bluuebunny/crossref_metadata_2025 huggingface dataset:
Job satisfaction across Europe: An analysis of the heterogeneous temporary workforce in 27 countries
Authors: Canzio Leandro Iván , Bühlmann Felix , Masdonati Jonas
Published: April 2022

The consequences of temporary jobs for job satisfaction are not clear. This article examines the effect of two crucial moderators in the association between temporary contracts and job satisfaction: the reason for being a temporary worker and the duration of temporary contracts. Using the ad-hoc module of the 2017 EU Labour Force Survey (EU-LFS), this study examines 27 European countries separately. Results show that involuntary temporary workers (those who wanted a permanent contract but could not find one) tend to be less satisfied than permanent employees. However, voluntary temporary workers (those who prefer temporary over permanent jobs) and temporary workers in apprenticeships or probation periods are generally as satisfied as permanent employees. Shorter contracts frequently exert negative effects on job satisfaction, but only among involuntary temporary workers. Results differ between countries: the differences between temporary and permanent workers are insignificant in Scandinavian countries but large in the post-Socialist states.
Teaching crisis management before and after the pandemic: Personal reflections
Authors: ‘t Hart Paul
Published: April 2022

This reflective contribution tells the story of a veteran public sector crisis management (CM) researcher’s 35-year journey with educating students and CM practitioners, It offers preliminary insights about how the pandemic experience might – and should – induce a significant rethink of how educators conceptualize the nature of crises and the challenges governments and public agencies face in coping with them.
COVID-19 immunization in people with cancer—Is it safe and efficient? What do we know?
Authors: Lazăr Diana-Elena , Munteanu Anca
Published: April 2022

Prior to the COVID-19 pandemic, vaccination of people with cancer or a recent history of cancer was advisable under specific conditions, depending on the type of vaccine (inactivated or live attenuated virus or bacterium), type of cancer, and whether they had undergone treatment for cancer. Some malignancies, especially hematological malignancies, and cancer treatments such as chemotherapy, radiotherapy, and splenectomy negatively impact the immune response. The clinical trials of currently used vaccines against COVID-19 did not include people with active cancer; thus, there is an important gap in the knowledge of safety and efficiency data for COVID-19 immunization in this population. However, considering the risk of mortality and morbidity due to possible infection with SARS-CoV-2, medical experts recommend immunization on an individual basis. As the worldwide prevalence of malignancies is high, reliable information on COVID-19 vaccination is expected to be revealed in future clinical trials. In this review, we examine the key aspects of cancer that may be affected by COVID-19 and summarize the current literature on COVID-19 immunization.
Examining Differences in the Effect of Vicarious and Personal Procedural Justice on Legal Orientations and Offending Across Race/Ethnicity Among a Sample of Serious Juvenile Offenders
Authors: Ray James V.
Published: April 2022

In the current study it is examined if the impact of vicarious and personal perceptions of procedural justice on legal cynicism, legitimacy, and offending across time is invariant across race/ethnicity. Using longitudinal data from a sample of serious juvenile offenders from the Pathways to Desistance, the within- and between-individual associations of procedural justice, legal orientations, and offending were tested. Race/ethnic-specific models were estimated to examine differences across race/ethnicity. Positive personal and vicarious experiences with police had positive effects on legal orientations (i.e., legitimacy and cynicism), while vicarious experiences were more influential on offending compared to personal experiences. These effects were consistent across race/ethnicity. Both changes in legitimacy (positive) and cynicism (negative) were important for understanding changes in offending; however, the effect of cynicism was more consistent across race/ethnicity. The findings suggest that procedurally just treatment of juveniles by police can enhance legal compliance.
Sensitivity Analysis of Sign Luminance as Function of Input Factors
Authors: Hawkins H. Gene
Published: April 2022

The luminance, or brightness, produced by a traffic sign at night is a function of several different factors including the performance of the retroreflective sheeting, the light output of the headlamp, the geometry between the headlamps and driver, and the position of the sign relative to the vehicle. In this study, the author calculated luminance for 27 different combinations of the factors affecting sign luminance. The result is eight figures comparing the sign luminance for the analyzed conditions to the luminance required for a dark rural or suburban roadway environment. The results indicated that there can be a wide range in luminance performance depending on the input variables, many of which are beyond the control of transportation agencies. The final comparison found that the difference between the best- and worst-case combinations of input variables resulted in a luminance difference of over 2,000%. Such a wide range of performance measurement means that traffic sign sheeting that is selected based on performance for a specific set of circumstances may perform in a vastly different manner because of other factors such as the type of vehicle, the headlamps on the vehicle, the roadway geometry, or the position of a sign relative to the roadway and vehicle.
Impact of Glucagon-Like Peptide 1 Receptor Agonists in Patients with Hemoglobin A1c of 9% or Greater
Authors: Tran Victor , Tran Henry , Demirel Shaban , Thompson-Moore Nathaniel
Published: April 2022

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 agonists) are effective hemoglobin A1c (HbA1c) and weight-lowering agents. The treatment effect is unknown in patients with HbA1c of 9% or greater. Objective: The purpose of this study was to evaluate glycemic control and weight loss after adding a GLP-1 agonist in patients with a baseline HbA1c of 9% (75 mmol/mol) or greater. Methods: A single-health system retrospective chart review screened adults with type 2 diabetes mellitus with a baseline hemoglobin A1c of 9% (75 mmol/mol) or greater and were prescribed a GLP-1 agonist for eligibility. The primary outcome assessed was the change in HbA1c from baseline to the first HbA1c check. Secondary outcomes included change in weight (kg) from baseline to the first HbA1c check. Results: Three hundred sixty-two patients were screened of which 151 (41.7%) were included in the final analysis. The mean change in HbA1c from baseline to first HbA1c check for all participants was −2.1% (95% CI: −2.3% to −1.8%; P < .001; −23 mmol/mol [95% CI: −25 to −20 mmol/mol]). The mean change in weight from baseline to first HbA1c check was −2.0 kg (95% CI: −2.6 kg to −1.4 kg; P < .001). Conclusion: In patients with type 2 diabetes mellitus with a baseline HbA1c ≥ 9%, GLP-1 agonist initiation resulted in a significant reduction of both HbA1c and weight compared to baseline. Large, prospective, multisite studies are needed to confirm findings of this retrospective study.
Droxidopa in the Management of Hepatorenal Syndrome
Authors: Bejjani Andrea , Zhang Youqi , Behrens Allison , Murray Brian , Shah Neil
Published: April 2022

Purpose

Hepatorenal syndrome (HRS) is renal dysfunction associated with the hemodynamic consequences of advanced liver disease and cirrhosis. HRS is associated with a high mortality, and there remain high failure rates with first-line therapy aimed at improving perfusion. We report the use of droxidopa, an oral norepinephrine precursor, to aid in the management of HRS-AKI refractory to first-line therapy. Summary: A 51-year-old Caucasian male with alcohol-related cirrhosis presented with 1-week history of pre-syncope and falls. He was found to have acute kidney injury meeting diagnostic criteria of HRS based on absence of identifiable contributing factors. After no response to volume expansion, medical management was initiated with midodrine and octreotide and eventually escalated to norepinephrine intravenous infusion. The patient’s renal function and urine output improved initially on norepinephrine, but worsened when attempting to wean to a suitable outpatient regimen, becoming dependent upon norepinephrine. On day 13 of hospitalization, droxidopa was initiated at a dose of 100 mg three times daily and titrated to a dose of 400 mg three times daily. Norepinephrine infusion was weaned and discontinued on day 16 of hospitalization. The patient remained hemodynamically stable and was able to be discharged on droxidopa 400 mg three times daily, midodrine 20 mg three times day, and octreotide 200 mcg three times daily. Conclusion: Droxidopa, an oral norepinephrine precursor, presents a novel adjunctive agent for management of HRS refractory to first-line medical management.
The Effect of Two Different Doses of Astaxanthin on Alveolar Bone Loss in an Experimental Model of Periodontitis in Diabetic Rats
Authors: Lektemur Alpan Aysan , Çalışır Metin
Published: April 2022

This study evaluated the effects of astaxanthin (ASX) on alveolar bone loss, receptor activator of nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG) activity in ligature-induced periodontitis in diabetic rats. Diabetes mellitus (DM) was induced with 50 mg/kg intraperitoneal streptozotocin in 40 male Wistar rats. The Wistar rats were divided into six experimental groups: non-ligated (NL; n = 6); ligature only (L; n = 6); DM only (D; n = 6); DM + ligature (DP; n = 6); DM + ligature + 1 mg/kg/day ASX (ASX 1 group; n = 8); and DM + ligature + astaxanthin 5 mg/kg/day ASX (ASX 5 group; n = 8). Silk ligatures were placed along the gingival margin of the left mandibular first molar tooth. The study duration was 11 days, after which the animals were euthanised. Changes in alveolar bone levels were clinically measured, and RANKL and OPG activities were immunohistochemically examined. Alveolar bone loss was the most significant in the DP group (p < 0.05). Decreased alveolar bone loss was observed in the ASX 5 group (p < 0.05). Although RANKL activity was highest in the DP group, it was observed at lower levels in the groups to which ASX was administered. OPG activity did not differ between groups (p > 0.05). The results of this study suggested that 1 and 5 mg/kg ASX administration reduced RANKL activity and alveolar bone loss in rats with experimentally induced periodontitis.
In-process monitoring of distortion and temperature in multi-layer laser cladding of Stellite 6 and Inconel 718 alloys
Authors: Thawari Nikhil , Gullipalli Chaitanya , Katiyar Jitendra K , Gupta T V K
Published: April 2022

In laser cladding, the development of rapid heating and cooling cycles generates high residual stresses and thermal gradients that lead to induce unwanted distortion in the parts. The paper deals with online monitoring of temperatures and the associated distortions in multi-layer laser cladding using pyrometers and laser displacement sensors. The alloys deposited in the present work are Stellite 6 and Inconel 718, having similar thermo-mechanical properties. The results show that variation in thermal gradients due to rapid heating and cooling allows the material to expand and contract, generating substantial distortions. In the current investigations, Stellite 6 deposits generated 28%, 21%, 15% higher deflection at 12 mm/s, 16 mm/s, 20 mm/s scan speeds respectively; and 23%, 20%, 17% at 2400 W, 2900 W, 3400 W laser power compared to Inconel 718. Irrespective of the coating material, the second layer cladding induced 10% to 30% lower distortion than the first layer because of the reduction in temperature gradient. However, Inconel 718 clads measured 10% to 15% less melt pool temperatures than Stellite 6. The study reveals that different cladding materials deposited under similar process conditions have greater impact on distortion and temperature. At last, the investigations provide an optimum set of parameters to produce homogeneous cladding with moderate deflection and temperature for both the alloys.
Discrete Boltzmann modeling of plasma shock wave
Authors: Liu Zhipeng , Song Jiahui , Xu Aiguo , Zhang Yudong , Xie Kan
Published: April 2022

Plasma shock waves widely exist and play an important role in high-energy-density environment, especially in the inertial confinement fusion. Due to the large gradient of macroscopic physical quantities and the coupled thermal, electrical, magnetic, and optical phenomena, there exist not only hydrodynamic non-equilibrium (HNE) effects but also strong thermodynamic non-equilibrium (TNE) effects around the wavefront. In this work, a two-dimensional single-fluid discrete Boltzmann model is proposed to investigate the physical structure of ion shock. The electron is assumed inertialess and always in thermodynamic equilibrium. The Rankine–Hugoniot relations for single-fluid theory of plasma shock wave is derived. It is found that the physical structure of shock wave in plasma is significantly different from that in normal fluid and somewhat similar to that of detonation wave from the sense that a peak appears in the front. The non-equilibrium effects around the shock front become stronger with increasing Mach number. The charge of electricity deviates oppositely from neutrality in upstream and downstream of the shock wave. The large inertia of the ions causes them to lag behind, so the wavefront charge is negative and the waverear charge is positive. The variations of HNE and TNE with Mach number are numerically investigated. The characteristics of TNE can be used to distinguish plasma shock wave from detonation wave.
A sliding mode control strategy for active horizontal seat suspension under realistic input vibration
Authors: Maciejewski Igor , Blazejewski Andrzej , Pecolt Sebastian , Krzyzynski Tomasz
Published: April 2022

In the paper, an innovative active control of a horizontal seat suspension system is discussed in context of realistic input vibration that occurs in the cabins of agricultural tractors. The vibration reduction system is represented by the state-space model and its numerical parameters are determined experimentally. For such a reliable mathematical representation of the system dynamics, the finite-time sliding mode controller is successfully designed for different spectral classes of the random excitation signal. A multi-objective control strategy is implemented in order to satisfy opposite requirements, that is, at the limited value of active force, a horizontal vibration of the seated human body is considerably reduced, but the suspension travel does not exceed unacceptable stroke of the system. Laboratory measurements of the seated human body have shown improved comfort of drivers under fore-and-aft vibrations.
An improved fuzzy controller on electromechanical nano-tweezers
Authors: Koochi Ali , Goharimanesh Masoud , Gharib Mohammad Reza
Published: April 2022

This paper aims to develop an improved fuzzy controller for position controlling of nano-wire-based electromechanical nano-tweezers. The nonlinear governing equation is developed by incorporating the Euler–Bernoulli beam model and Hamilton’s principle. Also, the quantum vacuum fluctuations are assimilated in the developed model in terms of Casimir attraction. The nonlinear constitutive equation is transformed into a nonlinear state-space form by employing the Galerkin method. Based on the linguistic explanation of the system, an improved fuzzy controller is designed to control the nano-tweezers for manipulating desired objects. The Taguchi technique has been used to decrease the number of independent experiments and improve the structure of membership functions, consequently. The designed controller is employed for both controlling and path tracking of nano-tweezers. The outcomes indicate that the proposed improved fuzzy controller has excellent performance for stabilizing the nano-tweezers at any desired gap.
Investigational New Drug Enabling Nonclinical Safety Assessment of the Iminosugar UV-4, a Broad-Spectrum Host-Targeted Antiviral Agent
Authors: Shearer Jeffry , Wolfe Gary , Sampath Aruna , Warfield Kelly L. , Kaufman Brian , Ramstedt Urban , Treston Anthony
Published: April 2022

The iminosugar UV-4 is a broad-spectrum antiviral drug candidate with activity in vitro and in vivo against multiple, diverse viruses. The toxicological profile of UV-4, dosed as the hydrochloride salt, was evaluated in single-dose and repeat-dose oral toxicity studies in mice, rats, dogs, and non-human primates (NHP). No moribundity or deaths were associated with the drug up to the maximum tolerated dose. No treatment-related adverse effects were observed following single oral doses in dogs, rats, and mice up to 250, 400, 1000 mg/kg, respectively, and in NHP up to 180 mg/kg administered three times daily for 10 days. UV-4-related findings were generally seen at higher doses after 7- or 14-day exposure. The most common clinical pathology findings (increase in aspartate aminotransferase and decreased platelet count) were consistently found across species and each appeared dose related. The kidney, mesenteric lymph nodes, stomach including gastrointestinal tract, and thymus were identified as target organs in mice, rats, and dogs. In 14-day repeat-dose toxicology studies in mice and dogs conducted in compliance with Good Laboratory Practice regulations, the dog was considered to be the most sensitive species to UV-4 exposure based on the treatment-related adverse effects noted in the identified target organs. The results of these studies demonstrate the safety profile of UV-4 hydrochloride and supported the selection of starting and maximal doses for a single ascending dose first-in-human clinical study.
Improving the seismic capacity of steel–concrete composite frames with spiral-confined slabs
Authors: Fasan Marco , Bedon Chiara , Troiano Nicola , Amadio Claudio
Published: April 2022

The seismic performance analysis of steel–concrete composite frames involves, as known, the interaction of several load-bearing components that should be properly designed, with multiple geometrical and mechanical parameters to account. Practical recommendations are given by the Eurocode 8 (EC8) – Annex C for the optimal detailing of transverse rebars, so as to ensure the activation of conventional resisting mechanisms. In this paper, the attention is focused on the analysis of effects and benefits due to a novel confinement solution for the reinforced concrete (RC) slab. The intervention is based on the use of diagonal steel spirals, that are expected to enforce the overall compressive response of the RC slab, thanks to the activation of an optimized strut-and-tie resisting mechanism. The final expectation is to first increase the resistance capacity of the slab that can thus transfer higher compressive actions under seismic loads. Further, as shown, the same resisting mechanism can be beneficial for the yielding of steel rebars, depending on the final detailing of components, and thus possibly improve the ductility of the system. To this aim, a refined finite element (FE) numerical analysis is carried out for several configurations of technical interest. The in-plane compressive behaviour and the activation of resisting mechanisms are explored for several spiral-confined slabs, based on various arrangements. Major advantage is taken from literature experimental data on RC slabs that are further investigated by introducing the examined confinement technique. The attention is hence given to the local and the global structural effects due to different arrangements for the proposed steel spirals. As shown, once the spirals are optimally placed into the slab, the strength and ductility parameters of the concrete struts can be efficiently improved, with marked benefits for the overall resisting mechanisms of the slab, and thus for the steel–composite frames as a whole.
Dynamic characterization of wind pressure fluctuations in separated and reattaching flows
Authors: Shu ZR , Li QS
Published: April 2022

Flow separation and reattachment over bluff bodies has been a primary concern in wind engineering community as it may generate large suction pressure. This study re-visits the characteristics of wind pressure underneath the separated shear layer, with emphasis on diagnosing the underlying dynamic properties. Nonlinear dynamic analysis techniques, namely recurrence plot and recurrence quantification analysis are applied to reveal and compare the wind pressure dynamics associated with different test conditions. The results indicate that the dynamic behaviour of wind pressure is closely tied with leading edge shape, turbulence intensity, as well as turbulence scale. Generally, the underlying dynamics of wind pressure become less deterministic as the measurement position moves from leading edge towards downstream. Such pattern is reversed once the descriptive indicator reaches its minimum. The position of such minimum value corresponds well to the downstream boundary of the reverse flow region. Moreover, the minimum value of dynamic descriptive indicator, as well as the reverse position in its distribution pattern, is correlated with the leading edge shape. On the other hand, the minimum value of dynamic descriptive indicator is also dependent on turbulence scale, while the reverse position in the distribution pattern of dynamic descriptive factor is dependent on turbulence intensity.
The Role of Perceived Entrepreneurial Passion on Creativity: A Study of Vietnamese Social Ventures
Authors: Thanh Le Truc , Paramita Widya , Tran Quan Ha Minh , Duc La Anh
Published: April 2022

This research aims to examine whether social venture founder’s entrepreneurial passion can increase employee creativity via creative process engagement and the moderating role of employee mindfulness. A survey was conducted by asking employees of 109 social ventures in Vietnam to evaluate the founders’ entrepreneurial passion and the supervisors to evaluate employees’ creativity as well as employee creative process engagement. Drawing on the broaden-and-build theory, this study found that employee creativity increases when the employees perceive that the social venture founders have strong entrepreneurial passion as explain by higher creative process engagement. In addition, we revealed that the indirect influence of entrepreneurial passion on employee creativity remains significant regardless the employees’ mindfulness. Theoretical and practical contributions are further discussed.
Memetic persuasion and WhatsAppification in Indonesia’s 2019 presidential election
Authors: Baulch Emma , Matamoros-Fernández Ariadna , Suwana Fiona
Published: April 2022

This article examines the interplay between the creation of ‘meme factories’ by political elites, and their operationalisation through WhatsApp. It uses the case study of Indonesian President Joko Widodo’s (Jokowi’s) bid for re-election in 2019 to argue that political elites are leveraging meme culture’s association with popular voice to ‘astroturf’ public discourse, and that WhatsApp’s unique infrastructure advances that project. Drawing on interview data, we offer a holistic picture of the processes and structures implicated in this instance of astroturfing, with a focus on how WhatsApp is positioned within them. The authors’ access to campaigners affords a rare inside view of these processes and structures, and contributes to a growing body of work on the WhatsAppification of election campaigns globally. In addition, the article builds on scholarship on social media election campaigning in Indonesia by drawing attention to the role WhatsApp’s unique features play in surreptitiously influencing public discourse.
It Is All About Money! What Drives Interest Groups’ Relations with Political Parties in Central and Eastern Europe?
Authors: Kamiński Paweł
Published: April 2022

This article studies contacts between interest groups and political parties. Existing research suggests that times of close and formal cooperation between parties and groups in Western Europe are over as the contacts have become more pragmatic and sometimes spontaneous. Studies usually point to ideological proximity and resource exchange as the main factors behind contacts, however, focusing mainly on parties’ power and ideological position. Here, by drawing on data from Poland, Slovenia, and Lithuania, we focus on young democracies from Eastern Europe by taking into account interest groups’ resources, their typology, and the system of interest groups’ representation. The article shows that financial resources are the main factor behind seeking contacts with the large number of political parties.
Down the Vertical Refuse Chutes in Singapore High-rise Living
Authors: Yuen Belinda , Jacobs Jane M.
Published: April 2022

In the first three decades of post-independence (1960–1990), Singapore underwent a radical housing transition into high-rise, high-density housing that required technical innovation to manage new scales and heights of household waste. Drawing on perspectives from urban political ecology, three questions are examined: What were the key challenges of household waste management policy and technology across this period? Who were the key actors and development partners? What was the environmental and social rationale for everyday waste management, and how did it change over time? We discern a pattern of innovation, which was driven by intersecting challenges around accessibility, affordability and adoption.
Wear calculation and life prediction model of disc brake based on elastoplastic contact mechanics
Authors: Sha Zhihua , Hao Qiang , Yin Jian , Ma Fujian , Liu Yu , Zhang Shengfang
Published: April 2022

For the friction and wear of the braking surface of the disc brake, the mechanism of friction contact deformation of rough surface is analyzed. Considering elastoplastic contact mechanics of the friction surfaces, combined with Archard wear calculation theory, a wear calculation model of fractal rough surface is established, and a wear life prediction of the brake disc is proposed. Based on high-speed and heavy-load braking conditions, the influence of different braking parameters on the surface wear of brake disc is studied. Moreover, a pin-on-disc wear test is used to verify the validity of the wear calculation model, and the average relative error of test and simulation is 4.97%. The research results show that the fractal parameters affect the complexity of the rough surface, and surface wear is mainly caused by interface plastic contact. The friction coefficient is large, which can strengthen the surface shear effect. Large load and high speed would increase the real contact area of the surface and increase the wear volume per unit time. Furthermore, the wear life of the brake disc could be estimated, which is of great significance for raising the wear life of the brake disc, improving braking life and braking efficiency.
The role of familiarity with the experimenter on cognitive performance, metacognition, pro-social behaviors, and the well-being of adults with moderate to severe intellectual disabilities
Authors: Igier Suzanne , Valérie Pennequin
Published: April 2022

Background

Few studies have evaluated the explanatory factors of poor performance and the effects of context in adults with intellectual disabilities. The aim of this study is to assess the role of a familiar experimenter on their cognitive performance, well-being, metacognitive experiences, and social behaviors.

Method

Participants with moderate to severe intellectual disability were recruited into two groups, one with a familiar and one with an unfamiliar experimenter. They carried out a categorization task. Before and after they reported their metacognitive experiences and level of well-being. The experimenter observed their pro-social behavior.

Results

Performance and some social behaviors were better when the participant knew the experimenter. However, he did not affect the level of well-being. The participants’ metacognitive experiences were poor, whether or not they knew the experimenter.

Conclusions

The familiarity of the experimenter plays a determining role, both on the participants’ performance, and on their compliance with certain pro-social behavior.
Intraosseous inflammatory pseudotumor of the maxilla: A case report
Authors: Al Khader Ali , Odeh Hadeel , Nsour Esra , Al Awamleh Abdel-Ghani Ibrahim
Published: April 2022

Inflammatory pseudotumors are benign lesions that are rarely reported in the head and neck. Moreover, intraosseous inflammatory pseudotumors of the maxilla are extremely rare, with less than 10 cases reported. A 52-year-old woman presented with recurrent dental infections; computed tomography scan of the osteolytic maxillary bone lesion and incisional biopsy were performed. Histopathological examination revealed that the lesion was composed of fascicles of fibroblasts and myofibroblasts, in addition to sheets of plasma cells, lymphocytes, and occasional other inflammatory cells. An infiltrative growth pattern was observed. Immunohistochemical staining confirmed an inflammatory pseudotumor. A partial maxillectomy was performed. There was no evidence of recurrence during the 4-month follow-up period. Inflammatory pseudotumors should be considered when treating destructive maxillary lesions. Immunohistochemical staining was performed to confirm polyclonal plasma cell proliferation.
Transcutaneous ultrasound-mediated gene delivery into canine livers achieves therapeutic levels of factor VIII expression
Authors: Manson Megan A. , Zhang Feng , Novokhodko Alexander , Chen Chun-Yu , Parker Maura , Loeb Keith R. , Kajimoto Masaki , Campbell Carley , Storb Rainer F. , Miao Carol H.
Published: April 2022

A safe, effective, and inclusive gene therapy will significantly benefit a large population of patients with hemophilia. We used a minimally invasive transcutaneous ultrasound-mediated gene delivery (UMGD) strategy combined with microbubbles (MBs) to enhance gene transfer into 4 canine livers. A mixture of high-expressing, liver-specific human factor VIII (hFVIII) plasmid and MBs was injected into the hepatic vein via balloon catheter under fluoroscopy guidance with simultaneous transcutaneous UMGD treatment targeting a specific liver lobe. Therapeutic levels of hFVIII expression were achieved in all 4 dogs, and hFVIII levels were maintained at a detectable level in 3 dogs throughout the 60-day experimental period. Plasmid copy numbers correlated with hFVIII antigen levels, and plasmid-derived messenger RNA (mRNA) was detected in treated livers. Liver transaminase levels and histology analysis indicated minimal liver damage and a rapid recovery after treatment. These results indicate that liver-targeted transcutaneous UMGD is promising as a clinically feasible therapy for hemophilia A and other diseases.
BreakAlign: a Perl program to align chimaeric (split) genomic NGS reads and allow visual confirmation of novel retroviral integrations
Authors: Marchi Emanuele , Jones Mathew , Klenerman Paul , Frater John , Magiorkinis Gkikas , Belshaw Robert
Published: April 2022

Background

Retroviruses replicate by integrating a DNA copy into a host chromosome. Detecting novel retroviral integrations (ones not in the reference genome sequence of the host) from genomic NGS data is bioinformatically challenging and frequently produces many false positives. One common method of confirmation is visual inspection of an alignment of the chimaeric (split) reads that span a putative novel retroviral integration site. We perceived the need for a program that would facilitate this by producing a multiple alignment containing both the viral and host regions that flank an integration.

Results

BreakAlign is a Perl program that uses blastn to produce such a multiple alignment. In addition to the NGS dataset and a reference viral sequence, the program requires either (a) the ~ 500nt host genome sequence that spans the putative integration or (b) coordinates of this putative integration in an installed copy of the reference human genome (multiple integrations can be processed automatically). BreakAlign is freely available from https://github.com/marchiem/breakalign and is accompanied by example files allowing a test run.

Conclusion

BreakAlign will confirm and facilitate characterisation of both (a) germline integrations of endogenous retroviruses and (b) somatic integrations of exogenous retroviruses such as HIV and HTLV. Although developed for use with genomic short-read NGS (second generation) data and retroviruses, it should also be useful for long-read (third generation) data and any mobile element with at least one conserved flanking region.
Answering medical questions in Chinese using automatically mined knowledge and deep neural networks: an end-to-end solution
Authors: Zhang Li , Yang Xiaoran , Li Shijian , Liao Tianyi , Pan Gang
Published: April 2022

Background

Medical information has rapidly increased on the internet and has become one of the main targets of search engine use. However, medical information on the internet is subject to the problems of quality and accessibility, so ordinary users are unable to obtain answers to their medical questions conveniently. As a solution, researchers build medical question answering (QA) systems. However, research on medical QA in the Chinese language lags behind work on English-based systems. This lag is mainly due to the difficulty of constructing a high-quality knowledge base and the underutilization of medical corpora in the Chinese language.

Results

This study developed an end-to-end solution to implement a medical QA system for the Chinese language with low cost and time. First, we created a high-quality medical knowledge graph from hospital data (electronic health/medical records) in a nearly automatic manner that trained a supervised model based on data labeled using bootstrapping techniques. Then, we designed a QA system based on a memory-based neural network and attention mechanism. Finally, we trained the system to generate answers from the knowledge base and a QA corpus on the internet.

Conclusions

Bootstrapping and deep neural network techniques can construct a knowledge graph from electronic health/medical records with satisfactory precision and coverage. Our proposed context bridge mechanisms perform training with a variety of language features. Our QA system can achieve state-of-the-art quality in answering medical questions with constrained topics. As we evaluated, complex Chinese language processing techniques, such as segmentation and parsing, were not necessary for practice and complex architectures were not necessary to build the QA system. Lastly, we created an application using our method for internet QA usage.
Discovery of moiety preference by Shapley value in protein kinase family using random forest models
Authors: Huang Yu-Wei , Hsu Yen-Chao , Chuang Yi-Hsuan , Chen Yun-Ti , Lin Xiang-Yu , Fan You-Wei , Pathak Nikhil , Yang Jinn-Moon
Published: April 2022

Background

Human protein kinases play important roles in cancers, are highly co-regulated by kinase families rather than a single kinase, and complementarily regulate signaling pathways. Even though there are > 100,000 protein kinase inhibitors, only 67 kinase drugs are currently approved by the Food and Drug Administration (FDA).

Results

In this study, we used “merged moiety-based interpretable features (MMIFs),” which merged four moiety-based compound features, including Checkmol fingerprint, PubChem fingerprint, rings in drugs, and in-house moieties as the input features for building random forest (RF) models. By using > 200,000 bioactivity test data, we classified inhibitors as kinase family inhibitors or non-inhibitors in the machine learning. The results showed that our RF models achieved good accuracy (> 0.8) for the 10 kinase families. In addition, we found kinase common and specific moieties across families using the Shapley Additive exPlanations (SHAP) approach. We also verified our results using protein kinase complex structures containing important interactions of the hinges, DFGs, or P-loops in the ATP pocket of active sites.

Conclusions

In summary, we not only constructed highly accurate prediction models for predicting inhibitors of kinase families but also discovered common and specific inhibitor moieties between different kinase families, providing new opportunities for designing protein kinase inhibitors.
Thorough statistical analyses of breast cancer co-methylation patterns
Authors: Sun Shuying , Dammann Jael , Lai Pierce , Tian Christine
Published: April 2022

Background

Breast cancer is one of the most commonly diagnosed cancers. It is associated with DNA methylation, an epigenetic event with a methyl group added to a cytosine paired with a guanine, i.e., a CG site. The methylation levels of different genes in a genome are correlated in certain ways that affect gene functions. This correlation pattern is known as co-methylation. It is still not clear how different genes co-methylate in the whole genome of breast cancer samples. Previous studies are conducted using relatively small datasets (Illumina 27K data). In this study, we analyze much larger datasets (Illumina 450K data).

Results

Our key findings are summarized below. First, normal samples have more highly correlated, or co-methylated, CG pairs than tumor samples. Both tumor and normal samples have more than 93% positive co-methylation, but normal samples have significantly more negatively correlated CG sites than tumor samples (6.6% vs. 2.8%). Second, both tumor and normal samples have about 94% of co-methylated CG pairs on different chromosomes, but normal samples have 470 million more CG pairs. Highly co-methylated pairs on the same chromosome tend to be close to each other. Third, a small proportion of CG sites’ co-methylation patterns change dramatically from normal to tumor. The percentage of differentially methylated (DM) sites among them is larger than the overall DM rate. Fourth, certain CG sites are highly correlated with many CG sites. The top 100 of such super-connector CG sites in tumor and normal samples have no overlaps. Fifth, both highly changing sites and super-connector sites’ locations are significantly different from the genome-wide CG sites’ locations. Sixth, chromosome X co-methylation patterns are very different from other chromosomes. Finally, the network analyses of genes associated with several sets of co-methylated CG sites identified above show that tumor and normal samples have different patterns.

Conclusions

Our findings will provide researchers with a new understanding of co-methylation patterns in breast cancer. Our ability to thoroughly analyze co-methylation of large datasets will allow researchers to study relationships and associations between different genes in breast cancer.
Genome-wide investigations reveal the population structure and selection signatures of Nigerian cattle adaptation in the sub-Saharan tropics
Authors: Mauki David H. , Tijjani Abdulfatai , Ma Cheng , Ng’ang’a Said I. , Mark Akanbi I. , Sanke Oscar J. , Abdussamad Abdussamad M. , Olaogun Sunday C. , Ibrahim Jebi , Dawuda Philip M. , Mangbon Godwin F. , Kazwala Rudovick R. , Gwakisa Paul S. , Yin Ting-Ting , Li Yan , Peng Min-Sheng , Adeola Adeniyi C. , Zhang Ya-Ping
Published: April 2022

Background

Cattle are considered to be the most desirable livestock by small scale farmers. In Africa, although comprehensive genomic studies have been carried out on cattle, the genetic variations in indigenous cattle from Nigeria have not been fully explored. In this study, genome-wide analysis based on genotyping-by-sequencing (GBS) of 193 Nigerian cattle was used to reveal new insights on the history of West African cattle and their adaptation to the tropical African environment, particularly in sub-Saharan region. 

Results

The GBS data were evaluated against whole-genome sequencing (WGS) data and high rate of variant concordance between the two platforms was evident with high correlated genetic distance matrices genotyped by both methods suggestive of the reliability of GBS applicability in population genetics. The genetic structure of Nigerian cattle was observed to be homogenous and unique from other African cattle populations. Selection analysis for the genomic regions harboring imprints of adaptation revealed genes associated with immune responses, growth and reproduction, efficiency of feeds utilization, and heat tolerance. Our findings depict potential convergent adaptation between African cattle, dogs and humans with adaptive genesSPRY2andITGB1BP1possibly involved in common physiological activities.

Conclusion

The study presents unique genetic patterns of Nigerian cattle which provide new insights on the history of cattle in West Africa based on their population structure and the possibility of parallel adaptation between African cattle, dogs and humans in Africa which require further investigations.
Accuracy of the COPD diagnostic questionnaire as a screening tool in primary care
Authors: Pagano Lisa , McKeough Zoe , Wootton Sally , Zwar Nicholas , Dennis Sarah
Published: April 2022

Background

The COPD Diagnostic Questionnaire (CDQ) was developed to identify people who would benefit from spirometry testing to confirm Chronic Obstructive Pulmonary Disease (COPD). The aim of this study was to determine the usefulness of a cut-off score of 16.5 on the CDQ in identifying those at increased risk of obstruction, in a mixed population of people ‘at risk’ of COPD and those with an ‘existing’ COPD diagnosis.

Methods

People ‘at risk’ of COPD (aged > 40 years, current/ex-smoker) and those with ‘existing’ COPD were identified from four general practices and invited to participate. Participants completed the CDQ and those with a CDQ score ≥ 16.5 were categorised as having intermediate to increased likelihood of airflow obstruction. Pre and post-bronchodilator spirometry determined the presence of airway obstruction (FEV1/FVC ratio < 0.7). Sensitivity, specificity and accuracy of the CDQ was determined compared to spirometry as the gold standard.

Results

One hundred forty-one participants attended an initial assessment (‘at risk’ = 111 (79%), ‘existing’ COPD = 30 (21%)). A cut-off score of 16.5 corresponded to a sensitivity of 81%, specificity of 36% and accuracy of 50%, in the entire mixed population. The area under the ROC curve was 0.59 ± 0.50 indicating low diagnostic accuracy of the CDQ. Similar results were found in the ‘existing’ COPD group alone.

Conclusion

Whilst a cut-off score of 16.5 on the CDQ may result in a large number of false positives, clinicians may still wish to use the CDQ to refine who receives spirometry due to its high sensitivity.

Trial registration

ANZCTR, ACTRN12619001127190. Registered 12 August 2019 – Retrospectively registered, http://www.ANZCTR.org.au/ACTRN12619001127190.aspx
Nuclear morphometry and chromatin texture changes in hepatocellular carcinoma samples may predict outcomes of liver transplanted patients
Authors: dos Santos Jordan Boeira , Starosta Rodrigo Tzovenos , Pilar Emily Ferreira Salles , Kunz Jefferson Daniel , Tomedi Joelson , Cerski Carlos Thadeu Schmidt , Ruppenthal Rúbia Denise
Published: April 2022

Background

Nuclear changes are typical in the carcinogenesis of hepatocellular carcinoma (HCC). Morphometry and chromatin texture analysis are quantitative methods for their quantification. In this study, we analyzed nuclear morphometry and chromatin texture parameters in samples of hepatocellular carcinoma from liver transplant patients and their associations with clinicopathologic variables.

Methods

Samples of HCC and adjacent tissue from 34 individuals were collected in tissue microarray blocks. Stained slides were microphotographed using an optical microscope and nuclear parameters analyzed in ImageJ (FracLac plug-in). ROC curve analysis was used to find accurate cut-offs for differentiation of neoplastic and non-neoplastic cells. The inter-rater agreement was also evaluated.

Results

Nuclear morphometric and textural differences were observed between the samples of HCC and adjacent tissue of liver transplant patients. Lower mean gray value (p = 0.034) and Feret diameter (p = 0.024) were associated with higher Model for End-Stage Liver Disease (MELD) scores. Nuclei with larger area (p = 0.014) and larger Feret diameter (p = 0.035) were associated with lower survival. Lower aspect ratio was associated with HCC recurrence after the transplant (p = 0.048). The cut-off of 1.13 μm (p =  < 0.001) for aspect ratio and cut-off of 21.15 μm (p = 0.038) for perimeter were established for the differentiation of neoplastic and non-neoplastic cells. The morphometric analysis was reproducible to area, circularity, Feret diameter, mean gray value and aspect ratio between observers (p =  < 0.001).

Conclusions

Nuclear morphometric differences between the HCC and the adjacent tissue samples were associated with prognostic variables (MELD scores, recurrence and survival) and may predict liver transplant patients’ outcomes.
Social trust and stress symptoms among older adults during the COVID-19 pandemic: evidence from Asia
Authors: Jiang Nan , Wu Alfred M. , Cheng Edmund W.
Published: April 2022

Objectives

To investigate whether social trust is associated with more stress symptoms among middle-aged and older adults in six East and Southeast Asia regions during the COVID-19 pandemic.

Methods

This multi-region study used cross-sectional survey data collected in May 2020. Participants were a probability-based internet sample of adults aged 55 or older.

Results

Government trust was negatively associated with stress in Singapore and South Korea. Higher levels of health care trust were significantly associated with less stress in Singapore and Taiwan. Trust in neighbors was associated with a higher likelihood of stress in Hong Kong and a lower likelihood in Singapore. Social trust was not associated with stress in Japan or Thailand.

Discussion

Findings suggest the level of social trust in relation to stress substantially varied by region. Interventions to strengthen trust during COVID-19 and other major health crises need to be tailored to fit regions’ unique circumstances.