bluuebunny/crossref_metadata_2025 huggingface dataset:
Transmissive 2-bit anisotropic coding metasurface
Authors: Lai Pengtao , Li Zenglin , Wang Wei , Qu Jia , Wu Liangwei , Lv Tingting , Lv Bo , Zhu Zheng , Li Yuxiang , Guan Chunying , Ma Huifeng , Shi Jinhui
Published: January 2022

Coding metasurfaces have attracted tremendous interests due to unique capabilities of manipulating electromagnetic wave. However, archiving transmissive coding metasurface is still challenging. Here we propose a transmissive anisotropic coding metasurface that enables the independent control of two orthogonal polarizations. The polarization beam splitter and the orbital angular momentum (OAM) generator have been studied as typical applications of the anisotropic 2-bit coding metasurface. The simulated far field patterns illustrate that the x and y polarized electromagnetic waves are deflected into two different directions, respectively. The anisotropic coding metasurface has been experimentally verified to realize an OAM beam with l = 2 of right-handed polarized wave, resulting from both contributions from linear-to-circular polarization conversion and the phase profile modulation. This work is beneficial to enrich the polarization manipulation field and develop transmissive coding metasurfaces.
Waveform processing using neural network algorithms on the front-end electronics
Authors: Miryala S. , Mittal S. , Ren Y. , Carini G. , Deptuch G. , Fried J. , Yoo S. , Zohar S.
Published: January 2022

In a multi-channel radiation detector readout system, waveform sampling, digitization, and raw data transmission to the data acquisition system constitute a conventional processing chain. The deposited energy on the sensor is estimated by extracting peak amplitudes, area under pulse envelopes from the raw data, and starting times of signals or time of arrivals. However, such quantities can be estimated using machine learning algorithms on the front-end Application-Specific Integrated Circuits (ASICs), often termed as “edge computing”. Edge computation offers enormous benefits, especially when the analytical forms are not fully known or the registered waveform suffers from noise and imperfections of practical implementations. In this work, we aim to predict peak amplitude from a single waveform snippet whose rising and falling edges containing only 3 to 4 samples. We thoroughly studied two well-accepted neural network algorithms, Multi-Layer Perceptron (MLP) and Convolutional Neural Network (CNN) by varying their model sizes. To better fit front-end electronics, neural network model reduction techniques, such as network pruning methods and variable-bit quantization approaches, were also studied. By combining pruning and quantization, our best performing model has the size of 1.5 KB, reduced from 16.6 KB of its full model counterpart. It can reach mean absolute error of 0.034 comparing to that of a naive baseline of 0.135. Such parameter-efficient and predictive neural network models established feasibility and practicality of their deployment on front-end ASICs.
Multi-threshold window discriminator based on SAR logic
Authors: Jirsa J. , Marcisovsky M. , Jakovenko J.
Published: January 2022

The new X-ray imaging detectors allow capturing an X-ray image in various photon energy ranges in one shot. This technique is called X-ray color imaging, and it is becoming a promising method in fields such as medical imaging, computed tomography, and non-destructive material testing. To measure the energy spectrum in one shot, discriminant circuits need to be integrated into the pixel front-end electronics. Several solutions of in-pixel discriminators exist. However, current designs suffer from a low number of discrimination bins and need to adjust each threshold separately, leading to relatively complicated calibration procedures. This work introduces a novel design of a multi-threshold window discriminator based on successive approximation register logic. This circuit realizes in-pixel binning to ten equidistant windows. Two variables are used for tuning the multi-threshold window discriminator: offset of the first window and width of the windows. Setting these parameters allows the user to fulfill the need of the target application.
A synthetic view of rainfall intensification in the West African Sahel
Authors: Chagnaud G , Panthou G , Vischel T , Lebel T
Published: January 2022

The West African Sahel has been facing for more than 30 years an increase in extreme rainfall with strong socio-economic impacts. This situation challenges decision-makers to define adaptation strategies in a rapidly changing climate. The present study proposes (i) a quantitative characterization of the trends in extreme rainfall at the regional scale, (ii) the translation of the trends into metrics that can be used by hydrological risk managers, (iii) elements for understanding the link between the climatology of extreme and mean rainfall. Based on a regional non-stationary statistical model applied to in-situ daily rainfall data over the period 1983–2015, we show that the region-wide increasing trend in extreme rainfall is highly significant. The change in extreme value distribution reflects an increase in both the mean and variability, producing a 5%/decade increase in extreme rainfall intensity whatever the return period. The statistical framework provides operational elements for revising the design methods of hydraulic structures which most often assume a stationary climate. Finally, the study shows that the increase in annual maxima of daily rainfall is more attributable to stronger storm intensities (80%) than to more frequent storm occurrences (20%), reflecting a major rainfall regime shift in comparison to those observed in the region since 1950.
Crop-climate feedbacks boost US maize and soy yields
Authors: Coffel Ethan D , Lesk Corey , Winter Jonathan M , Osterberg Erich C , Mankin Justin S
Published: January 2022

US maize and soy production have increased rapidly since the mid-20th century. While global warming has raised temperatures in most regions over this time period, trends in extreme heat have been smaller over US croplands, reducing crop-damaging high temperatures and benefiting maize and soy yields. Here we show that agricultural intensification has created a crop-climate feedback in which increased crop production cools local climate, further raising crop yields. We find that maize and soy production trends have driven cooling effects approximately as large as greenhouse gas induced warming trends in extreme heat over the central US and substantially reduced them over the southern US, benefiting crops in all regions. This reduced warming has boosted maize and soy yields by 3.3 (2.7–3.9; 13.7%–20.0%) and 0.6 (0.4–0.7; 7.5%–13.7%) bu/ac/decade, respectively, between 1981 and 2019. Our results suggest that if maize and soy production growth were to stagnate, the ability of the crop-climate feedback to mask warming would fade, exposing US crops to more harmful heat extremes.
A low-profile consolidated metastructure for multispectral signature management
Authors: Gupta Nitish Kumar , Singh Gaganpreet , Wanare Harshawardhan , Ramakrishna S Anantha , Srivastava Kumar Vaibhav , Ramkumar J
Published: January 2022

This work pertains to the design, numerical investigation, and experimental demonstration of an optically transparent, lightweight, and conformable metastructure that exhibits multispectral signature management capabilities despite its extremely low-profile configuration. In comparison to the existing hierarchical approaches of designing multispectral stealth solutions, attention has been paid to accommodate the conflicting requirements of radar and infrared (IR) stealth using a single metasurface layer configuration, which required a few constraints to be incorporated during the design stage to ensure compatibility. This methodology promulgates the desired multispectral response with minimal manufacturing footprint and facilitates an efficient integration with the other existing countermeasure platforms. The resulting design exhibits a polarization-insensitive and incident angle stable broadband microwave absorption with at least 90% absorption ranging from 8.2 to 18.4 GHz. Concomitantly it also exhibits an averaged IR emissivity of 0.46 in the 8–14µm long-wave IR regime, along with high optical transparency (71% transmission at 632.8 nm). Notably, the total thickness of the metastructure stands at 0.10λL(λLcorresponds to the wavelength at lowest frequency). The metastructure has been fabricated with indium tin oxide coated polyethylene terephthalate sheets, on which the frequency selective pattern is machined using Excimer laser micromachining, and the performances are verified experimentally. Furthermore, a hybrid theoretical model has been developed that not only provides crucial insights into the operation of metastructure but also presents a methodical semi-analytical approach to design.
Facile green synthesis of ZnO–CuO nanocomposites using areca catechu leaves and their in vitro antidiabetic and cytotoxicity studies
Authors: Shwetha U R , Latha M S , Betageri Virupaxappa S , Pujar G H , Rajith Kumar C R , Kiran M S , Sunita M S , Gokavi Nagappa B , Kollur Shiva Prasad
Published: January 2022

The fabrication and diverse applications of mixed oxides have received immense interest due to numerous prospects for better functional performance in tuning their properties compared to the basic metal oxides. Herein, we report synthesis of ZnO-CuO nanocomposites (NCs) using a simple and green route solution combustion method. The as-prepared ZnO-CuO NCs have been characterised through x-ray diffraction (XRD), energy dispersive x-ray (EDX) with scanning electron microscopy (SEM) and transmission electron microscopy (TEM) techniques. The results revealed that as-prepared ZnO-CuO NCs have spherical and rod-shaped structures with an average size between 10 and 30 nm. Further, ZnO-CuO NCs were tested for antidiabetic and anticancer properties. Amylase inhibition and MTT assays were carried out with different concentrations of NCs. The biological results depicted that the as-prepared nanocomposites exhibited significant cytotoxic effects with IC50 value of 13.29 μg mg−1. These observations further showed that the newly synthesised ZnO–CuO NCs are interesting and promising nanomaterials in pharmaceutical and healthcare sector.
Machinability study of Aluminium 6082 reinforced with boron carbide and titanium by stir casting method using Abrasive water jet machining process
Authors: Umanath K , Nithyanandhan T , Ajayan Adarsh , Devika D , Gokul Prasath M , Aravind Kumar S , Ganeesh R
Published: January 2022

Aluminium Metal Matrix Composite (AMMC) has broad uses in the medical, aerospace, and automobile industries, which have long sought lightweight materials with superior designs and improved properties to improve performance. This analysis has aimed to prepare an AMMC to investigate its machining and mechanical properties. The AMMC is produced using a stir casting process by reinforcing boron carbide and titanium with aluminium 6082. The material’s mechanical properties are studied by using wear test, hardness test, and corrosion test. The wear rate increases when the load increases by varying the load and time with speed as a constant. It is found that the hardness of a material is increased due to titanium and boron carbide as the reinforcement particle in the fabricated AMMC. Using the pitting corrosion technique, the corrosion occurs on the AMMC under the estimated time at room temperature. In order to illustrate the machining characteristics of the aluminium metal matrix composite, an Abrasive Water Jet Machining (AWJM) process has been used. The experiments use L9 orthogonal Array using Taguchi’s method and ANOVA analysis. The input parameters considered are Traverse rate, Stand-off distance, and Nozzle diameter. To find the optimum value of circularity, cylindricity, and surface roughness by varied input parameters. The respective graphs are also plotted. Scanning electron microscopic analysis was performed on the wear-tested specimen and machining surface of the material to determine the distribution of reinforced material and investigate the material’s fracture mechanism. It is found that wear tracks, voids, delamination, micro pits, embedded garnet abrasive particles are located on the machined surface of the AMMC.
Fast prediction of distances between synthetic routes with deep learning
Authors: Genheden Samuel , Engkvist Ola , Bjerrum Esben
Published: January 2022

We expand the recent work on clustering of synthetic routes and train a deep learning model to predict the distances between arbitrary routes. The model is based on a long short-term memory representation of a synthetic route and is trained as a twin network to reproduce the tree edit distance (TED) between two routes. The machine learning approach is approximately two orders of magnitude faster than the TED approach and enables clustering many more routes from a retrosynthesis route prediction. The clusters have a high degree of similarity to the clusters given by the TED-based approach and are accordingly intuitive and explainable. We provide the developed model as open-source.
2022 roadmap on neuromorphic computing and engineering
Authors: Christensen Dennis V , Dittmann Regina , Linares-Barranco Bernabe , Sebastian Abu , Le Gallo Manuel , Redaelli Andrea , Slesazeck Stefan , Mikolajick Thomas , Spiga Sabina , Menzel Stephan , Valov Ilia , Milano Gianluca , Ricciardi Carlo , Liang Shi-Jun , Miao Feng , Lanza Mario , Quill Tyler J , Keene Scott T , Salleo Alberto , Grollier Julie , Marković Danijela , Mizrahi Alice , Yao Peng , Yang J Joshua , Indiveri Giacomo , Strachan John Paul , Datta Suman , Vianello Elisa , Valentian Alexandre , Feldmann Johannes , Li Xuan , Pernice Wolfram H P , Bhaskaran Harish , Furber Steve , Neftci Emre , Scherr Franz , Maass Wolfgang , Ramaswamy Srikanth , Tapson Jonathan , Panda Priyadarshini , Kim Youngeun , Tanaka Gouhei , Thorpe Simon , Bartolozzi Chiara , Cleland Thomas A , Posch Christoph , Liu ShihChii , Panuccio Gabriella , Mahmud Mufti , Mazumder Arnab Neelim , Hosseini Morteza , Mohsenin Tinoosh , Donati Elisa , Tolu Silvia , Galeazzi Roberto , Christensen Martin Ejsing , Holm Sune , Ielmini Daniele , Pryds N
Published: January 2022

Modern computation based on von Neumann architecture is now a mature cutting-edge science. In the von Neumann architecture, processing and memory units are implemented as separate blocks interchanging data intensively and continuously. This data transfer is responsible for a large part of the power consumption. The next generation computer technology is expected to solve problems at the exascale with 1018 calculations each second. Even though these future computers will be incredibly powerful, if they are based on von Neumann type architectures, they will consume between 20 and 30 megawatts of power and will not have intrinsic physically built-in capabilities to learn or deal with complex data as our brain does. These needs can be addressed by neuromorphic computing systems which are inspired by the biological concepts of the human brain. This new generation of computers has the potential to be used for the storage and processing of large amounts of digital information with much lower power consumption than conventional processors. Among their potential future applications, an important niche is moving the control from data centers to edge devices. The aim of this roadmap is to present a snapshot of the present state of neuromorphic technology and provide an opinion on the challenges and opportunities that the future holds in the major areas of neuromorphic technology, namely materials, devices, neuromorphic circuits, neuromorphic algorithms, applications, and ethics. The roadmap is a collection of perspectives where leading researchers in the neuromorphic community provide their own view about the current state and the future challenges for each research area. We hope that this roadmap will be a useful resource by providing a concise yet comprehensive introduction to readers outside this field, for those who are just entering the field, as well as providing future perspectives for those who are well established in the neuromorphic computing community.
Almost PI algebras are PI
Authors: Larsen Michael , Shalev Aner
Published: January 2022

We define the notion of an almost polynomial identity of an associative algebra

R
R

, and show that its existence implies the existence of an actual polynomial identity of

R
R

. A similar result is also obtained for Lie algebras and Jordan algebras. We also prove related quantitative results for simple and semisimple algebras.
On geometrically finite degenerations II: convergence and divergence
Authors: Luo Yusheng
Published: January 2022

In this paper, we study quasi post-critically finite degenerations for rational maps. We construct limits for such degenerations as geometrically finite rational maps on a finite tree of Riemann spheres. We prove the boundedness for such degenerations of hyperbolic rational maps with Sierpinski carpet Julia set and give criteria for the convergence for quasi-Blaschke products

Q
B

d

\mathcal {QB}_d

, making progress towards the analogues of Thurston’s compactness theorem for acylindrical

3
3

-manifold and the double limit theorem for quasi-Fuchsian groups in complex dynamics. In the appendix, we apply such convergence results to show the existence of certain polynomial matings.
Exponential sums with multiplicative coefficients and applications
Authors: de la Bretèche Régis , Granville Andrew
Published: January 2022

We show that if an exponential sum with multiplicative coefficients is large then the associated multiplicative function is “pretentious”. This leads to applications in the circle method, and a natural interpretation of the local-global principle.
The local dimension of a finite group over a number field
Authors: König Joachim , Neftin Danny
Published: January 2022

Let

G
G

be a finite group and

K
K

a number field. We construct a

G
G

-extension

E

/

F

E/F

, with

F
F

of transcendence degree

2
2

over

K
K

, that specializes to all

G
G

-extensions of

K

p

K_\mathfrak {p}

, where

p

\mathfrak {p}

runs over all but finitely many primes of

K
K

. If furthermore

G
G

has a generic extension over

K
K

, we show that the extension

E

/

F

E/F

has the so-called Hilbert–Grunwald property. These results are compared to the notion of essential dimension of

G
G

over

K
K

, and its arithmetic analogue.
A mechanistic motor-clutch model that explains cell shape dynamics to cyclic stretch
Authors: Scandling Benjamin W. , Gou Jia , Thomas Jessica , Xuan Jacqueline , Xue Chuan , Gooch Keith J.
Published: January 2022

A computational model was developed to define cellular mechanisms involved with cellular reorientation in response to cyclic stretch. The model was used to accurately predict perpendicular alignment of actin filaments in response to stretch. The model can be used to further analyze mechanisms involved with cellular reorientation.
Effectiveness of Localized Lockdowns in the COVID-19 Pandemic
Authors: Li Yige , Undurraga Eduardo A , Zubizarreta José R
Published: January 2022

Nonpharmaceutical interventions, such as social distancing and lockdowns, have been essential to control of the coronavirus disease 2019 (COVID-19) pandemic. In particular, localized lockdowns in small geographic areas have become an important policy intervention for preventing viral spread in cases of resurgence. These localized lockdowns can result in lower social and economic costs compared with larger-scale suppression strategies. Using an integrated data set from Chile (March 3–June 15, 2020) and a novel synthetic control approach, we estimated the effect of localized lockdowns, disentangling its direct and indirect causal effects on transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our results showed that the effects of localized lockdowns are strongly modulated by their duration and are influenced by indirect effects from neighboring geographic areas. Our estimates suggest that extending localized lockdowns can slow down SARS-CoV-2 transmission; however, localized lockdowns on their own are insufficient to control pandemic growth in the presence of indirect effects from contiguous neighboring areas that do not have lockdowns. These results provide critical empirical evidence about the effectiveness of localized lockdowns in interconnected geographic areas.
Adverse Events of Nonablative Lasers and Energy-Based Therapies in Subjects with Fitzpatrick Skin Phototypes IV to VI: A Systematic Review and Meta-Analysis
Authors: Hu Shirley , Atmakuri Malika , Rosenberg Joshua
Published: January 2022

Background

Although there is an abundance of literature on nonablative laser and energy-based therapies for the management of skin conditions, adverse events are inconsistently addressed and range widely across studies. Fitzpatrick skin phototypes (SPTs) IV to VI are believed to be at higher risk.

Objectives

The aim of this study was to determine the types and rates of adverse events in nonablative laser and energy-based therapies among patients with SPTs IV to VI.

Methods

Articles addressing nonablative laser and energy-based therapies for skin rejuvenation and acne scarring in patients with SPTs IV to VI that provided data on adverse events were included. The pooled prevalence of each adverse event was calculated. To determine whether age, treatment indication, SPT, and device type influenced incidence, subgroup and meta-regression analyses were performed. Heterogeneity was evaluated with the I2 statistic.

Results

Forty-three studies were included in the meta-analysis. The sample size was 1654, and the median age of subjects was 39.4 years. The most common adverse events were postinflammatory hyperpigmentation (PIH) (rate, 8.1%) and prolonged erythema (rate, 0.6%). The rate of PIH was significantly higher for diode and erbium-doped lasers compared with intense pulsed light and radiofrequency. PIH correlated positively with SPT, laser density, and total energy delivered.

Conclusions

Although the overall rate of adverse events in nonablative laser and energy-based therapies for SPTs IV to VI is low, the incidence of PIH is not insignificant. Certain lasers, such as diode, Q-switched Nd:YAG, and erbium-doped lasers, tend to have higher rates of PIH, whereas intense pulsed light and radiofrequency have minimal risk. Higher SPTs and higher energy deliverance correlate positively with the incidence of PIH.

Level of Evidence: 4
Asystolic Cardiac Arrest Associated With Unstable Bradycardia During Augmentation Mammaplasty: A Case Report
Authors: Vingan Nicole R , Teitelbaum Steven , Moorman Rita , Kenkel Jeffrey M
Published: January 2022

Cardiac arrest is a rare but reported complication during breast augmentation surgery. It is even more rare in a reportedly healthy patient without preexisting cardiac disease. The authors present the case of a healthy 34-year-old female who underwent elective bilateral augmentation mammaplasty and experienced unanticipated asystolic cardiac arrest intraoperatively following general anesthesia supplemented by a regional pectoral (pec I) nerve block. The performing plastic surgeon provided cardiopulmonary resuscitation while the anesthesiologist initiated a rescue protocol per Advanced Cardiac Life Support (ACLS) guidelines. Fortunately, the patient was resuscitated in a timely manner and had a successful return of spontaneous circulation within 1 minute. This case report serves to briefly review the literature and recommendations on proper resuscitation of cardiac arrest per ACLS protocols as well as discuss unstable bradycardia in otherwise healthy patients undergoing breast augmentation surgery. Plastic surgeons and anesthesiologists who perform this procedure should be aware of the possible, rare but serious progression to asystole as well as the proper resuscitative measures to take should they be required.

Level of Evidence: 5
XPXP: improving polygenic prediction by cross-population and cross-phenotype analysis
Authors: Xiao Jiashun , Cai Mingxuan , Hu Xianghong , Wan Xiang , Chen Gang , Yang Can
Published: January 2022

Motivation

As increasing sample sizes from genome-wide association studies (GWASs), polygenic risk scores (PRSs) have shown great potential in personalized medicine with disease risk prediction, prevention and treatment. However, the PRS constructed using European samples becomes less accurate when it is applied to individuals from non-European populations. It is an urgent task to improve the accuracy of PRSs in under-represented populations, such as African populations and East Asian populations.

Results

In this article, we propose a cross-population and cross-phenotype (XPXP) method for construction of PRSs in under-represented populations. XPXP can construct accurate PRSs by leveraging biobank-scale datasets in European populations and multiple GWASs of genetically correlated phenotypes. XPXP also allows to incorporate population-specific and phenotype-specific effects, and thus further improves the accuracy of PRS. Through comprehensive simulation studies and real data analysis, we demonstrated that our XPXP outperformed existing PRS approaches. We showed that the height PRSs constructed by XPXP achieved 9% and 18% improvement over the runner-up method in terms of predicted R2 in East Asian and African populations, respectively. We also showed that XPXP substantially improved the stratification ability in identifying individuals at high genetic risk of type 2 diabetes.

Availability and implementation

The XPXP software and all analysis code are available at github.com/YangLabHKUST/XPXP.

Supplementary information

Supplementary data are available at Bioinformatics online.
Effect of perioperative FLOT versus ECF/ECX on short-term outcomes after surgery for resectable oesophagogastric adenocarcinoma: propensity score-matched study
Authors: Moussa Osama , Bhogal Ricky Harminder , Malietzis George , Fribbens Charlotte , Starling Naureen , Gerlinger Marco , Watkins David , Chau Ian , Rao Sheela , Cunningham David , Allum William H. , Chaudry Asif , Kumar Sacheen
Published: January 2022

Background

Perioperative FLOT (fluorouracil plus leucovorin, oxaliplatin, and docetaxel) chemotherapy is a recent regimen used to treat resectable oesophagogastric (OG) adenocarcinoma, associated with improved overall survival versus earlier chemotherapy strategies. This study compared short-term perioperative morbidity in a large tertiary centre series of FLOT to a matched cohort receiving ECX/ECF (epirubicin, cisplatin, capecitabine (X) or 5-fluorouracil (F)).

Methods

Consecutive patients completing four perioperative cycles of FLOT and proceeding to surgery with resectable OG adenocarcinoma were included. This was matched to patients from a historic ECX/ECF cohort from the same institution. A propensity score was calculated, and a secondary analysis using a propensity-matched group performed.

Results

Cohorts were matched by tumour location and operations performed. In total there were 129 (64.5 per cent) oesophageal and 71 (35.5 per cent) gastric resections (FLOT 57 oesophageal, 43 gastric; ECF/ECX 64 oesophageal, 36 gastric). The median length of stay after surgery was 12 days in the FLOT group versus 15 in ECF/ECX (P = 0.035). There were no significant differences in overall perioperative complications and, specifically, no difference in OG anastomotic leaks, analysed by site (gastric (FLOT 0/79 (0 per cent) versus ECX 2/79 (2.5 per cent); P = 0.123), oesophageal (FLOT 4/121 (3.3 per cent) versus ECX 5/121 (4.1 per cent); P = 0.868) or type of surgery (open FLOT 1/121 (0.8 per cent) versus ECX 3/121 (2.5 per cent); P = 0.368; minimally invasive (FLOT 3/121 (2.5 per cent) versus ECX 2/121 (1.7 per cent); P = 0.555)). There was no statistical difference in leak-related return to theatre, 30-day (FLOT 0 (0 per cent) versus ECX 3/100 (3.0 per cent); P = 0.081), or 90-day (FLOT 0 (0 per cent) versus ECX 2/100 (2.0 per cent); P = 0.155) mortality.

Conclusion

In terms of surgical complications, FLOT and ECX/ECF were equally safe in patients undergoing resection for OG adenocarcinoma.
Representation, trust and ethnicity within refugee communities: the case of Darfurians in Israel
Authors: Richlen Lisa
Published: January 2022

International discourse increasingly emphasizes refugee participation and the need for global forums to consult with refugees and refugee organizations. This process has been critiqued for, amongst other things, being driven by the needs of these organizations and for not meaningfully ensuring broad-based refugee participation including, for example, appropriate representation of women. This may contrast with the ways in which refugees understand representation and diversity within their communities. They may be more driven by notions of trust and, thus, prefer representatives from their ethnic group. Because of the power imbalance between refugees and external agencies, these agencies can wield outsized influence on refugees and their organizations and they may act in ways that are inconsistent with the understandings and needs of their communities. This article takes as a test case one such organization: the Sons of Darfur, founded by Darfurian Sudanese in Israel. In this case study, the Israeli government expected the organization to participate in a decision it made without addressing notions of diversity within the Darfurian community. The fallout from this incident resulted in less representative community organizing. Findings are based on interviews with fifty-two people along with professional and personal knowledge of and relationships with the research population spanning many years.
Innate stimulation of B cells ex vivo enhances antibody secretion and identifies tumour-reactive antibodies from cancer patients
Authors: Karagiannis Panagiotis , Correa Isabel , Chauhan Jitesh , Cheung Anthony , Dominguez-Rodriguez Diana , Terranova-Barberio Manuela , Harris Robert J , Crescioli Silvia , Spicer James , Bokemeyer Carsten , Lacy Katie E , Karagiannis Sophia N
Published: January 2022

Human B cells and their expressed antibodies are crucial in conferring immune protection. Identifying pathogen-specific antibodies following infection is possible due to enhanced humoral immunity against well-described molecules on the pathogen surface. However, screening for cancer-reactive antibodies remains challenging since target antigens are often not identified a priori and the frequency of circulating B cells recognizing cancer cells is likely very low. We investigated whether combined ex vivo culture of human B cells with three innate stimuli, interleukin-17 (IL-17), B-cell activation factor (BAFF), and the toll-like receptor 9 (TLR-9) agonist DNA motif CpG ODN 2006 (CpG), each known to activate B cells through different signalling pathways, promote cell activation, proliferation, and antibody production. Combined IL-17+BAFF+CpG prolonged B-cell survival and increased proliferation compared with single stimuli. IL-17+BAFF+CpG triggered higher IgG secretion, likely by activating differentiated, memory and class-switched CD19+CD20+CD27+IgD- B cells. Regardless of anti-FOLR antibody seropositive status, IL-17+BAFF+CpG combined with a monovalent tumour-associated antigen (folate receptor alpha [FOLR]) led to secreted antibodies recognizing the antigen and the antigen-expressing IGROV1 cancer cells. In a seropositive individual, FOLR stimulation favoured class-switched memory B-cell precursors (CD27-CD38-IgD-), class-switched memory B cells and anti-FOLR antibody production, while IL-17+BAFF+CpG combined with FOLR, promoted class-switched memory B-cell precursors and antibody-secreting (CD138+IgD-) plasma cells. Furthermore, IL-17+BAFF+CpG stimulation of peripheral blood B cells from patients with melanoma revealed tumour cell-reactive antibodies in culture supernatants. These findings suggest that innate signals stimulate B-cell survival and antibody production and may help identify low-frequency antigen-reactive humoral responses.
Evaluation of a gene expression biomarker to identify operationally tolerant liver transplant recipients: the LITMUS trial
Authors: Chruscinski Andrzej , Rojas-Luengas Vanessa , Moshkelgosha Sajad , Issachar Assaf , Luo Jane , Yowanto Handy , Lilly Leslie , Smith Robert , Renner Eberhard , Zhang Jianhua , Epstein Maor , Grant David , McEvoy Caitriona M , Konvalinka Ana , Humar Atul , Adeyi Oyedele , Fischer Sandra , Volmer Felix H , Taubert Richard , Jaeckel Elmar , Juvet Stephen , Selzner Nazia , Levy Gary A
Published: January 2022

LITMUS was a single-centre, Phase 2a study designed to investigate whether the gene biomarker FGL2/IFNG previously reported for the identification of tolerance in murine models could identify operationally tolerant liver transplant recipients. Multiplex RT-PCR was used to amplify eight immunoregulatory genes in peripheral blood mononuclear cells (PBMC) from 69 adult liver transplant recipients. Patients with PBMC FGL2/IFNG ≥ 1 and a normal liver biopsy underwent immunosuppression (IS) withdrawal. The primary end point was the development of operational tolerance. Secondary end points included correlation of tolerance with allograft gene expression and immune cell markers. Twenty-eight of 69 patients (38%) were positive for the PBMC tolerance biomarker and 23 proceeded to IS withdrawal. Nine of the 23 patients had abnormal baseline liver biopsies and were excluded. Of the 14 patients with normal biopsies, eight (57%) have achieved operational tolerance and are off IS (range 12–57 months). Additional studies revealed that all of the tolerant patients and only one non-tolerant patient had a liver gene ratio of FOXP3/IFNG ≥ 1 prior to IS withdrawal. Increased CD4+ T regulatory T cells were detected both in PBMC and livers of tolerant patients following IS withdrawal. Higher expression of SELE (gene for E-selectin) and lower expression of genes associated with inflammatory responses (GZMB, CIITA, UBD, LSP1, and CXCL9) were observed in the pre-withdrawal liver biopsies of tolerant patients by RNA sequencing. These results suggest that measurement of PBMC FGL2/IFNG may enrich for the identification of operationally tolerant liver transplant patients, especially when combined with intragraft measurement of FOXP3/IFNG. Clinical Trial Registration: ClinicalTrials.gov (LITMUS: NCT02541916).
Induction of memory-like CD8+ T cells and CD4+ T cells from human naive T cells in culture
Authors: Tokumoto Yasuhito , Araki Yasuto , Narizuka Yusuke , Mizuno Yosuke , Ohshima Susumu , Mimura Toshihide
Published: January 2022

Memory T cells are crucial players in vertebrate adaptive immunity but their development is incompletely understood. Here, we describe a method to produce human memory-like T cells from naive human T cells in culture. Using commercially available human T-cell differentiation kits, both purified naive CD8+ T cells and purified naive CD4+ T cells were activated via T-cell receptor signaling and appropriate cytokines for several days in culture. All the T-cell activators were then removed from the medium and the cultures were continued in hypoxic condition (1% O2 atmosphere) for several more days; during this period, most of the cells died, but some survived in a quiescent state for a month. The survivors had small round cell bodies, expressed differentiation markers characteristic of memory T cells and restarted proliferation when the T-cell activators were added back. We could also induce memory-like T cells from naive human T cells without hypoxia, if we froze the activated T cells or prepared the naive T cells from chilled filter buffy coats.
Metabolites as drivers and targets in rheumatoid arthritis
Authors: Hanlon Megan M , Canavan Mary , Barker Brianne E , Fearon Ursula
Published: January 2022

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by neovascularization, immune cell infiltration, and synovial hyperplasia, which leads to degradation of articular cartilage and bone, and subsequent functional disability. Dysregulated angiogenesis, synovial hypoxia, and immune cell infiltration result in a ‘bioenergetic crisis’ in the inflamed joint which further exacerbates synovial invasiveness. Several studies have examined this vicious cycle between metabolism, immunity, and inflammation and the role metabolites play in these interactions. To add to this complexity, the inflamed synovium is a multicellular tissue with many cellular subsets having different metabolic requirements. Metabolites can shape the inflammatory phenotype of immune cell subsets during disease and act as central signalling hubs. In the RA joint, the increased energy demand of stromal and immune cells leads to the accumulation of metabolites such as lactate, citrate, and succinate as well as adipocytokines which can regulate downstream signalling pathways. Transcription factors such as HIF1ɑ and mTOR can act as metabolic sensors to activate synovial cells and drive pro-inflammatory effector function, thus perpetuating chronic inflammation further. These metabolic intermediates may be potential therapeutic targets and so understanding the complex interplay between metabolites and synovial cells in RA may allow for identification of novel therapeutic strategies but also may provide significant insight into the underlying mechanisms of disease pathogenesis.
Patients diagnosed with COVID-19 and treated with anakinra: a real-world study in the USA
Authors: Rich Carly , Eriksson Daniel , Dolfi Fabrizio , Jablonska Katarzyna , Dabbous Firas , Nazir Jameel
Published: January 2022

Anakinra, a recombinant, non-glycosylated human interleukin (IL)-1 receptor antagonist, has been used in real-world clinical practice to manage hyperinflammation in coronavirus disease 2019 (COVID-19). This retrospective, observational study analyses US hospital inpatient data of patients diagnosed with moderate/severe COVID-19 and treated with anakinra between 1 April and 31 August 2020. Of the 119 patients included in the analysis, 63.9% were male, 48.6% were of black ethnicity, and the mean (standard deviation [SD]) age was 64.7 (12.5) years. Mean (SD) time from hospital admission to anakinra initiation was 7.3 (6.1) days. Following anakinra initiation, 73.1% of patients received antibiotics, 55.5% received antithrombotics, and 91.0% received corticosteroids. Overall, 64.7% of patients required intensive care unit (ICU) admittance, and 28.6% received mechanical ventilation following admission. Patients who did not require ICU admittance or who were discharged alive experienced a significantly shorter time between hospital admission and receiving anakinra treatment compared with those admitted to the ICU (5 vs. 8 days; P = 0.002) or those who died in hospital (6 vs. 9 days; P = 0.01). Patients with myocardial infarction or renal conditions were six times (P < 0.01) and three times (P = 0.01), respectively, more likely to die in hospital than be discharged alive. A longer time from hospital admission until anakinra treatment was associated with significantly higher mortality (P = 0.01). Findings from this real-world study suggest that a shorter time from hospital admission to anakinra treatment is associated with significantly lower ICU admissions and mortality among patients with moderate/severe COVID-19.
Safety of Treatment Regimens Containing Bedaquiline and Delamanid in the endTB Cohort
Authors: Hewison Catherine , Khan Uzma , Bastard Mathieu , Lachenal Nathalie , Coutisson Sylvine , Osso Elna , Ahmed Saman , Khan Palwasha , Franke Molly F , Rich Michael L , Varaine Francis , Melikyan Nara , Seung Kwonjune J , Adenov Malik , Adnan Sana , Danielyan Narine , Islam Shirajul , Janmohamed Aleeza , Karakozian Hayk , Kamene Kimenye Maureen , Kirakosyan Ohanna , Kholikulov Begimkul , Krisnanda Aga , Kumsa Andargachew , Leblanc Garmaly , Lecca Leonid , Nkuebe Mpiti , Mamsa Shahid , Padayachee Shrivani , Thit Phone , Mitnick Carole D , Huerga Helena
Published: January 2022

Background

Safety of treatment for multidrug-resistant tuberculosis (MDR/RR-TB) can be an obstacle to treatment completion. Evaluate safety of longer MDR/RR-TB regimens containing bedaquiline and/or delamanid.

Methods

Multicentre (16 countries), prospective, observational study reporting incidence and frequency of clinically relevant adverse events of special interest (AESIs) among patients who received MDR/RR-TB treatment containing bedaquiline and/or delamanid. The AESIs were defined a priori as important events caused by bedaquiline, delamanid, linezolid, injectables, and other commonly used drugs. Occurrence of these events was also reported by exposure to the likely causative agent.

Results

Among 2296 patients, the most common clinically relevant AESIs were peripheral neuropathy (26.4%), electrolyte depletion (26.0%), and hearing loss (13.2%) with an incidence per 1000 person months of treatment, 1000 person-months of treatment 21.5 (95% confidence interval [CI]: 19.8–23.2), 20.7 (95% CI: 19.1–22.4), and 9.7 (95% CI: 8.6–10.8), respectively. QT interval was prolonged in 2.7% or 1.8 (95% CI: 1.4–2.3)/1000 person-months of treatment. Patients receiving injectables (N = 925) and linezolid (N = 1826) were most likely to experience events during exposure. Hearing loss, acute renal failure, or electrolyte depletion occurred in 36.8% or 72.8 (95% CI: 66.0–80.0) times/1000 person-months of injectable drug exposure. Peripheral neuropathy, optic neuritis, and/or myelosuppression occurred in 27.8% or 22.8 (95% CI: 20.9–24.8) times/1000 patient-months of linezolid exposure.

Conclusions

AEs often related to linezolid and injectable drugs were more common than those frequently attributed to bedaquiline and delamanid. MDR-TB treatment monitoring and drug durations should reflect expected safety profiles of drug combinations.

Clinical Trials Registration

NCT03259269.
Necessity of Coronavirus Disease 2019 (COVID-19) Vaccination in Persons Who Have Already Had COVID-19
Authors: Shrestha Nabin K , Burke Patrick C , Nowacki Amy S , Terpeluk Paul , Gordon Steven M
Published: January 2022

Background

The aim was to evaluate the necessity of coronavirus disease 2019 (COVID-19) vaccination in persons with prior COVID-19.

Methods

Employees of the Cleveland Clinic working in Ohio on 16 December 2020, the day COVID-19 vaccination was started, were included. Anyone who tested positive for COVID-19 at least once before the study start date was considered previously infected. One was considered vaccinated 14 days after receiving the second dose of COVID-19 mRNA vaccine. Cumulative incidences of COVID-19, symptomatic COVID-19, and hospitalizations for COVID-19 were examined over the next year.

Results

Among 52 238 employees, 4718 (9%) were previously infected and 36 922 (71%) were vaccinated by the study’s end. Cumulative incidence of COVID-19 was substantially higher throughout for those previously uninfected who remained unvaccinated than for all other groups, lower for the vaccinated than unvaccinated, and lower for those previously infected than those not. Incidence of COVID-19 increased dramatically in all groups after the Omicron variant emerged. In multivariable Cox proportional hazards regression, both prior COVID-19 and vaccination were independently associated with significantly lower risk of COVID-19. Among previously infected subjects, a lower risk of COVID-19 overall was not demonstrated, but vaccination was associated with a significantly lower risk of symptomatic COVID-19 in both pre-Omicron (HR, .60; 95% CI, .40–.90) and Omicron (HR, .36; 95% CI, .23–.57) phases.

Conclusions

Both previous infection and vaccination provide substantial protection against COVID-19. Vaccination of previously infected individuals does not provide additional protection against COVID-19 for several months, but after that provides significant protection at least against symptomatic COVID-19.
The kidney in hantavirus infection—epidemiology, virology, pathophysiology, clinical presentation, diagnosis and management
Authors: Koehler Felix C , Di Cristanziano Veronica , Späth Martin R , Hoyer-Allo K Johanna R , Wanken Manuel , Müller Roman-Ulrich , Burst Volker
Published: January 2022

Hantavirus-induced diseases are emerging zoonoses with endemic appearances and frequent outbreaks in different parts of the world. In humans, hantaviral pathology is characterized by the disruption of the endothelial cell barrier followed by increased capillary permeability, thrombocytopenia due to platelet activation/depletion and an overactive immune response. Genetic vulnerability due to certain human leukocyte antigen haplotypes is associated with disease severity. Typically, two different hantavirus-caused clinical syndromes have been reported: hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). The primarily affected vascular beds differ in these two entities: renal medullary capillaries in HFRS caused by Old World hantaviruses and pulmonary capillaries in HCPS caused by New World hantaviruses. Disease severity in HFRS ranges from mild, e.g. Puumala virus-associated nephropathia epidemica, to moderate, e.g. Hantaan or Dobrava virus infections. HCPS leads to a severe acute respiratory distress syndrome with high mortality rates. Due to novel insights into organ tropism, hantavirus-associated pathophysiology and overlapping clinical features, HFRS and HCPS are believed to be interconnected syndromes frequently involving the kidneys. As there are no specific antiviral treatments or vaccines approved in Europe or the USA, only preventive measures and public awareness may minimize the risk of hantavirus infection. Treatment remains primarily supportive and, depending on disease severity, more invasive measures (e.g., renal replacement therapy, mechanical ventilation and extracorporeal membrane oxygenation) are needed.