bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Validity of a Serious Game (VirtualTer) for Postural Balance Rehabilitation in Older Adults
Authors: Medeiros Candice Simões Pimenta de , Pacheco Thaiana Barbosa Ferreira , Dantas Rummenigge Rudson , Cavalcanti Fabrícia Azevêdo da Costa
Published: November 2021

Background

Physiological changes resulting from aging can impair postural balance. Exergames have been used to treat balance disorders, enabling sensory-motor training due to their content, and with targeted goals and purposes beyond entertainment.

Aim

The aim of this investigation was to describe the development of a serious game, VirtualTer, and to test content validity.

Methods

A Brazilian group from the Federal University of Rio Grande do Norte developed a serious game called VirtualTer for postural balance rehabilitation in older adults. In game navigation, the avatar needed to save the environment from catching harmful energy that destroys nature. The avatar performs stationary walking, lateral reaching, and climbing up and down steps to capture the energies. Content validity was determined using content matter experts by the Delphi method. Eleven content matter experts played the game and expressed their opinions using the assessment instruments: VirtualTer Dimensions (VD) and System Usability Scale (SUS).

Results

VirtualTer was designed with regard to variability in practice, since the game was constructed under three levels and offers continuous and terminal feedback. The participants needed to achieve at least 70% of the total score to advance to the next phase. The limits of stability for lateral reach test were right 23.2 ± 4.77 cm and left 22.9 ± 4.86 cm, which was applied in the game. The content validity index of the VD was 0.8, and Cronbach’s alpha coefficient was 0.924. The content matter experts reported the game as having a 67.73 satisfaction with the SUS.

Conclusion

This game has good usability, low-cost investment, and supports access to innovative and valid technology for rehabilitation in countries with little investment in technology for health.
The Heresy of Relevance: Bonhoeffer's Warning to Preachers
Authors: Dean Robert J.
Published: November 2021

Amid a crisis in biblical interpretation brought to a head by the Church Struggle in Germany, Dietrich Bonhoeffer delivered an address in August 1935 to a group of Confessing Church pastors entitled “Contemporizing New Testament Texts.” Bonhoeffer sounded a clarion call for the retrieval of a thoroughly theological hermeneutic that would liberate preachers for the bold proclamation of the Gospel within a culturally compromised church. This paper will present a reading of Bonhoeffer's daring address that seeks to both situate it within its unique historical context and attend to the ways that it calls into question many of the cherished hermeneutical and homiletical assumptions that dominate contemporary preaching for the sake of a more faithful proclamation of the Gospel of Jesus Christ.
Bread preparation by partial replacement of wheat by germinated sorghum
Authors: Sharanagat Vijay Singh , Nema Prabhat K.
Published: November 2021

Published literature shows significant impact of sorghum type and flour on end-product quality, while demonstrating paucity in the studied varieties with respect to processing aspects (such as bread making) despite of enormous accessions available worldwide. Limited studies have reported usage of germinated flour for the above said purpose. The present study thus aimed at mitigating these gaps by utilizing results of sorghum (HJ-513) germination (Day 1-5) and flour derived from optimized condition (Day 3 as identified by partial least square analysis) to develop a composite functional bread (partial replacement of wheat). The germination process enhanced the total phenolics compounds (TPC, till day 3), water (14.01%) and oil absorption capacity (25.97%) while reducing the bulk density (760.99-644.69 kg/m3). This demonstrated increased potential of sorghum flour for development of bakery and confectionery products. The process also affected the pasting properties, total flavonoids compounds (TFC) and DPPH (2, 2-diphenyl-1-picrylhydrazyl) significantly (p < 0.05). The bread developed from partial replacement (10% and 20%) of refined wheat flour by sorghum was hard and darker than the control wheat bread. The bread developed at 20% was more dense and porous than the bread developed with 10% replacement. Specific volume of bread at 10% replacement was found higher than at 20% replacement. The study reports effective utilization of germinated sorghum flour for development of composite-functional bread without incorporation of any other additives/improvers. Future research however is warranted in the field to further increase the replacement of wheat flour by germinated sorghum flour to develop gluten free bread.
Expertise and the work of football match analysts in TV sport broadcasts
Authors: Fele Giolo , Campagnolo Gian Marco
Published: November 2021

In this paper we describe expertise as a way of seeing. We use match analysis `punditry’ as a setting to show how professional vision is interactionally achieved in TV sport broadcasts through environmentally coupled gestures enhanced by camera actions and a new technology of vision called telestrator. The paper is based on data from video sequences of (English) football TV broadcasts where the pundit shows to the TV host in the studio and to the non-expert audience at home what happened during a football match. We argue that the transparency of seeing is the product of an artfully instructed process whereby the pundit shows what should be seen, how it should be made accountable, and what the audience should expect in order to fully appreciate what they see. The paper shows how broadcasted match analysis expertise interactionally achieves this through the time-critical linking of talk, gesture, and technological environment.
Playing with happiness: Biopolitics, childhood and representations of play
Authors: Saltmarsh Sue , Lee I-Fang
Published: November 2021

Play is a central discourse in policy and practice pertaining to young children's learning, development and well-being in many countries around the world. Dominant ways of understanding and advocating for play often construct universalising notions of children and childhood, overlooking that play is always-already culturally situated and ideologically inflected. In play discourse, happiness is constituted as an unproblematised condition, goal and outcome of children's play, and as an antidote to contemporary childhoods burdened by geopolitical, social and environmental issues. In this article, the authors analyse images of children at play in curriculum frameworks, documents and reports, exploring the ways that happiness consistently features as a largely unspoken/unwritten expectation and rationale for policies and policy advocacy concerning play in early childhood. Informed by post-structural theories of biopolitical power, everyday practices and the cultural politics of emotion, and utilising analytical techniques from social semiotics and discourse analysis, the authors argue that visual representations in the documents analysed depict play and happiness as co-implicated. They contend that these representations function in the production of play discourses that both assume and obligate children and childhood to happiness. They interrogate play in these terms, critiquing discursive tropes that are contingent on the co-implication of play and happiness with biopolitical subjectification in order to consider the relevance and utility of play as a policy and pedagogical export to diverse parts of the world.
The framing of power in communicative planning theory: Analysing the work of John Forester, Patsy Healey and Judith Innes
Authors: Westin Martin
Published: November 2021

In this paper, I analyse the framing of power in streams of communicative planning influenced by American pragmatism, sociological institutionalism and alternative dispute resolution. While scholars have heavily debated Habermasian communicative planning theory, the broader conception of power across these linked, but distinct, streams of the theory remains to be explicated. Through analysis of 40 years’ of publishing by John Forester, Patsy Healey and Judith Innes – widely cited representatives of these three streams – a broader account of the treatment of power in communicative planning is established. The analysis shows that the streams of communicative planning provide distinct approaches to power with a joint focus on criticising conflictual illegitimate power over and developing ideas for how consensual power with might arise through agency in the micro practices of planning. Even if communicative planning thereby offers more for reflections on power than critics have acknowledged, the theory still leaves conceptual voids regarding constitutive power to and legitimate power over.
Investigating the braiding parameters and their effects on the mechanical and frictional properties of silk sutures
Authors: Sivanesan Natarajan , Venugopal Rameshbabu , Subramanian Ariharasudhan
Published: November 2021

In this research work, the simultaneous effects of braided sutures made up of silk filament were studied with respect to parameters such as filament twist (0-6 Twist/inch), braiding angle (28.8°–34.8°) and braid structure (1/1, 1/2 and 2/2) on tensile strength, elongation, bending stiffness and friction were investigated by using response surface methodology. The influence of independent and dependent values has been studied using the categorical central composite design of experiments. The optimum conditions for enhanced handling characteristics of braided silk suture were 3.7 twist /inch of silk filament twist level, at a 28.8°braid angle, and a 1/2 braided structure. The handling characteristics of the suture can be enhanced by choosing suitable braiding parameters.
Missed nursing care and complexity theory: a conceptual paper
Authors: Albsoul Rania Ali , FitzGerald Gerard , Hughes James A , Ahmed Alshyyab Muhammad
Published: November 2021

Background

Missed nursing care is a complex healthcare problem. Extant literature in this area identifies several interventions that can be used in acute hospital settings to minimise the impact of missed nursing care. However, controversy still exists as to the effectiveness of these interventions on reducing the occurrence of missed nursing care.

Aim

This theoretical paper aimed to provide a conceptual understanding of missed nursing care using complexity theory.

Methods

The method utilised for this paper is based on a literature review on missed care and complexity theory in healthcare.

Results

We found that the key virtues of complexity theory relevant to the missed nursing care phenomenon were adaptation and self-organisation, non-linear interactions and history. It is suggested that the complex adaptive systems approach may be more useful for nurse managers to inform and prepare nurses to meet uncertain encounters in their everyday clinical practice and therefore reduce instances of missed care.

Conclusions

This paper envisions that it is time that methods used to explore missed care changed. Strategies proposed in this paper may have an important impact on the ability of nursing staff to provide quality and innovative healthcare in the modern healthcare system.
Exploring Chinese folk religion: Popularity, diffuseness, and diversities
Authors: Zhang Chunni , Lu Yunfeng , Sheng He
Published: November 2021

Folk religion, as the basis of the religious landscape in traditional China, is a highly syncretic system which includes elements from Buddhism, Daoism, and other traditional religious beliefs. Due to the shortcomings of denomination-based measurement, most previous social surveys have documented a very low percentage of folk religion adherents in China, and found almost no overlapping among religious beliefs. This study offers a quantitative portrait of the popularity, the diffuseness, and the diversity of Chinese folk religion. With the improved instruments in the 2018 China Family Panel Studies, we first observe that nearly 50% of respondents claim to have multiple (two or even more than three) religious beliefs and the believers of folk religion account for about 70% of the population. By using latent class analysis, this article explores the pattern of inter-belief mixing and identifies four typical classes of religious believers: “non-believers and single-belief believers”, “believers of geomancy”, “believers of diffused Buddhism and Daoism”, and “believers embracing all beliefs”. Finally, we find that the degree of commitment varies across these religious classes. Believers of folk religion are found to be less committed than believers of Western institutional religions, but as committed as believers of Eastern institutional religions.
Hearing Aids Reduce Daily-Life Fatigue and Increase Social Activity: A Longitudinal Study
Authors: Holman Jack A. , Drummond Avril , Naylor Graham
Published: November 2021

People with hearing loss experience fatigue, and it is unknown whether this is alleviated by treatment with hearing aids. The objective of this study was to address this issue and to investigate the possible concomitant effect of hearing-aid fitting on activity levels. An intervention group ( n = 53) who were due to be fitted with their first-ever hearing aid(s) and a control group ( n = 53) who had hearing loss but no change in hearing aid status–completed a battery of self-report outcome measures four times: once before fitting, and at 2 weeks, 3 months, and 6 months post fitting. Self-report outcome measures at each assessment captured fatigue, listening effort, hearing handicap, auditory lifestyle, social participation restrictions, and work, social and physical activity levels. Hearing-aid fitting led to a significant reduction in listening-related fatigue, but not general fatigue, in the intervention group compared to the control group. Additionally, social activity level increased and social participation restriction decreased significantly after hearing aid fitting in the intervention group compared to the control group. No significant interaction was found between working status and change in listening-related fatigue score. This study is the first to make a longitudinal measurement of fatigue before and after first-ever hearing aid fitting and to identify an increase in social activity level after hearing aid fitting. These findings have important implications for future research and the clinical practice of hearing aid fitting.
The Legal Defect in the Conditional Prohibition of Manual Scavenging in India
Authors: Wankhede Asang
Published: November 2021

This article problematizes the definitional discourse of manual scavenging in Indian legislative interven-tions and its judicial treatment by the Supreme Court of India. It assesses the evolution of the definition of manual scavenging and the judicial treatment of it to cull out the insufficiency of legal doctrines and judicial interpretations in its elimination. It is argued that the career of legal prohibition of manual scavenging, despite deploying new measures to promote the elimination and rehabilitation, is antithetical to the very objectives of the legislations due to a paradoxical definitional discourse. The paradox is discerned by problema-tizing the condition-based permissibility of manual scavenging, where the usage of protective gear is the excluding criterion for identifying manual scavengers and perpetuates the practice. This condition-based permissibility has been a key burden on the discourse of elimination, as no such measures, it is argued, can mitigate discrimination, humiliation and stigma faced by manual scavengers. After identifying the conditional prohibition of manual scavenging, the article makes normative suggestions towards the adoption of a non-condition–based complete prohibition approach rooted in the understanding of human dignity. This must be complemented with the complete rehabilitation of individuals and complete mechanization of sewage work.
The ‘Tree of Life’ or Pohon-Budi: An International Exhibition Celebrates a Global Heritage
Authors: Dhamija Jasleen , Nirula Manjari , Ong Edric
Published: November 2021

This article by a team of scholars, activists and a designer describes an effort to understand a heritage shared across many cultures—the Tree of Life is a symbol that appears in the myths, crafts and arts of civilizations on every continent—and to bring that heritage alive through exhibits featuring present-day artisans and artists. After overcoming major administrative barriers, an exhibition on this sacred theme premiered in Kuala Lumpur in 2015, curated by a Malaysian–Indian team. Expressions brought together from 35 countries blended natural and cultural ecologies with the sensitivity of each creator, working with a range of materials. After Malaysia, the exhibition travelled to India, the USA, Canada, Taiwan and Thailand. It is expected to move to Bhutan, China, the UK and elsewhere once the pandemic condition allows. Meanwhile, documentation and publication have helped share a breathtaking resource of knowledge and design. Described as ‘a thread that links the world’, this Tree of Life celebration demonstrates the importance of investing in research to build a foundation of scholarship upon which heritage can be brought to life for new generations. Here, the creativity and innovation of those who are repositories of ancient wisdom make tradition relevant to new times, revealing heritage as a timeless process that can be managed and shared by bringing old and contemporary disciplines together in new and uniting partnerships that extend far beyond political borders. New opportunities have opened for participants, inspiring other efforts. Here, heritage not only identifies the identity of each participating culture. These identities also combine as a shared heritage of all humankind, with the Tree of Life as a symbol of caring for the earth and for each other.
The Impact of Medications on Esophageal Motility
Authors: Snyder Diana L. , Ravi Karthik
Published: November 2021

The purpose of this review is to highlight the impact of common medications on esophageal motility. Esophageal motility is mediated through a complex network of neural innervation. Opioids lead to excitatory esophageal motor abnormalities termed opioid-induced esophageal dysfunction or OIED. Prokinetics have mixed effects on esophageal motility. Nitrates and calcium channel blockers relax esophageal smooth muscle, but they are limited clinically due to side effects. Sildenafil also relaxes smooth muscle, but it is costly. Peppermint oil may reduce distal esophageal spasm. Anticholinergics, selective serotonin reuptake inhibitors, estrogen, and cannabis need further study to evaluate their effects on esophageal motility.
Sex and gender in respiratory physiology
Authors: LoMauro Antonella , Aliverti Andrea
Published: November 2021

Sex is a biological concept determined at conception. Gender is a social concept. Medicine recognises sex as a biological variable and recommends including sex as a factor in clinical practice norms and as a topic of bench and clinical research. Sex plays a role in respiratory physiology according to two pathways: hormones and anatomy, with females characterised by smaller dimensions at every level of the respiratory system. Sex hormones also play specific roles in lung inflammatory processes, breathing control and in response to diseases. The literature is extremely controversial because many factors need to be considered to avoid erroneous comparisons. The main difficulty lies in creating homogeneous groups of subjects according to age, body weight, lung/airway size, fluctuations in circulating hormone levels, and exercise protocol. Because almost all of the knowledge available in physiology is based on research in males, medicine for women is therefore less evidence-based than that being applied to men. Finally, the number of transsexual people is increasing and they represent new challenges for clinicians, due to the anatomical and physiological changes that they undergo.
Development and clinical translation of tubular constructs for tracheal tissue engineering: a review
Authors: Soriano Luis , Khalid Tehreem , Whelan Derek , O'Huallachain Niall , Redmond Karen C. , O'Brien Fergal J. , O'Leary Cian , Cryan Sally-Ann
Published: November 2021

Effective restoration of extensive tracheal damage arising from cancer, stenosis, infection or congenital abnormalities remains an unmet clinical need in respiratory medicine. The trachea is a 10–11 cm long fibrocartilaginous tube of the lower respiratory tract, with 16–20 tracheal cartilages anterolaterally and a dynamic trachealis muscle posteriorly. Tracheal resection is commonly offered to patients suffering from short-length tracheal defects, but replacement is required when the trauma exceeds 50% of total length of the trachea in adults and 30% in children. Recently, tissue engineering (TE) has shown promise to fabricate biocompatible tissue-engineered tracheal implants for tracheal replacement and regeneration. However, its widespread use is hampered by inadequate re-epithelialisation, poor mechanical properties, insufficient revascularisation and unsatisfactory durability, leading to little success in the clinical use of tissue-engineered tracheal implants to date. Here, we describe in detail the historical attempts and the lessons learned for tracheal TE approaches by contextualising the clinical needs and essential requirements for a functional tracheal graft. TE manufacturing approaches explored to date and the clinical translation of both TE and non-TE strategies for tracheal regeneration are summarised to fully understand the big picture of tracheal TE and its impact on clinical treatment of extensive tracheal defects.
Sex and gender in pulmonary arterial hypertension
Authors: Cheron Céline , McBride Susan Ainslie , Antigny Fabrice , Girerd Barbara , Chouchana Margot , Chaumais Marie-Camille , Jaïs Xavier , Bertoletti Laurent , Sitbon Olivier , Weatherald Jason , Humbert Marc , Montani David
Published: November 2021

Pulmonary arterial hypertension (PAH) is a rare disease characterised by pulmonary vascular remodelling and elevated pulmonary pressure, which eventually leads to right heart failure and death. Registries worldwide have noted a female predominance of the disease, spurring particular interest in hormonal involvement in the disease pathobiology. Several experimental models have shown both protective and deleterious effects of oestrogens, suggesting that complex mechanisms participate in PAH pathogenesis. In fact, oestrogen metabolites as well as receptors and enzymes implicated in oestrogen signalling pathways and associated conditions such asBMPR2mutation contribute to PAH penetrance more specifically in women. Conversely, females have better right ventricular function, translating to a better prognosis. Along with right ventricular adaptation, women tend to respond to PAH treatment differently from men. As some young women suffer from PAH, contraception is of particular importance, considering that pregnancy in patients with PAH is strongly discouraged due to high risk of death. When contraception measures fail, pregnant women need a multidisciplinary team-based approach. This article aims to review epidemiology, mechanisms underlying the higher female predominance, but better prognosis and the intricacies in management of women affected by PAH.
Long non-coding RNA TUG1 promotes proliferation and migration in PDGF-BB-stimulated HASMCs by regulating miR-216a-3p/SMURF2 axis
Authors: Wang Xinfang , Chen Junsong
Published: November 2021

Background

Abnormal proliferation and migration of human airway smooth muscle cells (HASMCs) play an important role in the development of childhood asthma. Long non-coding RNAs (lncRNAs) have been demonstrated to participate in HASMC proliferation and migration. We aimed to explore more effects and molecular mechanism of taurine upregulated gene 1 (TUG1) in childhood asthma.

Results

TUG1 and SMURF2 were overexpressed and miR-216a-3p was downregulated in childhood asthma patients and PDGF-BB-stimulated HASMCs. TUG1 knockdown attenuated PDGF-BB-triggered proliferation and migration of HASMCs. MiR-216a-3p was targeted by TUG1, and miR-216a-3p suppression counteracted the repressive effects of TUG1 interference on proliferation and migration in PDGF-BB-treated HASMCs. SMURF2 was a downstream target of miR-216a-3p, and SMURF2 upregulation abated the inhibiting effects of miR-216a-3p on migration and proliferation in PDGF-BB-exposed HASMCs. TUG1 sponged miR-216a-3p to positively regulate SMURF2 expression.

Conclusion

TUG1 downregulation inhibited PDGF-BB-induced HASMC proliferation and migration by regulating miR-216a-3p/SMURF2 axis, offering novel insight into the potential application of TUG1 for childhood asthma treatment.
RETRACTED ARTICLE: The association between neutrophil–lymphocyte ratio and poor outcomes following infant cardiac surgery
Authors: Gao Peng , Liu Jinping , Wang Xu , Zhang Peiyao , Jin Yu , Bai Liting , Li Yixuan
Published: November 2021

Background

Neutrophil–lymphocyte ratio (NLR) is a valuable indicator for evaluating inflammation and adverse outcomes after cardiac surgery. The objective of this study was to evaluate the association of perioperative NLR with clinical outcomes in infants undergoing congenital heart surgery with cardiopulmonary bypass.

Methods

We performed a retrospective review of 424 consecutive infants (≤ 1 year) undergoing cardiac surgery between January 2019 and September 2019. Neonates (≤ 28 days) and patients with incomplete NLR data were excluded. The study endpoint was a composite of poor outcomes after surgery. We assess the correlation between perioperative NLR and clinical outcomes. A receiver operating characteristic curve and multivariable logistic regression were applied to identify the prognosis performance of postoperative NLR for poor outcomes.

Results

A total of 68 (16%) infants experienced at least one of the poor outcomes. Postoperative NLR on the third day after the surgery showed the best prognostic significance (AUC = 0.763, 95%CI 0.700–0.826) among perioperative period, with a cut-off value of 2.05. Postoperative NLR was also strongly correlated with mechanical ventilation time, length of ICU and hospital stay (p < 0.001). Multivariable logistic regression revealed that elevated postoperative NLR (OR 3.722, 95%CI 1.895–7.309, p < 0.001) was an independent risk factor for poor outcomes in infants after cardiac surgery.

Conclusions

Postoperative NLR was correlated with increased mechanical ventilation time, length of ICU and hospital stay. Elevated postoperative NLR was an independent predictor for poor outcomes after cardiac surgery in infants.
Frequency and characteristics of promissory conference abstracts, i.e. abstracts without results, accepted at Cochrane Colloquia 1994-2020
Authors: Novak Darko , Puljak Livia
Published: November 2021

Background

The purpose of a conference abstract is to summarize the main points of a research-related report that will be presented at an academic conference. However, some conferences accept and publish abstracts without results, which is contrary to the basic idea of a conference abstract as a dissemination tool. A conference abstract without results included is called a “promissory abstract”. This study aimed to analyze the frequency and characteristics of promissory conference abstracts, i.e. abstracts submitted without results, accepted at Cochrane Colloquia.

Methods

We analyzed 8297 conference abstracts accepted at 25 Cochrane Colloquia, organized in 1994–2020, which were publicly available on the website of the Cochrane Library. Two authors screened abstracts to identify promissory abstracts. We extracted characteristics of promissory abstracts.

Results

Among abstracts accepted for Cochrane Colloquia, 8.7% were promissory; 475 (66%) were accepted as poster presentations, 241 (34%) as oral presentations and 1 as a workshop. The median number of authors in promissory abstracts was 4 (interquartile range: 3 to 6 authors). In 245 (34%) promissory abstracts, affiliations of authors were not reported. The authors were most commonly affiliated with the following countries: UK (472; 36%), Canada (N = 123; 26%), China (N = 76; 16%), United States (N = 66; 14%) and Australia (N = 53; 11%). There were 512 (71%) promissory abstracts in which study design was not reported.

Conclusion

Promissory abstracts were commonly accepted at Cochrane Colloquia. Such abstracts deserve further attention, as they are detrimental in terms of the dissemination of new knowledge presented at a conference. Conference organizers could ask authors to update the abstract results subsequently to enable the dissemination of information presented at a conference.
PGRMC1-dependent lipophagy promotes ferroptosis in paclitaxel-tolerant persister cancer cells
Authors: You Ji Hyeon , Lee Jaewang , Roh Jong-Lyel
Published: November 2021

Background

Progesterone receptor membrane component 1 (PGRMC1) is a heme-binding protein inducing dimerization with cytochrome P450, which mediates chemoresistance. Increased PGRMC1 expression is found in multiple types of resistant cancers, but the role of PGRMC1 in the ferroptosis of cancer cells remains unrevealed. Therefore, we examined the role of PGRMC1 in promoting ferroptosis in paclitaxel-tolerant persister cancer cells (PCC).

Methods

The effects of ferroptosis inducers and PGRMC1 gene silencing/overexpression were tested on head and neck cancer (HNC) cell lines and mouse tumor xenograft models. The results were analyzed about cell viability, death, lipid ROS and iron production, mRNA/protein expression and interaction, and lipid assays.

Results

PCC had more free fatty acids, lipid droplets, and fatty acid oxidation (FAO) than their parental cells. PCC was highly sensitive to inhibitors of system xc− cystine/glutamate antiporter (xCT), such as erastin, sulfasalazine, and cyst(e)ine deprivation, but less sensitive to (1S,3R)-RSL3. PGRMC1 silencing in PCC reduced ferroptosis sensitivity by xCT inhibitors, and PGRMC1 overexpression in parental cells increased ferroptosis by xCT inhibitors. Lipid droplets were degraded along with autophagy induction and autophagosome formation by erastin treatment in PCC. Lipophagy was accompanied by increased tubulin detyrosination, which was increased by SIRT1 activation but decreased by SIRT1 inhibition. FAO and lipophagy were also promoted by the interaction between lipid droplets and mitochondria.

Conclusion

PGRMC1 expression increased FAO and ferroptosis sensitivity from in vivo mice experiments. Our data suggest that PGRMC1 promotes ferroptosis by xCT inhibition in PCC.
Beech tree masting explains the inter-annual variation in the fall and spring peaks of Ixodes ricinus ticks with different time lags
Authors: Bregnard Cindy , Rais Olivier , Herrmann Coralie , Kahl Olaf , Brugger Katharina , Voordouw Maarten J.
Published: November 2021

Background

The tickIxodes ricinusis an important vector of tick-borne diseases including Lyme borreliosis. In continental Europe, the nymphal stage ofI. ricinusoften has a bimodal phenology with a large spring peak and a smaller fall peak. There is consensus about the origin of the spring nymphal peak, but there are two alternative hypotheses for the fall nymphal peak. In the direct development hypothesis, larvae quest as nymphs in the fall of the same year that they obtained their larval blood meal. In the developmental diapause hypothesis, larvae overwinter in the engorged state and quest as nymphs one year after they obtained their larval blood meal. These two hypotheses make different predictions about the time lags that separate the larval blood meal and the density of questing nymphs (DON) in the spring and fall.

Methods

Inter-annual variation in seed production (masting) by deciduous trees is a time-lagged index for the density of vertebrate hosts (e.g., rodents) which provide blood meals for larval ticks. We used a long-term data set on the masting of the European beech tree and a 15-year study on the DON at 4 different elevation sites in western Switzerland to differentiate between the two alternative hypotheses for the origin of the fall nymphal peak.

Results

QuestingI. ricinusnymphs had a bimodal phenology at the three lower elevation sites, but a unimodal phenology at the top elevation site. At the lower elevation sites, the DON in the fall was strongly correlated with the DON in the spring of the following year. The inter-annual variation in the densities ofI. ricinusnymphs in the fall and spring was best explained by a 1-year versus a 2-year time lag with the beech tree masting index. Fall nymphs had higher fat content than spring nymphs indicating that they were younger. All these observations are consistent with the direct development hypothesis for the fall peak ofI. ricinusnymphs at our study site. Our study provides new insight into the complex bimodal phenology of this important disease vector.

Conclusions

Public health officials in Europe should be aware that following a strong mast year, the DON will increase 1 year later in the fall and 2 years later in the spring. Studies ofI. ricinuspopulations with a bimodal phenology should consider that the spring and fall peak in the same calendar year represent different generations of ticks.

Graphical Abstract
Global diversity of the gene encoding the Pfs25 protein—a Plasmodium falciparum transmission-blocking vaccine candidate
Authors: Sookpongthai Pornpawee , Utayopas Korawich , Sitthiyotha Thassanai , Pengsakul Theerakamol , Kaewthamasorn Morakot , Wangkanont Kittikhun , Harnyuttanakorn Pongchai , Chunsrivirot Surasak , Pattaradilokrat Sittiporn
Published: November 2021

Background

Vaccines against the sexual stages of the malarial parasitePlasmodium falciparumare indispensable for controlling malaria and abrogating the spread of drug-resistant parasites. Pfs25, a surface antigen of the sexual stage ofP. falciparum, is a leading candidate for transmission-blocking vaccine development. While clinical trials have reported that Pfs25-based vaccines are safe and effective in inducing transmission-blocking antibodies, the extent of the genetic diversity ofPfs25in malaria endemic populations has rarely been studied. Thus, this study aimed to investigate the global diversity ofPfs25inP. falciparumpopulations.

Methods

A database of 307Pfs25sequences ofP. falciparumwas established. Population genetic analyses were performed to evaluate haplotype and nucleotide diversity, analyze haplotypic distribution patterns ofPfs25in different geographical populations, and construct a haplotype network. Neutrality tests were conducted to determine evidence of natural selection. Homology models of thePfs25haplotypes were constructed, subjected to molecular dynamics (MD), and analyzed in terms of flexibility and percentages of secondary structures.

Results

ThePfs25gene ofP. falciparumwas found to have 11 unique haplotypes. Of these, haplotype 1 (H1) and H2, the major haplotypes, represented 70% and 22% of the population, respectively, and were dominant in Asia, whereas only H1 was dominant in Africa, Central America, and South America. Other haplotypes were rare and region-specific, resulting in unique distribution patterns in different geographical populations. The diversity inPfs25originated from ten single-nucleotide polymorphism (SNP) loci located in the epidermal growth factor (EGF)-like domains and anchor domain. Of these, an SNP at position 392 (GGA/GCA), resulting in amino acid substitution 131 (Gly/Ala), defined the two major haplotypes. The MD results showed that the structures of H1 and H2 variants were relatively similar. Limited polymorphism inPfs25could likely be due to negative selection.

Conclusions

The study successfully established aPfs25sequence database that can become an essential tool for monitoring vaccine efficacy, designing assays for detecting malaria carriers, and conducting epidemiological studies ofP. falciparum. The discovery of the two major haplotypes, H1 and H2, and their conserved structures suggests that the current Pfs25-based vaccines could be used globally for malaria control.

Graphical Abstract
Multiscale heterogeneity in gastric adenocarcinoma evolution is an obstacle to precision medicine
Authors: Röcken Christoph , Amallraja Anu , Halske Christine , Opasic Luka , Traulsen Arne , Behrens Hans-Michael , Krüger Sandra , Liu Anne , Haag Jochen , Egberts Jan-Hendrik , Rosenstiel Philip , Meißner Tobias
Published: November 2021

Background

Cancer is a somatic evolutionary disease and adenocarcinomas of the stomach and gastroesophageal junction (GC) may serve as a two-dimensional model of cancer expansion, in which tumor subclones are not evenly mixed during tumor progression but rather spatially separated and diversified. We hypothesize that precision medicine efforts are compromised when clinical decisions are based on a single-sample analysis, which ignores the mechanisms of cancer evolution and resulting intratumoral heterogeneity. Using multiregional whole-exome sequencing, we investigated the effect of somatic evolution on intratumoral heterogeneity aiming to shed light on the evolutionary biology of GC.

Methods

The study comprised a prospective discovery cohort of 9 and a validation cohort of 463 GCs. Multiregional whole-exome sequencing was performed using samples form 45 primary tumors and 3 lymph node metastases (range 3–10 tumor samples/patient) of the discovery cohort.

Results

In total, the discovery cohort harbored 16,537 non-synonymous mutations. Intratumoral heterogeneity of somatic mutations and copy number variants were present in all tumors of the discovery cohort. Of the non-synonymous mutations, 53–91% were not present in each patient’s sample; 399 genes harbored 2–4 different non-synonymous mutations in the same patient; 175 genes showed copy number variations, the majority being heterogeneous, including CD274 (PD-L1). Multi-sample tree-based analyses provided evidence for branched evolution being most complex in a microsatellite instable GC. The analysis of the mode of evolution showed a high degree of heterogeneity in deviation from neutrality within each tumor. We found evidence of parallel evolution and evolutionary trajectories: different mutations of SMAD4 aligned with different subclones and were found only in TP53 mutant GCs.

Conclusions

Neutral and non-neutral somatic evolution shape the mutational landscape in GC along its lateral expansions. It leads to complex spatial intratumoral heterogeneity, where lymph node metastases may stem from different areas of the primary tumor, synchronously. Our findings may have profound effects on future patient management. They illustrate the risk of mis-interpreting tumor genetics based on single-sample analysis and open new avenues for an evolutionary classification of GC, i.e., the discovery of distinct evolutionary trajectories which can be utilized for precision medicine.
Patient-focused pathogen genetic counselling—has the time come?
Authors: Ferdinand Angeline S , Hocking Jane S , Denholm Justin T. , Howden Benjamin P. , Williamson Deborah A.
Published: November 2021

Ensuring accordance with principles of healthcare ethics requires improved communication of pathogen genomic data. This could include educating healthcare professionals in communicating pathogen genomic information to individuals, developing ethical frameworks for reporting pathogen genomic results to individuals, responsible media reporting guidelines, and counselling for individuals (‘pathogen genetic counselling’).
Disseminated tuberculosis with myelofibrosis presentation: a case report
Authors: Khatuni Mahdi , Ghalamkari Marziyeh , Ameli Fereshteh , Yekehtaz Habibeh
Published: November 2021

Background

Primary myelofibrosis is a rare myeloproliferative disorder in middle-aged and old adults and should be distinguished from secondary and reactive causes of bone marrow fibrosis because, in reactive fibrosis, treatment approaches depend on the underlying etiology.

Case presentation

Here we report the case of a middle-aged Iranian man who was diagnosed and treated as primary myelofibrosis at presentation, and whose final diagnosis was disseminated tuberculosis with reactive bone marrow fibrosis.

Conclusions

It is prudent to evaluate the potential causes of myelofibrosis in any patient with the diagnosis primary myelofibrosis. Tuberculosis can be an important etiology of bone marrow fibrosis, especially in endemic areas.
Alternative method’s results for the non targeted determination of xenobiotics in food by means of high resolution and accuracy mass spectrometry
Authors: Scarpone Rossana , Rocchi Rachele , Bacà Federico , Rosato Roberta , Chiumiento Francesco , Migliorati Giacomo
Published: November 2021

The application of a high resolution and accurate mass spectrometry (HRAMS) approach to detect xenobiotics in different food matrices by means of non targeted determination by UHPLC-Orbitrap followed by data processing analysis was described. Three case studies were reported to demonstrate the possibility to identify unexpected substances in different food commodities overcomes targeted method. This innovative approach could lay the foundation for its applicability to routine analysis in the near future giving the possibility to open new horizons to the research of a wide range of xenobiotics.
What motivates informal carers to be actively involved in research, and what obstacles to involvement do they perceive?
Authors: Malm Camilla , Andersson Stefan , Kylén Maya , Iwarsson Susanne , Hanson Elizabeth , Schmidt Steven M.
Published: November 2021

Background

Due to demographic changes and a strained public sector operating in many countries globally, informal care is increasing. Currently, at least 1.3 million adults in Sweden regularly provide help, support and/or care to a family member/significant other. With no sign of an imminent decrease in their caring activities, it is important that informal carers are considered as a key stakeholder group within research that affects them, e.g., the co-design of carer and/or dyadic support interventions. The objective of this descriptive, quantitative study was to investigate informal carers’ perceived motivations and obstacles to become involved in research.

Methods

A cross-sectional survey design was adopted, using first-wave data from a panel study. The data, collected in Sweden between September 2019 and March 2020, included survey responses from 147 informal carers who were either aged 60+ years themselves or were caring for someone who was aged 60+ years.

Results

Our main results showed that informal carers are, in general, interested in research. Slightly fewer were interested in becoming actively involved themselves, but older age was the only characteristic significantly associated with less interest of being actively involved. Two latent motivational dimensions emerged from the factor analysis: ‘family motivation’ and ‘the greater good motivation’. These, according to our results, almost equally valued dimensions, described the differing reasons for informal carers to become involved in research. The most common perceived obstacle was lack of time and it was reported by more women than men.

Conclusion

Our study contributes with new knowledge of informal carers’ perceived motivations and obstacles regarding carer involvement in research. Paying attention to the differing motivational dimensions held by informal carers could help researchers create conditions for more inclusive and systematic participation of informal carers within research. Thereby, increasing the opportunities for research that is deemed to be of higher societal impact. IRRID (International Registered Report Identifier): RR2-10.2196/17759.
More Venezuelans in Trinidad in the 21st century
Authors: Herbert Chinyere
Published: November 2021

Venezuelan 'asylum seekers' arriving at the coast of Trinidad enter a new reality and become a part of a world of politics and processing like most migrants do. By no fault of their own, they embody local and global tensions concerning migration policies, border control, government authority, and international human rights and protection. This paper raises questions about the complex status and identity of Venezuelan migrants in Trinidad who came seeking asylum in recent years. The results demonstrate that internationally accepted “refugee” and “asylum seeker” categorization is highly unstable in the present context due to the core economic issues underlying forced migration. In line with previous anthropological research, the study highlights the ways in which labels do not encapsulate the local and global causes underlying forced migration and displacement. While international law is well-meaning, there remains a lot to be desired in the long-term protection of displaced people. There are also geographic and economic limits of small islands to absorb large numbers of displaced persons which, to date, has not been recognized by international human rights organizations.
Molecular characterization and phylogenetic analysis of collected mosquitoes (Diptera: Culicidae) from Northcentral Nigeria using mitochondrial COI and ribosomal IGS gene regions
Authors: Iyiola Oluyinka A. , Kamaldeen-Ibrahim Aishat T. , Shaibu Rahmat D. , Shittu Olalere , Fadipe Temitope O. , Adelaja Olukayode J. , Tijani Muyideen K. , Afolabi Hajarat A.
Published: November 2021

Background

Mosquitoes are important vectors of disease-causing organisms such as filarial worms, malaria parasites, and arboviruses endemic to sub-Saharan Africa including Nigeria. Malaria is a disease caused by a plasmodium parasite, transmitted by the bite of infected mosquitoes and is no doubt a public health concern. There is limited information on the genetic diversity of mosquitoes in Nigeria. This is necessary because information about the genetic diversity of mosquitoes is a very important step towards vector control and management with the aim to mitigate or eliminate burden resulting from malaria and other diseases caused by mosquitoes. In the present study, we investigated the genetic variability and relatedness of mosquitoes based on the DNA sequences of the mitochondrial cytochrome oxidase subunit I (COI) and ribosomal intergenic non-coding spacer gene regions (IGS). Mosquitoes were collected from five different states in Northcentral Nigeria, they were morphologically identified using standard keys and genomic DNA was extracted. The specific regions of interests were amplified, and the PCR products were then sequenced.

Results

PCR was able to successfully amplify the expected amplicon sizes of COI and IGS sequences (710 and 169) base pairs, respectively. For COI sequence, pairwise genetic distance between mosquito species ranged from 0.00 to 0.17 in the COI sequences. The pairwise genetic distance among Culex, Aedes and Anopheles species in the IGS sequences ranged from 0.000 to 0.118. Phylogenetic analysis of the sequences of the mitochondrial cytochrome oxidase subunit showed that there was genetic diversity amongst the different mosquito species sampled. It effectively showed marked differences between Culicine and Anopheline mosquitoes.

Conclusions

The ribosomal IGS primers used for this study only amplified Anopheles spp. However, it revealed that there is diversity among the Anopheles gambiae and Anopheles arabiensis samples collected. This study concludes that the mitochondrial COI and ribosomal IGS gene regions are reliable markers for mosquito genetic diversity study and will surely yield a reliable result for molecular diversity assessment of mosquito species.