysis of treatment duration).

Ethics and dissemination

The study protocol has received approval from Hunter New England Health Human Research Ethics Committee (2021/ETH11356). The results will be disseminated via peer-reviewed publications, as well as presentation at relevant conferences.

Trial registration number

ACTRN12621001742864.