bluuebunny/crossref_metadata_2025 huggingface dataset:
The Potential of Digital Phenotyping and Mobile Sensing for Psycho-Diagnostics of Internet Use Disorders
Authors: Montag Christian , Rumpf Hans-Jürgen
Published: July 2021

Purpose of Review

The present paper provides an accessible overview on the potential of digital phenotyping and mobile sensing not only shedding light on the nature of Internet Use Disorders (IUD), but also to provide new ideas on how to improve psycho-diagnostics of mental processes linked to IUD.

Recent Findings

In detail, the psycho-diagnostic areas of prevention, treatment, and aftercare in the realm of IUDs are focused upon in this work. Before each of these areas is presented in more specificity, the terms digital phenotyping and mobile sensing are introduced against the background of an interdisciplinary research endeavor called Psychoinformatics. Obstacles to overcome problems in this emerging research endeavor—sensing psychological traits/states from digital footprints—are discussed together with risks and chances, which arise from the administration of online-tracking technologies in the field of IUDs.

Given the limited validity and reliability of traditional assessment via questionnaires or diagnostic interviews with respect to recall bias and tendencies to answer towards social desirability, digital phenotyping and mobile sensing offer a novel approach overcoming recall bias and other limitations of usual assessment approaches. This will not only set new standards in precisely mapping behavior, but it will also offer scientists and practitioners opportunities to detect risky Internet use patterns in a timely manner and to establish tailored feedback as a means of intervention.
Predicting Geolocation of Tweets: Using Combination of CNN and BiLSTM
Authors: Mahajan Rhea , Mansotra Vibhakar
Published: July 2021

Twitter is one of the most popular micro-blogging and social networking platforms where users post their opinions, preferences, activities, thoughts, views, etc., in form of tweets within the limit of 280 characters. In order to study and analyse the social behavior and activities of a user across a region, it becomes necessary to identify the location of the tweet. This paper aims to predict geolocation of real-time tweets at the city level collected for a period of 30 days by using a combination of convolutional neural network and a bidirectional long short-term memory by extracting features within the tweets and features associated with the tweets. We have also compared our results with previous baseline models and the findings of our experiment show a significant improvement over baselines methods achieving an accuracy of 92.6 with a median error of 22.4 km at city level prediction.
Methicillin-resistant Staphylococcus aureus of the clonal lineage ST5-SCCmecII-t2460 was associated with high mortality in a Wuhan hospital
Authors: Li Xuehan , Zhang Jing , Zhang Yifan , Zhou Junying , Li Xinwei , Feng Ruo , Li Yirong
Published: July 2021

Methicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen that can cause serious infectious diseases. An emerging MRSA strain, ST5-SCCmecII spa-type-t2460 (SMRSA), has spread rapidly since its recent emergence in China, but little information is available about this lineage. In this study, 91 MRSA isolates were collected from patients treated in the Zhongnan Hospital, Wuhan University, from 2018 to 2019, and investigated for their molecular characteristics, antibiotic resistance profiles, and clinical characteristics. The predominant lineage, SMRSA, accounted for 37.4% (34/91) of the isolates, followed by ST239-SCCmecIII-t030 (19.8%, 18/91) and ST59-SCCmecIV-t437 (8.8%, 8/91). In contrast to the latter two non-SMRSA (nSMRSA) lineages, which are among the main MRSA found in Chinese settings, SMRSA exhibited small colony variant (SCV) phenotype and had extremely high resistance rates to erythromycin (100.0%), clindamycin (100.0%), levofloxacin (100.0%), tetracycline (97.1%), moxifloxacin (97.1%), and ciprofloxacin (100%), but was more susceptible to rifampicin (resistance rate 3%). The levels of white blood cells (WBC) and procalcitonin (PCT) and the 30-day mortality in patients infected with SMRSA were (12.54 ± 6.61) × 109/L, 0.66 ng/mL, and 52.9%, respectively, which were much higher than those in patients infected with nSMRSA. In addition, patients infected with SMRSA were more frequently admitted to the intensive care unit (ICU) and submitted to invasive procedures than those infected with nSMRSA. In conclusion, SMRSA showed SCV phenotype and exhibited multiple antibiotic-resistance profiles. In this study, SMRSA was associated with serious infections and poor prognosis. Compared with ST239, ST59, or other nSMRSA strains, patients infected with SMRSA strains have higher 30-day mortality, increased levels of inflammatory biomarkers, and more frequent ICU hospitalization and invasive procedures.
The production of valuable products and fuel from plastic waste in Africa
Authors: Amankwa M. Opoku , Tetteh E. Kweinor , Mohale G. Thabang , Dagba G. , Opoku P.
Published: July 2021

Global plastic waste generation is about 300 million metric tons annually and poses crucial health and environmental problems. Africa is the second most polluted continent in the world, with over 500 shipping containers of waste being imported every month. The US Environmental Protection Agency (EPA) report suggests that about 75% of this plastic waste ends up in landfills. However, landfills management is associated with high environmental costs and loss of energy. In addition, landfill leachates end up in water bodies, are very detrimental to human health, and poison marine ecosystems. Therefore, it is imperative to explore eco-friendly techniques to transform plastic waste into valuable products in a sustainable environment. The trade-offs of using plastic waste for road construction and as a component in cementitious composites are discussed. The challenges and benefits of producing liquid fuels from plastic waste are also addressed. The recycling of plastic waste to liquid end-products was found to be a sustainable way of helping the environment with beneficial economic impact.
The Prevalence and Predictors of Penile Pain in Men with Peyronie's Disease
Authors: Flores Jose M. , Salter Carolyn A. , Nascimento Bruno , Terrier Jean-Etienne , Taniguchi Hisanori , Bernie Helen L. , Miranda Eduardo , Jenkins Lawrence , Schofield Elizabeth , Mulhall John P.
Published: July 2021

Introduction

Penile pain is one of the most stressful symptoms in men with Peyronie's disease (PD).

Aim

To evaluate the prevalence, clinical presentation and risk factors associated with penile pain in men with PD as well as to assess the psychosocial impact.

Methods

We revised our institution's database of men diagnosed with PD. The information collected included penile pain assessments, and the scores of the PD Questionnaire (PDQ), Self-Esteem and Relationship Questionnaire (SEAR) and Center for Epidemiologic Studies Depression Scale Questionnaire (CES-D). Descriptive and comparative statistics were used. Logistic regression analyses were performed to evaluate predictive factors associated with penile pain.

Main outcome measures

Penile pain descriptive assessment and factors associated with penile pain in men with PD. Comparison of SEAR, CES-D and PDQ domain scores of men with and without penile pain.

Results

431 men with PD were included for this analysis with a mean age of 55.9 years. Penile pain was reported by 36.7%; 65.2% of those had painful erection, 7% pain with flaccid state only, and 20% in both stages. The median pain severity was 3 with erection and 1 with flaccid stage. After adjusted logistic regression analyses, advanced age was associated with less pain (OR 0.94, P ≤ 0.001). Men with penile pain had no significant difference in CES-D and SEAR mean scores compared to men without penile pain. The PDQ scores for the physical/psychological symptoms domain and the bother domain were significantly higher in men with penile pain (12 vs 8.7; P < 0.01 and 9 vs 7.1; P < 0.01 respectively). Men with penile pain had a higher rate of clinically significant bother scores than men without penile pain (52% vs 35%, P ≤ 0.001).

Conclusion

Penile pain is common in men with PD. It was more common in young men and was associated with physical and psychological bothers in this population.

Flores JM, Salter CA, Nascimento B, et al. The Prevalence and Predictors of Penile Pain in Men with Peyronie's Disease. Sex Med 2021;9:100398.
Erectile and Ejaculatory Dysfunction Associated with Use of Psychotropic Drugs: A Systematic Review
Authors: Trinchieri Margherita , Trinchieri Martina , Perletti Gianpaolo , Magri Vittorio , Stamatiou Konstantinos , Cai Tommaso , Montanari Emanuele , Trinchieri Alberto
Published: July 2021

Background

Sexual dysfunction may be a side effect of treatment with antipsychotics, antidepressants, and other psychotropic drugs.

Aim

To review the evidence concerning male sexual dysfunctions in patients taking psychotropic drugs to provide specific information to nonpsychiatric physicians for the management of these dysfunctions.

Methods

A systematic search of Medline and Embase databases was performed up to October 15th, 2020. We included randomized controlled trials comparing the effects of psychotropic drugs versus placebo or versus another drug of the same class, for at least 5 weeks.

Outcomes

We considered studies whose male population could be evaluated separately from the female population and with a separate analysis of the different phases of the male sex cycle.

RESULTS

We included 41 studies in the final review. There was a significant association between sexual dysfunction and antidepressant drug therapy, compared to placebo (decreased libido OR 1.89, 95% CI:1.40 to 2.56, 22 series, 11 trials, 7706 participants; erectile dysfunction OR = 2.28, 95% CI: 1.31 to 3.97; 11 trials, 3008 participants; ejaculatory dysfunction OR = 7.31, 95% CI: 4.38 to 12.20,19 trials, 3973 participants). When the effects of selective serotonin reuptake inhibitors (SSRIs) were evaluated separately from those of serotonin/norepinephrine reuptake inhibitors (SNRIs), the use of SNRIs but not that of SSRIs was characterized by significantly higher odds of erectile dysfunction compared to placebo. Only limited data were found regarding the effects of antipsychotics on the phases of the male sexual cycle, as it was shown that aripiprazole and risperidone showed lower and higher odds for erectile or ejaculatory dysfunction, respectively, compared to other atypical antipsychotics.

Clinical Implications

Treatment of male sexual dysfunction in patients taking psychotropics requires a basic knowledge of the different drugs that affect sexual function with different mechanisms.

Strengths & Limitations

The effects of psychotropic drugs on erectile function and ejaculation were evaluated separately. The great variability of the mechanisms of action makes it difficult to make comparisons between the effects of the different classes of psychotropic drugs.

CONCLUSIONS

Administration of antipsychotics affects male sexual function with different mechanisms, although the increase in prolactin values associated with the administration of first-generation antipsychotics and some atypical, such as risperidone, seems to play a primary role in determining male sexual dysfunction. Most antidepressants cause decreased libido, ejaculatory and erectile dysfunction, however the administration of SNRIs appears to be possibly associated with a specific risk of erectile dysfunction.
The Dravidian Model
Authors: A. Kalaiyarasan , M. Vijayabaskar
Published: July 2021

This book adds to the growing literature on dynamics of regional development in the global South by mapping the politics and processes contributing to the distinct developmental trajectory of Tamil Nadu, southern India. Using a novel interpretive framework and drawing upon fresh data and literature, it seeks to explain the social and economic development of the state in terms of populist mobilization against caste-based inequalities. Dominant policy narratives on inclusive growth assume a sequential logic whereby returns to growth are used to invest in socially inclusive policies. By focusing more on redistribution of access to opportunities in the modern economy, Tamil Nadu has sustained a relatively more inclusive and dynamic growth process. Democratization of economic opportunities has made such broad-based growth possible even as interventions in social sectors reinforce the former. The book thus also speaks to the nascent literature on the relationship between the logic of modernisation and status based inequalities in the global South.
New flight plan optimisation method utilising a set of alternative final point arrival time targets (RTA constraints)
Authors: Dancila R.I. , Botez R.M.
Published: July 2021

This study investigates a new aircraft flight trajectory optimisation method, derived from the Non-dominated Sorting Genetic Algorithm II method used for multi-objective optimisations. The new method determines, in parallel, a set of optimal flight plan solutions for a flight. Each solution is optimal (requires minimum fuel) for a Required Time of Arrival constraint from a set of candidate time constraints selected for the final waypoint of the flight section under optimisation. The set of candidate time constraints is chosen so that their bounds are contiguous, i.e. they completely cover a selected time domain. The proposed flight trajectory optimisation method may be applied in future operational paradigms, such as Trajectory-Based Operations/free flight, where aircraft do not need to follow predetermined routes. The intended application of the proposed method is to support Decision Makers in the planning phase when there is a time constraint or a preferred crossing time at the final point of the flight section under optimisation. The Decision Makers can select, from the set of optimal flight plans, the one that best fits their criteria (minimum fuel burn or observes a selected time constraint). If the Air Traffic Management system rejects the flight plan, then they can choose the next best solution from the set without having to perform another optimisation. The method applies for optimisations performed on lateral and/or vertical flight plan components. Seven proposed method variants were evaluated, and ten test runs were performed for each variant. For five variants, the worst results yielded a fuel burn less than 90kg (0.14%) over the ‘global’ optimum. The worst variant yielded a maximum of 321kg (0.56%) over the ‘global’ optimum.
Towards a new design with generic modeling and adaptive control of a transformable quadrotor
Authors: Derrouaoui S.H. , Bouzid Y. , Guiatni M.
Published: July 2021

Recently, transformable Unmanned Aerial Vehicles (UAVs) have become a subject of great interest in the field of flying systems, due to their maneuverability, agility and morphological capacities. They can be used for specific missions and in more congested spaces. Moreover, this novel class of UAVs is considered as a viable solution for providing flying robots with specific and versatile functionalities. In this paper, we propose (i) a new design of a transformable quadrotor with (ii) generic modeling and (iii) adaptive control strategy. The proposed UAV is able to change its flight configuration by rotating its four arms independently around a central body, thanks to its adaptive geometry. To simplify and lighten the prototype, a simple mechanism with a light mechanical structure is proposed. Since the Center of Gravity (CoG) of the UAV moves according to the desired morphology of the system, a variation of the inertia and the allocation matrix occurs instantly. These dynamics parameters play an important role in the system control and its stability, representing a key difference compared with the classic quadrotor. Thus, a new generic model is developed, taking into account all these variations together with aerodynamic effects. To validate this model and ensure the stability of the designed UAV, an adaptive backstepping control strategy based on the change in the flight configuration is applied. MATLAB simulations are provided to evaluate and illustrate the performance and efficiency of the proposed controller. Finally, some experimental tests are presented.
Infectious complications of probiotic use: A matched case–control study
Authors: Tom Florissa S. , Tucker Kendall J. , McCracken Caitlin M. , McGregor Jessina C. , Gore Sara J.
Published: July 2021

In this matched case–control study, we sought to determined the association between probiotic use and invasive infections caused by typical probiotic organisms. The odds of probiotic use in cases were 127 times the odds of probiotic use in controls (95% CI, 6.21–2600). Further research into these rare but severe complications is needed.
The relationship of bovine milk somatic cell count to neutrophil level in samples of cow's milk assessed by an automatic cell counter
Authors: Chengolova Zlatina , Ivanov Yavor , Grigorova Galina
Published: July 2021

This research communication describes the application of a fluorescent automatic cell counter Lactoscan SCC for simultaneous determination of somatic cell count and neutrophils in bovine milk. The obtained results were compared with results obtained by a flow cytometer and a light microscope. The Pearson correlations between the methods were calculated. A comparison between the main characteristics of the three kinds of analysis was made – the assay duration and the intra-assay precision. A relation between the SCC and neutrophil cells was observed in 55 milk samples. The obtained results confirm that the simultaneous determination of SCC and neutrophil analysis are necessary and support the early diagnosis of mastitis, the timely treatment of the animal and the avoidance of major economic losses.
‘Knowing me, knowing you’: an exploration of the views and experiences of nursing home residents and staff on their nursing home as ‘home’
Authors: Ryan Assumpta A. , Moore Kevin
Published: July 2021

The overall aim of this grounded theory study was to explore the context of a nursing home as ‘home’ from the perspective of residents and staff. Sixteen focus group interviews were used to collect qualitative data from nursing home residents (N = 48) and staff (N = 44). Five distinct categories captured the views and experiences of participating residents and staff. These were: (a) Starting off on the right foot, ‘First impressions can be the lasting ones; (b) Making new and maintaining existing connections, ‘There is great unity between staff and residents’; (c) The nursing home as home, ‘It's a bit like home from home for me’; (d) Intuitive knowing, ‘I don't even have to speak, she just knows’; and (e) Feeling at home in a regulated environment, ‘It takes the home away from nursing home’. Together these five categories formed the basis of the core category ‘Knowing me, knowing you’, which captures the experiences of participants who repeatedly highlighted the importance of relationships and feelings of mutuality and respect between and among staff and residents as central to feeling at home in a nursing home. The reciprocity and mutuality associated with the core category, ‘Knowing me, knowing you’, was at times challenged by staff shortages, time constraints, and conflicting priorities associated with the co-existence of a regulated and homely environment.
‘The care circle consists of me.’ Loneliness and social isolation for older male spousal care-givers. A qualitative study
Authors: Fee Anne , McIlfatrick Sonja , Ryan Assumpta
Published: July 2021

Whilst loneliness and social isolation amongst older care-givers are becoming increasingly recognised, little is known about how these concepts impact on specific sub-groups of care-givers, such as older males. In the current study, we aimed to gain a better understanding of the experiences of loneliness and social isolation amongst older spousal male care-givers. Semi-structured interviews were undertaken with 24 participants, caring for a spouse/partner with a long-term chronic condition. After thematic analysis of the data, three themes were identified: dwindling social interactions, loneliness in the spousal relationship, and living with loneliness and social isolation. Study findings suggest that opportunities for social interactions gradually ‘dwindled’ due to a reluctance by older male care-givers to leave their spouse/partner at home alone, to accept offers of help or respite, or to attend social events without their spouse/partner. Consequently, social isolation increased. Feelings of physical and emotional loneliness were evident, and the loss of spousal companionship (such as loss of conversation and shared interests) increased loneliness. Individualised coping strategies were adopted including focusing on moments of positivity, talking to others and using prescribed medication. Findings provide insight into the experience of loneliness and social isolation for many older male spousal care-givers. This may facilitate a better understanding of older male care-givers’ support needs in addressing loneliness and social isolation, and should help to inform the development of targeted support services for this population.
Changes in family composition and their effects on social capital in old age: evidence from a longitudinal study conducted in Switzerland
Authors: Sauter Julia , Widmer Eric , Kliegel Matthias
Published: July 2021

Previous studies have shown that family networks evolve over time. Nonetheless, little research has linked family expansion or shrinking to the levels of available family-based social capital in older adults’ family networks. To address this research gap, this paper explores the following question: to what extent are changes in family composition and family-related life events associated with current levels of family-based social capital in later years? We use the two waves of the longitudinal CIGEV-LIVES Vivre-Leben-Vivere study, a large survey addressing the family and health conditions of older people in Switzerland. We combine data on life events occurring during old age and family configurations. We find that family networks are indeed highly dynamic, with distinct patterns of losses and gains observed among respondents. Adding and omitting significant family members has distinct significant effects on social capital, while family-related life events only have marginal effects.
Digital ageing in Europe: a comparative analysis of Italian, Finnish and Swedish national policies on eHealth
Authors: Valokivi Heli , Carlo Simone , Kvist Elin , Outila Marjo
Published: July 2021

Ageing Europeans are today healthier than previous generations and often manage to live independently up to a high age. The proportion of people 80 years of age and older has increased significantly, and with high age the risk of multi-illness and dementia increases. Strong urbanisation processes have changed the demographic structure in rural areas, and young women and men have migrated towards the urban areas to study and work, while older persons have remained behind. This demographic challenge of increasing numbers of persons older than 80 years with care needs living in remote rural areas has become a major European social problem. In tackling this dilemma, many European countries have high expectations for eHealth, digitalisation and welfare technology. In this comparative study of policy debates in Italy, Finland and Sweden, we analyse how – between 2009 and 2019 – the issues of eHealth have been articulated in national and regional policies of the three countries with deep differences in terms of digitalisation and health systems, but with similar ageing populations. We identify in the documents three core topics – the role of technology, the rural issue and responsibility for care. These topics are treated in the documents with differences and similarities between the three countries. Beyond the differences and similarities, the documents reveal both a certain techno-enthusiasm about the role of eHealth in the life of the older adults as well as a limited understanding of the complexity (relationally as well as spatially) of the digital landscape of caring for older adults.
On the meaning(s) of norms: Ambiguity and global governance in a post-hegemonic world
Authors: Linsenmaier Thomas , Schmidt Dennis R. , Spandler Kilian
Published: July 2021

This article offers a new conceptualisation of the meaning of norms in world politics. It starts from the observation that existing norm scholarship in International Relations has underestimated the role of ambiguity in the constitution of norm meaning. To address this shortcoming, we advance a conceptualisation that sees norm polysemy – the empirically observable plurality of norm meanings-in-use – as resulting from the enactment of inherently ambiguous norms in different contexts. By foregrounding norm ambiguity, this view offers a radically non-essentialist understanding of norm meaning, one that eschews any attempt to salvage final or ‘true’ meanings behind the polysemy of norms. Using empirical illustrations from different fields of contemporary global governance, we identify four mechanisms through which actors practically cope with the multiplicity of norm meanings that arises from norm ambiguity (deliberation, adjudication, uni- or multilateral fixation attempts, and ad hoc enactment) and outline their varying effects on the legitimacy and effectiveness of global governance. Based on this discussion, the article points to the normative implications of a radically non-essentialist conception of norms and suggests harnessing the positive potential of norm ambiguity as an ethically desirable condition that promotes human diversity and the plurality of global life.
Counting and equidistribution in quaternionic Heisenberg groups
Authors: PARKKONEN JOUNI , PAULIN FRÉDÉRIC
Published: July 2021

We develop the relationship between quaternionic hyperbolic geometry and arithmetic counting or equidistribution applications, that arises from the action of arithmetic groups on quaternionic hyperbolic spaces, especially in dimension 2. We prove a Mertens counting formula for the rational points over a definite quaternion algebraAover${\mathbb{Q}}$in the light cone of quaternionic Hermitian forms, as well as a Neville equidistribution theorem of the set of rational points overAin quaternionic Heisenberg groups.
Radial Anisotropy in East Asia From Multimode Surface Wave Tomography
Authors: Witek M. , Chang S.‐J. , Lim D. Y. , Ning S. , Ning J.
Published: July 2021

We present a model of radial anisotropy in the crust and upper mantle of East Asia from a combination of new group velocity measurements and previously published surface wave dispersion data sets. Our combined data set ranges 5–375 s period and contains dispersion data up to the fifth overtone. We directly relate the data to variations in isotropic and radially anisotropic shear wave crustal and mantle structure via surface wave ray theory applied to a prior 3‐D reference model. Our isotropic S‐velocity model shares high correlations with previous studies, including a model derived from a full waveform inversion methodology. The short period dispersion measurements in our data set allow us to resolve crustal structure without the need for crustal corrections, and as a result, our radial anisotropy model has significant differences with previous studies. We find strong positive radial anisotropy (ξ > 1) across the entire region in the middle to lower crust and uppermost mantle. We perform a cluster analysis and find high levels of radial anisotropy (ξ > 1.12) in the lithospheric mantle of the back‐arc basin and in collisional belts, while low levels of radial anisotropy (ξ ∼ 1.04) are found in the mantle wedge of NE Japan and in the mantle upwelling under Mt. Baekdu. High radial anisotropy is found in the lower crust in regions that experienced continental rifting and lithospheric thinning, while the lowest crustal radial anisotropy is found in stable cratons.
Elliott Receives 2020 John Wahr Early Career Award
Authors:   AGU
Published: July 2021

John R. Elliott received the 2020 John Wahr Early Career Award at AGU’s virtual Fall Meeting 2020. The award recognizes “significant advances in geodetic science, technology, applications, observations, or theory.”
Large Air Quality and Public Health Impacts due to Amazonian Deforestation Fires in 2019
Authors: Butt Edward W. , Conibear Luke , Knote Christoph , Spracklen Dominick V.
Published: July 2021

Air pollution from Amazon fires has adverse impacts on human health. The number of fires in the Amazon has increased in recent years, but whether this increase was driven by deforestation or climate has not been assessed. We analyzed relationships between fire, deforestation, and climate for the period 2003 to 2019 among selected states across the Brazilian Legal Amazon (BLA). A statistical model including deforestation, precipitation and temperature explained ∼80% of the variability in dry season fire count across states when totaled across the BLA, with positive relationships between fire count and deforestation. We estimate that the increase in deforestation since 2012 increased the dry season fire count in 2019 by 39%. Using a regional chemistry‐climate model combined with exposure‐response associations, we estimate this increase in fire resulted in 3,400 (95UI: 3,300–3,550) additional deaths in 2019 due to increased exposure to particulate air pollution. If deforestation in 2019 had increased to the maximum recorded during 2003–2019, the number of active fire counts would have increased by an additional factor of 2 resulting in 7,900 (95UI: 7,600–8,200) additional premature deaths. Our analysis demonstrates the strong benefits of reduced deforestation on air quality and public health across the Amazon.
Pericytes augment glioblastoma cell resistance to temozolomide through CCL5-CCR5 paracrine signaling
Authors: Zhang Xiao-Ning , Yang Kai-Di , Chen Cong , He Zhi-Cheng , Wang Qiang-Hu , Feng Hua , Lv Sheng-Qing , Wang Yan , Mao Min , Liu Qing , Tan Yao-Yao , Wang Wen-Ying , Li Tian-Ran , Che Lin-Rong , Qin Zhong-Yi , Wu Ling-Xiang , Luo Min , Luo Chun-Hua , Liu Yu-Qi , Yin Wen , Wang Chao , Guo Hai-Tao , Li Qing-Rui , Wang Bin , Chen Wei , Wang Shuang , Shi Yu , Bian Xiu-Wu , Ping Yi-Fang
Published: July 2021

Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. We found that increased pericyte proportion correlates with accelerated tumor recurrence and worse prognosis. Genetic depletion of pericytes in GBM xenografts enhances TMZ-induced cytotoxicity and prolongs survival of tumor-bearing mice. Mechanistically, C-C motif chemokine ligand 5 (CCL5) secreted by pericytes activates C-C motif chemokine receptor 5 (CCR5) on GBM cells to enable DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-mediated DDR upon TMZ treatment. Disrupting CCL5-CCR5 paracrine signaling through the brain-penetrable CCR5 antagonist maraviroc (MVC) potently inhibits pericyte-promoted DDR and effectively improves the chemotherapeutic efficacy of TMZ. GBM patient-derived xenografts with high CCL5 expression benefit from combined treatment with TMZ and MVC. Our study reveals the role of pericytes as an extrinsic stimulator potentiating DDR signaling in GBM cells and suggests that targeting CCL5-CCR5 signaling could be an effective therapeutic strategy to improve chemotherapeutic efficacy against GBM.
Degradation of lipid droplets by chimeric autophagy-tethering compounds
Authors: Fu Yuhua , Chen Ningxie , Wang Ziying , Luo Shouqing , Ding Yu , Lu Boxun
Published: July 2021

Degrading pathogenic proteins by degrader technologies such as PROTACs (proteolysis-targeting chimeras) provides promising therapeutic strategies, but selective degradation of non-protein pathogenic biomolecules has been challenging. Here, we demonstrate a novel strategy to degrade non-protein biomolecules by autophagy-tethering compounds (ATTECs), using lipid droplets (LDs) as an exemplar target. LDs are ubiquitous cellular structures storing lipids and could be degraded by autophagy. We hypothesized that compounds interacting with both the LDs and the key autophagosome protein LC3 may enhance autophagic degradation of LDs. We designed and synthesized such compounds by connecting LC3-binding molecules to LD-binding probes via a linker. These compounds were capable of clearing LDs almost completely and rescued LD-related phenotypes in cells and in two independent mouse models with hepatic lipidosis. We further confirmed that the mechanism of action of these compounds was mediated through LC3 and autophagic degradation. Our proof-of-concept study demonstrates the capability of degrading LDs by ATTECs. Conceptually, this strategy could be applied to other protein and non-protein targets.
Viral vector gene delivery of the novel chaperone protein SRCP1 to modify insoluble protein in in vitro and in vivo models of ALS
Authors: Luecke Ian W. , Lin Gloria , Santarriaga Stephanie , Scaglione K. Matthew , Ebert Allison D.
Published: July 2021

Protein misfolding and aggregation are shared features of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), and protein quality control disruption contributes to neuronal toxicity. Therefore, reducing protein aggregation could hold therapeutic potential. We previously identified a novel chaperone protein, serine-rich chaperone protein 1 (SRCP1), that effectively prevents protein aggregation in cell culture and zebrafish models of Huntington’s disease. Here we tested whether this benefit extends to aggregated proteins found in ALS. We used viral-mediated expression of SRCP1 in in vitro and in vivo models of ALS. We found that SRCP1 reduced insoluble SOD1 protein levels in HEK293T cells overexpressing either the A4V or G93R mutant SOD1. However, the reduction of insoluble protein was not observed in either mutant C9orf72 or SOD1 ALS iPSC-derived motor neurons infected with a lentivirus expressing SRCP1. SOD1-G93A ALS mice injected with AAV-SRCP1 showed a small but significant reduction in insoluble and soluble SOD1 in both the brain and spinal cord, but SRCP1 expression did not improve mouse survival. These data indicate that SRCP1 likely reduces insoluble protein burden in a protein and/or context-dependent manner indicating a need for additional insight into SRCP1 function and therapeutic potential.
Whole genome survey of big cats (Genus: Panthera) identifies novel microsatellites of utility in conservation genetic study
Authors: Hyun Jee Yun , Pandey Puneet , Kim Kyung Seok , Chon Alvin , Jeong Daecheol , Bhak Jong , Yu Mihyeon , Song Hye Kyung , Singh Randeep , Min Mi-Sook , Goyal Surendra Prakash , Bayarkhagva Damdingiin , Marchenkova Taisia , Vitkalova Anna , Lee Hang
Published: July 2021

Big cats (Genus: Panthera) are among the most threatened mammal groups of the world, owing to hunting, habitat loss, and illegal transnational trade. Conservation genetic studies and effective curbs on poaching are important for the conservation of these charismatic apex predators. A limited number of microsatellite markers exists for Panthera species and researchers often cross-amplify domestic cat microsatellites to study these species. We conducted data mining of seven Panthera genome sequences to discover microsatellites for conservation genetic studies of four threatened big cat species. A total of 32 polymorphic microsatellite loci were identified in silico and tested with 152 big cats, and were found polymorphic in most of the tested species. We propose a set of 12 novel microsatellite markers for use in conservation genetics and wildlife forensic investigations of big cat species. Cumulatively, these markers have a high discriminatory power of one in a million for unrelated individuals and one in a thousand for siblings. Similar PCR conditions of these markers increase the prospects of achieving efficient multiplex PCR assays. This study is a pioneering attempt to synthesise genome wide microsatellite markers for big cats.
Physical processes controlling the diurnal cycle of convective storms in the Western Ghats
Authors: Krishna U. V. Murali , Das Subrata Kumar , Deshpande Sachin M. , Pandithurai G.
Published: July 2021

Diurnal variation of convective storms (CSs) during monsoon season and associated physical mechanisms are significantly important for accurate forecast of short-time and extreme precipitation. The diurnal cycle of CSs is investigated using ground-based X-band radar, Tropical Rainfall Measuring Mission Precipitation Radar, and reanalysis data during the summer monsoon (June–September of 2014) over complex mountain terrain of Western Ghats, India. Diurnally, CSs show a bimodal distribution in the coastal areas, but this bimodality became weak along the upslope regions and on the mountain top. The first occurrence mode of CSs is in the afternoon–evening hours, while the second peak is in the early-morning hours. The diurnal cycle’s intensity varies with location, such that it reaches maximum in the afternoon–evening hours and early morning on the mountain top and coastal areas, respectively. Two possible mechanisms are proposed for the observed diurnal variation in CSs (a) the radiative cooling effect and (b) the surface wind convergence induced by the interaction between land-sea breeze, local topography and large-scale monsoon winds. It is also observed that the CSs developed on the mountain top during afternoon–evening hours are deeper than those along the coast. The higher moisture in the lower- and mid-troposphere, higher instability and strong upward motion facilitate deeper CSs during afternoon–evening hours.
The ammonia oxidizing bacterium Nitrosomonas eutropha blocks T helper 2 cell polarization via the anti-inflammatory cytokine IL-10
Authors: Maura Damien , Elmekki Nazik , Goddard C. Alex
Published: July 2021

The prevalence of atopic diseases has been steadily increasing since the mid twentieth century, a rise that has been linked to modern hygienic lifestyles that limit exposure to microbes and immune system maturation. Overactive type 2 CD4+ helper T (Th2) cells are known to be closely associated with atopy and represent a key target for treatment. In this study, we present an initial characterization of ammonia oxidizing bacteria (AOB) Nitrosomonas eutropha D23, an environmental microbe that is not associated with human pathology, and show AOB effectively suppress the polarization of Th2 cells and production of Th2-associated cytokines (IL-5, IL-13, and IL-4) by human peripheral blood mononuclear cells (PBMC). We show that AOB inhibit Th2 cell polarization not through Th1-mediated suppression, but rather through mechanisms involving the anti-inflammatory cytokine IL-10 and the potential inhibition of dendritic cells, as evidenced by a reduction in Major Histocompatibility Complex Class II (MHC II) and CD86 expression following AOB treatment. This is the first report of immunomodulatory properties of AOB, and provides initial support for the development of AOB as a potential therapeutic for atopic diseases.
A novel index-based decision support toolkit for safe reopening following a generalized lockdown in low and middle-income countries
Authors: Shonchoy Abu S. , Ishtiaq Khandker S. , Talukder Sajedul , Ahmed Nasar U. , Chowdhury Rajiv
Published: July 2021

While the effectiveness of lockdowns to reduce Coronavirus Disease-2019 (COVID-19) transmission is well established, uncertainties remain on the lifting principles of these restrictive interventions. World Health Organization recommends case positive rate of 5% or lower as a threshold for safe reopening. However, inadequate testing capacity limits the applicability of this recommendation, especially in the low-income and middle-income countries (LMICs). To develop a practical reopening strategy for LMICs, in this study, we first identify the optimal timing of safe reopening by exploring accessible epidemiological data of 24 countries during the initial COVID-19 surge. We find that a safe opening can occur two weeks after the crossover of daily infection and recovery rates while maintaining a negative trend in daily new cases. Epidemiologic SIRM model-based example simulation supports our findings. Finally, we develop an easily interpretable large-scale reopening (LSR) index, which is an evidence-based toolkit—to guide/inform reopening decision for LMICs.
Phytochemical composition and antioxidant properties of methanolic extracts of whole and dehulled Bambara groundnut (Vigna subterranea) seeds
Authors: Adedayo Bukola C. , Anyasi Tonna A. , Taylor Malcolm J. C. , Rautenbauch Fanie , Le Roes-Hill Marilize , Jideani Victoria A.
Published: July 2021

The distribution of phytochemicals and their contribution to antioxidant potentials in whole and dehulled Bambara groundnut (BGN) seeds was evaluated. Whole BGN seeds were sorted using the testa and hilium colour and further grouped into whole and dehulled BGN seeds. Extractions of both whole and dehulled BGN seeds was done using methanol and the extracts assayed for total phenolics (TPC), flavanol, flavonol, anthocyanin content, oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP). Methanolic extract of whole BGN seed exhibited higher flavanol and flavonol content as well as significantly higher in-vitro antioxidant activities than dehulled BGN seeds. The TPC of whole BGN seed extract ranged from 3.6 to 11.0 GAE/g, while that of dehulled BGN ranged from 2.7 to 3.2 GAE/g. Identification of phenolics in whole and dehulled BGN seed extract using UPLC-qTOF-MS, revealed the presence of monoterpenoids (iridoids), phenolic acids, flavonoids and lignans. Bivariate correlations showed anthocyanin demonstrated weak positive correlation between flavanol, flavonol and ORAC for whole BGN seed extract; and negative correlation between flavanol, TPC, FRAP and ORAC for dehulled BGN. Aside the effect of dehulling, whole BGN seeds exhibited the presence of phytochemicals with beneficial properties for food and industrial application.
Impact of plasma 5-hydroxyindoleacetic acid, a serotonin metabolite, on clinical outcome in septic shock, and its effect on vascular permeability
Authors: Tanaka Takeshi , Mori Masahiko , Sekino Motohiro , Higashijima Ushio , Takaki Masahiro , Yamashita Yoshiro , Kakiuchi Satoshi , Tashiro Masato , Morimoto Konosuke , Tasaki Osamu , Izumikawa Koichi
Published: July 2021

Septic shock is characterized by dysregulated vascular permeability. We hypothesized that the vascular permeability of endothelial cells (ECs) would be regulated by serotonin via serotonin-Rho-associated kinase (ROCK) signaling. We aimed to determine the impact of 5-hydroxyindoleacetic acid (5-HIAA) on septic shock as a novel biomarker. Plasma 5-HIAA levels and disease severity indices were obtained from 47 patients with sepsis. The association between 5-HIAA levels and severity indices was analyzed. Permeability upon serotonin stimulation was determined using human pulmonary microvascular ECs. 5-HIAA were significantly higher in septic shock patients than in patients without shock or healthy controls (p = 0.004). These elevated levels were correlated with severity indexes (SOFA score [p < 0.001], APACHE II [p < 0.001], and PaO2:FiO2 [p = 0.02]), and longitudinally associated with worse clinical outcomes (mechanical ventilation duration [p = 0.009] and ICU duration [p = 0.01]). In the experiment, serotonin increased the permeability of ECs, which was inhibited by the ROCK inhibitor (p < 0.001). Serotonin increases vascular permeability of ECs via ROCK signaling. This suggests a novel mechanism by which serotonin disrupts endothelial barriers via ROCK signaling and causes the pathogenesis of septic shock with a vascular leak. Serotonin serves as a novel biomarker of vascular permeability.
Exploratory and territorial behavior in a reintroduced population of Iberian lynx
Authors: Rueda Carmen , Jiménez José , Palacios María Jesús , Margalida Antoni
Published: July 2021

In reintroduction projects, an analysis of dispersal, exploratory movements and territorial behavior of the species concerned offers valuable information on the adaptive management of threatened species and provides a basis for the management of future reintroductions. This is the case of the Iberian lynx (Lynx pardinus) an endemic and endangered species reintroduced in Extremadura (Spain) in 2014. We analysed spatial data from 32 individuals just after their reintroduction. Our findings show exploratory movements sufficient to colonise and connect population nuclei within a radius of about 50 km of the reintroduction area. No significant differences were found in the exploratory movements capacity or in any directionality of males and females. Our results showed an effect of sex on the sizes of the territories established, as well as an inverse relationship between them and the time elapsed since release. No effects of rabbit abundance and lynx density on the size of territories are occurring during the early stages of reintroduction. On average, the territories of reintroduced individuals were less stable than those previously described in natural populations. Findings indicate that the reintroduced population has successfully been established but it takes more than 5 years to stabilize the territories in the area. Exploratory movements of reintroduced lynx can be large and in any direction, even when there is still a lot of high quality habitat available, which should be taken into account when reintroducing species, especially terrestrial carnivores.
Efficacy and safety of ticagrelor versus clopidogrel in patients with non-ST-elevation myocardial infarction in Taiwan
Authors: Lee Chih-Kuo , Wang Tzung-Dau , Juang Hsiao-Ting , Chang Shu-Chen , Pan Heng-Yu , Lin Donna Shu-Han , Chang Chee-Jen
Published: July 2021

The clinical efficacy of ticagrelor versus clopidogrel has not been replicated in East Asian populations. The pronounced bleeding risk with ticagrelor was of concern given the increased bleeding tendency in Asian populations. This study evaluated efficacy and safety of ticagrelor versus clopidogrel in patients with non-ST-elevation myocardial infarction (NSTEMI) in the entire Taiwan. We used the Taiwan National Health Insurance Research Database to identify 6203 patients aged ≥ 20 years with NSTEMI hospitalization and prescription of dual antiplatelets at discharge between January 2014 and December 2014. Cohorts of ticagrelor and clopidogrel were matched 1:1 based on propensity score matching to balance baseline covariates. The primary composite efficacy endpoints included death from any cause, non-fatal myocardial infarction, and non-fatal stroke. The secondary efficacy endpoints were the individual components. The primary safety endpoint was major bleeding requiring hospitalization. The incidence of primary efficacy endpoint was 20.3% in the ticagrelor users and 20.7% in the clopidogrel users (adjusted HR 0.94; 95% CI 0.73–1.22), with the median (interquartile range, IQR) follow-up period of 5.2 (2.3–8.5) months. The incidence of primary safety endpoint was 2.3% in the ticagrelor users and 3.2% in the clopidogrel users (adjusted HR 0.67; 95% CI 0.33–1.35). Regarding the secondary efficacy endpoint, patients treated with ticagrelor had significantly lower incidence of stroke (adjusted HR 0.44; 95% CI 0.21–0.94; p = 0.033). In this nationwide Taiwanese cohort of NSTEMI, treatment with ticagrelor after discharge, as compared to clopidogrel, had similar rates of ischemic composite events and major bleeding. Nevertheless, the median follow-up time was only 5.2 months, and the reduced stroke events with ticagrelor compared to clopidogrel needs further verification.