bluuebunny/crossref_metadata_2025 huggingface dataset:
Support preferences for Arabic people with a chronic condition living in Australia: A descriptive survey
Authors: Alananzeh Ibrahim , Halcomb Elizabeth , Chan Alex
Published: September 2020

Chronic diseases are becoming increasingly common and are a priority for action in the Australian health sector. This study investigated the models of support groups preferred by Arab Australians living with chronic conditions. Two hundred fifty‐one Arab people with chronic conditions completed a descriptive survey. More than half of participants thought that information on palliative care, financial advice and guidance, social and emotional support for self and family, complementary therapies, and being involved in treatment decisions were extremely useful. Conversely, information about palliative care, financial advice and guidance, and complementary therapies was seen as least useful. Eighty‐five percent of participants reported willingness to attend a support program. Participants indicated they preferred the program to be held at a local community organization and facilitated by health care professionals. There was a high level of agreement in the views of Arab participants about the preferred location, type of facilitator, and content of a support program. These findings should inform the design of future programs for Arab immigrants with chronic conditions.
Natural environment and childhood obesity: A systematic review
Authors: Jia Peng , Dai Shaoqing , Rohli Kristen E. , Rohli Robert V. , Ma Yanan , Yu Chao , Pan Xiongfeng , Zhou Weiqi
Published: September 2020

The associations between built and food environments and childhood obesity have been studied extensively. However, the association between the natural environment and childhood obesity has received too little scholarly attention. This study reviewed the literature published before 1 January 2019, which described associations between a full range of natural environmental factors (e.g., rainfall, temperature, sunlight, natural disasters, flood and drought) and weight‐related behaviours and childhood obesity. Five cross‐sectional studies and one longitudinal study were identified. Measures of natural environmental factors varied across six included studies, falling into five broad categories: weather conditions, altitude, natural disaster risk, air quality and day length. It was found that temperature was a significant weather indicator in most included studies and was associated with a reduction of daily physical activity. Children living in high‐altitude areas were more likely to be shorter and heavier than their counterparts in low‐altitude areas. Findings of this study will contribute to helping multiple stakeholders, including policy makers and urban planners, and formulate health policies and interventions to mitigate the detrimental impact of the natural environment on childhood obesity. More longitudinal studies should be designed to confirm these effects and explore the potential health effects of more natural environmental factors.
Who is Afraid of the Big Bad Debt? A Modern Money Theory Perspective on Federal Deficits and Debt
Authors: Douglas James W. , Raudla Ringa
Published: September 2020

The U.S. federal government's deficit is expected to grow to over one trillion dollars in fiscal year (FY) 2020, and the national debt held by the public will likely grow to over $16.7 trillion. Budgeting scholars in the field of public administration have expressed concern over the increasing debt levels. The field of public administration, however, is largely unaware of Modern Money Theory (MMT) and the mechanics of money, which is its focus. MMT argues that understanding the mechanics of money in the U.S. financial system should lead scholars to different conclusions regarding the debt and deficit. This article presents the core arguments of the MMT perspective in this regard, with the goal to trigger further debates about debt and deficit among the community of budgeting scholars.
Retrospective case series of increased oral propranolol dosage for infantile hemangiomas
Authors: Huang Amy H. , Mannschreck Diana , Aggarwal Prachi , Mahon Mark , Cohen Bernard A.
Published: September 2020

Background

Infantile hemangiomas (IH) are the most common benign tumor of infancy. Although oral propranolol is currently first‐line therapy, optimal dosing for treatment of IH remains debated. We sought to identify hemangioma characteristics associated with poor response to standard dosing (2 mg/kg/d) and to assess the therapeutic benefit of higher dosing.

Methods

Retrospective chart review was conducted of 559 patients with IH seen at Johns Hopkins between 2008 and 2018, of whom 245 (44%) were treated with propranolol. Baseline characteristics were compared between patients who received increased propranolol dosing (≥2.5 mg/kg/d) and those who remained on standard dose (2 mg/kg/d). Changes in the Hemangioma Activity Score (HAS) during the increased dosage period were scored by two trained, blinded pediatric dermatologists.

Results

Of 245 patients, 204 (83%) received standard 2 mg/kg/d propranolol dosing while 41 (17%) received a higher dose of ≥2.5 mg/kg/d. The most common location of IH in both groups was the face. In the increased dosage group, 85.4% of IH were of mixed or deep morphology with a mean greatest diameter of 4.6 cm. IH requiring increased dosing received longer courses of propranolol (mean of 389 vs. 282 days, P < .001) and underwent higher rates of excision by plastic surgery (26.8% vs. 5.9%, P < .001). Mean change in HAS over the period with dosage ≥2.5 mg/kg/d was minimal (−0.70; P < .001).

Conclusions

Most recalcitrant IH were located on the face, larger in diameter, and of mixed or deep morphology. Patients had little improvement in HAS score with increased propranolol dosing implemented late in the treatment course with over one‐fourth ultimately receiving surgical excision.
Efficacy of liposomal amphotericin against febrile neutropenia in pediatric patients receiving prophylactic voriconazole
Authors: Kobayashi Ryoji , Matsushima Satoru , Hori Daiki , Sano Hirozumi , Suzuki Daisuke , Kishimoto Kenji , Nakano Takaaki , Yanagi Masato , Kodama Kouya , Kobayashi Kunihiko
Published: September 2020

Background

The risk factors for invasive fungal infection have gradually become evident for pediatric patients with hematological diseases. Here we analyze the efficacy of liposomal amphotericin (L‐AMB) for pediatric patients with febrile neutropenia using prophylactic voriconazole (VRCZ).

Method

We administered L‐AMB (2.5 mg/kg/day) in patients with febrile neutropenia who were receiving prophylactic VRCZ (10 mg/kg/day, orally) and were resistant to second‐line antibiotics therapy. Thirteen patients (5 males, 8 females) with 19 febrile neutropenia episodes were targeted in this analysis. The median age of the patients was 14 years (range, 1–19 years). Eighteen out of 19 episodes occurred in patients with acute myeloid leukemia, with the remaining episode occurring in a patient with acute unclassified leukemia.

Results

The median period from start of L‐AMB administration to resolution of fever was 4 days (1–27 days). In 15 out of 19 episodes, fever resolved within 5 days from commencement of L‐AMB administration. Using criteria proposed by T. J. Walsh et al., the success rate of L‐AMB for febrile neutropenia was 89.5% in this study.

Conclusions

Although the sample size of our study was small, the extremely high efficacy of L‐AMB warrants its administration in patients with febrile neutropenia who are receiving VRCZ.
Additional value of superb microvascular imaging for assessing hepatic arterial blood flow after pediatric liver transplantation
Authors: Gu Li‐hong , Fang Hua , Liu Xue‐song , Xia Qiang , Li Feng‐hua
Published: September 2020

Background

The aim of this study was to explore the value of SMI compared with conventional ultrasonography for assessing hepatic arterial blood flow after pediatric liver transplantation.

Methods

From March 2018 to November 2018, a total of 105 pediatric recipients with biliary atresia underwent liver transplantation in our hospital. Ultrasound examinations were performed at the bedside in the intensive care unit to check the patency of the blood flow in the hepatic allograft. CDI, PDI, cSMI, and mSMI were performed to assess the display, orientation, and distribution of the graft hepatic artery. Ultrasound examinations were performed by one radiologist, and the images were judged by two observers.

Results

The median age, weight, and height of the recipients were 6.97 (5.92, 9.58) months, 6.50 (6.00, 7.80) kg, and 64.00 (62.00, 68.00) cm, respectively. The measure of kappa agreement was 0.902, 0.889, 0.882, and 0.882 for CDI, PDI, cSMI, and mSMI, respectively. HAT occurred in 7 pediatric recipients and was confirmed by CTA (computed tomography angiography) and surgery. The diagnostic performance of sensitivity, specificity, PPV (positive predictive value), NPV (negative predictive value), and accuracy were 100%, 92.86%, 50%, 100%, and 93.33% for CDI and 100%, 98.98%, 87.50%, 100%, and 99.05% for SMI.

Conclusions

As an additional method to CDI, SMI can clearly show the distribution of hepatic arterial blood flow and provide more details, thereby markedly improving the diagnostic performance of postoperative HAT.
Swiss‐Army Knife of Social Control: Administrative Exile in Late Imperial Russia
Authors: DALY JONATHAN W.
Published: September 2020

Punitive exile was imposed more extensively in late imperial Russia than in any other major contemporaneous country. Roughly one‐half of exiles were convicted by courts for heinous nonpolitical crimes, for which the penalty would be death in European countries. The other half of exiles were sent largely by peasant communities wishing to dispose of unproductive and otherwise unwanted members. Most exiles were transported to Siberia, but significant proportions ended up in remote areas of European Russia. Although both penal and administrative exile were often more humane than imprisonment, which imposed greater restrictions on prisoners, the practice met with staunch criticism, both in public and within the corridors of officialdom. Its use, consequently, was in decline before the revolution of 1905. Suppressing social and political unrest involved an intensive application of exile, both penal and administrative. The fact that its use ebbed again in the years before World War I confirms senior officials' ongoing commitment to the rule of law. That the Russian government continued to rely on exile, however, can best be explained by the inadequacy of personnel, training, professional discipline, and investigative practices of most Russia policemen and the authoritarian and paternalistic attitudes and fear of disorder among officials.
Reconstructing History: Pushkin, Poltava, and Imperial Nation‐Building
Authors: KNEPER GENNADI
Published: September 2020

This article aims to analyze Alexander Pushkin's narrative poem Poltava (1828–29) as an attempt of literary reconstruction of history within the context of a broad public debate about Russia's past and its implications for the politics of the day. It will show how Pushkin used the Battle of Poltava as a topic that allowed him to make a public statement about Russia's imperial development and nation‐building, which he connected to the concept of narodnost'. The discussion of historical events and the analysis of Pushkin's interpretation of the past will be equally important in order to examine Poltava as an unusual piece of literature with considerable influence on posterity.
Painting against Empire: Béla Uitz and the Birth and Fate of Internationalist Socialist Realism
Authors: LUCENTO ANGELINA
Published: September 2020

This manuscript describes the significance of the Hungarian‐Soviet artist Béla Uitz's contribution to the definition of Socialist Realism through the development of a style of anti‐imperialist painting based on national form that I call Internationalist Socialist Realism. Relying on previously unpublished archival documents, articles from the Soviet press, and analyses of artworks themselves, the manuscript shows specifically how Uitz developed his internationalist style through transnational encounters with leftist activists in Paris and avant‐garde artists in Soviet Ukraine. It also shows how the artist used his position as a policy maker in the Soviet cultural administration to create a platform for the exploration of the role of national form in Soviet art known as the International Bureau of Revolutionary Artists (MBRKh) and how he used that platform to ensure that Internationalist Socialist Realism became a key component of the official style of visual representation in the early 1930s. The manuscript further demonstrates that while the Soviet state's turn to Russocentrism and Slavocentrism in the late 1930s denuded Internationalist Socialist Realism of many of its radically collectivist, anti‐imperial elements, the cultural apparatus accepted Uitz's core idea that the tactile connection between the human body and the affective materiality of national forms could help catalyze political change and establish connections between different peoples. The manuscript shows that changes in representations of national form in Socialist Realism over time can reveal valuable new insight into the politics of Soviet culture, both during and beyond Stalinism.
A spectral parameter for the estimation of soil total nitrogen and nitrate nitrogen of winter wheat growth period
Authors: Zhang Juanjuan , Wei Qinqin , Xiong Shuping , Shi Lei , Ma Xinming , Du Pan , Guo Jianbiao
Published: September 2020

Real‐time monitoring of crop nitrogen and soil nutrient status can provide an important basis for the rational application of nitrogen during fertilization. Two field experiments were conducted in Henan Province, China, using three main wheat cultivars and four nitrogen levels, across two consecutive growing seasons. Canopy spectral reflectance, plant nitrogen and soil nitrogen were synchronously measured during the wheat's main growth stages. Furthermore, the quantitative relationship between the soil nitrogen and plant nitrogen concentrations was analysed, and the relationship with existing spectral parameters and several kinds of hyperspectral indices, including normalized difference spectral indices (NDVI), ratio spectral indices (RVI) and difference spectral indices (DVI), was extracted. All the combinations of two wavebands between 350 and 1 050 nm were calculated, and their quantitative relationships with soil nitrogen content were analysed. The results were used to build a remote monitoring model of soil total nitrogen and nitrate nitrogen (NO3‐‐N) content by using the canopy spectral reflectance. The results showed that the correlation between soil NO3‐‐N and plant nitrogen concentration was superior to the correlation between total nitrogen and plant nitrogen concentrations. After systematically analysing the quantitative relationship between wheat canopy spectra, soil total nitrogen content and NO3‐‐N content, we found that the correlation with the original reflectance in the visible region was superior and that the first derivative spectrum significantly improved the correlation in the near‐infrared region. Furthermore, the soil total nitrogen content, NO3‐‐N content and canopy spectral data were analysed in different growth stages (jointing stage, flowering stage and filling stage). The results showed that NDVI (FD747, FD699) was the best indicator for monitoring soil total nitrogen and NO3‐‐N content modelling, as the modelling decision coefficient and prediction decision coefficient were both above 0.8 for all test cases. Thus, during wheat growth, crop canopy spectroscopy can be used to estimate soil nitrogen nutrition status, and NDVI (FD747, FD699) can be used as an effective spectral parameter for estimating soil total nitrogen and NO3‐‐N content.
Intravenous immunoglobulin as adjunctive therapy in kidney transplant recipients with severe pneumocystis pneumonia
Authors: Edey Matthew M. , Gunasekera Pumali N. , Lobb Mark , Imran Muhammad
Published: September 2020

Pneumocystis jirovecii is an opportunistic pathogen that may cause severe, life‐threatening respiratory infections in immunocompromised patients such as those with kidney transplants. Although antimicrobial prophylaxis is now universally recommended in the early post‐transplant period, Pneumocystis pneumonia (PCP) can occur later. If such infection occurs, mortality rates are high. Beyond standard therapy with trimethoprim‐sulfamethoxazole, there is a lack of evidence‐based options for intensifying treatment when initial therapy fails to show improvement. Moreover, it is usual to minimize immunosuppression in life‐threatening infection, but graft damage may occur, particularly in kidney transplant recipients at above‐average immunological risk. Here we present two cases of severe PCP in high immunological risk recipients who were managed with adjunctive intravenous immunoglobulin and withdrawal of immunosuppression. Both patients recovered and were discharged from hospital with functioning grafts.
Repeatability of in vitro carboplatin elution from carboplatin‐impregnated calcium sulfate hemihydrate beads made in a clinic setting
Authors: Worth David B. , Risselada Marije , Cooper Bruce R. , Moore George E.
Published: September 2020

Objective

To evaluate the intra‐lot and inter‐lot consistency and total carboplatin elution over 25 days from carboplatin‐impregnated calcium sulfate hemihydrate (C‐I CSH) beads manufactured in a clinic setting.

Study design

In vitro elution study.

Methods

Two volumes of carboplatin were mixed with CSH to yield 4 mg and 8 mg C‐I CSH doses. Two lots of beads were made for each concentration and split into five doses (n = 10 per concentration). Beads hardened in molds and were placed in a covered six‐well plate, submerged in phosphate‐buffered saline, and incubated with samples collected at 12 time points (0, 6, 12, and 24 hours and 2, 3, 5, 7, 10, 14, 18, and 25 days). The amount of carboplatin in each sample was evaluated by high‐performance liquid chromatography/mass spectrometry. Correction for carboplatin degradation and dilution was applied, and eluted carboplatin was calculated. Intra‐lot and inter‐lot coefficient of variation (CV) was calculated for each concentration.

Results

The intra‐lot CV ranged between 7.9% and 23.1%, and the inter‐lot CV ranged from 3.5% to 10.3%, with improvement noted in each successive lot of beads. Mean peak eluted carboplatin was 2.45 ± 0.43 mg (61%) and 3.68 ± 0.41 mg (45.9%) for the 4‐mg and 8‐mg C‐I CSH beads, respectively, with both occurring at the 12‐hour timepoint.

Conclusion

Progressive improvement in variability with successive lots of beads indicated a learning curve with bead manufacturing with a low variation both within and between lots of C‐I CSH beads.

Clinical significance

On‐site mixing of carboplatin with commercial CSH bead powder leads to a low variation of carboplatin per bead dose.
Improvement on Simulation Methods of Fluid Transient Processes in Turbine Tailrace Tunnel
Authors: Zhang Boran , Wan Wuyi , Bi Li
Published: September 2020

In numerical simulations of hydroturbine systems, the fluid in the draft tube keeps alternating between the free surface flow condition and the pressured flow condition. This combination of free surface flow model and pressured flow model has been a focus of researchers. Because of the huge difference in pressure wave speed, the two models differ much in terms of meshing even in the same method. To track the interaction point between free surface flow and pressured flow, a type of interaction point tracking method (IPTM) is proposed, which is based on the method of characteristics. Using a controllable iteration to solve the controlling equations of the boundary conditions, the concrete interaction point can be tracked accurately at each time-step. The method is validated in an actual turbine draft tube and compared with experimentally measured data. The results show that IPTM is equipped with high reliability and offers some advantages compared to the other existing methods.
Erratum: Mites of the genera Leioseius Berlese and Protogamasellus Karg (Mesostigmata, Ascidae) in mangrove forests in southern Iran, with a key to the genera and species of Ascidae recorded from Iran. Systematic and Applied Acarology, 24(7): 1319–1336.

Authors: Kazemi Shahrooz
Published: September 2020

Page 1323, Figure 7: Coxae IV. In the key to the genera and species of Ascidae recorded from Iran, one species of the genus Arctoseius Thor, A. venustulus (Berlese 1916), was not mentioned. Therefore, couplet 29 was divided into two parts (couplets 29–30) to accommodate this species as follows (therefore, in page 1332, second part of the couplet 18 reaches to the couplet number 31 instead of 30):
Review of electrical contacts to phase change materials and an unexpected trend between metal work function and contact resistance to germanium telluride
Authors: Cooley Kayla A. , Aldosari Haila M. , Yang Kezhou , Mohney Suzanne E.
Published: September 2020

Devices based on the unique phase transitions of phase change materials (PCMs) like GeTe and Ge2Sb2Te5 (GST) require low-resistance and thermally stable Ohmic contacts. This work reviews the literature on electrical contacts to GeTe, GST, GeCu2Te3 (GCuT), and Ge2Cr2Te6 (GCrT), especially GeTe due to the greater number of studies. We briefly review how the method used to measure the contact resistance (Rc) and specific contact resistance (ρc) can influence the values extracted, since measurements of low contact resistances are susceptible to artifacts, and we include a direct comparison of Au-, Pt-, Ni-, Mo-, Cr-, Sn-, and Ti-based contacts using a systematic approach. Premetallization surface treatment of GeTe, using ex situ or in situ approaches, is critical for minimizing contact resistance (Rc). Transmission electron microscopy reveals that interfacial reactions often occur and also clearly influence Rc. The lowest Rc values (∼0.004 ± 0.001 Ω mm) from the direct comparison were achieved with as-deposited Mo/Ti/Pt/Au (Ar+ plasma treatment) contacts and annealed Sn/Fe/Au (de-ionized H2O premetallization treatment). In the case of Sn-based contacts, low Rc was attributed, in part, to the formation of SnTe at the contact interface; however, for Mo-based contacts, no such interfacial reaction was observed. Comparing all contact metals tested beneath a cap of at least 100 nm of Au, Mo/Ti/Pt/Au offered the lowest contact resistance as-deposited, even though the work function of Mo is only 4.6 eV, and the low contact resistance remained stable even after annealing at 200 °C for 30 min. This trend is surprising, as high work function metals, like Ni and Pt, would be expected to provide lower Rc values when they are in contact with a p-type semiconductor like GeTe. Through materials’ characterization, an inverse relationship between the metal work function and Rc for higher work function metals can be attributed to the reactivity of many of the metals with GeTe. Studies of contacts to GST in the literature involve only a small number of contact materials (Ti, TiN, TiW, W, Pt, and graphene) and employ varied geometries for extracting contact resistance. For hexagonal GST, TiW is reported to provide the lowest ρc of ∼2 × 10−7 Ω cm2, while TiN provided the lowest reported ρc of ∼3 × 10−7 Ω cm2 to cubic GST. For the ternary PCMs GCuT and GCrT, contact resistance studies in the literature are also limited, with W being the only metal studied. While more extensive work is necessary to draw wider conclusions about trends in current transport at metal/GST, metal/GCuT, and metal/GCrT interfaces, reduction of Rc and high thermal stability are critical to engineering more efficient and reliable devices based on these materials.
Effect of High-Intensity Interval Training Versus Small-Sided Games Training on Sleep and Salivary Cortisol Level
Authors: Bonato Matteo , La Torre Antonio , Saresella Marina , Marventano Ivana , Merati Giampiero , Banfi Giuseppe , Vitale Jacopo A.
Published: September 2020

Purpose:The authors compared sleep quality and salivary cortisol concentration after high-intensity interval training (HIIT) and small-sided games (SSGs) performed at the habitual training time in nonprofessional male soccer players.Methods:A total of 32 players (age = 24 [6] y, height = 1.77 [0.06] m, and body mass = 75 [12] kg) were randomized into an HIIT group or an SSG group. Actual sleep time, sleep efficiency (SE), sleep latency, immobility time (IT), moving time (MT), and fragmentation index were monitored using actigraphy before (PRE) and 2 nights after (POST 1 and POST 2) the training session. Salivary cortisol levels were measured before (PRE) and after (POST) training. Cortisol awakening response was evaluated.Results:Significant intragroup differences in the HIIT group were noted for actual sleep time (P < .0001), SE (P < .0001), sleep latency (P = .047), IT (P < .0001), MT (P < .0001), and fragmentation index (P < .0001) between PRE and POST 1 and for SE (P = .035), IT (P = .004), MT (P = .006), and fragmentation index (P = .048) between PRE and POST 2. Intergroup differences for actual sleep time (P = .014), SE (P = .048), IT (P < .0001), and MT (P = .046) were observed between the HIIT and the SSGs group at POST 1 were detected. Significant intragroup variations were observed in PRE and POST salivary cortisol levels (P < .0001 for HIIT;P = .0003 for SSGs) and cortisol awakening response (P < .0001 for HIIT;P < .0001 for SSGs). Significant intergroup differences between the HIIT and the SSGs group were found at POST (P < .0001) and in cortisol awakening response (P = .017).Conclusions:Changes in actigraphy-based sleep parameters and salivary cortisol levels were greater after an acute session of HIIT than SSGs in this sample of nonprofessional male soccer players.
Enhanced Cycling Time-Trial Performance During Multiday Exercise With Higher-Pressure Compression Garment Wear
Authors: Williams Ewan R. , McKendry James , Morgan Paul T. , Breen Leigh
Published: September 2020

Purpose: Compression garments are widely used as a tool to accelerate recovery from intense exercise and have also gained traction as a performance aid, particularly during periods of limited recovery. This study tested the hypothesis that increased pressure levels applied via high-pressure compression garments would enhance “multiday” exercise performance. Methods: A single-blind crossover design, incorporating 3 experimental conditions—loose-fitting gym attire (CON), low-compression (LC), and high-compression (HC) garments—was adopted. A total of 10 trained male cyclists reported to the laboratory on 6 occasions, collated into 3 blocks of 2 consecutive visits. Each “block” consisted of 3 parts, an initial high-intensity protocol, a 24-hour period of controlled rest while wearing the applied condition/garment (CON, LC, and HC), and a subsequent 8-km cycling time trial, while wearing the respective garment. Subjective discomfort questionnaires and blood pressure were assessed prior to each exercise bout. Power output, oxygen consumption, and heart rate were continuously measured throughout exercise, with plasma lactate, creatine kinase, and myoglobin concentrations assessed at baseline and the end of exercise, as well as 30 and 60 minutes postexercise. Results: Time-trial performance was significantly improved during HC compared with both CON and LC (HC = 277 [83], CON = 266 [89], and LC = 265 [77] W; P < .05). In addition, plasma lactate was significantly lower at 30 and 60 minutes postexercise on day 1 in HC compared with CON. No significant differences were observed for oxygen consumption, heart rate, creatine kinase, or subjective markers of discomfort. Conclusion: The pressure levels exerted via lower-limb compression garments influence their effectiveness for cycling performance, particularly in the face of limited recovery.
Limited Role of Mincle in the Host Defense against Infection with Cryptococcus deneoformans
Authors: Sato Yuki , Sato Ko , Yamamoto Hideki , Kasamatsu Jun , Miyasaka Tomomitsu , Tanno Daiki , Miyahara Anna , Kagesawa Takafumi , Oniyama Akiho , Kawamura Kotone , Yokoyama Rin , Kitai Yuki , Umeki Aya , Ishizuka Shigenari , Takano Kazuki , Shiroma Ryuhei , Nakahata Nana , Kawakami Kaori , Kanno Emi , Tanno Hiromasa , Yamasaki Sho , Hara Hiromitsu , Ishii Keiko , Kawakami Kazuyoshi
Published: September 2020

Cryptococcus deneoformansis an opportunistic fungal pathogen that frequently causes fatal meningoencephalitis in patients with impaired cell-mediated immune responses such as AIDS. Caspase-associated recruitment domain 9 (CARD9) plays a critical role in the host defense against cryptococcal infection, suggesting the involvement of one or more C-type lectin receptors (CLRs). In the present study, we analyzed the role of macrophage-inducible C-type lectin (Mincle), one of the CLRs, in the host defense againstC. deneoformansinfection.
Targeted Metagenomics for Clinical Detection and Discovery of Bacterial Tick-Borne Pathogens
Authors: Kingry Luke , Sheldon Sarah , Oatman Stephanie , Pritt Bobbi , Anacker Melissa , Bjork Jenna , Neitzel David , Strain Anna , Berry Jon , Sloan Lynne , Respicio-Kingry Laurel , Dietrich Elizabeth , Bloch Karen , Moncayo Abelardo , Srinivasamoorthy Ganesh , Hu Bin , Hinckley Alison , Mead Paul , Kugeler Kiersten , Petersen Jeannine
Published: September 2020

Tick-borne diseases, due to a diversity of bacterial pathogens, represent a significant and increasing public health threat throughout the Northern Hemisphere. A high-throughput 16S V1-V2 rRNA gene-based metagenomics assay was developed and evaluated using >13,000 residual samples from patients suspected of having tick-borne illness and >1,000 controls. Taxonomic predictions for tick-borne bacteria were exceptionally accurate, as independently validated by secondary testing. Overall, 881 specimens were positive for bacterial tick-borne agents.
Structure-Based Design of Hepatitis C Virus E2 Glycoprotein Improves Serum Binding and Cross-Neutralization
Authors: Pierce Brian G. , Keck Zhen-Yong , Wang Ruixue , Lau Patrick , Garagusi Kyle , Elkholy Khadija , Toth Eric A. , Urbanowicz Richard A. , Guest Johnathan D. , Agnihotri Pragati , Kerzic Melissa C. , Marin Alexander , Andrianov Alexander K. , Ball Jonathan K. , Mariuzza Roy A. , Fuerst Thomas R. , Foung Steven K. H.
Published: September 2020

Hepatitis C virus infects approximately 1% of the world’s population, and no vaccine is currently available. Due to the high variability of HCV and its ability to actively escape the immune response, a goal of HCV vaccine design is to induce neutralizing antibodies that target conserved epitopes. Here, we performed structure-based design of several epitopes of the HCV E2 envelope glycoprotein to engineer its antigenic properties. Designs were tested
in vitro
and
in vivo
, demonstrating alteration of the E2 antigenic profile in several cases, and one design led to improvement of cross-neutralization of heterologous viruses. This represents a proof of concept that rational engineering of HCV envelope glycoproteins can be used to modulate E2 antigenicity and optimize a vaccine for this challenging viral target.
Transcriptional Profiling Suggests T Cells Cluster around Neurons Injected with Toxoplasma gondii Proteins
Authors: Merritt Emily F. , Johnson Hannah J. , Wong Zhee Sheen , Buntzman Adam S. , Conklin Austin C. , Cabral Carla M. , Romanoski Casey E. , Boyle Jon P. , Koshy Anita A.
Published: September 2020

Like other persistent intracellular pathogens,Toxoplasma gondii, a protozoan parasite, has evolved to evade the immune system and establish a chronic infection in specific cells and organs, including neurons in the CNS. UnderstandingT. gondii’s persistence in neurons holds the potential to identify novel, curative drug targets. The work presented here offers new insights into the neuron-T. gondiiinteractionin vivo. By transcriptionally profiling neurons manipulated byT. gondii, we unexpectedly revealed that immune cells, and specifically CD8+T cells, appear to cluster around these neurons, suggesting that CD8+T cells specifically recognize parasite-manipulated neurons. Such a possibility supports evidence from other labs that questions the long-standing dogma that neurons are often persistently infected because they are not directly recognized by immune cells such as CD8+T cells. Collectively, these data suggest we reconsider the broader role of neurons in the context of infection and neuroinflammation.
Insights into the Evolutionary Origin of Mediterranean Sandfly Fever Viruses
Authors: Marklewitz Marco , Tchouassi David P. , Hieke Christian , Heyde Verena , Torto Baldwyn , Sang Rosemary , Junglen Sandra
Published: September 2020

Studies on the genetic diversity of arthropod-borne viruses circulating in rural regions can provide critical early indications on new emerging viruses essential for global epidemic preparedness. In this study, we describe the discovery of four phleboviruses in sandflies from the Kenyan Rift Valley. The novel viruses are related to the two medically important serocomplexes, sandfly fever Naples and sandfly fever Sicilian, that are associated with febrile illness and neuroinvasive infections and which were previously not known to occur in sub-Saharan Africa. Knowledge on the occurrence of sandfly-borne phleboviruses in Kenya and elsewhere in Africa can help to decipher their contributions in the etiologies of fevers of unknown origin in patients. Our findings on five genetically diverse phleboviruses detected in Kenya suggest that the common ancestor of Old World phleboviruses existed in sub-Saharan Africa, a hot spot for emerging arboviruses.
Hepatitis B virus persistence and reactivation
Authors: Shi Yu , Zheng Min
Published: September 2020

Hepatitis B virus (HBV) infection causes chronic hepatitis and has long term complications. Individuals ever infected with HBV are at risk of viral reactivation under certain circumstances. This review summarizes studies on HBV persistence and reactivation with a focus on the definitions and mechanisms. Emphasis is placed on the interplay between HBV replication and host immunity as this interplay determines the patterns of persistence following viral acquisition. Chronic infections exhibit as overt persistence when a defective immune response fails to control the viral replication. The HBV genome persists despite an immune response in the form of covalently closed circular DNA (cccDNA) and integrated DNA, rendering an occult state of viral persistence in individuals whose infection appears to have been resolved. We have described HBV reactivation that occurs because of changes in the virus or the immune system. This review aims to raise the awareness of HBV reactivation and to understand how HBV persists, and discusses the risks of HBV reactivation in a variety of clinical settings.
Knowledge transfer and retention of simulation-based learning for
neurosurgical instruments: a randomised trial of perioperative nurses
Authors: Clarke David B , Galilee Alena I , Kureshi Nelofar , Hong Murray , Fenerty Lynne , D’Arcy Ryan C N
Published: September 2020

Introduction

Previous studies have shown that simulation is an acceptable method of
training in nursing education. The objectives of this study were to determine
the effectiveness of tablet-based simulation in learning neurosurgical
instruments and to assess whether skills learnt in the simulation environment
are transferred to a real clinical task and retained over time.

Methods

A randomised controlled trial was conducted. Perioperative nurses
completed three consecutive sessions of a simulation. Group A performed
simulation tasks prior to identifying real instruments, whereas Group B
(control group) was asked to identify real instruments prior to the simulation
tasks. Both groups were reassessed for knowledge recall after 1 week.

Results

Ninety-three nurses completed the study. Participants in Group A, who had
received tablet-based simulation, were 23% quicker in identifying real
instruments and did so with better accuracy (93.2% vs 80.6%, p<0.0001) than
Group B. Furthermore, the simulation-based learning was retained at 7 days with
97.8% correct instrument recognition in Group A and 96.2% in Group B while
maintaining both speed and accuracy.

Conclusion

This is the first study to assess the effectiveness of tablet-based
simulation training for instrument recognition by perioperative nurses. Our
results demonstrate that instrument knowledge acquired through tablet-based
simulation training results in improved identification and retained recognition
of real instruments.
Facilitators, barriers and lessons learnt from the first state-wide naloxone distribution conducted in West Virginia
Authors: Rudisill Toni Marie , Ashraf Alexandria J , Linn Herbert I , Sayres Sheena , Jeffries James E , Gurka Kelly K
Published: September 2020

Background

Overdose education and naloxone distribution programmes are known to reduce opioid-related deaths. A state-wide naloxone distribution effort of 8250 rescue kits was undertaken by government, community and university partners in West Virginia in 2016–2017. The purpose of this study was to discern the barriers, facilitators and lesson learnt from implementing this endeavour in a rural state with the highest opioid overdose fatality rate in the US.

Methods

Structured interviews (n=26) were conducted among both internal and external stakeholders. Those who participated were >18 years of age and were the lead representative from agencies that either received naloxone (ie, external stakeholders) or helped implement the distribution (ie, internal stakeholders). The interviews followed standardised scripts and lasted approximately 40 min. Sessions were audio-recorded and transcribed. Qualitative content analysis was performed by two researchers to determine themes surrounding facilitators or barriers to programme implementation.

Results

The primary facilitators reported by stakeholders included collaborative partnerships, ease of participating in the programme, being established in prevention efforts, demand for naloxone and the need for personal protection from overdose. The primary barriers identified by stakeholders included bureaucracy/policy/procedures of their organisation or agency, stigma, logistical or planning issues, problems with reporting, lack of communication post distribution and sustainability. Numerous lessons were learnt.

Conclusions

Based on the implementation of the programme in 87 organisations, including law enforcement and fire departments, the impact of facilitators outweighed that of barriers. These findings may inform others planning to conduct a similar, large-scale project.
Custom pyrosequencing assay to detect shortBRAFdeletions in Langerhans cell histiocytic lesions
Authors: Jouenne Fanélie , Sadoux Aurélie , Lorillon Gwenaël , Louveau Baptiste , Bugnet Emmanuelle , Meignin Veronique , Mourah Samia , Tazi Abdellatif
Published: September 2020

Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplastic disease driven by activating mutations in the mitogen-activating protein kinase signalling pathway, including theBRAFV600Emutation andBRAFdeletions (BRAFdel). Next-generation sequencing and whole exome sequencing (WES) are valuable and powerful approaches forBRAFdel identification, but these techniques are costly and time consuming. Pyrosequencing is an alternative method that has the potential to rapidly and reliably identify gene deletions. We developed a custom pyrosequencing assay to detect the exon-12BRAFdel in 18 biopsies from adult patients with LCH, which were all genotyped in parallel using Sanger sequencing and WES. ABRAFdel was detected in 7/18 (39%), 6/18 (33%) and 3/18 (17%) LCH lesions using WES, pyrosequencing and Sanger, respectively, with good concordance between the WES and pyrosequencing results (Kappa-coefficient=0.88). Therefore, our pyrosequencing assay is reliable and useful for detectingBRAFdel, particularly inBRAFV600E-negative LCH lesions, for which targeted treatment is indicated.
Gene of the month:TMPRSS2(transmembrane serine protease 2)
Authors: Thunders Michelle , Delahunt Brett
Published: September 2020

Transmembrane serine protease 2 is encoded by theTMPRSS2gene. The gene is widely conserved and has two isoforms, both being autocatalytically activated from the inactive zymogen form. A fusion gene between theTMPRSS2gene andERG(erythroblast-specific-related gene), an oncogenic transcription factor, is the most common chromosomal aberration detected in prostate cancer, responsible for driving carcinogenesis. The other key role ofTMPRSS2is in priming the viral spike protein which facilitates viral entry essential for viral infectivity. The protease activates a diverse range of viruses. Both SARS-CoV and SARS-CoV-2 (COVID-19) useangiotensin-converting enzyme 2 (ACE2)andTMPRSS2to facilitate entry to cells, but with SARS-CoV-2 human-to-human transmission is much higher than SARS-CoV. As TMPRSS2 is expressed outside of the lung, and can therefore contribute to extrapulmonary spread of viruses, it warrants further exploration as a potential target for limiting viral spread and infectivity.
IFN-γ treatment protocol for MHC-Ilo/PD-L1+ pancreatic tumor cells selectively restores their TAP-mediated presentation competence and CD8 T-cell priming potential
Authors: Stifter Katja , Krieger Jana , Ruths Leonie , Gout Johann , Mulaw Medhanie , Lechel Andre , Kleger Alexander , Seufferlein Thomas , Wagner Martin , Schirmbeck Reinhold
Published: September 2020

Background

Many cancer cells express a major histocompatibility complex class I low/ programmed cell death 1 ligand 1 positive (MHC-Ilo/PD-L1+) cell surface profile. For immunotherapy, there is, thus, an urgent need to restore presentation competence of cancer cells with defects in MHC-I processing/presentation combined with immune interventions that tackle the tumor-initiated PD-L1/PD-1 signaling axis. Using pancreatic ductal adenocarcinoma cells (PDACCs) as a model, we here explored if (and how) expression/processing of tumor antigens via transporters associated with antigen processing (TAP) affects priming of CD8 T cells in PD-1/PD-L1-competent/-deficient mice.

Methods

We generated tumor antigen-expressing vectors, immunized TAP-competent/-deficient mice and determined de novo primed CD8 T-cell frequencies by flow cytometry. Similarly, we explored the antigenicity and PD-L1/PD-1 sensitivity of PDACCs versus interferon-γ (IFN-γ)-treated PDACCs in PD-1/PD-L1-competent/deficient mice. The IFN-γ-induced effects on gene and cell surface expression profiles were determined by microarrays and flow cytometry.

Results

We identified two antigens (cripto-1 and an endogenous leukemia virus-derived gp70) that were expressed in the Endoplasmic Reticulum (ER) of PDACCs and induced CD8 T-cell responses either independent (Cripto-1:Kb/Cr16-24) or dependent (gp70:Kb/p15E) on TAP by DNA immunization. IFN-γ-treatment of PDACCs in vitro upregulated MHC-I- and TAP- but also PD-L1-expression. Mechanistically, PD-L1/PD-1 signaling was superior to the reconstitution of MHC-I presentation competence, as subcutaneously transplanted IFN-γ-treated PDACCs developed tumors in C57BL/6J and PD-L1-/- but not in PD-1-/- mice. Using PDACCs, irradiated at day 3 post-IFN-γ-treatment or PD-L1 knockout PDACCs as vaccines, we could selectively bypass upregulation of PD-L1, preferentially induce TAP-dependent gp70:Kb/p15E-specific CD8 T cells associated with a weakened PD-1+ exhaustion phenotype and reject consecutively injected tumor transplants in C57BL/6J mice.

Conclusions

The IFN-γ-treatment protocol is attractive for cell-based immunotherapies, because it restores TAP-dependent antigen processing in cancer cells, facilitates priming of TAP-dependent effector CD8 T-cell responses without additional check point inhibitors and could be combined with genetic vaccines that complement priming of TAP-independent CD8 T cells.
Post-registration experience of nivolumab in advanced hepatocellular carcinoma: an international study
Authors: Fessas Petros , Kaseb Ahmed , Wang Yinghong , Saeed Anwaar , Szafron David , Jun Tomi , Dharmapuri Sirish , Rafeh Naqash Abdul , Muzaffar Mahvish , Navaid Musharraf , Khan Uqba , Lee ChiehJu , Bulumulle Anushi , Yu Bo , Paul Sonal , Nimkar Neil , Bettinger Dominik , Benevento Francesca , Hildebrand Hannah , Pressiani Tiziana , Abugabal Yehia I , Personeni Nicola , Huang Yi-Hsiang , Rimassa Lorenza , Ang Celina , Marron Thomas , Pinato David J
Published: September 2020

Background

Nivolumab is Food and Drug Administration approved in sorafenib-experienced, advanced hepatocellular carcinoma (HCC). Post-registration data of treatment in a real-world setting is lacking.

Patients and methods

We performed an international, multicenter observational study to confirm safety and efficacy of nivolumab in 233 patients treated outside clinical trials from eight centers in North America, Europe and Asia.

Results

Patients received nivolumab for Barcelona Clinic Liver Cancer stage C (n=191, 92.0%) and Child-Pugh (CP) A (n=158, 67.8%) or B (n=75, 32.2%) HCC as first (n=85, 36.5%) or second to fourth systemic therapy line (n=148, 63.5%). Objective response rate (ORR) was 22.4% and disease control rate was 52.1%. Median overall survival (OS) was 12.2 months (95% CI 8.4 to 16.0) and median progression-free survival was 10.1 months (95% CI 6.1 to 14.2). Treatment-related adverse events of grade >2 occurred in 26 patients (11.2%). Efficacy and safety were similar across CP classes and therapy line. OS was shorter in CP-B than A (7.3 months vs 16.3 months, p<0.001) and in post-first line use (10.4 months vs 16.3 months, p=0.05). Achievement of an objective response predicted for improved OS (25.4 months vs 13.2 months, p<0.001).

Conclusions

This study confirms safety and efficacy of nivolumab in advanced HCC across various lines of therapy and degrees of liver dysfunction. Despite equal ORR and toxicity to nivolumab, patients with CP-B functional class have shorter survival than the patients with CP-A.
Analgesic efficacy of adding the IPACK block to a multimodal analgesia protocol for primary total knee arthroplasty
Authors: Ochroch Jason , Qi Victor , Badiola Ignacio , Grosh Taras , Cai Lu , Graff Veena , Nelson Charles , Israelite Craig , Elkassabany Nabil M
Published: September 2020

Background and objectives

Peripheral nerve blocks have been integrated into most multimodal analgesia protocols for total knee arthroplasty (TKA). The adductor canal block (ACB) has gained popularity because of its quadriceps muscle sparing. Similarly, local anesthetic injection between the popliteal artery and the posterior capsule of the knee, IPACK block, has been described to provide analgesia to the posterior capsule of the knee with motor-sparing qualities. This prospective randomized controlled trial aimed to assess the analgesic efficacy of adding the IPACK block to our current multimodal analgesic regimen, including the ACB, in patients undergoing primary TKA.

Methods

119 patients were randomized to receive either an IPACK or a sham block in addition to multimodal analgesia and an ACB. We were set to assess pain in the back of the knee 6 hours after surgery. Other end points included quality of recovery after surgery, pain scores, opioid requirements, and functional measures.

Results

Patients who received the IPACK block had less pain in the back of the knee 6 hours after surgery when compared with the sham block: 21.7% vs 45.8%, p<0.01. There was marginal improvement in other pain measures in the first 24 hours after surgery. However, opioid requirements, quality of recovery and functional measures were similar between the two groups.

Conclusion

The IPACK block reduced the incidence of posterior knee pain 6 hours postoperatively.